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Fortezza, Fulvio, Alessandro Pagano, and Roberta Bocconcelli. "Serial crowdfunding in start-up development: a business network view." Journal of Business & Industrial Marketing 36, no. 13 (2021): 250–62. http://dx.doi.org/10.1108/jbim-05-2020-0243.
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Purpose Even though the crowdfunding (CF) literature is rapidly reaching its maturity phase, the topic of serial CF (i.e. the participation in more than one CF campaign) is as much promising as still largely under explored. This study thus aims to offer a thorough view of the dynamic and complex processes characterizing the participation of the start-ups to more than one campaign adopting a business network perspective. Design/methodology/approach In line with an explorative research aim, a multiple case study analysis is performed by taking into consideration four start-ups engaged in more than one CF campaigns with different combinations of equity and non-equity CF, adopting the actor–resource–activity (ARA) model as theoretical framework. Findings Multiple CF campaigns are embedded in the overall changing startup’s network and are affected by the concurrent and overlapping startup’s development processes. From this standpoint, the adoption of the ARA model suggests to reconsider the “serial” dimension of multiple CF campaigns. These processes can be more or less “linear” as they could be affected by the combination of CF schemes and by the degree of alignment of actors, activities and resources, whose “assembly” can be facilitated by learning processes and impaired by unexpected circumstances. Originality/value This paper explores in depth the startup’s serial CF journey, building on recent studies calling for stronger analyses of the directions and outcomes of innovative funding trajectories pursued and implemented by new business ventures. From this standpoint, to the best of the authors’ knowledge, this is the first study to consider a complete spectrum of combinations between CF schemes within serial CF, thus allowing for a better understanding of the role of such a factor within a dynamic and contextual view, that is, that offered by the business network perspective. This paper also contributes to the Industrial Marketing and Purchasing research on start-ups.
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Ooi, Joo-On, Fawnizu Azmadi Hussin, and Mohd Nordin Zakaria. "Fine-Grained Overhead Characterisation of Cross-ISA DBTO for Multicore Processor." Indonesian Journal of Electrical Engineering and Computer Science 10, no. 3 (2018): 1036. http://dx.doi.org/10.11591/ijeecs.v10.i3.pp1036-1044.
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<span>The emergence of modern portable software, start to behaved hybrid short-long running combined applications, in which an active apps may invoked others to fulfill task requirements. Thus the implementation of Dynamic Translation and Optimisation (DBTO) into heterogeneous multicore system-on-chip (SoC) will require careful re-study, to ensure efficient usage of most available cores. In order to improve efficiency in supporting this Instruction Set Architecture (ISA) diversity of computing platforms, mix modes of statically and dynamically Binary Translation and Optimization system, or DBTO, need to utilize concurrent compilation techniques, to better service the combined applications processing. This research deep dived into finer-grained DBTO overhead analysis, to provide categorization and characterization of overhead sources in breakdown stages during concurrent instruction processing. A dual-engine of translation and optimization is constructed for finer managemnt of start-up overheads. Helper functions, i.e. LoadLink/StoreCondition (LL/SC) are derived from atomic instructions, to create multiple helper thread supported by multiple host cores, for better instruction translation and optimization operation concurrently. Our experiment platform, evaluated through PARSEC-3.0 benchmark suite, shows performance improvement approaching 2.0x for apps based programs and 1.25x for kernel based programs, for x86 to X86-64 emulation. This technique possess great potential and serve as research based platform for future binary translation technique development, including adaptive method.</span>
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Braune, H., K. J. Brunner, H. P. Laqua, et al. "Concurrent operation of 10 gyrotrons at W7-X experience and improvement opportunities." EPJ Web of Conferences 187 (2018): 01003. http://dx.doi.org/10.1051/epjconf/201818701003.
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At the stellarator Wendelstein 7-X (W7-X) Electron Cyclotron Resonance Heating (ECRH) is the main heating system for steady-state operation and was the only available heating system during the operation phase OP1.2a in 2017. The ECRH, equipped with 10 operational 140 GHz gyrotrons [1], was used for different tasks at W7-X such as wall conditioning, controlled plasma start-up from the neutral gas up to steady state plasma control and different heating scenarios such as X2-mode and O2-mode heating as well as current drive (ECCD). The operational experiences and improvement opportunities of the ECRH plant will be discussed.
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Thng, Shiqi, Simon Pearson, and Justin W. L. Keogh. "Pushing up or pushing out—an initial investigation into horizontal- versus vertical-force training on swimming start performance: a pilot study." PeerJ 9 (February 24, 2021): e10937. http://dx.doi.org/10.7717/peerj.10937.
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Background The block phase in the swimming start requires a quick reaction to the starting signal and a large take-off velocity that is primarily horizontal in direction. Due to the principle of specificity of training, there is a potential benefit of performing a greater proportion of horizontal force production exercises in a swimmers’ dry-land resistance training sessions. Therefore, the purpose of this pilot study was to provide an insight into the effects of a horizontal- (HF) vs vertical-force (VF) training intervention on swim start performance. Methods Eleven competitive swimmers (six males (age 20.9 ± 1.8 years, body mass 77.3 ± 9.7 kg, height 1.78 ± 0.05 m) and five females (age 21.4 ± 2.0 years, body mass 67.5 ± 7.4 kg, height 1.69 ± 0.05 m)) completed 2 weekly sessions of either a horizontal- or vertical-force focused resistance training programme for 8 weeks. Squat jump force-time characteristics and swim start kinetic and kinematic parameters were collected pre- and post-intervention. Results Across the study duration, the swimmers completed an average of nine swimming sessions per week with an average weekly swim volume of 45.5 ± 17.7 km (HF group) and 53 ± 20.0 km (VF group), but little practice of the swim start per week (n = 9). Within-group analyses indicated a significant increase in predicted one repetition maximum (1RM) hip thrust strength in the HF group, as well as significant increases in grab resultant peak force but reductions in resultant peak force of the block phase for the VF group. No significant between-group differences in predicted 1RM hip thrust and back squat strength, squat jump force-time and swim start performance measures were observed after 8 weeks of training. Significant correlations in the change scores of five block kinetic variables to time to 5 m were observed, whereby increased block kinetic outputs were associated with a reduced time to 5 m. This may be indicative of individual responses to the different training programmes. Discussion The results of this current study have been unable to determine whether a horizontal- or vertical-force training programme enhances swim start performance after an 8-week training intervention. Some reasons for the lack of within and between group effects may reflect the large volume of concurrent training and the relative lack of any deliberate practice of the swim start. Larger samples and longer training duration may be required to determine whether significant differences occur between these training approaches. Such research should also look to investigate how a reduction in the concurrent training loads and/or an increase in the deliberate practice of the swim start may influence the potential changes in swim start performance.
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Hwang, Steven R., Alexandra Higgins, Betsy LaPlant, et al. "Effect of antibiotic use prior to or concurrent with immune checkpoint inhibitors on outcomes in patients with Hodgkin lymphoma." Journal of Clinical Oncology 38, no. 15_suppl (2020): 8030. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.8030.
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8030 Background: There is growing interest in the identification of modifiable patient-specific factors that may predict response to immune checkpoint inhibitors (ICIs) in classical Hodgkin lymphoma (cHL). Recently, it has been proposed that antibiotic use could decrease the efficacy of ICIs in the treatment of advanced solid malignancies. The objective of our study is to assess whether antibiotic use prior to or concurrent with ICIs is associated with changes in outcomes in patients with cHL. Methods: Patients who received a PD-1 or CTLA-4 blocker for the treatment of cHL at Mayo Clinic Rochester between January 1, 2011 and October 20, 2018 were identified. We conducted a longitudinal retrospective chart review to identify those who received antibiotics within 30 or 90 days prior to initiation or concurrent with ICI therapy. Univariate cox regression analysis was used to assess for an association between antibiotic use and overall survival (OS) and progression-free survival (PFS) within these groups; a time-dependent variable was used for concurrent antibiotic use. Results: A total of sixty-two patients were identified (61% male, median age at ICI initiation 35 years [range: 19-87]). Median duration of follow up from ICI start was 38 months (range: 4-78). Twenty-one patients (34%) received antibiotics within 90 days of initiation of ICI, of which thirteen (21%) received antibiotics within 30 days. Thirty-five patients (57%) received antibiotics concurrently with ICI. Concurrent and prior antibiotic use within 90 days of ICI were both associated with inferior PFS (concurrent HR = 6.38 [95% CI 3.02-13.47]; 90-day HR = 2.21 [95% CI 1.10-4.47]) and OS (concurrent HR = 8.77 [95% CI 1.91-40.36]; 90-day HR = 2.96 [95% CI 1.09-8.04]). Conclusions: Antibiotic use is associated with inferior outcomes in patients with cHL treated with ICIs in this single institution cohort. This may reflect potential antibiotic effects on the gut microbiome (GMB) and immune system as has been suggested in prior studies. Further confirmatory studies and examination of potential confounding covariates are needed.
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Bendixen, Alexandra, Gábor P. Háden, Renáta Németh, Dávid Farkas, Miklós Török, and István Winkler. "Newborn Infants Detect Cues of Concurrent Sound Segregation." Developmental Neuroscience 37, no. 2 (2015): 172–81. http://dx.doi.org/10.1159/000370237.
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Separating concurrent sounds is fundamental for a veridical perception of one's auditory surroundings. Sound components that are harmonically related and start at the same time are usually grouped into a common perceptual object, whereas components that are not in harmonic relation or have different onset times are more likely to be perceived in terms of separate objects. Here we tested whether neonates are able to pick up the cues supporting this sound organization principle. We presented newborn infants with a series of complex tones with their harmonics in tune (creating the percept of a unitary sound object) and with manipulated variants, which gave the impression of two concurrently active sound sources. The manipulated variant had either one mistuned partial (single-cue condition) or the onset of this mistuned partial was also delayed (double-cue condition). Tuned and manipulated sounds were presented in random order with equal probabilities. Recording the neonates' electroencephalographic responses allowed us to evaluate their processing of the sounds. Results show that, in both conditions, mistuned sounds elicited a negative displacement of the event-related potential (ERP) relative to tuned sounds from 360 to 400 ms after sound onset. The mistuning-related ERP component resembles the object-related negativity (ORN) component in adults, which is associated with concurrent sound segregation. Delayed onset additionally led to a negative displacement from 160 to 200 ms, which was probably more related to the physical parameters of the sounds than to their perceptual segregation. The elicitation of an ORN-like response in newborn infants suggests that neonates possess the basic capabilities of segregating concurrent sounds by detecting inharmonic relations between the co-occurring sounds.
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Skołud, Bożena, Damian Krenczyk, and Marcin Zemczak. "An Idea of the Continuous Flow for Concurrent Multi-Assortment Production." Applied Mechanics and Materials 809-810 (November 2015): 1444–49. http://dx.doi.org/10.4028/www.scientific.net/amm.809-810.1444.
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Nowadays in the era of advanced stage of Lean Manufacturing concept forces manufacturers to research of new idea of the production flow organization and to implement more and more innovative organizational solutions. The article presents the authors concept of implementation the combination of continuous flow and concurrent multi assortment production. Continuous flow is an approach to discrete manufacturing that contrast with batch production and is associated with just-in-time and Kanban production. The goal is an optimal balanced line. The paradigm aim is to achieve single-piece flow. For this purpose the similarity of the products that use the shared resources and start their production one by one in a predetermined sequence is searched. In addition, it is recommended to transform the internal setup into external one for eliminating investment in set-up times. This concept is similar to the group technology developed down in 70’s and based on the classification of products into four groups.
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Plut, Domen, and Tamara Gorjanc. "A case of a newborn with an intrahepatic congenital portosystemic venous shunt with concurrent congenital duodenal web." Acta Radiologica Open 8, no. 6 (2019): 205846011985417. http://dx.doi.org/10.1177/2058460119854173.
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Intrahepatic congenital portosystemic venous shunts are rare vascular anomalies. We report a unique case of a neonate with an intrahepatic congenital portosystemic venous shunt with concurrent congenital duodenal web. Such association has not been previously reported to our knowledge. Interestingly, the shunt became apparent on the seventh day, after a delayed start of oral feeding due to the neonate’s recovery from the duodenal web surgery. The shunt was small and the clinical symptomatology mild. No direct treatment was required. The laboratory and the ultrasound follow-up of the child noted a spontaneous resolution of the shunt by the age of six months.
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Amara, Sofiene, Tiago Manuel Barbosa, Oussama Gaied Chortane, et al. "Effect of Concurrent Resistance Training on Lower Body Strength, Leg Kick Swimming, and Sport-Specific Performance in Competitive Swimmers." Biology 11, no. 2 (2022): 299. http://dx.doi.org/10.3390/biology11020299.
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The present study investigated the effect of 9 weeks of combined resistance training (aquatic and dry land resistance) on maximum lower body strength, leg kick, and swimming performance in competitive swimmers. Twenty-two male national competitive swimmers were randomly assigned into two groups: experimental group (EG: age = 16.2 ± 0.3 years) or control group (CG: age = 16.3 ± 0.3 years). The EG performed a combined resistance training while the CG group completed their usual training. One repetition maximum (1RM) back squat, 30 m leg kick, and swimming performance (100 m front crawl, start and turn) were evaluated in pre and post test. The findings showed a significant increase in 1RM back squat (d = 1.90; 14.94 ± 1.32%) after 9 weeks of combined resistance training. In addition, ours results revealed a significant improvement in 30 m leg kick swimming (d = 2.11; 5.84 ± 0.16%) and in all swimming, start and turn performances (d = 1.83 to 2.77; 2.69 ± 0.18% to 15.14 ± 1.06%) in EG. All dependent variables remained unchanged in the CG. To sum up, 9 weeks of combined resistance training can improve the maximum lower body strength and leg kick swimming performance. These improvements can be the essential factors that subsequently positively affected swimming, start and turn performances. Combined resistance training is an effective training that can be incorporated by coaches and swimmers into their programs to improve strength, leg kick swimming, and, subsequently, swimming performance in competitive swimmers.
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Cao, Yen Thi Kim Hong, Michael Elias, Janson Trieu, Vanessa Rojas, Michael J. Anderson, and Nicholas J. Vogelzang. "Fracture rates in radium223 (Ra223) treated mCRPC patients (pts): A real-world analysis in 177 pts treated at a single community center 2010-2018." Journal of Clinical Oncology 38, no. 6_suppl (2020): 41. http://dx.doi.org/10.1200/jco.2020.38.6_suppl.41.
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41 Background: Ra223 was FDA approved 5/15/13 as a life extending therapy in conjunction with Standard of Care (SOC) agents for mCRPC in the ALSYMPCA trial. However, agents such as abiraterone (abi) and enzalutamide (enza) were not part of the SOC regimens allowed during conduct of ALSYMPCA. Phase 2 and expanded access programs (EAPs) suggested enhanced activity when abi or enza were given with Ra223. A phase 3 trial (ERA223 Smith et al. Lancet Oncology 2019) comparing Ra223 +/-abi showed an increased fracture (Fx) rate (29% vs 11%) and no survival advantage for the combo, leading to regulatory restrictions on abi and Ra223 combination therapy. However, only 41% of pts in ERA223 received bone health agents (BHAs). This center participated in ALSYMPCA and in the US EAP and based on those data, BHAs were consistently administered monthly during Ra223. The Fx rate in ERA223 did not mirror our clinical experience and thus our institutional Ra223 database was reviewed. Methods: Cohort analysis of pts who received Ra223 for mCRPC under the supervision of NJV. Follow-up was until date of death or last data entry. Results: 177 pts received Ra223 between 11/2010 and 8/2018. Median age 73 at 1st Ra223 (range 40-93); Median PSA (15.8- at 1st Ra223 (range 0.1-1952); Demographics-AA-10, C-130, Asian-9, unspecified- 28; Median Gleason score 8, Median Alk Phos 95 at 1st Ra233 (range 25-1515). Median mos of prior ADT 23 (range 0-247mos). Pts on concurrent abi + pred + Ra223 69 (39%); abi + Ra223 7 (4%); abi + pred prior to Ra223 54 (31%); abi prior to Ra223 4 (2.3%). Enza + Ra223 51 (29%); enza prior to Ra223 39 (22%). 164 pts (93%) were on BHAs before or during Ra223 (denosumab 86 concurrent vs zoledronic acid 64 concurrent). 10 pts (5.6%) had Fxs reported after the start of Ra223 (4 with concurrent abi, 3 with concurrent enza, 3 on Ra 223 w/o concurrent abi or enza; 8/10 Fxs occurred while on BHA’s). Conclusions: In contrast to the ERA223 study where 11-29% of pts experienced Fxs, this real-world experience with Ra223 in which 164/177 pts (93%) received BHAs before or during Ra223 saw a 5.6% Fx rate. When Ra223 was given concurrently with abi or enza and BHAs, the Fx rate was 6/177 (3.4%).
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Hofer, Thomas Philipp, Lukas Käsmann, Carolyn Pelikan, et al. "Dynamic changes of lymphocyte subsets during multimodal treatment of patients with inoperable stage III NSCLC." Journal of Clinical Oncology 38, no. 15_suppl (2020): e21011-e21011. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.e21011.
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e21011 Background: Lymphocytopenia is associated with deterioration of patient survival in solid cancers treated with concurrent chemo/radiotherapy (cCRT). A prospective analysis of peripheral blood mononuclear cells during cCRT in inoperable stage III NSCLC patients was performed to determine dynamic changes of individual lymphocyte subsets. Methods: Twenty-one patients were prospectively enrolled in this study. Eighteen patients received platinum-based cCRT, seven of them received, additionally, concurrent and/or sequential immune checkpoint-inhibition (ICI). Thoracic irradiation (TRT) was delivered with median total dose of 62Gy (31 daily fractions of 2Gy) in all patients. Peripheral blood was collected 5-10 days before treatment (A1), three weeks after start of cCRT (A3), on the last day of TRT (RTend) and during follow-up. Samples were analyzed using polychromatic flow cytometry. Results are reported for time-points A1, A3 and RTend. Results: Sixteen patients met final analysis criteria, 50% of them received concurrent and/or sequential ICI. All patients developed severe lymphocytopenia; in 81% of them lymphocyte nadir was documented at A3. Lymphocyte subsets, B cells, T cells (CD4, CD8), regulatory T cells, and NK cells, decreased with medians between 99.9% and 59%. Lymphocyte nadir was independent of the absolute numbers of immune cells that a patient had before start of cCRT or whether additional ICI was applied. From A3 to RTend, all lymphocyte subsets started to recover in patients treated with cCRT alone, while they remained low in patients who received additional ICI. The ratios of CD4/CD8 and CD8/Treg cells did not change during treatment (A1 to RTend) and was not different between the patients treated with or without ICI. However, the fraction of PD-1 cells among CD8 T-cells decreased in patients treated with ICI and remained low until RTend (range 0.55%-13.8%). In contrast, in 50% of patients treated with cCRT alone, PD-1 T-cell among CD8 T-cells increased and remained high (range 6.8%-46.3%) until RTend. Conclusions: Delayed recovery of lymphocyte subsets in peripheral blood was observed in patients treated with cCRT combined with concurrent or sequential ICI. A decrease of PD-1 T-cells among CD8 T-cells was described exclusively in patients treated with additional ICI.
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Plastaras, John Peter, Abigail Berman, Smith Apisarnthanarax, et al. "Proton reirradiation of locally recurrent pancreatic and ampullary adenocarcinomas." Journal of Clinical Oncology 31, no. 4_suppl (2013): 317. http://dx.doi.org/10.1200/jco.2013.31.4_suppl.317.
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317 Background: Local recurrences of pancreatic and ampullary cancer can be painful and cause significant morbidity. Their treatment after resection and chemoradiation is particularly challenging. A second course of radiotherapy (RT) in a previously radiated field carries the risk of RT-induced tissue injury. Proton therapy (PRT) may offer an advantage in the reirradiation setting due to the lack of exit dose and potential sparing of normal tissues. Methods: Between 2/2011 and 8/2012, 10 adult patients (pts) with locally recurrent pancreatic or ampullary malignancies in or near prior treatment fields began reirradiation. Toxicity was graded according to the CTC v4.0. Acute toxicity was defined within 90 days from start of PRT. Results: Median follow-up was 8.2 months (1.1-19.1) from the start of retreatment and 15 months (2.4-27.8) from the development of local recurrence. Mean age was 67 (54-75). Nine of the pts had pancreatic adenocarcinoma and 1 had ampullary adenocarcinoma. Median clinical target volume size was 86.4 cc (15-236). Nine received concurrent 5-fluorouracil or capecitabine-based chemotherapy. The median total dose was 59.4 Gy(RBE)(45-59.4); all pts were treated with PRT exclusively, except for one pt who was treated with 36% photon volumetric arc therapy. The median prior dose was 50.4 Gy (30-59.4). The median interval between RT courses was 34 months (17-461). Nine pts had Grade 2 and 1 had only Grade 1 non-hematologic acute toxicity. No Grade 2 or higher non-hematologic RT-related toxicities were observed after 90 days from the start of RT. Five pts developed metastatic disease at a median of 7.4 months (4.8-13.2) after starting RT, 1 of whom died at 5.3 months. One pt developed progressive regional (paraaortic) disease inferior to the fields while on treatment and was stopped early at 45 Gy. One pt developed a regional metastasis (porta hepatis) outside of the retreated volume. The other 8 pts were controlled locally within the retreated fields. Conclusions: Reirradiation of pancreatic/ampullary cancers with PRT and concurrent chemotherapy has minimal acute toxicity and encouraging short-term local control. Further follow-up on these pts is needed to assess the long-term morbidity and utility of PRT reirradiation. Clinical trial information: NCT01126476.
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Alexakis, C., J. Robinson, R. Yeates, et al. "P731 Biologics use in elderly patients with IBD: Experience in a UK secondary care setting." Journal of Crohn's and Colitis 14, Supplement_1 (2020): S588. http://dx.doi.org/10.1093/ecco-jcc/jjz203.859.
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Abstract Background The combination of an ageing population coupled with a rising incidence in inflammatory bowel disease (IBD) will undoubtedly result in increased use of biologic agents in older patients with IBD, yet long-term data on the use of these drugs in this population remains scarce. We describe our experience of biologic treatment in IBD patients aged 60 years or greater at a UK district general hospital. Methods This was a retrospective descriptive study performed at Royal Surrey NHS Foundation Trust which serves a population of 300,000 people. IBD patients on biologic therapy are all registered on a prospectively collated database. Patients were included in this study if their biologic start date was on or after their 60th birthday. Each patient had their clinical records assessed and the following baseline data were recorded: sex, IBD subtype, concurrent medication use, relevant medical history and co-morbid status (using the Charleston Morbidity Index (CMI)), age at biologic start date and biologic subtype. Patients were followed up from biologic start date to biologic end date, death or end of study period (01.07.2019). Kaplan Meier analysis was used to generate biologic survival or ‘persistence’. During follow-up, we recorded the incidence of both infective and non-infective complications, and the incidents of both IBD surgery and malignancy. Results Of 220 patients on biologic therapy, 19 (8.7%) were aged ≥60 years at initiation, of whom 18 had data included in the analysis including 431 patient-months of follow-up. 78% were male. Half of patients had Crohn’s disease. Median CMI was 4. Only 1 patient had a history of malignancy prior to biologic initiation. Mean age at biologic initiation was 69 years. 72% of patients were on concurrent immune suppression medication. Most patients (72%) were commenced on Infliximab (Adalimumab 17%, Vedolizumab 11%). Median biologic treatment time was 17 months. The 6, 12 and 24 month biologic persistence rates were 78%, 67% and 28% respectively. 22% of patients were subsequently treated with a second biologic. 17% required surgery despite biologic use. Over half (56%) of patients suffered a complication post first biologic initiation, the most frequent being infection which affected 44% of patients during follow-up. Where recorded or available, 41% of patients developed antibodies to biologic, with a mean time of 11.4 months treatment. There were no recorded malignancies in any patient following biologic initiation. Conclusion Just under one in 10 of our biologic cohort is above the age of 60 on commencement of therapy. Despite a heavy burden of infective complications, there is reasonable biologic persistence in this group, and importantly a negligible malignancy risk following treatment initiation.
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Keene, K. S., L. C. Klepczyk, R. Meredith, et al. "An update on the dosimetric analysis of concurrent radiation therapy and trastuzumab on early cardiac events." Journal of Clinical Oncology 29, no. 27_suppl (2011): 121. http://dx.doi.org/10.1200/jco.2011.29.27_suppl.121.
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121 Background: The impact of radiation therapy (RT) with concurrent trastuzumab on early cardiac morbidity is relatively unknown. Trastuzumab’s radiosensitizing properties may augment both early and late effects of RT. This retrospective review update provides an analysis of cardiac event (CE) development in patients treated with concurrent RT and trastuzumab with a focus on RT heart dose. Methods: Sixty-five patients treated with concurrent RT (30 left, 33 right, 2 bilateral) and trastuzumab at the University of Alabama at Birmingham were identified. Patient data for pre-existing heart disease, cardiac risk factors, drug regimen, and CEs were recorded. Dosimetric parameters of maximum heart dose, mean heart dose, heart volume receiving 5, 10, 15, 20 and 30Gy (V5, V10, V15, V20, V30) were also analyzed. Endpoints include the occurrence of CEs at any time in relation to RT and those specifically after the start of RT. Results: In addition to receiving trastuzumab, 80% of patients received doxorubicin. 15.4% had preexisting heart disease. The mean heart dose for all patients was 248cGy. With a median follow-up of 24.5 months, six patients developed CEs (9.2%), and three of these cases occurred after RT initiation (4, 4, and 0.5 months post-RT). All six CEs occurred during treatment with trastuzumab and consisted of congestive heart failure. Analysis of the heart dose maximum, mean, V5, V10, V15, and V20, V30 were similar in patients with and without CEs, and small differences between groups did not reach statistical significance. CE incidence was significantly associated with smoking (p=0.0037) but not hypertension, diabetes or pre-existing heart disease. Conclusions: This updated retrospective dosimetric analysis did not find a correlation between concurrent trastuzumab and RT on the development of early cardiac events. Modern era RT with 3D conformal planning, the use of heart blocks, and breath hold techniques will continue to decrease the dose to the heart. Longer follow-up will be needed for analysis of the impact of modern technologic advances and late cardiac morbidity.
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Diehl, Adam, Mark Yarchoan, Ting Yang, et al. "Relationship of lymphocyte and eosinophil counts and immune-related adverse events in recipients of programmed death-1 (PD-1) inhibitor therapy: A single-center retrospective analysis." Journal of Clinical Oncology 35, no. 15_suppl (2017): e14586-e14586. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.e14586.
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e14586 Background: Inhibition of the PD-1 checkpoint can cause immune activation in non-target tissues, resulting in immune-related adverse events (irAE) in up to 50% of patients. Biomarkers that are associated with irAEs in patients treated with PD-1 inhibitors may have implications for patient selection and clinical management. Methods: We performed an IRB-approved retrospective chart review of adult solid tumor patients treated with nivolumab or pembrolizumab at a single institution from January 2015 until November 2016. Patients were excluded if concurrently receiving investigational therapies, or on unreported clinical trials. Data were collected on treatment history, leukocyte counts, and irAE, defined as adverse events with a potential immunologic basis with grading performed using CTCAE v.4.0. Results: 172 patients were included (lung n = 54; melanoma n = 61; kidney n = 25; esophageal n = 12; bladder n = 8; other tumors n = 12) with median age 67. 18% were treated with concurrent ipilimumab. 31% experienced an adverse event of any grade with a mean time to develop an irAE of 3.5 months. Of those with an irAE, 85% required treatment, 68% were grade ≥ 2, 32% were grade 3 or 4 and 35% required therapy discontinuation due to the irAE. In univariate analysis, a higher ALC at both the start of therapy and at 1 month was associated with increased risk of an irAE of grade ≥ 2 (p < 0.05). A higher absolute lymphocyte count (ALC) or higher absolute eosinophil count (AEC) at 1 month into therapy was associated with increased risk of all irAE (p < 0.05) as well as irAE requiring treatment (p < 0.05). In addition, in a multivariate regression analysis including age, race, tumor type, prior chemotherapy, prior radiation, and concurrent ipilimumab therapy, an ALC > 2000 at the start of therapy was a significant predictor of irAE of grade ≥ 2 (p < 0.05 and OR 2.0), as was an ALC > 2000 at 1 month into therapy (p < 0.05 and OR 1.86). Conclusions: These results suggest that high lymphocyte and eosinophil counts early in the course of anti-PD1 therapy may be associated with a higher risk for clinically significant irAE.
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Gen, Lin, Huamin Xu, Jun Zhao, et al. "Concurrent TP53 mutation adversely impact the efficacy of crizotinib in ROS1-rearranged lung cancer patients." Journal of Clinical Oncology 37, no. 15_suppl (2019): e20535-e20535. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.e20535.
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e20535 Background: ROS1 tyrosine kinase inhibitors (TKIs) are now standard of care for patients with advanced ROS1-rearranged NSCLC. But factors that may affect the efficacy of ROS1 TKIs remain to be explored. Methods: We conducted a retrospective multicenter study of lung cancer patients with ROS1 rearrangements. Treatment and survival follow-up was done and clinical records were reviewed. PFS distribution was analyzed by Kaplan-Meier method with log-rank test. Results: In total, we included 94 lung cancer patients with ROS1 fusion genes profiled by next-generation sequencing from May 2016 to September 2018. Fifty of them were female. The median diagnosis age was 54 (25-83). The most common histologic type was adenocarcinoma, which was confirmed in 75 of 78 patients with available pathological results. The most common fusion partners were CD74, EZR, SDC4 and SLC34A2 identified in 42, 19, 12 and 8 patients respectively. Concurrent actionable mutations were uncommon for ROS1 fusion-positive patients. The most frequent concomitant mutated gene was TP53, which was detected in 33% of all the patients. After excluding 29 patients who were lost to follow-up at the very start, the median follow-up time was 8.5 (0-28) months from the moment when mutation profiling was performed. Thirty-nine patients received treatment with crizotinib, among whom 27 were treatment-naïve patients. The median PFS of the 39 patients with crizotinib was not reached yet. Patients with baseline CNS metastasis tend to have shorter PFS compared to patients without (median, 12 vs NR, p = 0.0073). Besides, concurrent TP53 mutations were correlated with worse PFS (median, both NR, p = 0.0417). Mutation profiles of 10 patients were derived from ctDNA testing. No difference was found in PFS between these 10 patients with others whose genomic profiles were based on fresh tissue or FFPE specimens, suggesting that plasma ctDNA serves as good specimen source for mutation profiling to monitor clinical treatment. Conclusions: Concurrent TP53 mutation and presence of CNS metastasis are associated with decreased PFS of ROS1-positive patients treated with crizotinib.
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Kleef, Ralf, Ralph Moss, A. Marcell Szasz, Arthur Bohdjalian, Hans Bojar, and Tibor Bakacs. "Complete Clinical Remission of Stage IV Triple-Negative Breast Cancer Lung Metastasis Administering Low-Dose Immune Checkpoint Blockade in Combination With Hyperthermia and Interleukin-2." Integrative Cancer Therapies 17, no. 4 (2018): 1297–303. http://dx.doi.org/10.1177/1534735418794867.
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The prognosis of triple-negative breast cancer with metastases after chemotherapy remains dismal. We report the case of a 50-year-old female with first disease recurrence at the axillary lymph node and, later on, bilateral pulmonary metastases with severe shortness of breath. The patient received low-dose immune checkpoint blockade (concurrent nivolumab and ipilimumab) weekly over 3 weeks with regional hyperthermia 3 times a week, followed by systemic fever-range hyperthermia induced by interleukin-2 for 5 days. She went into complete remission of her pulmonary metastases with transient WHO I-II diarrhea and skin rash. The patient remained alive for 27 months after the start of treatment, with recurrence of metastases as a sternal mass, and up to 3 cm pleural metastases. This exceptional response should instigate further research efforts with this protocol, which consists only of approved drugs and treatments.
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Miranda, Kayla, Matthew Tucker, Yu-Wei Chen, Kathryn Beckermann, and Brian Rini. "731 Concurrent immunotherapy and dipeptidyl peptidase-4 inhibition among patients with solid tumors." Journal for ImmunoTherapy of Cancer 9, Suppl 2 (2021): A760. http://dx.doi.org/10.1136/jitc-2021-sitc2021.731.
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BackgroundDurable remissions are possible for patients with solid tumors treated with immune checkpoint inhibitors (IO); however, response rates remain relatively low. Recent preclinical data with dipeptidyl peptidase-4 inhibitors (DPP4i), widely used for diabetes management, have shown synergistic anti-tumor activity with IO in mouse models.1 2 However, there are no currently available data on concurrent use of DPP4i among patients treated with IO.MethodsWe performed a retrospective, IRB-approved, review of all patients with solid tumors treated with IO at Vanderbilt-Ingram Cancer Center and concurrent DDP4i treatment for diabetes mellitus through review of the electronic medical record. Inclusion criteria required patients were to be on DPP4i at the start of IO treatment. The cutoff date was June 22, 2021. Outcomes measured were objective response rate (ORR), time on treatment, time to next treatment (TTNT), immune-related adverse events (iRAE), and overall survival (OS). All patients were included in the toxicity analysis; however, patients treated in the adjuvant setting, those without measurable radiographic disease, and those without available post-treatment scan were excluded from the response analysis.ResultsIn total, 34 patients were identified on concurrent IO plus DPP4i. The most common tumor types were melanoma (29%), renal cell carcinoma (21%), and non-small cell lung cancer (21%). Pembrolizumab was the most common IO agent (47%), followed by nivolumab (41%), ipilimumab (15%), atezolizumab (6%), and durvalumab (3%). Sitaglipitin (74%) was the most common DPP4i, followed by linagliptin (18%), saxagliptin (6%), and alogliptin (3%). 14/34 patients (41%) developed any grade IRAE while on treatment with 6/34 (18%) requiring discontinuation of IO. Of the 26 patients who met inclusion criteria for the response analysis, 18 (69%) had PR or CR, 4 (15%) had stable disease, and 4 (15%) had PD as best response (figure 1). The median follow-up time was 19.0 months (IQR: 11–25.2) and the median time on treatment was 10.1 months (95 CI: 4.9–14.5). The median TTNT was 23.9 months (95% CI:10.7–34.5) and median OS was 31.4 months (95% CI: 21.0-NE).ConclusionsThis analysis represents the first data on concurrent DPP4i with IO in the treatment of solid tumors. While the cohort for response analysis was small, the ORR was high. Prospective evaluation of IO plus DPP4-i is needed to determine potential clinical efficacy of this combination.ReferencesBarreira da Silva R, Laird ME, Yatim N, Fiette L, Ingersoll MA, Albert ML. Dipeptidylpeptidase 4 inhibition enhances lymphocyte trafficking, improving both naturally occurring tumor immunity and immunotherapy. Nat Immunol 2015;16(8):850–858. doi:10.1038/ni.3201.Hollande C, Boussier J, Ziai J, et al. Inhibition of the dipeptidyl peptidase DPP4 (CD26) reveals IL-33-dependent eosinophil-mediated control of tumor growth. Nat Immunol. 2019;20(3):257–264. doi:10.1038/s41590-019-0321-5Ethics ApprovalVanderbilt University Institutional Review Board approved this study under “exempt” status (IRB# 202314). All patient information was de-identified and secured.Abstract 731 Figure 1Swimmers plot. An illustration of clinical events for 26 patients treated with concurrent checkpoint inhibitor (IO) and dipeptidyl peptidase-4 inhibitors (DPP4i). The timeline begins on the date of IO initiation. Each subject is represented along the y axis, with various symbols noting events such as Partial Response (PR), Complete Response (CR), start date of next line of therapy, continued response, or death. Duration of follow up ended with either patient death or study completion (6/22/21)
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McNamara, Michael J., Lisa A. Rybicki, Thomas W. Rice, et al. "Relationship between treatment duration and outcomes in patients receiving concurrent chemoradiotherapy (CCRT) and surgery for locoregionally advanced (LRA) esophageal and gastroesophageal junction (E/GEJ) adenocarcinoma (ACA)." Journal of Clinical Oncology 30, no. 15_suppl (2012): e14665-e14665. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.e14665.
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e14665 Background: Retrospective studies in breast, colon, and head and neck cancer have suggested that delays in administration of adjuvant chemotherapy result in inferior outcomes. We explore this question in patients with LRA E/GEJ ACA. Methods: From 11/99 to 7/06, 152 patients with cT3, N1, or M1a disease were enrolled on one of two clinical trials at the Cleveland Clinic. Two courses of CCRT consisting of 30Gy radiation (@1.5Gy BID) with continuous infusion cisplatin (20mg/m2/day x 4 days) and 5Fu (1000mg/m2/d x 4 days) were given both before and after surgical resection. In the second trial, 75 patients also received gefitinib during the 4 week induction and for a total of two years postoperatively. Using recursive partitioning analysis (RPA), we retrospectively explored the relationship between treatment duration and loco-regional control (LRC), distant metastatic control (DMC), freedom from recurrence (FFR), and overall survival (OS) in the 115 patients (76%) who completed all treatment. Outcomes were estimated using the Kaplan-Meier method and compared among groups using the log-rank test. Results: RPA analysis identified three groups of patients: 19 patients in whom resection occurred ≤45 days from the start of CCRT to resection (short treatment), 63 patients who underwent resection >45 days from the start of CCRT and required <50 days to complete treatment after surgery (intermediate treatment), and 33 patients who underwent resection >45 days from the start of CCRT but required ≥50 days to complete treatment after surgery (prolonged treatment). With a median follow-up of 90 (range 57-126) months, we found that patients with shorter treatment times had better 5 year DMC [64% (short) v 26% (intermediate) v 16% (prolonged); p=0.004], FFR [57% (short) v 23% (intermediate) v 16% (prolonged); p=0.015)], and OS [42% (short) v 30% (intermediate) v 12% (prolonged); p=0.08]. LRC was not different between the groups. Conclusions: Treatment delays in patients receiving multimodality therapy for LRA E/GEJ ACA may result in a greater risk of recurrence and decreased survival.
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Benschop, Laura, Johannes J. Duvekot, and Jeanine E. Roeters van Lennep. "Future risk of cardiovascular disease risk factors and events in women after a hypertensive disorder of pregnancy." Heart 105, no. 16 (2019): 1273–78. http://dx.doi.org/10.1136/heartjnl-2018-313453.
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Hypertensive disorders of pregnancy (HDP), such as gestational hypertension and pre-eclampsia, affect up to 10% of all pregnancies. These women have on average a twofold higher risk to develop cardiovascular disease (CVD) later in life as compared with women with normotensive pregnancies. This increased risk might result from an underlying predisposition to CVD, HDP itself or a combination of both. After pregnancy women with HDP show an increased risk of classical cardiovascular risk factors including chronic hypertension, renal dysfunction, dyslipidemia, diabetes and subclinical atherosclerosis. The prevalence and onset of cardiovascular risk factors depends on the severity of the HDP and the coexistence of other pregnancy complications. At present, guidelines addressing postpartum cardiovascular risk assessment for women with HDP show a wide variation in their recommendations. This makes cardiovascular follow-up of women with a previous HDP confusing and non-coherent. Some guidelines advise to initiate cardiovascular follow-up (blood pressure, weight and lifestyle assessment) 6–8 weeks after pregnancy, whereas others recommend to start 6–12 months after pregnancy. Concurrent blood pressure monitoring, lipid and glucose assessment is recommended to be repeated annually to every 5 years until the age of 50 years when women will qualify for cardiovascular risk assessment according to all international cardiovascular prevention guidelines.
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Andruska, Neal, Temitope Agabalogun, Benjamin Walker Fischer-Valuck, et al. "Neoadjuvant versus concurrent androgen deprivation therapy plus radiotherapy for unfavorable intermediate-risk and high-risk prostate cancer with low PSA." Journal of Clinical Oncology 39, no. 6_suppl (2021): 243. http://dx.doi.org/10.1200/jco.2021.39.6_suppl.243.
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243 Background: Dose-escalated radiotherapy (RT) with androgen-deprivation therapy (ADT) is a standard definitive treatment for localized prostate cancer (LPCa), but the optimal sequencing of hormone therapy with RT is unclear, with most patients treated with neoadjuvant ADT. Clinical trials addressing this question have not yielded definitive results. During COVID-19, there has been greater interest in neoadjuvant ADT as a way to delay initiation of RT to reduce risk of COVID transmission from daily RT visits with recent analysis from the NCDB showing that RT can be delayed for up to 6 months after neoadjuvant ADT. It is unclear if neoadjuvant ADT is appropriate for all patients or if select cohorts may benefit from concurrent ADT and upfront RT, such as patients with higher grade disease and low PSA who may have less hormone-responsive disease. Methods: Using the NCDB, we identified men diagnosed from 2004 to 2015 with NCCN unfavorable intermediate risk or high-risk adenocarcinoma of the prostate with a presenting PSA ≤ 5 ng/mL treated with definitive RT and either ADT initiated 2-4 months prior to RT (neoadjuvant ADT) or ADT started within 7 days of RT (concurrent ADT). OS was the primary endpoint. OS was estimated using the Kaplan-Meier method. Multivariable Cox proportional hazards analyses was performed using age, facility type, Charlson-Deyo comorbidity score, clinical T stage, and Gleason score. Results: 2393 patients were identified, with 2103 receiving neoadjuvant ADT and 290 receiving concurrent ADT. Multivariable analysis (MVA) showed that concurrent ADT was associated with a lower risk of death relative to patients receiving neoadjuvant ADT {hazard ratio (HR): 0.58 [95% confidence interval: 0.36-0.94], p = 0.02}. The number of days from diagnosis to the start of RT was not associated with worse OS (HR:[0.99-1.01], p = 0.61) on MVA. Age (HR = 1.03 [1.01-1.05], p = 0.002) and treatment at an academic center (HR: 0.71 [0.53-0.94], p = 0.02) were also significantly associated with OS on MVA. The benefit of concurrent ADT relative to neoadjuvant ADT was greatest in patients with Gleason 4 and Gleason 5 disease (HR: 0.31 [0.14-0.71], p = 0.005). Conclusions: For patients with unfavorable intermediate-risk or high-risk prostate cancer and a PSA ≤ 5 ng/mL, concurrent ADT and upfront RT was associated with improved OS compared to neoadjuvant ADT and RT. The associated benefit appeared to be more pronounced for Gleason Score ≥ 8. Results are hypothesis generating and require validation in a randomized trial.
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de Ruiter, Ben-Max, Jons Wouter van Hattum, Theo Maria De Reijke, Jorg Reinier Oddens, Maarten C. C. M. Hulshof, and Adriaan Dirk Bins. "Safety evaluation of combined PD-1+CTLA4 inhibition concurrently to chemoradiotherapy (CRT) in localized muscle invasive bladder carcinoma (MIBC)." Journal of Clinical Oncology 39, no. 15_suppl (2021): 4531. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.4531.
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4531 Background: Neoadjuvant nivolumab (nivo) + ipilimumab (ipi) prior to radical cystectomy showed efficacy in localized MIBC. The safety of PD-1 and PDL-1+CTLA4 inhibition concurrent with CRT in localized MIBC has not been assessed. We present the first clinical trial data on concurrent 3 doses of q4w nivo 480mg (cohort1) and concurrent 4 doses of q3w nivo 3mg/kg + ipi 1kg/mg (nivo3+ipi1, cohort2) in combination with Mitomycin C/Capecitabin (MMC/Cape) CRT. Methods: We report the first 2 cohorts of a phase 1b, EC approved, study with nivo only or nivo3+ipi1 added to MMC/Cape CRT. CRT consists of MMC i.v. on day 1 with Cape 750mg/m2 on days of radiotherapy. Radiotherapy schedule comprises a 20x2Gy whole bladder irradiation with a simultaneous tumorboost of 20x0.75Gy. Patients with MIBC, T2-4N0-1, ECOG performance status <2 were included. A dose escalation scheme, with a staggered enrollment is used. The first 10 patients received nivo 480mg on week 1, 5, 9. Cohort2 of 10 patients received nivo3+ ipi1 at week 1, 4, 7 and 10. Relevant severe Adverse Events (AEs) were registered as Dose Limiting Toxicity (DLT) when they occurred within 6 weeks after start of treatment. Clinical efficacy is evaluated by cystoscopy and CT at week 12 and 24. Results: Both cohorts enrolled 10 patients. Median age was 68 [IQR 61-75] and 70 [IQR 66-75] years in cohort1 and 2, respectively. In cohort1 no patients experienced DLT. No dose reductions were applied. In cohort2, 2 patients experienced DLT, 1 trombocytopenia (grade 4) and 1 asystole (grade 5). 50% of patients did not receive all 4 q3w nivo3+ipi1 infusions, due to AEs. Table 1 reports an overview of AEs. In cohort2 6 SAE’s occurred in 3 patients. Median follow up is 71 [IQR 59-86] and 30 weeks [IQR 12-45] in cohort1 and 2, respectively. 1year OS and DFS is 100% in cohort1. Conclusions: Concurrent 3 doses nivo 480mg q4w added to MMC/Cape based CRT is feasible with a favorable toxicity profile and shows promising efficacy in MIBC patients. An escalated regimen with 4 doses nivo 3mg/kg + ipi 1mg/kg q3w concurrent to CRT shows acceptable toxicity. Cohort3 with ipi 3mg/kg and nivo 1mg/kg is enrolling. Clinical trial information: NCT03844256. [Table: see text]
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Liu, FangJie, Bo Qiu, DaQuan Wang та ін. "A preliminary analysis of integrating thymosin α1 into concurrent chemoradiotherapy and consolidative immunotherapy." Journal of Clinical Oncology 41, № 16_suppl (2023): e20569-e20569. http://dx.doi.org/10.1200/jco.2023.41.16_suppl.e20569.
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e20569 Background: The study aimed to investigate the efficacy of integrating Thymosin into concurrent chemoradiotherapy (CCRT) and consolidative immunotherapy in unresectable locally advanced non-small cell lung cancer (LA-NSCLC). Methods: Ninety-one stage IIIA-IIIC LA-NSCLC patients enrolled from Jan 1, 2020, to Oct 31, 2022 were analyzed retrospectively. All patients received CCRT (total irradiation dose of 60Gy and weekly concurrent docetaxel and cisplatin) and consolidative immunotherapy (Nivolumab/Tislelizumab). Thymosin α1 (1.6 mg) was administered once a week from the start of treatment till 2 months after CCRT or till the last prescription of consolidative immunotherapy. The primary endpoint was progression-free survival (PFS). The secondary endpoints included the overall survival (OS) and toxicity. Results: There were 31 patients who received Thymosin α1 till the last prescription of consolidative immunotherapy, 40 patients received Thymosin α1 till 2 months after CCRT and 20 patients without the administration of Thymosin α1. The median follow-up time was 28.3 months (range 8.2~31.6 months). The median PFS was 26.1 months in Thymosin α1+consolidative immunotherapy group, 15.3 months in Thymosin α1+CCRT group and 12.6 months in control group (P = 0.116). The median OS was not reached in Thymosin α1+consolidative immunotherapy group, 26 months in Thymosin α1+CCRT group and 16.5 months in control group (P = 0.046). The median courses of consolidative immunotherapy were 8 Thymosin α1+consolidative immunotherapy group, 6 in Thymosin α1+CCRT group and 3 in control group (P = 0.060). There were higher ≥grade 3 acute lymphopenia (62.3%) and acute grade 2 pneumonitis (8.0%) in the control group. The long-term use of Thymosin α1 was also found to be related to the lower level of IL-6(P = 0.048), CD 16+NK cells and CD56+NK cells (P = 0.043). Conclusions: The integration of Thymosin α1 into CCRT and consolidative immunotherapy could yield synergistic effect in LA-NSCLC patients. The combination might contribute to prolonged use of consolidative immunotherapy and survival benefit.
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Nim, Ranjit Kumar, Vivek Kumar Verma, Manoj Kumar, et al. "HIV and hepatitis B co-infection - prevalence and clinical spectrum in a rural tertiary care centre of Northern India." International Journal of Research in Medical Sciences 5, no. 7 (2017): 3154. http://dx.doi.org/10.18203/2320-6012.ijrms20173005.
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Background: HBV and HIV are both endemic in India. Currently, it is not well established what proportion of HIV-positive patients harbours HBV infection in India. No study was done to know the epidemiology of HBV HIV Co infection in rural population of Northern India. So, this study was done to explore the impact of HBV in HIV patients.Methods: Prospective cohort study was conducted on HIV-HBV co infected patients who attended the ART Clinic at ART centre, Department of Medicine, UPUMS, Saifai, Etawah, after obtaining informed consent.Results: Out of these 1751 HIV patients 919 were eligible for start on ART and the remaining were treatment naïve patients. Out of these 1751 HIV positive patients 79 patients were HBS Ag positive. Thus, the prevalence of HBV-HIV co infection at our ART centre was found to be around 4.5%. 68 patients were found to be eligible for start of ART drugs. Out of these 68 patients on ART, 46 (67.6%) patients were alive, 9 (13.2%) were transferred out, 5 (7.4%) patients were lost to follow up (LFU) and 8 (11.8%) expired till the end of the study.Conclusions: HBV co infection is common in HIV serology positive and can cause significant morbidity and mortality especially in the presence of other concurrent cause of liver injury. HBV co infection might associate with severe hepatotoxicity during intake of HAART regimen. For these reasons, prevention and treatment of HBV infection is mandatory in HIV serology positive.
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Kim, Lyndon, Fred H. Hochberg, Allan F. Thornton, et al. "Procarbazine, lomustine, and vincristine (PCV) chemotherapy for Grade III and Grade IV oligoastrocytomas." Journal of Neurosurgery 85, no. 4 (1996): 602–7. http://dx.doi.org/10.3171/jns.1996.85.4.0602.
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✓ The authors provided procarbazine, lomustine (CCNU), and vincristine (PCV) chemotherapy to 32 patients whose tumors contained varying mixtures of oligodendroglial and astrocytic cells. Twenty-five patients had oligodendroglioma—astrocytoma (oligoastrocytoma) with a histological Grade of III (19 patients) or IV (six patients); seven had anaplastic oligodendroglioma. The PCV therapy was administered every 6 weeks for a total of at least 124 cycles. The median duration of follow-up review from the start of chemotherapy was 19.3 months. Nineteen patients were treated before receiving radiation therapy and 12 after receiving it (one patient received concurrent radiotherapy and chemotherapy). Grade 3 or 4 hematological toxicity was experienced by nine (31%) of 29 patients. Ten patients had delayed treatment due to treatment-related toxicities (34.5%). Ninety-one percent of the 32 patients responded to the therapy. These included 10 patients with a complete response and 19 with a partial response. The median time to progression was 15.4 months for all patients and 23.2 months for those with Grade III tumors. The median time to progression for patients with Grade III oligoastrocytomas was 13.8 months; for those with Grade IV oligoastrocytoma it was 12.4 months and for those with anaplastic oligodendrogliomas it was 63.4 months (p = 0.0348). These patients survived a median of 49.8 months, 16 months, and 76 or more months, respectively, from the start of chemotherapy (p = 0.0154). The PCV therapy provides durable responses in patients with Grade III or IV oligoastrocytomas.
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van den Heuvel, Michel M., Andrew D. Vincent, Wilma Uyterlinde, et al. "A randomized, multicenter phase II study investigating additional weekly cetuximab to concurrent chemoradiotherapy in locally advanced non-small cell lung carcinoma: Reporting on the efficacy." Journal of Clinical Oncology 30, no. 15_suppl (2012): 7019. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.7019.
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7019 Background: Modest benefits from concurrent chemoradiotherapy (CRT) in patients with locally advanced NSCLC warrant more effective treatment regimen. Cetuximab, a monoclonal antibody against the epidermal growth factor receptor has shown activity in NSCLC. Feasibility data and toxicity have been published previously. We report treatment outcome of a multicenter phase II study of the combination of high dose accelerated RT and daily dose cisplatin with or without weekly cetuximab. Methods: Patients with locally advanced NSCLC received accelerated RT (66 Gy in 24 fractions) and concurrent daily cisplatin (6 mg/m2) with (Arm A) or without (Arm B) additional weekly cetuximab (400 mg/m2 loading dose one week prior to the RT start followed by weekly 250 mg/m2). The Objective Local Response Control (OLRC) was determined at 6 and 24 weeks after treatment using response evaluation criteria in solid tumours criteria. Results: Between Feb 2009 and May 2011, 102 patients were included. Median follow-up was 13 months. Patients and tumor characteristics are shows in the Table. Stage distribution was: II (8%), IIIa (51%), and IIIb (40%). The CRT was well tolerated. The OLRC at 24 weeks was 79% in Arm A and 80% in Arm B. The one-year progression free survival and overall survival were 58% (45%-76%) and 76% (64%-91%) for Arm A and 49% (35%-68%) and 72% (58%-89%) for Arm B respectively. Conclusions: The addition of cetuximab to low dose cisplation CRT does not improve OLRC in an unselected patient cohort but data on longterm disease control and survival are to be awaited. [Table: see text]
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Beg, Muhammad S., Leticia Khosama, Stefanie Conley, et al. "Interaction between regorafenib and warfarin therapy." Journal of Clinical Oncology 35, no. 4_suppl (2017): 651. http://dx.doi.org/10.1200/jco.2017.35.4_suppl.651.
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651 Background: Regorafenib is an oral multi kinase inhibitor with clinical activity in colorectal cancer, gastrointestinal stromal tumors and hepatocellular cancer. Drug- drug interactions are commonly encountered in clinical practice and warfarin continues to be the most commonly prescribed anticoagulant among cancer patients in the clinic. The interaction of regorafenib with warfarin has not been studied. Methods: Patients at a single institution being prescribed regorafenib were identified and charts reviewed for concurrent warfarin therapy. Baseline characteristics, indications for regorafenib and warfarin therapy was determined. Patients were followed up to the first 8 weeks of combination therapy. Results: We identified 6 patients on concurrent regorafenib and warfarin. All patients had refractory colon cancer. Median age was 74, 4 were male and 5 white. Indication for warfarin was venous thromboembolism in 5 and atrial fibrillation in 1. Baseline INR ranged from 1.1 to 2.4. An increase in INR was seen in all six patients (peak INR range 4.5 to > 12) which improved with dose modification. Time to peak INR was less than 6 weeks (INR trends in all patients shown in figure 1). There were no bleeding complications noted in any patient. Conclusions: We report a clinically significant interaction between warfarin and regorafenib with patients demonstrating an increase in INR. Patients who are anticoagulated with warfarin and start regorafenib should be closely monitored and upfront warfarin dose reduction should be considered. Further drug-drug interaction studies are needed to determine the exact mechanism of drug-drug interaction between these medications.
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Cheng, Yao, Hyeonmi Kim, and Gang-Len Chang. "Design of a Dual-Modal Signal Progression Model for Urban Arterials Accommodating Heavy Transit and Passenger Car Flows." Transportation Research Record: Journal of the Transportation Research Board 2673, no. 10 (2019): 1–13. http://dx.doi.org/10.1177/0361198119846091.
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Despite extensive studies aiming at contending with congestion on urban arterials, an effective model to produce optimal signal progression for an arterial experiencing heavy bus and passenger car flows remains unavailable. In response to such needs, this study presents a bandwidth maximization model that can offer concurrent progression to both modes or to a selected mode(s) in a selected direction(s), based on traffic volume, bus ratio, and geometric conditions. To capture the operational features of both modes, the proposed model has effectively taken into account all critical issues that may result in mutual impedance between them, which include the potential blockage by passenger car queues of roadside bus stops, the excessive start-up delays caused by transit vehicles queueing at the intersection stop line, and the reduced travel lanes for progressing flows caused by buses dwelling at roadside stations with limited storage capacity. In addition, by weighting the bandwidths with the passenger volumes by mode and by direction, the proposed model is capable of offering progression only to the mode(s) and the direction(s) for which it is justified from the perspective of maximizing the benefits to all arterial users. The numerical analysis results have confirmed the effectiveness of the proposed model in producing concurrent progression bands for both modes under various realistic constraints and volume levels. Further evaluation with extensive simulation experiments has also demonstrated that the benefits offered by the proposed model will not be at the cost of other measures of effectiveness.
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Zhang, Qinhua, Mingfen Lai, Fangming Li, et al. "A retrospective analysis of tislelizumab and GP regimen neoadjuvant therapy followed by concurrent chemoradiotherapy plus nimotuzumab in patients with high-risk nasopharyngeal carcinoma." Journal of Clinical Oncology 41, no. 16_suppl (2023): e18060-e18060. http://dx.doi.org/10.1200/jco.2023.41.16_suppl.e18060.
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e18060 Background: Efficacy of nasopharyngeal carcinoma (NPC) with T4 or N3 remains unsatisfactory due to high-risk of distant metastasis or recurrence, indicating the need of more comprehensive treatment. We aim to analysis the efficacy and safety of tislelizumab and GP regimen in combination with neoadjuvant therapy and concurrent chemoradiotherapy (CCRT) plus nimotuzumab in patients with high-risk NPC. Methods: Our team conducted a retrospective analysis of 44 adult patients with high-risk locally advanced (T4 or N3; M0) nasopharyngeal carcinoma between March 2021 and January 2022, the median follow-up time was 599 days. The patients had received neoadjuvant chemotherapy (gemcitabine,1000 mg/m2, days 1 and 8, cisplatin,80 mg/m2, day 1), and tislelizumab (200mg) on day 1 every 3 weeks for 4 cycles followed by chemoradiotherapy including intensity modulated radiotherapy (IMRT), lobaplatin and nimotuzumab. Lobaplatin was intravenously administered at a dose of 30 mg/m2 on days 1 and 22. Nimotuzumab was intravenously administered at a dose of 200 mg on day 1 every week for 6 weeks. All patients underwent response assessments during neoadjuvant therapy, chemoradiotherapy and follow-up at regular intervals. Results: 44 patients were identified with the median age being 50y(24y-70y). At neoadjuvant treatment period, 44 patients completed 170 cycles of the combination of tislelizumab and GP regimen. During concurrent chemo-radiotherapy period, 42 (95.45%) of 44 patients completed 6 weeks of nimotuzumab treatment and 41 (93.18%) of 44 patients completed 2 cycles of lobaplatin treatment. Overall, 20 patients (45.5%) had a complete response, and 24 (54.5%) had a partial response after neoadjuvant therapy before the start of chemoradiotherapy. At 3 months and 6 months after radiotherapy, 90.9% (40 of 44) and 97.7% (43 of 44) of the patients had a complete response. 42 of the 44 patients were alive (95.5%). 3 events of recurrence(1) or death(2) were recorded. 19 (43.2%) of 44 patients had grade 3-4 treatment-related adverse events, and grade 3-4 immune-related adverse events(irAE) was recorded in 3 patients (6.8%) in the entire treatment. Grade 3-4 irAEs were rash(2) and hypothyroidism(1). Conclusions: Neoadjuvant therapy with tislelizumab and GP regimen followed by concurrent chemoradiotherapy plus nimotuzumab seems to have promising efficacy, lower toxic effects and better treatment compliance, which is a new treatment strategy for high-risk NPC.
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Shen, Jing, Xin Lian, Qiu Guan, Lei He, Fuquan Zhang, and Jie Shen. "Neoadjuvant Chemo-Radiation Using IGRT in Patients with Locally Advanced Gastric Cancer." Current Oncology 29, no. 10 (2022): 7450–60. http://dx.doi.org/10.3390/curroncol29100586.
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The goal of this study was to see how effective and safe neoadjuvant chemoradiation with image-guided IMRT was in patients with locally advanced resectable gastric cancer. Between January 2013 and June 2019, patients with locally advanced (cT3/cT4 or N+) gastric cancer treated with neoadjuvant chemoradiotherapy at PUMCH (Peking Union Medical College Hospital) were retrospectively studied. Using concurrent chemotherapy (Capecitabine alone or XELOX*2 cycles), radiotherapy (IMRT (intensity-modulated radiation therapy) 45 Gy, 25#, 5 weeks) was delivered with IGRT (image-guided radiotherapy) before the start of each weeks therapy to ensure accuracy and repeatability. A total of 95 patients were enrolled in the study, 93 (97.9%) stage cT3/T4 and 85 (89.5%) stage N+. Of these, 85 patients (89.5%) had a tumor located in the upper 1/3 of the stomach, and 93/95 patients (97.9%) completed neoadjuvant chemoradiation, with 80 patients (84.2%) undergoing stomach resection (58 D2 and 22 D1 gastrostomies). Pathology downstaging was found in 68 patients (85.0%), with 66 patients (82.5%) receiving T downstaging and 56 patients (70.0%) receiving N downstaging. There were 11 individuals (13.8%) who had a pathological complete response (PCR). The average period of follow-up was 44.7 months (19–96 months). The 5-year OS (overall survival), LRFS (local recurrence-free survival), and DMFS (distant metastasis free survival) rates of patients were 47.0% (95% CI: 38.6–55.4), 86.55% (95% CI: 79.1–93.99) and 60.71% (95% CI: 51.49–69.93%), respectively. Thirteen (13.7%) patients had grade 3–4 leukopenia, anemia, and thrombocytopenia, while 9 (9.5%) patients had grade 3–4 anemia, and 5 (5.3%) patients had grade 3–4 thrombocytopenia. PCR was found to be a significant predictive factor for OS in multivariate analysis (HR = 11.211, 95% CI: 1.500–83.813, p = 0.024). The method of using IGRT image-guided IMRT (45 Gy, 25 fractions, 5 weeks) combined with concurrent chemotherapy in patients with locally advanced resectable gastric cancer was equally effective when compared to the clinical efficacy of neoadjuvant chemoradiotherapy, with clinical outcomes achieving equal efficacy, with similar PCR rates and high rates of OS, LRFS, and DMFS, as well as good tolerances of concurrent chemoradiotherapy with acceptable side effects.
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Wilke, Derek R., Nikhilesh Gajanan Patil, Helmut Hollenhorst, David Bowes, and Robert Rutledge. "Incidence of testosterone escape with LHRH agonists in patients receiving radiotherapy for prostate cancer." Journal of Clinical Oncology 34, no. 2_suppl (2016): 24. http://dx.doi.org/10.1200/jco.2016.34.2_suppl.24.
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24 Background: LHRH agonists (LHRHa) are commonly combined with radiotherapy in the neoadjuvant, concurrent, and adjuvant setting. Testosterone escape (TTE) (>1.74 nmol/L or >50 ng/dL) during therapy with LHRHa has been described, but the incidence and impact of TTE on outcome in this patient group needs to be characterized further. Methods: We performed a retrospective review of a database used for clinical outcomes and research ethics board approved studies, including chart audit of select patients (pts) where information was missing. To be included in the study, there had to be information on: 1) type of LHRHa, date of initiation, date of cessation, or duration of therapy and 2) radiotherapy information, with at least 6 months of follow-up after radiotherapy, 3) had to have radiotherapy to the prostate or prostate bed, and 4) had to have a least one testosterone- (TT) and prostatic-specific antigen (PSA) measurement. Results: 670 pts had a start date for androgen deprivation therapy (ADT) in the database. 630 pts had received an LHRHa, 560 pts had a start date for radiotherapy. 375 pts had sufficient information on ADT, radiotherapy, TT, and PSA levels, and 361 of these patients had information regarding their LHRHa. Median follow-up of patients still alive is 4.7 years. The median duration of LHRHa was 2.02 years. The median number of testosterone measurements per patient was 6. The incidence of TTE per patient course of treatment was: buserelin 9.3%; goserelin 10.5%; leuprolide IM 11.5%; leuprolide sc 23.9%; triptorelin 6.7% (p=0.02). Biochemical failure was defined as per the "nadir +2" definition, or at a value > 0.2 in those patients having had previous radical prostatectomy. There was no significant difference in either biochemical failure-free survival or overall survival in patients who experienced TTE versus those who did not. The most common PSA level during a TTE was an undetectable PSA. Conclusions: Even though there appears to be no impact of TTE on either biochemical relapse-free survival or overall survival, this study demonstrates that a rising PSA does not rule out TTE. Longer-term follow-up is planned.
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Yang, Li, Zhiyuan Xu, Victor Ho-Fun Lee, and Anne W. M. Lee. "A potential survival impact of blood immune cells in patients with locoregionally advanced nasopharyngeal carcinoma treated with concurrent chemoradiotherapy." Journal of Clinical Oncology 39, no. 15_suppl (2021): e18027-e18027. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.e18027.
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e18027 Background: To exam the changes of blood immune cells during concurrent chemoradiotherapy (CCRT) and explore their effects on survival in patients with locoregionally advanced nasopharyngeal carcinoma. Methods: Study population included stage III-IVA (TNM-8th edition) locoregionally advanced nasopharyngeal carcinoma (NPC) patients treated with induction chemotherapy followed by CCRT from January 2015 to October 2019. Patients received induction PX (cisplatin: 80mg/m2 on day 1 + capecitabine: 1000mg/m2 twice daily from day 1 to 14 every 3 weeks for 3 cycles) followed by CCRT (cisplatin: 100mg/m2 every 3 weeks for a total of 2-3 cycles or 40mg/m2 weekly for a total of 6 weeks concurrent with intensity-modulated radiation therapy [IMRT]). IMRT with doses of 70Gy, 63Gy and 56Gy were delivered to 3 levels of planning target volumes (PTV) (high, intermediate and low risk) respectively and simultaneously in 35 fractions/7 weeks. All had complete blood counts with differentials at baseline and before each chemotherapy. The primary endpoint was progression-free survival (PFS). “Immune cells” of our interest included lymphocytes, neutrophils and platelets. Results: A total of 139 patients were eligible and recruited. The median follow-up was 34 months (range 4-72). All immune cells decreased significantly during CCRT; the rate of grade 3/4 lymphopenia, neutropenia and thrombocytopenia during CCRT were 96.4%, 25.2% and 9.4%, respectively. The median (interquartile range, IQR) time to nadir from the start of CCRT were 40 (32-44), 26 (20-42) and 30 (15-39) days for lymphocytes, neutrophils and platelets, respectively. The median PFS was not reached and estimated 2-year PFS was 90.2%. Patients with lymphocyte nadir ≤ 0.2×109/L had better PFS compared with those with lymphocyte nadir > 0.2×109/L（2-yr PFS 95.5% vs. 87.5%, P=0.048). Patients with platelet nadir < 100×109/L had better PFS compared with those with platelet nadir ≥ 100×109/L(2-yr PFS 96.9% vs. 84.2%, P=0.011). Neutrophil nadir was not associated with PFS in univariate analysis. Multivariate analysis including prognostic variables in univariate analysis showed that platelet nadir (< 100 × 109/L vs ≥ 100 × 109/L, hazard ratio [HR] 0.279, 95% confidence interval [CI] 0.091-0.857, P=0.026), stage (III vs IVA, HR 0.321, 95% CI 0.115-0.901, P=0.031) and cumulative concurrent cisplatin dose (< 180mg/m2 vs ≥ 180mg/m2, HR 3.422, 95% CI 1.366-8.577, P=0.009) were prognostic of PFS by adjusting lymphocyte nadir and baseline hemoglobin. Conclusions: Blood immune cells decreased during CCRT and thrombocytopenia was prognostic of PFS in patients with LANPC. Longer follow-up is warranted to identify prognostic factors of overall survival.
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Khatri, Vaseem, Matthew Mills, Daniel Oliver, Michael Yu, and Kamran Ahmed. "LMAP-15 INTRACRANIAL RADIOTHERAPY WITH TUCATINIB FOR BRAIN METASTASIS FROM HER2-POSITIVE BREAST CANCER: A SINGLE-INSTITUTION SERIES." Neuro-Oncology Advances 5, Supplement_3 (2023): iii12. http://dx.doi.org/10.1093/noajnl/vdad070.046.
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Abstract BACKGROUND Tucatinib, a HER-2 TKI, has demonstrated intracranial efficacy in the HER2CLIMB study. Treatment of brain metastases frequently includes stereotactic radiosurgery (SRS) or whole brain radiotherapy (WBRT); however, HER2CLIMB did not detail outcomes with RT. METHODS Patients who received tucatinib at our institution from 2020-2022 were identified. Patients who had brain metastases and received intracranial RT within 6 months of receiving tucatinib were included. Patients with history of prior leptomeningeal disease (LMD) were excluded. The Kaplan-Meier (KM) method was used to estimate intracranial failure (ICF), overall survival (OS), and local control (LC). Adverse events and details regarding symptomatic radionecrosis were collected. RESULTS Between 2020 and 2022, 50 patients were treated with tucatinib. Forty patients had diagnosed brain metastasis and received intracranial RT. Median age at tucatinib start was 51 years (range: 33-83). All patients were HER-2+, 47.5% were HR+. Fifty-four separate RT courses were delivered within 6 months of tucatinib, including 45 courses of stereotactic RT (83%) and 9 (17%) WBRT. Twenty-three patients (57.5%) underwent concurrent tucatinib and intracranial RT, defined as RT within 2 months of tucatinib initiation. Median follow up for surviving patients was 18.9 months. Fifteen patients (37%) died at the time of analysis. Median OS was 25.1 months with 24-month KM OS of 52%. Median time to ICF was 12.5 months with 24-month KM ICF of 48%. At the time of ICF, 7 patients (17.5%) developed LMD. In total, 132 discrete lesions were treated with SRS. Ten lesions (7.5%) underwent local failure, with 24-month KM LC of 82%. Three patients (9.1%) undergoing SRS developed symptomatic radionecrosis; all completely resolved with dexamethasone. DISCUSSION In this first series reporting outcomes with RT and tucatinib, no evidence of excess toxicity was noted. Intracranial control appears favorable compared to previous reports. Concurrent RT with tucatinib should be assessed prospectively.
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Kosydar, Samuel R., Sameer Ashok Parikh, Scott Lester, et al. "Safety of concurrent use of radiotherapy for second primary malignancy (SPM) in patients with chronic lymphocytic leukemia (CLL) receiving novel agent therapy." Journal of Clinical Oncology 41, no. 16_suppl (2023): e19507-e19507. http://dx.doi.org/10.1200/jco.2023.41.16_suppl.e19507.
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e19507 Background: Patients (pts) with CLL are at elevated risk of developing non-hematologic malignancies. Radiation therapy (RT) is a critical component of management in localized solid organ malignancies. Novel agents (NA) are widely used in CLL treatment; however, safety data are lacking to guide treatment of pts requiring concurrent RT and NA. Methods: We identified pts treated concurrently with NA for CLL and RT for second primary malignancy (SPM) at Mayo Clinic from 2014-2022. Adverse events within 3 months of RT were evaluated using the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria for hematological toxicity and the Common Terminology Criteria for Adverse Events (CTCAE) version 5 for non-hematological toxicity. Patients without seamless, concurrent treatment with NA and RT were excluded. Results: Twenty-six pts were included. NA therapy consisted of ibrutinib (n = 23), acalabrutinib (n = 2), and venetoclax (n = 1). Median follow up time since RT completion was 1.5 years. The median age at NA initiation was 67 years (range:46-85) and at RT start was 68 years (range: 51-85); 92% of pts were male. NA was first treatment in 23% of pts; the median number of prior lines of therapy was 1 (range: 0-4). IGHV was unmutated in 82% and TP53 aberration was present in 24% of evaluable patients. SPM sites included prostate (n = 9), head/neck (n = 8), lung (n = 3), and brain, breast, bone, skin, kidney, and thymus (n = 1 each). The most common conventionally fractionated prescriptions (cGy/fx) were 6000/30 (n = 6) and > 6000-7020/20-33 (n = 7). SBRT ranged from 3300/5 to 5400/3 (n = 8). Five pts received other, varied RT prescriptions. Overall, 3 (12%) pts experienced at least one grade 3/4 toxicity. Grade 3/4 thrombocytopenia was observed in 2 (8%) pts and grade 3/4 neutropenia was observed in 2 pts per iwCLL criteria. Grade ≥3 non-hematological toxicities occurred in two pts that required hospitalization for critical illness, including 1 pt with grade 5 respiratory failure within 6 weeks after RT. Dose de-escalation of ibrutinib was reported in one case for pancytopenia attributed to use of a radiosensitizing agent. There were no cases of RT dose modification. Conclusions: Continuing NA CLL therapy during RT did not result in unexpected toxicities. This approach may maintain CLL disease control without compromising management of the SPM. [Table: see text]
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Takeda, Atsuya, Naoko Sanuki, Yuichiro Tsurugai, Yohei Oku, and Yousuke Aoki. "Stereotactic body radiotherapy for patients with oligometastases from colorectal cancer: risk-adapted dose prescription with a maximum dose of 83–100 Gy in five fractions." Journal of Radiation Research 57, no. 4 (2016): 400–405. http://dx.doi.org/10.1093/jrr/rrw029.
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Abstract We previously reported that the local control of pulmonary metastases from colorectal cancer (CRC) following stereotactic body radiotherapy (SBRT) with moderate prescription dose was relatively worse. We investigated the treatment outcomes and toxicities of patients with oligometastases from CRC treated by SBRT using risk-adapted, very high- and convergent-dose regimens. Among patients referred for SBRT from August 2011 to January 2015, those patients were extracted who had liver or pulmonary metastases from CRC, and they were treated with a total dose of 50–60 Gy in five fractions prescribed to the 60% isodose line of the maximum dose covering the surface of the planning target volume. Concurrent administration of chemotherapy was not admitted during SBRT, while neoadjuvant or adjuvant chemotherapy was allowed. A total of 21 patients (12 liver, 9 lung) with 28 oligometastases were evaluated. The median follow-up duration was 27.5 months (range: 6.5–43.3 months). Four patients were treated with SBRT as a series of initial treatments, and 17 patients were treated after recurrent oligometastases. The local control rates at 1 and 2 years from the start of SBRT were 100%. The disease-free and actuarial overall survival rates were 62% and 55%, and 79% and 79%, respectively. No severe toxicities (≥grade 3) occurred during follow-up. The outcomes following high-dose SBRT were excellent. This treatment can provide an alternative to the surgical resection of oligometastases from CRC. Prospective studies are needed to validate the effectiveness of SBRT.
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Tan, Si, and Araz Taeihagh. "Smart City Governance in Developing Countries: A Systematic Literature Review." Sustainability 12, no. 3 (2020): 899. http://dx.doi.org/10.3390/su12030899.
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Smart cities that make broad use of digital technologies have been touted as possible solutions for the population pressures faced by many cities in developing countries and may help meet the rising demand for services and infrastructure. Nevertheless, the high financial cost involved in infrastructure maintenance, the substantial size of the informal economies, and various governance challenges are curtailing government idealism regarding smart cities. This review examines the state of smart city development in developing countries, which includes understanding the conceptualisations, motivations, and unique drivers behind (and barriers to) smarty city development. A total of 56 studies were identified from a systematic literature review from an initial pool of 3928 social sciences literature identified from two academic databases. Data were analysed using thematic synthesis and thematic analysis. The review found that technology-enabled smart cities in developing countries can only be realised when concurrent socioeconomic, human, legal, and regulatory reforms are instituted. Governments need to step up their efforts to fulfil the basic infrastructure needs of citizens, raise more revenue, construct clear regulatory frameworks to mitigate the technological risks involved, develop human capital, ensure digital inclusivity, and promote environmental sustainability. A supportive ecosystem that encourages citizen participation, nurtures start-ups, and promotes public–private partnerships needs to be created to realise their smart city vision.
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Schweiger, Vittorio, Erica Secchettin, Cinzia Castellani, et al. "Comparison between Acupuncture and Nutraceutical Treatment with Migratens® in Patients with Fibromyalgia Syndrome: A Prospective Randomized Clinical Trial." Nutrients 12, no. 3 (2020): 821. http://dx.doi.org/10.3390/nu12030821.
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Objectives: Fibromyalgia syndrome (FMS) is a chronic clinical condition characterized by pain, fatigue, altered sleep, and cognitive disturbances. The purpose of this study was to compare two alternative treatments (nutraceutical and acupuncture) in FMS patients through a randomized clinical trial. Research Methods: A total of 60 FMS female patients were randomized for treatment with a nutritional combination containing coenzyme Q10, vitamin D, alpha-lipoic acid, magnesium, and tryptophan (Migratens® Group) or acupuncture treatment (Acupuncture Group) performed according the principles of traditional Chinese medicine (TCM), both for 3 months. Changes in pain and in quality of life (QoL) measured with a Fibromyalgia Impact Questionnaire Score-Revised (FIQ-R) and the Fibromyalgia Severity Scale (FSS) were performed at 1, 3, and 6 months after the start of treatments. Results: A total of 55 patient completed the study (21 in the Migratens® Group and 34 in the Acupuncture Group). Migratens® treatment shows a statistically significant reduction of pain 1 month after the start of therapy (T1, p = 0.025), strengthened after 3 months with maintenance of treatment (p = 0.012). The efficacy in reducing pain was apparent in the Acupuncture Group at all post-treatment determinations and at follow-up (T1 and T2 p = <0.001). Regarding QoL, improvement in FIQ-R and FSS values was revealed in both groups. Conclusion: The nutraceutical approach with Migratens® seems to be an effective option to for patients with FMS. Our experience confirmed also the validity of acupuncture in these patients. Considering the complexity of the management of FMS patients, our results suggest a cyclical and sequential, or even concurrent treatment with different approaches, to improve the efficacy and the compliance of patients to long-term treatment
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Carapella, C. M., A. M. Mirri, A. Felici, et al. "Prolonged gemcitabine infusion as radiosensitizer for newly diagnosed glioblastoma multiforme (GBM): A phase I study." Journal of Clinical Oncology 24, no. 18_suppl (2006): 1581. http://dx.doi.org/10.1200/jco.2006.24.18_suppl.1581.
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1581 Background: The use of cytotoxic drugs concurrent with RT represents a promising approach in the combined treatment of malignant gliomas. Gemcitabine (dFdCyd) is a drug widely explored for its potential radiomimetic activity in different tumors. The present study was aimed to evaluate the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of weekly prolonged dFdCyd infusion, administered in combination with RT as first line treatment, in adult pts affected by supratentorial GBM. Methods: Within 6 weeks after surgery, in the presence of measurable residual disease and KPS >70, pts were treated with fractionated RT at a dose of 2.0 Gy/daily fractions, 5 days a week (global dose 60 Gy). From 24 to 72 hours before the first RT application, and afterwards once weekly, pts received concurrent dFdCyd, at fixed dose rate of 10 mg/m2/min, over a total period of six weeks. Planned dose levels of dFdCyd started from 200 mg/m2/weekly (level 1), with sequential steps of 25 mg/m2/w based on toxicity. Results: Ten pts were enrolled into the study: six were male, median age 55.2 years (range 44–75), with a median KPS at baseline of 85 (SD 9.71). The median time from diagnosis to the start of treatment was six weeks (range 4–7). The median RT duration was 6 weeks (range 4–7), all but one pt received the planned dose and all pts received concomitant CT. Four pts entered at Level 1; one pt was excluded from the study, due to rapid progressive disease during the treatment. Two of the three valuable pts presented a relevant neurological worsening; on this basis the dFdCyd dose was reduced to 175 mg/m2/w (Level -1). A total of six pts were entered at Level -1, and none of them reported DLT. No hematological grade 3–4 toxicity was reported. Grade 3 non-hematological toxicity was observed in one pt (transaminases increase). After a median follow-up of 13.4 months (range 3–24), the median progression-free survival was 8 months (CI 95% 1–18), and the median overall survival was 14 months (CI 95% 12–17). Conclusions: The recommended dose of prolonged infusion of dFdCyd concomitant with RT is 175 mg/m2/w. The observed activity has been considered interesting enough to support a phase II study of this concurrent CT-RT schedule as first line treatment in GBM. [Table: see text]
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Zhang, Chong, Li Lu, Yihang Song та ін. "Butterfly: μW Level ULP Sensor Nodes with High Task Throughput". Sensors 22, № 8 (2022): 3082. http://dx.doi.org/10.3390/s22083082.
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The rapid development of Internet of Things (IoT) applications calls for light-weight IoT sensor nodes with both low-power consumption and excellent task execution efficiency. However, in the existing system framework, designers must make trade-offs between these two. In this paper, we propose an “edge-to-end integration” design paradigm, Butterfly, which assists sensor nodes to perform sensing tasks more efficiently with lower power consumption through their (high-performance) network infrastructures (i.e., a gateway). On the one hand, to optimize the power consumption, Butterfly offloads the energy-intensive computational tasks from the nodes to the gateway with only microwatt-level power budget, thereby eliminating the power-consuming Microcontroller (MCU) from the node. On the other hand, we address three issues facing the optimization of task execution efficiency. To start with, we buffer the frequently used instructions and data to minimize the volume of data transmitted on the downlink. Furthermore, based on our investigation on typical sensing data structures, we present a novel last-bit transmission and packaging mechanism to reduce the data amount on the uplink. Finally, we design a task prediction mechanism on the gateway to support efficient scheduling of concurrent tasks on multiple MCU-free Butterfly nodes. The experiment results show that Butterfly can speed up the task rate by 4.91 times and reduce the power consumption of each node by 94.3%, compared to the benchmarks. In addition, Butterfly nodes have natural security advantages (e.g., anti-capture) as they offload the control function with all application information up to the gateway.
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Berman, Abigail T., Annemarie Therese Fernandes, Stefan Both, et al. "Prospective trial of proton reirradiation of locally recurrent esophageal cancer." Journal of Clinical Oncology 32, no. 3_suppl (2014): 159. http://dx.doi.org/10.1200/jco.2014.32.3_suppl.159.
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159 Background: Local recurrences of esophageal cancer occur in approximately 25% of patients and cause significant morbidity. Their treatment after esophagectomy and chemoradiation is particularly challenging. A second course of radiotherapy in a previously radiated field carries the risk of radiation-induced tissue injury. Proton therapy (PRT) may offer an advantage in the re-irradiation setting due to the lack of exit dose and potential sparing of normal tissues. Methods: Between 6/2011 and 8/2013, 10 adult patients (pts) with locally recurrent esophageal cancer, initially cT1b-T4N0-1, in or near prior treatment fields began reirradiation. Toxicity was graded according to the Common Toxicity Criteria version 4.0. Acute toxicity was defined as occurring within 90 days from start of PRT. Results: The median follow-up was 7.9 months (1-23) from the start of retreatment, and 15 months (2.4-27.8) from the development of local recurrence. Mean age was 70 (53-91). ECOG PS was 0 (n=4), 1 (4), 2 (2). Eight pts had intraluminal and two had paratracheal nodal recurrences. Eight of the pts had adenocarcinoma and two squamous cell carcinoma. Median CTV size was 138 cc (32-390). Seven received concurrent chemotherapy. The median total dose was 54.0 Gy (50.4-61.2); all pts were treated with PRT exclusively (9 double scatter and 1 uniform scanning), except for two pts who were treated with 15-30% IMRT. The median prior dose was 55.8 Gy (45-70). The median interval between radiation courses was 31.4 mos (12-105). Maximum acute toxicity was grade 2 (30%), 3 (30%), and 4 (40%). Of the grade 4 toxicities, one was an esophagopleural fistula and respiratory failure unlikely related to RT, and 3 were neutropenic toxicities possibly related to RT. Three pts developed metastatic disease at a median of 28 mos after starting RT. Three pts developed in-field locoregional recurrence at a median of 13 mos. Five pts died after a median of 13 mos. Conclusions: Preliminary results using PRT for reirradiation of esophageal cancers shows that local control can be achieved in a large proportion of pts with moderate but acceptable acute toxicity. Further follow-up on these pts is needed to assess the long-term utility of PRT reirradiation. Clinical trial information: NCT01126476.
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Tanzawa, Shigeru, Sunao Ushijima, Kazuhiko Shibata, et al. "A phase II study of S-1 and cisplatin with concurrent thoracic radiotherapy followed by durvalumab for unresectable, locally advanced non-small-cell lung cancer in Japan (SAMURAI study)." Therapeutic Advances in Medical Oncology 13 (January 2021): 175883592199858. http://dx.doi.org/10.1177/1758835921998588.
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Background: Based on the results of the PACIFIC study, chemoradiotherapy followed by 1-year consolidation therapy with durvalumab was established as the standard of care for unresectable, locally advanced non-small-cell lung cancer (LA-NSCLC). However, some topics not foreseen in that design can be explored, including progression-free survival (PFS) and overall survival (OS) after the start of chemoradiotherapy, the proportion of patients who proceeded to consolidation therapy with durvalumab, and the optimal chemotherapeutic regimens. In Japan, the combination regimen of S-1 + cisplatin (SP), for which the results of multiple clinical studies have suggested a good balance of efficacy and tolerability, is frequently selected in clinical settings. However, the efficacy and safety of consolidation therapy with durvalumab following this SP regimen have not been evaluated. We therefore planned a multicenter, prospective, single-arm, phase II study. Methods: In treatment-naïve LA-NSCLC, two cycles of combination chemotherapy with S-1 (80–120 mg/body, Days 1–14) + cisplatin (60 mg/m2, Day 1) will be administered at an interval of 4 weeks, with concurrent thoracic radiotherapy (60 Gy). Responders will then receive durvalumab every 2 weeks for up to 1 year. The primary endpoint is 1-year PFS rate. Discussion: Compared with the conventional standard regimen in Japan, the SP regimen is expected to be associated with lower incidences of pneumonitis, esophagitis, and febrile neutropenia, which complicate the initiation of consolidation therapy with durvalumab, and have higher antitumor efficacy during chemoradiotherapy. Therefore, SP-based chemoradiotherapy is expected to be successfully followed by consolidation therapy with durvalumab in more patients, resulting in prolonged PFS and OS. Toxicity and efficacy results of the SP regimen in this study will also provide information important to the future establishment of the concurrent combination of chemoradiotherapy and durvalumab. Trial registration: Japan Registry of Clinical Trials, jRCTs031190127, registered 1 November 2019, https://jrct.niph.go.jp/latest-detail/jRCTs031190127
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Wass, Romana, Maximilian Hochmair, Bernhard Kaiser, et al. "Durvalumab after Sequential High Dose Chemoradiotherapy versus Standard of Care (SoC) for Stage III NSCLC: A Bi-Centric Trospective Comparison Focusing on Pulmonary Toxicity." Cancers 14, no. 13 (2022): 3226. http://dx.doi.org/10.3390/cancers14133226.
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Introduction: The standard of care (SoC) for unresectable stage III non-small-cell lung cancer (NSCLC) is durvalumab maintenance therapy after concurrent chemoradiation in patients with PD-L1 > 1%. However, the concurrent approach is only amenable for about one-third of patients due to co-morbidities. Although sequential regimens are usually not regarded as curative, these schedules applied in a dose-escalated manner may be similarly radical as SoC. As combining high-dose radiation and durvalumab remains a question of debate this retrospective bi-center study aims to evaluate pulmonary toxicity after high-dose chemoradiotherapy beyond 70 Gy compared to SoC. Patients and Methods: Patients with NSCLC stage III received durvalumab after either sequential high-dose chemoradiation or concomitant SoC. Chemotherapy consisted of platinum combined with either pemetrexed, taxotere, vinorelbine, or gemcitabine. The primary endpoint was short-term pulmonary toxicity occurring within six months after the end of radiotherapy (RT). Results: A total of 78 patients were eligible for this analysis. 18F-FDG-PET-CT, cranial MRT, and histological/cytological verification were mandatory in the diagnostic work-up. The high-dose and SoC group included 42/78 (53.8%) and 36/78 (46.2%) patients, respectively, which were matched according to baseline clinical variables. While the interval between the end of RT and the start of durvalumab was equal in both groups (p = 0.841), more courses were administered in the high-dose cohort (p = 0.031). Pulmonary toxicity was similar in both groups (p = 0.599), whereas intrathoracic disease control was better in the high-dose group (local control p = 0.081, regional control p = 0.184). Conclusion: The data of this hypothesis-generating study suggest that sequential high-dose chemoradiation followed by durvalumab might be similar to SoC in terms of pulmonary toxicity and potentially more effective with respect to intra-thoracic disease control. Larger trials with a prospective design are warranted to validate these results.
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Käsmann, Lukas, Natalia Christina Cabeza-Boeddinghaus, Julian Taugner, et al. "Prognostic impact of inflammatory profiling during and after multimodal treatment for stage III NSCLC." Journal of Clinical Oncology 39, no. 15_suppl (2021): e20559-e20559. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.e20559.
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e20559 Background: Immune cells have a broad impact on tumor initiation, growth, and progression, and many of these effects are mediated by proinflammatory cytokines. The prognostic impact of dynamic changes of inflammatory cytokines in non-operable stage III NSCLC patients treated with (chemo)-radiotherapy ± immune checkpoint inhibition is unknown. In a prospective analysis, pro-inflammatory cytokines including interleukin 2, 6, and 8 from peripheral blood samples were evaluated 5-10 days before treatment start (T1), on the last day of thoracic radiotherapy (T2), and 3 weeks after radiation (T3) for their impact on overall survival (OS) and progression-free survival (PFS). Methods: Twenty patients, 85% male, at a median age of 65.5 (range 33-77) years were prospectively enrolled in this study. Eighteen (90%) patients received platinum-based concurrent chemoradiotherapy (CRT); seven (35%) patients additional concurrent and/or sequential immune checkpoint inhibition (four patients nivolumab and three durvalumab); patients treated with nivolumab received induction chemotherapy. Thoracic irradiation (TRT) was applied in all patients with a median cumulative dose in equivalent 2Gy fractions (EQD2) of 64Gy (range: 52-65Gy). Results: Median follow-up achieved 25 (range 14-30) months, median OS was not reached and median PFS was 11.8 (95%CI 5.2-18.4) months. To analyze pre-treatment data, median values were used as cut-off for dichotomization. Higher IL6 levels (≥9.75pg/ml) before irradiation (T1) were associated with impaired OS (median 11 months vs. not reached; p < 0.001) and PFS (median 7.0 months vs. not reached; p = 0.041). Higher IL8 levels (≥4.62pg/ml) were also associated with shorter OS (median 16 months vs. not reached; p = 0.009) and PFS (median 7 months vs. not reached p = 0.040). Patients with a decline of ≥10% of IL8 level between T1 and T2 had a significantly shorter PFS (11.8 months vs. not reached; p = 0.028). Conclusions: High proinflammatory cytokine levels were significantly associated with deterioration of outcome regarding OS and PFS in patients enrolled in multimodal treatment for stage III NSCLC. A decline of ≥10% of IL8 level during TRT was associated with impaired PFS.
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Schnuelle, Christian, Kasper Kisjes, Torben Stuehrmann, et al. "From Niche to Market—An Agent-Based Modeling Approach for the Economic Uptake of Electro-Fuels (Power-to-Fuel) in the German Energy System." Energies 13, no. 20 (2020): 5522. http://dx.doi.org/10.3390/en13205522.
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The transition process towards renewable energy systems is facing challenges in both fluctuating electricity generation of photovoltaic and wind power as well as socio-economic disruptions. With regard to sector integration, solutions need to be developed, especially for the mobility and the industry sector, because their ad hoc electrification and decarbonization seem to be unfeasible. Power-to-fuel (P2F) technologies may contribute to bridge the gap, as renewable energy can be transferred into hydrogen and hydrocarbon-based synthetic fuels. However, the renewable fuels production is far from economically competitive with conventional fuels. With a newly developed agent-based model, potential developments in the German energy markets were simulated for a horizon of 20 years from 2016 to 2035. The model was constructed through a participatory modeling process with relevant actors and stakeholders in the field. Model findings suggest that adjusted regulatory framework conditions (e.g., exemptions from electricity surtaxes, accurate prices for CO2-certificates, strong start-up subsidies, and drastic emission reduction quotas) are key factors for economically feasible P2F installations and will contribute to its large-scale integration into the German energy system. While plant capacities do not exceed 0.042 GW in a business-as-usual scenarios, the above-mentioned adjustments lead to plant capacities of at least 3.25 GW in 2035 with concurrent reduction in product prices.
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Youssef, Ibrahim, Naba Saeed, Mohammad El Abdallah, Kara Huevelhorst, and Kais Zakharia. "Metronidazole-Induced Pancreatitis: Is There Underrecognition? A Case Report and Systematic Review of the Literature." Case Reports in Gastrointestinal Medicine 2019 (June 9, 2019): 1–6. http://dx.doi.org/10.1155/2019/4840539.
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Introduction. Acute pancreatitis (AP) is the most common cause of gastroenterological hospitalization in the USA, with a mortality ranging from 5 to 20%. Up to 80% of cases are caused by cholelithiasis and alcohol abuse. Less common etiologies that need to be explored include hypertriglyceridemia, trauma, ERCP, infections, and drugs. A number of medications are known to cause acute pancreatitis, with 0.3-1.4% of all cases of pancreatitis being drug induced (DIP). Here, we present a case of metronidazole-induced acute pancreatitis. Case Summary. A 60-year-old female presented with constant severe epigastric pain associated with nausea, vomiting, and anorexia for one day. She had no past medical history of alcohol use or hypertriglyceridemia and was s/p cholecystectomy in the distant past. Symptoms had begun three days after starting metronidazole for Clostridium difficile colitis. Lipase was > 396, and CT abdomen revealed peripancreatic fat stranding. She was diagnosed with AP, metronidazole was suspected to be responsible and hence stopped, and supportive management initiated. Her symptoms improved rapidly, and pancreatic enzymes normalized within 2 days. Of note, she had had an episode of acute pancreatitis 3 years ago, also following metronidazole use, with resolution at discontinuation of the drug. She had concurrently been on omeprazole during both episodes. Discussion. Metronidazole is a commonly used antibiotic and is infrequently reported as a cause of DIP. Our review suggests the possibility of a dose-response and duration-response effect between metronidazole use and occurrence of pancreatitis. The most common presenting symptom and sign was moderate to severe epigastric pain and tenderness, accompanied by nausea/vomiting. Symptoms usually start within 2-7 days of starting the medication and usually resolve 2-5 days after discontinuation of therapy and pancreatitis treatment. The most common causative dose was 1-1.5 g/day. Our review also supports findings by Norgaard et al. suggesting that concurrent use of omeprazole potentiates the risk of metronidazole-induced pancreatitis. Conclusion. Metronidazole is a commonly used antibiotic that may cause metronidazole-induced pancreatitis, especially if patients are concurrently taking PPIs. Awareness needs to be raised amongst clinicians regarding this association, in order to correctly identify etiology of pancreatitis and discontinue metronidazole promptly when suspected as the causative factor.
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Munk PhD, LMT, Niki, Jasmine Dyson-Drake, BS, and Diane Mastnardo, LMT. "What Should We Do Different, More, Start and Stop? Systematic Collection and Dissemination of Massage Education Stakeholder Views from the 2017 Alliance for Massage Therapy Educational Congress†." International Journal of Therapeutic Massage & Bodywork: Research, Education, & Practice 12, no. 1 (2019): 29–39. http://dx.doi.org/10.3822/ijtmb.v12i1.441.
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Introduction: The Future of MT and Bodywork Forum, held July 27 during the 2017 Alliance for Massage Therapy Education (AFMTE) Educa-tional Congress in Tucson, Arizona, systematically gathered the thoughts and opinions of various massage education stakeholders through an exercise following the principles of the World Café model.Methods: Forum attendees participated in three, concurrent 30-minute Breakout Group Sessions (Rounds) in three different adjacent rooms, focused on Continuing Education, Schools, or Employment. During each session, participants rotated for 3, 2.5, 2, and 1.5 min-utes between four tables, asking what should be stopped, started, done differently, or changed in massage education related to the focus topic. Participants recorded their responses in marker on large Post-it® notes (3M, Maplewood, MN). These were reviewed by each of that round’s participants who awarded “importance points” to each response, with 6 blue and 3 orange dots each worth 1 and 3 points, respectively. The Post-it® notes with comments and point alloca-tions were transcribed into a data spreadsheet and analyzed for descriptive statistics and top scoring comments from each room.Results: 85–91 attendees participated in the three breakout sessions resulting in 674 comments with 3,744 assigned value points. The top five scor-ing comments from each room per session (N = 45) determined stakeholder’s most critical views. Stop comments made up the smallest total comments proportion (19%), yet largest top scoring com-ment proportion (36%)—potentially highlighting unified frustration for various massage education practices. Comparatively, Start comments made up 26% of total comments, but the smallest high-est scoring proportion (18%)-perhaps suggesting stakeholders feel it more important to improve what is already being done rather than beginning new endeavors in these areas.Conclusion: Stakeholder opinions on the future of massage therapy education can be system-atically gathered in large conference settings and organized, analyzed, and disseminated to inform field decision-making.
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De Sa, Hong, Demitrios Dedousis, Sree Harsha Tirumani, et al. "Impact of BRAF mutations on outcomes in metastatic melanoma with central nervous system metastases treated with immune checkpoint inhibitors." Journal of Clinical Oncology 39, no. 15_suppl (2021): e21500-e21500. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.e21500.
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e21500 Background: Half of patients (pts) with melanoma (mel) develop central nervous system (CNS) metastases (mets), leading to death in over 90% in the pre-immune checkpoint inhibitor (ICI) era. Overall survival (OS) has improved in the ICI era for those with CNS mets, yet the association of survival with ICI treatment for those with tumors harboring genomic variants (var) remains unclear. Methods: We retrospectively reviewed our electronic medical records to identify pts with mel and CNS mets who received ICI from 2010 to 2018. Treatment history, systemic and CNS responses, and genomic data were recorded. Genomic var were categorized as BRAFV600E (BRAF), NRAS, cKIT, other var, and no var. Concurrent RT (CRT) was defined as RT to CNS mets within 30 days of ICI. OS was calculated from date of first ICI or RT to date of death or last follow up, and comparison analyses made using Kaplan-Meier estimate. Fisher's exact or Chi-squared tests were used to compare categorical variables and Wilcoxon or Kruskal-Wallis tests to compare continuous variables. A two-sided p-value of < 0.05 was considered statistically significant. Results: A total of 49 pts were identified; 37 had var results available. BRAFV600E was the most common var identified (32%), followed by NRAS (19%), cKIT (5%), and other (5%); 38% had no var. BRAFV600K was not identified. Pts with BRAF had lower rates of CNS progression on ICI at 3 and 6 months than all other pts (17% vs 50%, p< 0.01 and 12.5% vs 40%, p< 0.01, respectively). Of 38 pts (10 BRAF) who had CNS mets at the start of ICI, 6-month OS was 50% in pts with BRAF, compared to 0% in pts with non-BRAF var ( p= 0.01) and 36% in pts with no var ( p= 0.7). 4 of the 10 pts with BRAF who had CNS mets at start of ICI received BRAF-targeted therapy after ICI. On ICI, only 30% of pts with BRAF developed new CNS mets, compared to 57% of all other pts ( p= 0.08). Pts who developed new CNS mets on ICI had worse OS than pts who did not (median OS (mOS) 314 days vs 662 days, p= 0.04). A majority of pts (55%) received anti-CTLA4 monotherapy as first ICI, and 39% received anti-CTLA4 plus anti-PD1. Pts with BRAF were just as likely to receive dual anti-CTLA4/PD-1 as pts without BRAF (33% vs 40%, p= 0.74). 40 pts underwent RT for CNS mets, of whom 22 received CRT. There was no difference in mOS between pts who received CRT and non-concurrent RT/no RT (468 days vs 314 days, p= 0.8). Rates of CRT between pts with BRAF and pts without BRAF were similar ( p> 0.9), and there was no difference in mOS between these groups (400 days vs 536 days, p= 0.9). Conclusions: Pts with BRAF-mutated mel with CNS mets receiving ICI had lower rates of progression in CNS and improved OS compared to other var. CRT was not associated with improved survival over non-concurrent RT. There has been significant improvement in OS of pts with mel CNS mets in the era of ICI and additional studies are warranted to understand the biology of BRAF var and the host immune system response in the CNS.
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Kalinina, Svetlana N., Vladimir N. Fesenko, Anton V. Nikolskii, Oleg O. Burlaka, and Natalia V. Marchenko. "Assesment of the efficiency of conservative treatment of Peyronie’s disease." Urologicheskie vedomosti 8, no. 1 (2018): 5–10. http://dx.doi.org/10.17816/uroved815-10.
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There were 27 men under observation who got conservative treatment for Peyronie's disease. The criteria for inclusion in the study were the maximum size of the plaque of the penis up to 1.5 cm and the angle of curvature of the penis is less than 45 degrees. Before treatment, after 6 and 12 months, patients underwent ultrasonic dopplerography of the penis, the velocity of blood flow in the cavernous and dorsal arteries and the size of the plaque were determined. All observed patients were prescribed combined therapy, such as symptomatic, immunological and physiotherapeutic treatment. In this case, the patients of the 1st group (n = 15) additionally got longidase treatment (intramuscularly for 3000 IU every 3 days, for a course of 10 injections with concurrent administration of rectal suppositories with longidase at the same dose for a course of 10 suppositories). Locally, these patients were assigned phonophoresis with lengidase on the plaque area (10 sessions). The remaining 12 patients (2nd group) didn’t got longidase treament. Six months after the start of treatment the absence of plaques was recorded in 8 (53.3%) patients in the 1st group and 4 (33.3%) in the 2nd group of patients and in 12 months in 11 (73.3%) and 6 (41.6%) patients. Thus, conservative therapy in Peyronie's disease is effective in patients in the early stages of the disease with moderate deviation of the penis and plaques up to 1.5 cm. The inclusion of longidase in the complex therapy increases the effectiveness of the treatment. (For citation: Kalinina SN, Fesenko VN, Nikolskii AV, et al. Assesment of the efficiency of conservative treatment of Peyronie’s disease. Urologicheskie vedomosti. 2018;8(1):5-10. doi: 10.17816/uroved815-10).
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Kong, Fengming, Randall K. Ten Haken, Matthew J. Schipper, et al. "A phase II trial of mid-treatment FDG-PET adaptive, individualized radiation therapy plus concurrent chemotherapy in patients with non-small cell lung cancer (NSCLC)." Journal of Clinical Oncology 31, no. 15_suppl (2013): 7522. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.7522.
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7522 Background: We have found that FDG-PET response during chemoradiation for patients with NSCLC is heterogeneous and predicts outcome. We hypothesized that dose escalated treatment targeted to the FDG-avid tumor would improve local tumor control. Methods: This is a phase II trial for patients with locally advanced, inoperable/unresectable NSCLC. Conformal radiotherapy (RT) was given in 30 daily fractions. RT dose was individualized to a fixed risk of lung toxicity and adaptively escalated to the residual tumor on mid-tx FDG-PET up to a total physical dose of 86 Gy. Patients had concurrent weekly followed by consolidation carboplatin/paclitaxel. The primary endpoint was local-regional tumor control (LRTC) at 2 years. Survival was calculated from RT start. Results were compared to stage-matched patients treated during the same time period with standard RT dosing (60-66 Gy). The data are presented as median (95% CI) unless otherwise specified. Results: 42 patients were enrolled: median age 63 years (range 45-83); 28 (67%) male; 39 (93%) smokers; 39 (93%) stage III; and 45% squamous cell. The mean gross tumor volume was 154 cc (range 10-617 cc). Median physical dose reached was 84 Gy (range 63-86 Gy), equivalent to 90 Gy in 2 Gy fractions (biological effective dose 108 Gy). 8 patients (19%) had RT-induced lung toxicity and 13 (31%) grade ≥2 esophagitis. Minimum and median follow-up were 10 and 25 months, respectively. The 2-year rates of in-field LRTC, overall LRTC, and LR-PFS were 84% (63-94%), 68% (47-82%), and 43% (27-58%), respectively. 14 patients progressed: 7 (50%) first at distant sites; 5 (36%) at nodal regions; 2 (14%) at primary tumor. Median overall survival was 26 months and 2-year overall survival rate was 51% (34-65%). These results compared favorably to stage-matched patients treated with standard-dose RT [2-year overall survival 23% (8-41%)]. Conclusions: These results support our hypothesis that adapting RT by escalating dose to the FDG avid region detected mid-tx improves 2-year local-regional tumor control. Adaptive RT may also improve overall survival. RTOG 1106 is currently testing this regimen in a randomized fashion. Clinical trial information: NCT01190527.
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Cabanillas, Maria E., Gary Brandon Gunn, Mark E. Zafereo, et al. "IMRT followed by pembrolizumab in the adjuvant setting in anaplastic cancer of the thyroid (IMPAACT): Phase II trial adjuvant pembrolizumab after IMRT in ATC." Journal of Clinical Oncology 41, no. 16_suppl (2023): TPS6117. http://dx.doi.org/10.1200/jco.2023.41.16_suppl.tps6117.
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TPS6117 Background: Anaplastic thyroid carcinoma (ATC) has historically been an almost uniformly rapidly fatal disease. In patients with loco-regional disease with no distant metastasis (stage IVB), and without a targetable mutation, a combination of external beam radiation delivered via intensity modulated techniques (IMRT) +/- concurrent cytotoxic chemotherapy is the current standard of care. However, the relapse rate is very high within the first year of diagnosis. Our data show that 90% of ATCs express PD-L1, with 43% having expression levels greater than 50%. A clinical trial with an anti-PD1 drug in ATC patients with active disease showed that patients with ATC had a response rate of 19%. Additionally, as tumor PD-L1 expression has been linked to radioresistance and there is a need to target micrometastatic disease, using adjuvant checkpoint inhibitor is a rational strategy in these patients. Methods: This is an open label, single center, phase 2 trial of adjuvant pembrolizumab after external beam radiation to the primary tumor in patients with stage IVB ATC. The primary cohorts will include those with gross, locoregional disease who have completed treatment with IMRT +/- concurrent radiosensitizing chemotherapy. Patients will be treated with adjuvant pembrolizumab (400mg IV Q6 weeks for up to 9 cycles), 2-6 weeks after completion of radiation. Patients will be enrolled based on dose of radiation in cohort 1 (high dose group, > 51 Gy), cohort 2 (palliative dose group, < 50 Gy). Cohort 3, consisting of those who underwent surgery followed by IMRT plus concurrent chemotherapy will be an exploratory cohort. Restaging scans will be performed every 12 weeks after enrollment. MRI brain will be repeated every 6 months in the absence of evidence of progression. The primary endpoint is median PFS (from the start of adjuvant pembrolizumab) in cohorts 1 and 2. Secondary endpoint is median overall survival in cohorts 1 and 2. Cohort 3 (5 patients) will have an exploratory endpoint, to estimate the median disease-free survival (DFS). Statistics: Survival analyses will be performed using the Kaplan-Meier method. Based on historical data, the median PFS for unresected patients is 6.8 months. For an expected improvement of median PFS by 3.7 months, with a combined total of 30 evaluable patients in cohorts 1 and 2, we anticipate having 80.0% power using 1-sided 10% alpha for a one-sample log rank test. The trial began enrollment in July 2022. This trial is sponsored by philanthropic funds and Merck. ClinicalTrials.gov ID NCT05059470. Clinical trial information: NCT05059470 .