Journal articles on the topic 'Congresses Immunotherapy'

Introduction and objectives. The combination of radiotherapy and immune checkpoint inhibitors has demonstrated antitumor activity in numerous preclinical studies and is currently being investigated in the clinical setting. This study aims to compare the efficacy of radiotherapy alone (RT) vs. the combination of radio- and immunotherapy (IT-RT) and identify the treatment regimen associated with maximal efficacy by using a meta-analysis. Materials and methods. A systematic literature search was performed using the PubMed database and materials of the key oncology congresses. Studies reporting 1-year overall survival (OS) of patients with brain metastases undergoing IT-RT treatment were included in the analysis. Information about 1-year OS, individual patients characteristics, and treatment regimens for both IT-RT and control RT arms was extracted. Identification of the optimal treatment regimen was performed using a mixed meta-regression modeling approach. Analysis was performed using the R statistical environment (metafoR package). Results. In total, 30 studies were identified, of which 13 reported outcomes for the control RT groups. The analysis revealed that IT inclusion into RT is associated with a significant increase in 1-year OS; given simultaneously, IT and RT demonstrated the highest efficacy with a 1-year OS of 68% (95% confidence interval (CI): 60%75%), followed by a sequential regimen: 1-year OS = 54% (95% CI: 47%61%) and RT alone: 1-year OS = 32% (95% CI: 2539%). Conclusion. The current study demonstrates the superiority of combined IT-RT over RT alone; simultaneous IT and RT treatment is associated with the highest efficacy.

Background: Ovarian cancer (OC) represents the eighth most common cancer and the fifth leading cause of cancer-related deaths among the female population. In an advanced setting, chemotherapy represents the first-choice treatment, despite a high recurrence rate. In the last ten years, immunotherapy based on immune checkpoint inhibitors (ICIs) has profoundly modified the therapeutic scenario of many solid tumors. We sought to summarize the main findings regarding the clinical use of ICIs in OC. Methods: We searched PubMed, Embase, and Cochrane Databases, and conference abstracts from international congresses (such as ASCO, ESMO, SGO) for clinical trials, focusing on ICIs both as monotherapy and as combinations in the advanced OC. Results: 20 studies were identified, of which 16 were phase I or II and 4 phase III trials. These trials used ICIs targeting PD1 (nivolumab, pembrolizumab), PD-L1 (avelumab, aterolizumab, durvalumab), and CTLA4 (ipilimumab, tremelimumab). There was no reported improvement in survival, and some trials were terminated early due to toxicity or lack of response. Combining ICIs with chemotherapy, anti-VEGF therapy, or PARP inhibitors improved response rates and survival in spite of a worse safety profile. Conclusions: The identification of biomarkers with a predictive role for ICIs’ efficacy is mandatory. Moreover, genomic and immune profiling of OC might lead to better treatment options and facilitate the design of tailored trials.

e18580 Background: Progression-free survival (PFS) is accepted as a surrogate endpoint for cancer drugs approval by the Food and Drug Association. In the expanding immunotherapy era, there is no convincing data for reliable surrogacy of PFS. Methods: We systematically searched PubMed and included all phase III trials of ICIs. Besides, we manually included phase III trials of ICIs presented in congresses. Trials including non-metastatic patients and hematologic malignancies were excluded. The primary endpoint was the relationship between treatment effects (i.e., hazard ratio (HR) of PFS and overall survival (OS)). The secondary endpoint was the relationship between the median PFS (mPFS) and median OS (mOS). We also performed subgroup analyses by ICIs subtypes (i.e., anti-programmed death-1 (PD-1) and anti-programmed death ligand-1 (PD-L1)), treatment lines (i.e., the first-line and subsequent treatments), ICI plus CT combination, and ICI monotherapy. To ensure parametric assumptions, we addressed logarithmic conversion to HRs by using log10. We used Pearson’s correlationand weighted linear regression for parametric variables and Spearman’s rank-order correlation for non-parametric variables. We assessed the relationship between variables by using correlation coefficient (r) and coefficient of determination (R2). Results: We included 57 phase III clinical trials with 39,525 patients. A total of 67 outcomes were compared. There was a good correlation between the logarithmic HR of PFS (log HRPFS) and OS (log HROS) (r=0.71, R2=0.50 p<0.001). In subgroup analyses, there was a weak or moderate correlation between the log HRPFS and log HROS in anti-PD-L1, ICI plus CT, and the first-line treatment subgroups (r=0.61, R2=0.38 p=0.004 for anti-PD-L1; r=0.65, R2=0.43 p=0.008 for ICI plus CT; r=0.70, R2=0.49 p<0.001 for the first-line treatment). Conversely, there was a good correlation between the log HRPFS and log HROS in the anti-PD-1, ICI monotherapy, and subsequent treatment line subgroups (r=0.81, R2=0.66 p<0.001 for anti-PD-1; r=0.71, R2=0.51 p<0.001 for ICI monotherapy; r=0.78, R2=0.62 p<0.001 for subsequent treatment line). Correlations between the mPFS and mOS were good or strong in all subgroups. (Table). Conclusions: PFS might be considered a reliable surrogate endpoint for OS, particularly in anti-PD-1 ICIs, ICI monotherapy, and subsequent metastatic cancer treatment lines.[Table: see text]

In recent years, it has been noted that the combination of radiation and immunotherapy is more benefitial than both modalities used separately. The interactions between immune checkpoint inhibitors and high-dose radiotherapy are curently an important topic of ongoing scientific trials. This review highlights some of the presented papers during the ESTRO 37 congress in 2018.

As part of the 2019 Immunotherapy Bridge congress (December 4–5, Naples, Italy), the Great Debate session featured counterpoint views from leading experts on six topical issues in immunotherapy today. These were the use of chimeric antigen receptor T cell therapy in solid tumors, whether the Immunoscore should be more widely used in clinical practice, whether antibody-dependent cellular cytotoxicity is important in the mode of action of anticytotoxic T-lymphocyte-associated protein 4 antibodies, whether the brain is immunologically unique or just another organ, the role of microbiome versus nutrition in affecting responses to immunotherapy, and whether chemotherapy is immunostimulatory or immunosuppressive. Discussion of these important topics are summarized in this report.

Lung cancer is a substantial global burden for patients, healthcare professionals and healthcare systems. Multiple scientific international and national initiatives are tackling the various problems associated with this disease, which is currently the leading cause of cancer-related mortality worldwide. During the European Respiratory Society International Congress 2018 in Paris, France, lung cancer experts gathered to present the most recent aspects of lung cancer care, and discuss the need for joint initiatives and an international lung cancer alliance, aiming to provide high quality, accessible health care. The US experience and American Lung Association/American Thoracic Society implementation guide on lung cancer screening programmes, the key features of optimising and implementing such programmes, the challenges of treatment in the subset of patients where lung cancer is combined with interstitial lung disease, and novel lung cancer biomarkers and immunotherapy were among the most anticipated issues covered during the congress.

Head and neck squamous cell carcinoma (HNSCC) is a challenging cancer to treat and cure. A great proportion of patients present with advanced disease and appropriate treatment options include surgical resection with adjuvant radiotherapy (RT) or chemoradiotherapy (CRT), radical concurrent CRT or RT with monoclonal antibody cetuximab. Despite improved outcomes with CRT, overall prognosis is still unsatisfactory and treatment-related toxicity is a matter of major importance. To obtain improved outcomes and mitigate disease recurrence, current research is focused on novel molecular targeted agents, immunotherapy and discovery of predictive markers. Herein, we summarise recent advances in treatment of head and neck cancer, as presented in European Society for Medical Oncology (ESMO) Congress 2014.

<p>The fast growing field of immunotherapy was one of the topics extensively discussed during the recently concluded ESMO Asia Congress 2016, held from December 16– 19th December at the Suntec Convention and Exhibition Centre in Singapore. <br /> <br />Unlike drug-based chemotherapy, immunotherapy exploits the body’s own immune system to fight cancer and is increasingly touted as the future of cancer treatment. The concept of using the immune system as a disease-fighting tool was introduced by Dr. William Bradley Coley, the ‘Father of Cancer Immunotherapy’, in the 19th century based on his work that sought to stimulate a patient’s own immune system against bacterial infection. However, a persistent question remains since the advent of immunotherapy over a century ago – can the immune system accurately recognize malignant tumor and eliminate it effectively? The answer to this question remains hotly debated owing to the differing opinions and attitudes on the application of immunotherapy. <br /><br />Dr. Coley noticed that in a number of cases, patients with cancer went into spontaneous remission after developing erysipelas. In 1891, Dr. Coley injected streptococcal organisms (which cause erysipelas) into a patient with inoperable cancer and observed remarkable tumor regression. Although he had treated almost 900 patients with bacterial preparations that eventually became known as “Coley’s toxins”, his treatment method was not widely accepted by the medical community possibly owing to the low cure rates and the severe fever caused by the bacteria. Some physicians also feared that the immune system might not have adapted well enough to recognize and eliminate malignant cells exclusively. As a consequence, most oncologists relied on another treatment that was rapidly gaining acceptance at that time, i.e. radiation. <br /><br />It was only after about a century later that the medical community observed a revived interest in immunotherapy. In 1976, a trial was conducted to test the effectiveness of the tuberculosis vaccine Bacille Calmette-Guérin (BCG) in treating superficial bladder cancer. The BCG treatment, in which BCG bacilli are inserted directly into a patient’s bladder via a catheter, proved to be an effective form of immunotherapy and the groundbreaking technique is still used today. <br /> <br />In general, studies on immunotherapy have presented researchers with two important conclusions: First and foremost, researchers were finally able to prove that the immune system is indeed capable of recognizing cancer cells as a ‘foreign entity’ although they originate from the body’s own tissues. Secondly, by boosting the immune response, researchers are able to enhance other cancer-killing agents at the same time, thus increasing the chances of a successful treatment via immunotherapy. Based on these conclusions, researchers all over the world now face the challenge of figuring out which therapy works best for a specific type of cancer and why some cancer patients respond better than others to the prescribed treatments.</p><p> </p><p>At the ESMO Asia 2016 congress, lead author Dr. Makoto Tahara presented his paper ‘Asian head and neck cancer patients live longer with immunotherapy than mixed race group’, in which his team of researchers reported the sub-analysis results on the safety and efficacy of pembrolizumab in 26 patients (of Asian Pacific origin) who received a fixed dose of the humanized antibody for 24 months until the detection of disease progression or adverse events. They observed that both the median overall survival and the disease control rate were better in Asians than the overall population, i.e. 11.5 versus 8.4 months and 50.5% versus 37.9%, respectively.</p><p> </p><p>According to Dr. Tahara, “The fixed dose of pembrolizumab was well-tolerated in Asian Pacific patients with recurrent/metastatic head and neck cancer. Although the Asian population was small, our findings suggest that they have better median overall survival with pembrolizumab than a mixed population. The clinical benefit of the fixed dose of pembrolizumab in the first and second line treatment of recurrent/metastatic head and neck cancer is being evaluated head-to-head with standard of care chemotherapy in phase 3 trials around the world, including Asia Pacific.” </p><p><br />Meanwhile, another research paper on immunotherapy presented at the ESMO Asia 2016 was by Dr. Herbert Loong, Clinical Assistant Professor at the Department of Clinical Oncology of the Chinese University of Hong Kong, who discussed about the cost-effectiveness of immunotherapy with pembrolizumab for advanced melanoma patients in Hong Kong. Dr. Loong said, “We have determined that whilst pembrolizumab is expensive, the increase in quality adjusted life years (QALYs) compared with standard cytotoxic chemotherapy, and even so with ipilimumab, qualifies it as a cost-effective approach.” <br /><br />Commenting on the results of the research by Dr. Loong and his colleagues, Dr. Mark Tang – a senior consultant dermatologist said, “Given the high costs of these new treatment options, cost effectiveness studies such as this one are timely and useful as further evidence for the use of pembrolizumab in the treatment of advanced melanoma. This is particularly important in an Asian context where, although rare, acral melanoma has unfortunately been known to present late advanced disease.” <br /> <br />Taking all these exciting discoveries into account, a good number of studies have repeatedly shown that progress in cancer immunotherapy has accelerated and resulted in the development of several effective and promising therapies for multiple forms of cancer. At this critical juncture, oncological organizations such as ESMO provide an important knowledge transfer platform for the sharing of expertise and interaction between regional and international experts in the area of onco-immunology. Moving forward, immunotherapy and targeted medicine are expected to remain in the spotlight and will be an indispensable arsenal in the long fight against cancer.</p>

On February 7, 2019, a one-day Consensus Conference of the International Liver Transplantation Society was held to discuss oncology issues. Representatives of world's leading clinics gathered in Rotterdam (Netherlands). The presentations made on that day covered the following topics: hepatocellular cancer, bile duct cancer, immunotherapy and its place in the treatment of liver tumors, the possibility of liver transplantation in patients with metastatic liver disease, world trends in pediatric oncohepatology. A separate session in the working groups was allocated to discuss the most actual topics. The Conference identified the main global trends and the most crucial issues in the field of liver transplantation in patients with oncological diagnosis. It is likely that these presentations will “set the tone” for the large Transplantationt Congress in Toronto in May 2019.

This year, I followed a young patient who is being investigated for a probable leukemia, He said he was a gardener. I tried to explain what his diagnostic hypothesis was, but I had a distinct feeling that he hadn't quite understood the situation. I always feel this feeling of anguish, a certain impotence, because the exact understanding involves a minimum amount of knowledge that this gentleman must have about health, citizenship or even general education, which a good part of the population that we treat in public hospitals does not have. This patient who does not understand his illness very well and what effectively needs to be done for a correct diagnosis and treatment. Added to this is the difficulty of having access to new expensive drugs and, as if that were not enough, some essential drugs for the treatment of cancer, such as carmustine, used to conditioning regimen of Bone Marrow transplant, which simply disappeared from the Brazilian market and left with restrict options to treat these patients. In any case, it is not the first time that we have dealt with this reality, and many will say that there is nothing new in my report or that it used to be much worse. I agree with these two statements, but this process remains very difficult, painful and very worrying. I participated in february of a congress in the United States; there I could see the main updates in the treatments of onco-hematology and bone marrow transplantation. I presented an article and, throughout the debate, I tried to show my professional colleagues the profound differences, not to say abysmal, between our realities in Latin America and first world countries. This distance becomes increasingly larger as treatment progresses based on targeted and cellular therapies, with drugs such as immunotherapy associated with chemotherapy or the use of "smart" cells that destroy cancer, which are difficult to access. Thus, we come to the difficult trinomial that consists of cancer, poverty and lack of access. This leads us to a deep reflection on the real paths we are taking and where this modern, technological and fast society will take us all, if we do not pay attention to the need to place the individual as the priority center of all our actions.

Introduction The antibody-drug conjugate polatuzumab vedotin (Pola) has recently been approved in combination with bendamustine and rituximab (Pola-BR) for patients with r/r diffuse LBCL (DLBCL). Methods To characterize the efficacy of Pola-BR in a real-world setting, we retrospectively analyzed data from 97 patients with r/r LBCL who were treated with Pola in 24 German centers within the national CUP. Clinical baseline and follow-up (FU) data were collected by chart review and summarized descriptively. Progression-free survival (PFS) and overall survival (OS) were analyzed using Kaplan-Meier and Cox regression methods. Fisher's exact test was used to compare categorical factors between groups of patients. Results 97 patients with LBCL (DLBCL n=90, High-grade B-cell lymphoma n=6, Primary mediastinal B-cell lymphoma n=1) were included as of July 22nd, 2020. 49 patients were treated with Pola as bridging concept to immunotherapies (bridging cohort: chimeric antigen receptor T-cells (CART) n=39, allogeneic stem cell transplantation (alloSCT) n=9, bispecific antibodies n=1), and 48 patients were treated with Pola in palliative intention (palliative cohort). Within the bridging cohort the median age was 61 years (range: 22-82). Patients were heavily pretreated with a median of 3 treatment lines (range: 2-6). 84% (41/49 patients) had been refractory to their last treatment line, and 31% had failed an autologous stem cell transplantation. Notably, 14% and 10% of patients had failed prior CART and alloSCT, respectively, and were planned for the alternate cellular immunotherapy. Based on an individual decision, patients were treated with Pola-Rituximab (Pola-R, n=20), Pola-chemotherapy (Pola-chemo, BR n=25; R-CHP n=1) or Pola-monotherapy (Pola-mono, n=3). With a median of 2 Pola cycles (range 1-6), overall response rate (ORR) of all evaluable patients was 33% (15/46 patients) including patients with complete response (CR n=1), partial response (PR n=9) and clinical response (n=5). Although not significant, ORR tended to be better in patients treated with Pola-chemo versus Pola-R/Pola-mono (ORR: 42% versus 20%, Fishers test p=0.1). 11 of these 15 responders (24% of the entire bridging cohort) proceeded to CART or alloSCT, while 4 responders (8% of entire bridging cohort) experienced fast progression after their initial response and were referred to best supportive care. 15 of 31 non-responders (33% of entire bridging cohort) underwent immunotherapy with either stable disease (n=6), mixed response (n=2), or progression on Pola (n=7). The remaining 16 patients (35% of entire bridging cohort) were all refractory to Pola and either received alternative salvage treatments which enabled 8 further patients to proceed to the intended immunotherapy, or best supportive care. Taking the effects of CART or alloSCT into account, median OS from initiation of Pola treatment was 8.2 months (median FU 7.2 months, Fig. 1A). The palliative cohort tended to be older than the bridging cohort with a median age of 73.5 years (range: 37-86, p&lt;0.001). Patients were pretreated with a median of 3 treatment lines (range: 2-8), and 85% (41/48 patients) had been refractory to their last treatment line. Patients in the palliative cohort were treated with a median of 4 Pola cycles (range: 1-9). 65% received Pola-chemo (BR, n=30; R-Gemcitabine, n=1) and 35% Pola-R. The CR rate and ORR was 19% (9/48) and 56% (27/48), respectively. The 6-month PFS and OS from initiation of Pola was 36% and 51%, respectively (median FU of 9.7 months, Fig. 1B). Again, ORR and OS tended to be better in patients treated with Pola-chemo versus Pola-R (ORR: 61% versus 47%, Fishers test p=0.4; median OS 7.2 versus 4 months, HR 0.8, 95%CI 0.4-1.9, p=0.7). In univariate analysis, failure to respond to the last treatment line predicted inferior PFS (HR 2.4, 95%CI 1.2-5.0 p=0.02) and OS (HR 2.5, 95%CI 1.2-5.4 p=0.02). Patients with more than two prior treatment lines in total tended to have a shorter PFS (HR 2.0, 95% CI 0.9-4.5, p=0.1) and OS (HR 1.8, 95% CI 0.8-4.0, p=0.2), although significance was not reached. Conclusion Pola permits effective bridging to CART and alloSCT in r/r LBCL. In the palliative setting, Pola represents an effective salvage option for patients with transplantation-ineligible r/r LBCL. Compared to the approval study, the inferior outcome of the patients of this real-world analysis might be explained by their more advanced disease course. Disclosures Duell: Morphosys: Research Funding. Kerkhoff:BMS: Honoraria. Leng:Roche: Other: lecture fee; Celgene: Other: traveling expenses and congress attendance fee. Holtick:Miltenyi Biotec B.V. & Co. KG: Honoraria. Mayer:Amgen: Honoraria, Other: travel grants; Abbvie: Other: travel grants; Novartis: Honoraria; Roche: Honoraria. Hüttmann:Celgene: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Gilead: Honoraria; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Roche: Other: Travel expenses; Seattle Genetics: Research Funding; University Hospital Essen, University of Duisburg-Essen, Essen, Germany: Current Employment; Lead Discovery Center GmbH: Consultancy. Brunnberg:Gilead: Membership on an entity's Board of Directors or advisory committees; Hexal: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Other: travel grants; MSD: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees, Other: Travel grants; Amgen: Other: Travel grants. Bullinger:Menarini: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Hexal: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees. Hess:Roche: Research Funding; Celgene: Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Genmab: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Astra: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; EUSA: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Morphosys: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Mueller-Tidow:Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding; Deutsche Krebshilfe: Research Funding; BMBF: Research Funding; Wilhelm-Sander-Stiftung: Research Funding; Jose-Carreras-Siftung: Research Funding; Bayer AG: Research Funding; Daiichi Sankyo: Research Funding; BiolineRx: Research Funding; Janssen-Cilag Gmbh: Membership on an entity's Board of Directors or advisory committees; Deutsche Forschungsgemeinschaft: Research Funding. Lenz:Verastem: Research Funding; AQUINOX: Research Funding; BMS: Consultancy; AstraZeneca: Consultancy, Honoraria, Research Funding; Bayer: Consultancy, Honoraria, Research Funding, Speakers Bureau; Agios: Research Funding; Gilead: Consultancy, Honoraria, Research Funding, Speakers Bureau; Roche: Consultancy, Honoraria, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy; Morphosys: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau. Dreger:Roche: Consultancy, Speakers Bureau; Neovii: Research Funding; AbbVie: Consultancy, Speakers Bureau; AstraZeneca: Consultancy; Gilead: Consultancy, Speakers Bureau; Janssen: Consultancy; Novartis: Consultancy, Speakers Bureau; Riemser: Consultancy, Research Funding, Speakers Bureau. Dietrich:Roche: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; KITE: Membership on an entity's Board of Directors or advisory committees.

BackgroundRecurring cutaneous squamous cell carcinoma (SCC) remains an area of high unmet medical need. While anti-PD-1 antibodies are now approved for this diagnosis, more than half the patients will need more effective treatments, supporting the development of new or combination regimens. Weekly cetuximab targets EGFR and has anti-tumor immunogenic properties that could complement anti-PD-1 immunotherapy. Cetuximab is being evaluated in combination clinical trials. Panitumumab also targets EGFR but is felt to function as a signal transduction inhibitor with weaker anti-tumor immunogenic properties; however, this medication is dosed every two weeks rather than weekly and has a relatively favorable toxicity profile.MethodsTwo consecutive elderly patients with significant comorbidities presented with a performance status of ECOG 3 and rapidly progressive recurrent cutaneous SCC of the face. The patients were presented treatment with an anti-PD-1 antibody, with an option - were there an inadequate palliative response - to include an EGFR antibody provided tolerance was adequate and molecular markets supported so doing. Each patient signed consent for treatment and consent for photographs. Dosing was per package insert, starting conservatively with pembrolizumab 2 mg/kg or nivolumab 3 mg/kg, respectively, escalating in both cases to flat dosing once it was apparent that tolerance was acceptable. The first cycle of panitumumab (6 mg/kg), when needed to be invoked, was administered solo between two cycles of PD-1 inhibitor, then every two weeks while the PD-1 inhibitor continued every two - four weeks.ResultsA 78 year old women with significant cardiac disease and a St Jude tissue aortic valve, had undergone prior surgeries and radiation therapy for her recurring SCC of the face followed then by major resection, parotidectomy, flap reconstruction, and supraomohyoid neck dissection; only two weeks after the latter surgery, she presented with over 20 new in-radiation field metastases (see photo below). A 90 year old woman with emphysema on home oxygen and living in a facility presented with diffuse local recurrence 4 months after orbital exenteration, parotidectomy, neck dissection, and flap. Both patients‘ tumors were characterized: PDL1 (clone E1L3N) 2% and 10%, respectively; scant peritumoral or intratumoral lymphocytes; tumor mutation burden high (33 and 30 mutations per megabase, respectively); epidermal growth factor receptor (EGFR) high 3+ by IHC, but with no gene mutations detected in EGFR, kras or nras; microsatellite stable. In the 78 yo woman, after two cycles of pembrolizumab, the ~ 5 mm pink nodules grew further to up to 3 cm with facial erythema, edema, sealing the eye closed. Only by criteria was this not considered pseudoprogression, Panitumumab was integrated between cycles 2 and 3, resulting in a dramatic abrupt response: the masses became centrally necrotic, flaking, pouring off her face with prompt resolution in edema and complete response (CR) within 2 months - now lasting over 18 months - a period during which pembrolizumab and panitumumab were continued for 27 and 26 cycles respectively). Her major toxicity was diffuse erythema involving ~ 30% of her torso; this resolved early on with triamcinolone 0.1% cream. She also developed scabs in her uninvolved scalp - some where other squamous and basal carcinomas had previously been resected and these all healed slowly (see photo), suggesting we were preventing similar future cancers from emerging in these areas. Similarly, the 90 yo woman achieved only a mixed response to nivolumab over 3 months with shrinking level V neck node but continued stubborn diffuse disease over her face and into the exenteration field. When panitumumab was added, however, there was clear improvement (See photo). With each of eight cycles, prolific crusting/scabbing would occur, shed, and reoccur, some in areas of the face without visible tumor, Mild acneiform rash and mild hypomagnesemia were readily managed. Her performance status and appetite improved and she gained back 14 pounds. After only 6 months, with pathologically confirmed CR, treatment had to be held because she was restricted to her assisted living facility in the midst of the COVID-19 pandemic. Now after a year, the remaining scabs are largely gone (see photo).Abstract 467 Figure 1Panitumumab + pembrolizumab for metastatic cutaneous SCC #1Dramatic durable response in 22 metastases on face and also scabbing then healing on scalp where there was no evidence of tumor but history of prior resected.squamous cell and basal cell carcinomas, suggesting effective prevention of future such lesionsAbstract 467 Figure 2Panitumumab + pembrolizumab for metastatic cutaneous SCC #2Durable response lasting a year after 6 months of treatment in a 90 yo womanConclusionsThe excellent tolerance of multiple cycles of out-patient combination treatment in these two consecutive patients with the same diagnosis, coupled with the observed durable anti-tumor clinical activity lasting now over a year - all support further exploration of panitumumab in combination with anti-PD-1 antibody treatment. A randomized trial would be needed to establish whether outcomes are truly better with the combination. Deciding on hyperprogression v pseudoprogression while getting anti-PD-1 antibody treatment remains a challenge. Laboratory studies would evaluate how such specific signal transduction inhibition by panitumumab might interfere with immune suppressive mechanisms in metastases, rendering them more sensitive to an induced anti-tumor cellular immune response by an anti-PD-1 antibody. Finally such combination treatment should help reduce the need for increasingly cosmetically and functionally altering surgeries.Ethics Approval‘Per our Hartford Health Care IRB, case series of three or less patients does not constitute research.’ConsentWritten informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.ReferencesChen A1,2, Ali N3,4, Boasberg P5,6, Ho AS7,8. Clinical Remission of Cutaneous Squamous Cell Carcinoma of the Auricle with Cetuximab and Nivolumab. J Clin Med 2018 Jan 10;7(1). pii: E10.Foote MC, McGrath M, Guminski A, Hughes BG, Meakin J, Thomson D, Zarate D, Simpson F, Porceddu SV Phase II study of single-agent panitumumab in patients with incurable cutaneous squamous cell carcinoma. Ann Oncol 2014 Oct;25(10):2047–52.Ferris RL, Gillison ML, Harris J, et al. Safety evaluation of nivolumab concomitant with cetuximab-radiotherapy for intermediate and high-risk local-regionally advanced head and neck squamous cell carcinoma (HNSCC): RTOG 3504. Oral presentation at: 2018 ASCO Annual Meeting; June 1–5, 2018; Chicago, IL.Jong Chul Park, Lori J. Wirth, Keith Flaherty, Donald P. Lawrence, Shadmehr Demehri, Stefan Kraft, Immune checkpoint inhibition in advanced cutaneous squamous cell carcinoma: Clinical response and correlative biomarker analysis. Journal of Clinical Oncology36, no. 15_suppl (May 20 2018) 9564.FDA approves pembrolizumab for cutaneous squamous cell carcinoma. FDA website. Published June 24, 2020. fda.gov/drugs/drug-approvals-and-databases/fda-approves-pembrolizumab-cutaneous-squamous-cell-carcinoma.Edith Borcoman, MD, Amara Nandikolla, MD, Georgina Long, BSc, PhD, MBBS, FRACP, Sanjay Goel, MD, and Christophe Le Tourneau, MD, PhD. Patterns of Response and Progression to Immunotherapy American Society of Clinical Oncology Educational Book 38 (May 23, 2018) 169–1787.Migden MR, Rischin D, Schmults CD, Guminski A, Hauschild A, Lewis KD, Chung CH, Hernandez-Aya L, Lim AM, Chang ALS, Rabinowits G, Thai AA, Dunn LA, Hughes BGM, Khushalani NI, Modi B, Schadendorf D, Gao B, Seebach F, Li S, Li J, Mathias M, Booth J, Mohan K, Stankevich E, Babiker HM, Brana I, Gil-Martin M, Homsi J, Johnson ML, Moreno V, Niu J, Owonikoko TK, Papadopoulos KP, Yancopoulos GD, Lowy I, Fury MG. PD-1 Blockade with Cemiplimab in Advanced Cutaneous Squamous-Cell Carcinoma. N Engl J Med 2018 Jul 26;379(4):341–351.Eve Maubec, Marouane Boubaya, Peter Petrow, Nicole Basset-Seguin, Jean-Jacques Grob, Brigitte Dreno,. Pembrolizumab as first line therapy in patients with unresectable squamous cell carcinoma of the skin: Interim results of the phase 2 CARSKIN trial. Journal of Clinical Oncology 36, no. 15_suppl (May 20 2018) 9534.Burtness B, et al. First-line pembrolizumab a new standard for recurrent, metastatic head and neck squamous cell carcinoma. Abstract LBA8_PR. Presented at: European Society for Medical Oncology Congress; Oct. 19–23, 2018; Munich. 10. Teruki Yanagi,* Shinya Kitamura, and Hiroo Hata. Novel Therapeutic Targets in Cutaneous Squamous Cell Carcinoma. Front Oncol 2018; 8: 79.

AbstractThe Great Debate session at the 2020 Melanoma Bridge virtual congress (December 3rd–5th, Italy) featured counterpoint views from experts on five specific controversial issues in melanoma. The debates considered whether or not innate immunity is important in the response to cancer and immunotherapy, how useful are the revised American Joint Committee on Cancer (AJCC) classification for the staging of patients, the use of sentinel node biopsy for staging patients, the use of triplet combination of targeted therapy plus immunotherapy versus combined immunotherapy, and the respective benefits of neoadjuvant versus adjuvant therapy. As is usual with Bridge congresses, the debates were assigned by meeting Chairs and positions taken by experts during the debates may not have necessarily reflected their own personal opinion.

AbstractAs part of the 2020 Immunotherapy Bridge virtual congress (December 2nd–3rd, Italy), the Great Debate session featured counterpoint views from leading experts on three clinical questions in immunotherapy today. The first of these was whether antitumoral vaccination is still a treatment option. The second topic debated whether anti-programmed death (PD)-1/PD-ligand (L)1 blockade should be the backbone for immunotherapy combination. Finally, the use of innovative study designs and surrogate endpoints was considered from both an academic and industry perspective. For each topic, two experts presented the argument and counter-argument in support of two different points of view. As with previous Bridge congresses, the debates were assigned by meeting Chairs and positions taken by experts during the debates may not have necessarily reflected their respective personal view. The views summarised in this article are based on available evidence but may reflect personal interpretation of these data, clinical experience and subjective opinion of the speaker.

SINGAPORE – Biofourmis to Run New Study on How Singapore’s Lifestyle Affects Heart Health SingHEART Vitals Study with Support from IMDA. SINGAPORE – Smart Nation Boost: Singapore Engineers Develop Remote Vital Signs Monitoring System. ESMO ASIA 2016 CONGRESS, SINGAPORE – Routine Blood Test Predicts How Long Cancer Patients Will Survive. ESMO ASIA 2016 CONGRESS, SINGAPORE – Cancer Costs Leaving Patients in Debt. ESMO ASIA 2016 CONGRESS, SINGAPORE – Asian Head and Neck Cancer Patients Live Longer with Immunotherapy than Mixed Race Group. JAPAN – Avastin® Received Orphan Drug Designation for the Treatment of Malignant Pleural Mesothelioma. UNITED STATES – Recovery from Brain Injury and Better Sleep Go Hand in Hand. UNITED STATES – Erasing the Line between Imaging and Analysing.

Neuroendocrine neoplasias (NENs) are a heterogeneous group of rare tumors scattered throughout the body. Surgery, locoregional or ablative therapies as well as maintenance treatments are applied in well-differentiated, low-grade NENs, whereas cytotoxic chemotherapy is usually applied in high-grade neuroendocrine carcinomas. However, treatment options for patients with advanced or metastatic NENs are limited. Immunotherapy has provided new treatment approaches for many cancer types, including neuroendocrine tumors, but predictive biomarkers of immune checkpoint inhibitors (ICIs) in the treatment of NENs have not been fully reported. By reviewing the literature and international congress abstracts, we summarize the current knowledge of ICIs, potential predicative biomarkers in the treatment of NENs, implications and efficacy of ICIs as well as biomarkers for NENs of gastroenteropancreatic system, lung NENs and Merkel cell carcinoma in clinical practice.

Fortis Escorts Heart Institute wins ‘Best Single Specialty Hospital - Cardiology‘ title. Probiodrug transfers its CDK9 inhibitor program to AstraZeneca. GE to expand in life sciences with acquisition of strategic assets from Thermo Fisher Scientific. MD Anderson teams up with Pfizer to advance cancer immunotherapy. Trovagene and US Oncology Research collaborate on a prospective study for urine-based KRAS testing in patients with metastatic pancreatic cancer. MedImmune and Immunocore enter immunotherapy agreement to develop novel cancer therapies. Nodality enters into a strategic collaboration with Johnson & Johnson Innovation in autoimmune diseases. Knopp Biosciences and NIH to collaborate in evaluating dexpramipexole in patients with hypereosinophilic syndrome. AMN Healthcare receives top workplace award. National Cancer Centre Singapore and Clearbridge BioMedics partner to bring circulating tumor cell technology closer to clinic. Latest updates on soaps, detergents, cosmetics, hair care industry at 4th Emerging HPC Surfactants Markets. CMT's 11th Phenol/ Acetone & Derivatives Markets in Shanghai, hones in on feedstock costs, excess capacities and more. A*STAR signs agreement with Nestlé to strengthen food & nutrition R&D in Singapore. Amorfix enters into agreement with a major global pharmaceutical company for Alzheimer's disease diagnostic. PHARM Connect Congress- One step before the future.

Coming back from our summer holidays, we find our desks and agendas overloaded with working pieces, to-do´s and our agendas stuffed with meetings and appointments. However, the „fuelled batteries“ and the fresher air will support our endeavours us to tackle those challenges – and may it be by chance or not, in this autumn´s fresh air, respiratory medicine is a focus topic of this 3rd issue of Gazeta Médica. In this, and amongst others, manuscripts from Prof. António Bugalho about Pneumologia in Portugal, and two up-to-date reports dealing with the most innovative treatments in lung cancers - from Prof. Bárbara Parente in a congress report and as an exclusive interview with Prof. Rolf Stahel from University of Zurich, about immunotherapy in lung cancers and other cancer types - enrich our knowledge. As yet to see, cancer medicine is a second topic of this issue. Cancer is a specific challenge for all of us involved in medicine: One out of three Europeans will be diagnosed with a cancer disease during lifetime, and this has a massive impact on both, our private lives as well as our professional tasks: in which field of medicine we are practicing and taking care, many of our patients will have to deal with a cancer disease, demanding our support and consultation, even if the field of expertise is seen as „non-oncology“ part of medicine. Cancer is terrifying and concerning, and it generally is associated with fear and the image of suffering and hopelessness. At some points, for good reason. On the other side, there is plenty of good news about cancer: more and more patients can – and will – be cured. And even if cure cannot be reached: more and more patients live with their malignant disease under the conditions of a chronic disease, without numerous or severe symptoms and complaints. New diagnostical methods and new multidisciplinary treatment strategies, incorporating up-to-date surgery, modern radiotherapy, as well as highly innovative (and efficacious) treatments are contributing to this success. The complexity of cancer diagnostics and treatments are mirrored in some manuscripts in this Gazeta Médica, as yet mentioned above. Immunotherapy is one oft he „big topics“ of those days, but also other treatments change the landscape of therapeutic standards – to stay with pictures: in a breath-taking speed. Just before the summer break, the Instituto CUF de Oncologia (ICO) was formally opened, representing a „state-of-the art“ cancer centre, which is designed in the model of other European cancer care institutes: Given the complexity of the disease, its various clinical presentation (a nice saying of the Cancer Survivor´s Council is: „cancer is not a disease, it is like 10 diseases....“), the numerous diagnostic and therapeutic modalities as well as all other aspects from patients (and their relatives), including co-morbidity and of course their personalities and psychological backgrounds it is obvious that this deserves a specific setting and organisation of best care. Structures like the ICO facilitate this, by optimizing diagnostic and therapeutic algorithms, identifying and integrating the „best specialists“, facilitating access to the most innovative treatments, and this across the whole network of its members and partners, accross Portugal. Cancer medicine is not limited to the most recent standards. It rather is „high innovation medicine“, with standards very often changing within a very short time, also where access to clinical trials is a key factors. And as mentioned above, trials are of utmost importance, and as ICO also organizes access to cancer medicine trials - please see the História dos ensaios clínicos from Dr. Vasco Salgado in this issue of the Gazeta Médica. And beyond innovative cancer treatments, the ICO also assembles disciplines which deal with the „whole picture“ and needs of our cancer patients and their families – palliative care, nursing, psychosocial support, nutrition consultations, etc. And of course, for information and education. Prof. Rolf Stahel, the former president of the European Society of Medical Oncology (ESMO, being Europe´s 2nd largest medical society), visited us during the ICO opening, and I had the chance to discuss the concept of cancer centers and their various challenges in a European landscape and the Portuguese healthcare environment – and we can proudly say that our ICO concept, which started now within the Lisbon CUF units but will expand soon to other sites, is on the right track to facilitate this. Coming back to our daily perspective: As yet stated, the increased rate of cured patients – and of those living with cancer - results in an increasing number in „cancer survivors“. And in which field ever we are working, we all will be involved more and more into care of more-or-less-active-cancer patients. So, there is an urgent need to know more about, and structures like ICO will also take care for this. As well as the Gazeta Médica does, and in saying this, I would like to draw your attention to all of the other reports in this issue. And therefore, enjoy reading, and have a successful re-start, with a breath of fresh air. Dirk ArnoldEditorial Board / Conselho Editorial

Aim: Young adulthood is a period when individuals experiment health risk substances such as illicit substance and tobacco use that may predispose them to sexually transmitted diseases. Minority young adults living in HIV prevalent urban communities are notably more likely to engage in these behaviors. In the United States, minority young adults over-represented with HIV infection. To resolve this problem, the United States Congress has invested over $100million in grants. In the United States, few studies have examined illicit substance and tobacco use among this vulnerable population. This study aimed to evaluate the impact of a comprehensive HIV prevention program (CIHPP) on illicit substance and tobacco use among minority young adults living in a high prevalence of HIV infection urban community. Methods: The data of illicit substance and tobacco use was collected using a survey of a random sample of minority young adults who participated in the CIHPP. for12-months. Change in illicit substance and tobacco use during 24 months of minority young adults' participation in CIHPP was recorded. The data was analyzed using the latent growth curve (LGC) model within the framework of the structural equation modeling procedure. The evaluation included the change in the intercept and slope of the Mean, Variance, covariance, and predictor variable in three waves for 24months. Result: The average score for illegal substance use of 5.411 decreased significantly over the 24months. Young adults exhibited a low rate of increase in their illicit use substance over the 24months. This finding indicates that the CIHPP was effective in decreasing the substance use of young adults under study. There were significant inter individual differences in the original score of illicit substance use between the young adults at the beginning of the implementation of the CIHPP and its change over time, as the as the minority young adult progressed from the beginning of the CIHPP intervention through the 24 months. Using gender as a predictor of change showed no difference between male and female young adults. For tobacco use, the average score for tobacco (16.631) decreased significantly over the three 24months. There was no meaningful difference between minority young adult males and minority young adult females in illicit substances use at the beginning of CIHPP. However, during CIHPP intervention, minority young adult’s males had an increase in the rate of change in tobacco use than minority young adult females. The mean estimate for tobacco use indicates that the average score for tobacco use increased significantly over the three 12-months periods. The covariance between the intercept and slope factor for tobacco use was statistically significant. Minority young adult males exhibited a higher rate of tobacco use than their female counterparts over the 24 months. This finding suggests that the Comprehensive, integrated HIV prevention program was not effective in decreasing the tobacco use of the minority young adults studied, The variance estimate related 2 Annals of Immunology & Immunotherapy Mongkuo MY, et al. Latent Growth Curve Model Evaluation of Illicit Substance and Tobacco Use among Young Adults in Cumberland County, North Carolina. Ann Immunol Immunother 2020, 2(2): 000124. Copyright© Mongkuo MY, et al. to the intercept and slope for tobacco use is statistically significant (p=.001) suggesting that there were vast inter-individual differences both at the beginning of CIHPP and the rate of change of tobacco use between the minority young adults at the beginning of the implementation of the CIHPP and its rate of change over time, as the young adult progressed from the beginning of the CIHPP intervention through the 24months. Such evidence provides sturdy support for further investigation of variability or heterogeneity related to the growth trajectory. Specifically, the incorporation of time-invariant of change into the model can explain the young adults' tobacco use variability. This incorporation involves testing the latent growth curve model with the demographic or static variable as a time-invariant predictor of change. This study incorporated gender in the LGC model as a predictor of change. The prediction module with gender as predictor found that there was no meaningful difference in illicit substance and tobacco use between minority young adult males and females.