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1
Nutik, Stephen L., and Michael J. Babb. "Determinants of tumor size and growth in vestibular schwannomas." Journal of Neurosurgery 94, no. 6 (2001): 922–26. http://dx.doi.org/10.3171/jns.2001.94.6.0922.
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Object. This study was undertaken to analyze factors associated with the size of unilateral vestibular schwannomas (VSs). Methods. A retrospective analysis of an unselected and sequential series of 433 patients with unilateral VSs was conducted. Tumor size was defined by the largest dimension of the tumor in the cerebellopontine angle, and the size was tested for a relationship with patient age and sex. In a subgroup of 231 patients in whom data were available, tumor size was also tested for a relationship with tumor cysts or the absence of an internal auditory canal (IAC) component. Some patients underwent a period of surveillance with serial imaging studies to monitor for tumor growth. Data from these patients, excluding those with cystic tumors, were analyzed to see if tumor growth was related to patient age, sex, or tumor size. Conclusions. Larger tumors were found in younger patients, in females, in the subgroup of cystic tumors, and in patients in whom there was no tumor component in the IAC. The probable explanations for these larger tumors are a faster growth rate and/or a delay in symptom onset. When untreated tumors are managed with observation, measurable growth is more often seen in larger tumors, although smaller tumors have a faster relative growth rate than larger ones.
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Ryu, Sung Mo, Sun-Ho Lee, Kyung Min Lee, Whan Eoh, and Eun-Sang Kim. "Subtotal resection of cervical schwannomas and growth rate of residual tumors." Journal of Neurosurgery: Spine 30, no. 6 (2019): 794–800. http://dx.doi.org/10.3171/2018.11.spine181168.
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OBJECTIVEThe objective of this study was to elucidate the features and surgical outcomes of cervical schwannomas.METHODSThe authors retrospectively reviewed the records of 90 patients who underwent surgically treated cervical schwannomas from January 1995 to December 2017, with an emphasis on MRI findings such as tumor location, tumor size, extent of tumor resection, and growth of a residual tumor.RESULTSThis study included 51 men (56.7%) and 39 women (43.3%) with a mean age of 44.5 years (range 7–77 years). Dumbbell-shaped tumors comprised 62 (68.9%) of 90 cases and gross-total resection (GTR) was achieved in 59 (65.6%) of 90 cases. All nondumbbell tumors (n = 28) underwent GTR. Only 1 case of recurrence in the GTR group showed a gradual increase in size (by 8.9 mm) during the 150-month follow-up period. For the regrowth patients in the subtotal resection group, the mean percentage increase in tumor size was 47.5% ± 33.1% and the mean growth rate was 5.8 ± 4.6 mm/year during the 20.3-month follow-up period. However, the size of residual tumor spontaneously decreased by a mean of 8.3% ± 11.1% during the 48.4-month follow-up period in the nonregrowth group.CONCLUSIONSThese findings suggested that frequent MRI follow-up examinations are required for residual schwannomas in the cervical spine for at least 2 years, and continuous MRI follow-ups are also required thereafter.
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Derenzini, Massimo, Lorenzo Montanaro, Alessandra Chillà, et al. "Evaluation of Thymidylate Synthase Protein Expression by Western Blotting and Immunohistochemistry on Human Colon Carcinoma Xenografts in Nude Mice." Journal of Histochemistry & Cytochemistry 50, no. 12 (2002): 1633–40. http://dx.doi.org/10.1177/002215540205001207.
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In this study we investigated the relationship between thymidylate synthase (TS) protein expression, evaluated by Western blotting analysis and by immunohistochemistry (IHC), and growth rate in human colon xenograft tumors in nude mice. Human colon cancer cell lines were used to induce xenograft tumors and the tumor mass growth rate was calculated by measuring tumor size variations over time. TS 106 monoclonal antibody was used for both Western blotting and IHC TS detection. Tumor cell growth fraction was measured by Ki67/MIB1 immunolabeling and tumor cell growth rate by evaluating the mean nucleolar size in silver-stained sections. TS Western blotting values were related to tumor mass growth rate ( p<0.001) and cell growth rate ( p=0.002) but not to cell growth fraction ( p=0.676). The degree of the IHC staining showed only a trend to be associated with TS protein expression measured on Western blotting, and was not related either to tumor mass growth or cell proliferation rate. Tumor xenografts were also characterized for TS promoter tandem repeat and p53 status. No relationship was observed between these variables and TS expression evaluated by both Western blotting and IHC analysis. Our results demonstrate that TS expression evaluated by Western blotting analysis is directly related to the tumor mass growth rate and question the use of the IHC approach to obtain precise quantitative information on TS expression in tumor samples.
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Nakamura, Makoto, Florian Roser, Julia Michel, Cornelius Jacobs, and Madjid Samii. "The Natural History of Incidental Meningiomas." Neurosurgery 53, no. 1 (2003): 62–71. http://dx.doi.org/10.1227/01.neu.0000068730.76856.58.
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Abstract OBJECTIVE Little information about the natural history of incidental meningiomas exists in the literature. The aim of this study was to determine the natural history of asymptomatic meningiomas by comparing different methods of growth rate calculation to establish a strategy for dealing with these tumors. METHODS In 47 asymptomatic patients, hospital charts, follow-up records, and imaging studies were reviewed. Of these patients, 6 underwent surgery. Tumor growth rates were determined by calculating the absolute and relative growth rates and the tumor volume doubling times. RESULTS In 41 patients with conservative management, the average tumor size was 9 cm3, and the majority (66%) of growth rates were less than 1 cm3/yr. The absolute growth rate ranged from 0.03 to 2.62 cm3/yr (mean, 0.796 cm3/yr). Relative annual growth rates ranged from 0.48 to 72.8% (mean, 14.6%). The tumor doubling time ranged from 1.27 to 143.5 years (mean, 21.6 yr). A moderate correlation between the age and growth rates was found. In young patients, annual growth rates tended to be higher and tumor doubling times shorter. There was no clear correlation between the initial tumor size and tumor doubling time. The mean annual growth rate of meningiomas with calcification was lower than in tumors without calcification. Also, tumors with hypointense or isointense T2 signals on magnetic resonance imaging had a lower growth rate. In the group of six patients with surgical excision, tumor growth rates were higher and tumor doubling times shorter than in the nonsurgical group. CONCLUSION The majority of incidental meningiomas show minimal growth; thus, they may be observed without surgical intervention unless specific symptoms appear. Tumor growth is associated with patient age. The initial tumor size is not considered a predictive factor for tumor growth. Radiological features, such as calcification or T2 signal intensity, may provide useful information to predict the growth potential of meningiomas.
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Marston, Alexander P., Jeffrey T. Jacob, Matthew L. Carlson, Bruce E. Pollock, Colin L. W. Driscoll, and Michael J. Link. "Pretreatment growth rate as a predictor of tumor control following Gamma Knife radiosurgery for sporadic vestibular schwannoma." Journal of Neurosurgery 127, no. 2 (2017): 380–87. http://dx.doi.org/10.3171/2016.5.jns153013.
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OBJECTIVEOver the last 30 years, stereotactic radiosurgery (SRS) has become an established noninvasive treatment alternative for small- to medium-sized vestibular schwannoma (VS). This study aims to further define long-term SRS tumor control in patients with documented pretreatment tumor growth for whom conservative observation failed.METHODSA prospective clinical database was queried, and patients with sporadic VS who elected initial observation and subsequently underwent SRS after documented tumor growth between 2004 and 2014 were identified. Posttreatment tumor growth or shrinkage was determined by a ≥ 2-mm increase or decrease in maximum linear dimension, respectively.RESULTSSixty-eight patients met study inclusion criteria. The median pre- and posttreatment observation periods were 16 and 43.5 months, respectively. The median dose to the tumor margin was 13 Gy (range 12–14 Gy), and the median maximum dose was 26 Gy (range 24–28 Gy). At the time of treatment, 59 tumors exhibited extracanalicular (EC) extension, and 9 were intracanalicular (IC). Of the 59 EC VSs, 50 (85%) remained stable or decreased in size following treatment, and 9 (15%) enlarged by > 2 mm. Among EC tumors, the median pretreatment tumor growth rate was 2.08 mm/year for tumors that decreased or were stable, compared with 3.26 mm/year for tumors that grew following SRS (p = 0.009). Patients who demonstrated a pretreatment growth rate of < 2.5 mm/year exhibited a 97% tumor control rate, compared with 69% for those demonstrating ≥ 2.5 mm/year of growth prior to SRS (p = 0.007). No other analyzed variables were found to predict tumor growth following SRS.CONCLUSIONSOverall, SRS administered using a marginal dose between 12–14 Gy is highly effective in treating VSs in which initial observation fails. Tumor control is achieved in 97% of VSs that exhibit slow (< 2.5 mm/year) pretreatment growth; however, SRS is less successful in treating tumors exhibiting rapid growth (≥ 2.5 mm/year).
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Bederson, Joshua B., Klaus von Ammon, Werner W. Wichmann, and Gazi M. Yasargil. "Conservative Treatment of Patients with Acoustic Tumors." Neurosurgery 28, no. 5 (1991): 646–51. http://dx.doi.org/10.1227/00006123-199105000-00002.
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Abstract Seventy of 178 patients with acoustic tumors initially were treated conservatively and have been followed up for an average of 26 ± 2 months. The tumor size was determined by the mean maximum anteroposterior and mediolateral diameters, using computed tomographic or magnetic resonance imaging scans obtained sequentially throughout the follow-up period. The average tumor growth was 1.6 ± 0.4 mm the 1st year, and 1.9 ± 1.0 mm the 2nd year (range, -2 to 17 mm/y): 4 tumors showed apparent regression, 28 (40%) had no detectable growth, and 37 (53%) exhibited growth (average, 3.8 ± 1.2 mm/y). Within individual patients, the tumor growth rate determined during the 1st year of follow-up was predictive of tumor growth rate during the following year. Rapid tumor growth or clinical deterioration in 9 of the 70 patients (13%) who initially were treated conservatively necessitated subsequent surgery an average of 14 ± 5 months after the patient was initially seen. This group had a larger initial tumor size (27.0 ± 3.4 mm vs. 21.3 ± 0.9 mm, P&lt;0.05), and a faster 1-year growth rate (7.9 ± 2.3 mm/y vs. 1.3 ± 0.3 mm/y, P&lt;0.05) than the 61 patients who did not require surgery. Two patients, however, experienced neurological deterioration that required surgery, even though there was no tumor growth. The high incidence of acoustic tumors with no detectable growth or apparent spontaneous regression must be taken into account when evaluating the indications for surgery and the efficacy of radiotherapy. Beacuse surgery carries some risk and acoustic tumors are generally slow growing, a trial of conservative treatment is possible in selected patients, provided serial radiological studies are obtained. Knowledge of the tumor growth rate established by these studies may be helpful in the treatment of individual patients.
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Bakkouri, Wissame El, Romain E. Kania, Jean-Pierre Guichard, Guillaume Lot, Philippe Herman, and Patrice Tran Ba Huy. "Conservative management of 386 cases of unilateral vestibular schwannoma: tumor growth and consequences for treatment." Journal of Neurosurgery 110, no. 4 (2009): 662–69. http://dx.doi.org/10.3171/2007.5.16836.
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Object The object of this study was to evaluate the natural history, pattern, and occurrence of tumor growth and its consequences for treatment of small-sized vestibular schwannomas (VSs). Methods From 1990 to 2005, 386 patients underwent conservative management for VS because of the following: age > 60 years, poor health/medical risks, risk of deterioration of good hearing, small tumor size, minimal or no incapacitating symptoms, and/or patient preference. Tumor size was measured by MR imaging according to the guidelines of the Committee on Hearing and Equilibrium. The first MR imaging study was performed 1 year after diagnosis, and subsequent imaging was performed yearly or every 2 years depending on the appearance of new symptoms, tumor growth, or both. Results Sixty-one patients were lost to follow-up the first year after presentation. Of the 325 patients for whom 1-year follow-up data were available, 39 showed tumor growth ≥ 3 mm. Conservative management was discontinued for these 39 patients. The patients who returned for follow-up were evaluated at 1- or 2-year intervals depending on tumor growth. The authors extrapolated to obtain data for 2-year intervals, yielding data for 160, 56, 21, and 8 patients at 3, 5, 7, and 9 years after initial presentation, respectively. The overall mean tumor growth rate (±standard deviation) was 1.15 ± 2.4 mm/year. This rate was estimated by pooling all values of tumor growth that had been determined for all patients and dividing by the total number of “events,” with each assessment constituting an event. In 58.6% of patients, the annual tumor growth rate was < 1 mm/year; in 29.2%, 1–3 mm/year; and in 12.2%, ≥ 3 mm/ year. The growth rates of intrameatal (1.02 ± 1.8 mm/year) and extrameatal (1.40 ± 3.1 mm/year) tumors did not differ significantly. No significant association was found between tumor growth rate and sex, age, initial hearing status, or initial tumor grade. Delay in diagnosis was the only significant factor associated with tumor growth rate. During follow-up, conservative management was discontinued for 77 (23.7%) of the 325 patients for whom at least 12-month follow-up data were available; surgery was performed in 60 (77.9%) and radiation therapy in 17 (22.1%). Conclusions The results of this study support the role of a conservative “wait-and-scan” policy of management for small-sized VSs because most have a slow growth rate. Long-term neuroimaging follow-up is needed even with non-growing tumors.
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Hather, Gregory, Ray Liu, Syamala Bandi, et al. "Growth Rate Analysis and Efficient Experimental Design for Tumor Xenograft Studies." Cancer Informatics 13s4 (January 2014): CIN.S13974. http://dx.doi.org/10.4137/cin.s13974.
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Human tumor xenograft studies are the primary means to evaluate the biological activity of anticancer agents in late-stage preclinical drug discovery. The variability in the growth rate of human tumors established in mice and the small sample sizes make rigorous statistical analysis critical. The most commonly used summary of antitumor activity for these studies is the T/C ratio. However, alternative methods based on growth rate modeling can be used. Here, we describe a summary metric called the rate-based T/C, derived by fitting each animal's tumor growth to a simple exponential model. The rate-based T/C uses all of the data, in contrast with the traditional T/C, which only uses a single measurement. We compare the rate-based T/C with the traditional T/C and assess their performance through a bootstrap analysis of 219 tumor xenograft studies. We find that the rate-based T/C requires fewer animals to achieve the same power as the traditional T/C. We also compare 14-day studies with 21-day studies and find that 14-day studies are more cost efficient. Finally, we perform a power analysis to determine an appropriate sample size.
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Olivero, William C., J. Richard Lister, and Patrick W. Elwood. "The natural history and growth rate of asymptomatic meningiomas: a review of 60 patients." Journal of Neurosurgery 83, no. 2 (1995): 222–24. http://dx.doi.org/10.3171/jns.1995.83.2.0222.
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✓ Little is known about the natural history and growth rate of asymptomatic meningiomas. To better delineate this problem, the authors reviewed the clinical records and imaging studies of the last 60 patients diagnosed with asymptomatic meningiomas at their institution. There were 45 women and 15 men, whose ages ranged from 38 to 84 years, with a mean age of 66 years. The most common tumor location was convexity (25 patients), but virtually all locations were represented. Three patients were lost to follow up. The average clinical follow-up review of the remaining 57 patients was 32 months (range 6 months to 15 years). None of the patients became symptomatic from an enlarging tumor during their follow-up period. Typically, once a meningioma was diagnosed, follow-up scans were obtained at 3 months, 9 months, and then yearly or every other year thereafter. Forty-five patients underwent follow-up scans, with comparison of tumor size to that found on the initial scan, over a period ranging from 3 months to 15 years. Thirty-five patients have shown no growth in their tumor size, with an average imaging follow up of 29 months (range 3–72 months). Ten patients have shown tumor growth calculated as an increase in the maximum diameter of the tumor. This growth ranged from 0.2 cm over 180 months to 1 cm over 12 months, with an average of 0.24 cm per year. Average imaging follow up for these patients was 47 months (range 6 months to 15 years). The authors conclude that patients with asymptomatic meningiomas need close clinical and radiological follow up to rule out other disease processes and to rule out rapidly enlarging tumors. Although the average follow-up time was short, the vast majority of these tumors appeared to show minimal or no growth over periods of time measured in years. With modern noninvasive imaging techniques, these tumors can be safely observed until they enlarge significantly or become symptomatic.
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Charabi, Samih, Peter Engel, Mirko Tos, Grete Krag Jacobsen, and Jens Thomsen. "Growth Rate of Acoustic Neuroma Expressed by Ki-67 Nuclear Antigen versus Symptom Duration." Annals of Otology, Rhinology & Laryngology 102, no. 10 (1993): 805–9. http://dx.doi.org/10.1177/000348949310201013.
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The growth rate of acoustic tumors varies widely. An immunohistochemical study with Ki-67 monoclonal antibody was performed on a random sample of 21 acoustic neuromas. The tumors belonged to 2 well-defined groups: 1 with a short duration of preoperative symptoms (<1 year) and 1 with a long duration of preoperative symptoms (>5 years). The tumors were of small to medium size (7 to 27 mm), and no large, cystic, or Recklinghausen tumors were included. The tumor proliferative fraction expressed by monoclonal antibody Ki-67 was determined. The results revealed a significant relation between the tumor proliferative fraction and symptom duration. Tumors with a high proliferative status had a short preoperative symptom duration, while tumors with a low proliferative status had a long symptom duration. The clinical implications of these results are discussed.
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Hunter, Jacob B., Brendan P. O’Connell, Matthew L. Carlson, et al. "Tumor Progression Following Petroclival Meningioma Subtotal Resection: A Volumetric Study." Operative Neurosurgery 14, no. 3 (2017): 215–23. http://dx.doi.org/10.1093/ons/opx098.
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Abstract BACKGROUND One study has investigated postoperative growth rates following subtotal resection of petroclival meningiomas utilizing linear measurements, which are insensitive to the multidimensional complex growth of meningiomas, to estimate tumor volume. OBJECTIVE To describe petroclival meningioma growth patterns following less-than-complete resection utilizing volumetric analysis and to identify variables associated with tumor progression. METHODS Patients with surgically resected WHO grade I petroclival meningiomas were retrospectively reviewed (1999-2015). Image analysis software was utilized to perform volumetric analyses of tumor size and growth on serial MRI studies. The impact of preoperative and postoperative variables on tumor growth after subtotal resection was analyzed. An increase in tumor volume of at least 20% was defined as “tumor growth.” RESULTS Twenty-three patients had immediate preoperative and serial postoperative MRI studies available for review. The mean preoperative tumor volume was 20.9 cm3 (range 0.4-54.6). The mean extent of resection was 75.5% (range 31.5%-100.0%). At a mean follow-up of 24.8 mo, 12 tumors (66.7%) exhibited radiological tumor growth, while 6 tumors did not change in size. The median annual volumetric growth rate was 2.82 cm3/yr (range –0.34 to 10.1). Extent of resection and immediate postoperative tumor volume were significantly correlated with the annual volumetric growth rate following resection. At last follow-up, 3 (13%) patients required further intervention. CONCLUSION The majority of petroclival meningiomas exhibit growth following subtotal resection. Extent of resection is strongly associated with risk for disease progression following surgery.
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Pettersson, Olof Joakim, Katarzyna Fröss-Baron, Joakim Crona, and Anders Sundin. "Tumor growth rate in pancreatic neuroendocrine tumor patients undergoing PRRT with 177Lu-DOTATATE." Endocrine Connections 10, no. 4 (2021): 422–31. http://dx.doi.org/10.1530/ec-21-0027.
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Background Monitoring of pancreatic neuroendocrine tumors (PanNET) undergoing peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE depends on changes in tumor size, which often occur late. Tumor growth rate (TGR) allows for quantitative assessment of the tumor kinetics expressed as %/month. We explored how TGR changes before and during/after PRRT and evaluated TGR as a biomarker for progression-free survival (PFS). Methods In PanNET patients undergoing PRRT with 177Lu-DOTATATE from 2006 to 2018, contrast-enhanced CT or MRI was performed before and during the therapy. Patients with at least one hypervascular liver metastasis were included. TGR was calculated for the period preceding treatment and for two intervals during/after PRRT. Cox regression was used for the survival analysis. Results Sixty-seven patients (43 men, 24 women), median age 60 years (range 29–77), median Ki-67 10% (range 1–30) were included. TGR before baseline (n = 57) (TGR0) was mean (s.d.) 6.0%/month (s.d. = 8.7). TGR at 4.5 months (n = 56) (TGR4) from baseline was −3.4 (s.d. = 4.2) %/month. TGR at 9.9 months (n = 57) (TGR10) from baseline was −3.0 (s.d. = 2.9) %/month. TGR4 and TGR10 were lower than TGR0 (TGR4 vs TGR0, P < 0.001 and TGR10 vs TGR0, P < 0.001). In the survival analysis, patients with TGR10 ≥ 0.5%/month (vs <0.5%/month) had shorter PFS (median = 16.0 months vs 31.5 months, hazard ratio 2.82; 95% CI 1.05–7.57, P = 0.040). Discussion TGR in PanNET patients decreases considerably during PRRT with 177Lu-DOTATATE. TGR may be useful as a biomarker to identify patients with the shortest PFS.
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Chan, Jammy Kin Iong, Wah Cheuk, Luen Cheong Ho, and Jian-Ming Wen. "Recurrent Meningeal Hemangiopericytoma with Multiple Metastasis and Hypoglycemia: A Case Report." Case Reports in Medicine 2012 (2012): 1–3. http://dx.doi.org/10.1155/2012/628756.
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Aims. We report on the unusual case of a 43-year-old man who developed recurrent meningeal hemangiopericytoma and presented with hypoglycemia 6 years after excision of the tumor.Methods and Results. We utilized computed tomography to assure multiple tumor metastasis and cranial recurrence of previous meningeal hemangiopericytoma and clinical laboratory tests and immunohistochemical staining to characterize this case. Magnetic resonance imaging and computed tomography showed the recurrent tumor at original torcular site was increased in size. Abnormal low levels of growth hormone, insulin, and insulin-like growth factor-I except insulin-like growth factor-II were detected in the serum. By immunohistochemistry, the neoplastic cells characteristically express diffusely CD99, bcl2, and variable CD34. After radio- and chemotherapy, serum glucose level of the patient returned to normal.Conclusions. Comparing other brain tumors, meningeal hemangiopericytoma has a higher recurrent and metastatic rate, but this tumor with hypoglycemia is very rare.
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Isidro, Ulysses, Liam M. O'Brien, and Ronnie Sebro. "Linear mixed-effects models for estimation of pulmonary metastasis growth rate: implications for CT surveillance in patients with sarcoma." British Journal of Radiology 93, no. 1114 (2020): 20190856. http://dx.doi.org/10.1259/bjr.20190856.
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Objectives: Sarcoma patients often undergo surveillance chest CT for detection of pulmonary metastases. No data exist on the optimal surveillance interval for chest CT. The aim of this study was to estimate pulmonary metastasis growth rate in sarcoma patients. Methods: This was a retrospective review of 95 patients with pulmonary metastases (43 patients with histologically confirmed metastases and 52 with clinically diagnosed metastases) from sarcoma treated at an academic tertiary-care center between 01 January 2000 and 01 June 2019. Age, sex, primary tumor size, grade, subtype, size and volume of the pulmonary metastasis over successive chest CT scans were recorded. Two metastases per patient were chosen if possible. Multivariate linear mixed-effects models with random effects for each pulmonary metastasis and each patient were used to estimate pulmonary metastasis growth rate, evaluating the impact of patient age, tumor size, tumor grade, chemotherapy and tumor subtype. We estimated the pulmonary metastasis volume doubling time using these analyses. Results: Maximal primary tumor size at diagnosis (LRT statistic = 2.58, df = 2, p = 0.275), tumor grade (LRT statistic = 1.13, df = 2, p = 0.567), tumor type (LRT statistic = 7.59, df = 6, p = 0.269), and patient age at diagnosis (LRT statistic = 0.735, df = 2, p = 0.736) were not statistically significant predictors of pulmonary nodule growth from baseline values. Chemotherapy decreased the rate of pulmonary nodule growth from baseline (LRT statistic = 7.96, df = 2, p = 0.0187). 95% of untreated pulmonary metastases are expected to grow less than 6 mm in 6.4 months. There was significant intrapatient and interpatient variation in pulmonary metastasis growth rate. Pulmonary metastasis volume growth rate was best fit with an exponential model in time. The volume doubling time for pulmonary metastases assuming an exponential model in time was 143 days (95% CI (104, 231) days). Conclusions: Assuming a 2 mm nodule is the smallest reliably detectable nodule by CT, the data suggest that an untreated pulmonary metastasis is expected to grow to 8 mm in 8.4 months (95% CI (4.9, 10.2) months). Tumor size, grade and sarcoma subtype did not significantly alter pulmonary metastasis growth rate. However, chemotherapy slowed the pulmonary metastasis growth rate. Advances in knowledge: CT surveillance intervals for pulmonary metastases can be estimated based on metastasis growth rate. There was significant variation in the pulmonary metastasis growth rate between metastases within patient and between patients. Pulmonary nodule volume growth followed an exponential model, linear in time.
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Hellmén, E., R. Bergström, L. Holmberg, I. B. Spångberg, K. Hansson, and A. Lindgren. "Prognostic Factors in Canine Mammary Tumors: A Multivariate Study of 202 Consecutive Cases." Veterinary Pathology 30, no. 1 (1993): 20–27. http://dx.doi.org/10.1177/030098589303000103.
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The prognostic variables of 223 consecutively sampled spontaneous mammary tumors from female dogs were studied. These variables included flow cytometric DNA analysis and cell proliferation measured as cells in S-phase rate evaluated from DNA histograms. The dogs were surgically treated, in most cases with unilateral mastectomy (all mammary glands), and 202 of the 223 dogs were studied temporally following surgery. Univariate analysis with correction for age indicated that the variables of lymph node metastasis, elevated S-phase rate, presence of a sarcoma, DNA aneuploidy, and ulceration and infiltrative growth into underlying tissue had a statistically significant negative influence on the survival rates of dogs with a diagnosed malignant tumor. Similar results were obtained from tests on all dogs, but tumor size and its relative hazard increased with increasing size of the tumors, regardless of whether total or disease-specific mortality was considered. Using multivariate-analysisconducted Cox's proportional hazards model, elevated S-phase rate, increased age, and presence of a sarcoma remained statistically significant risk factors. The prognostic value of DNA ploidy and lymph node status varied depending on choice of end point. The study of tumor growth pattern and tumor size provided no prognostic information in the multivariate analysis. Flow cytometric cell analysis, including S-phase rate and DNA ploidy, is of value in predicting the prognosis of canine mammary tumors and can be used as a new prognostic tool to improve the preoperative diagnostics of canine mammary tumors.
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Ahmeti, Hajrullah, Homajoun Maslehaty, Athanasios K. Petridis, et al. "Extensive Growth of an Anaplastic Meningioma." Case Reports in Neurological Medicine 2013 (2013): 1–4. http://dx.doi.org/10.1155/2013/527184.
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We present the case of a 30-year-old male patient with an almost complete destruction of the calvarial bone through an anaplastic meningioma diagnosed in line with dizziness. Neuroimaging revealed an extensive growing, contrast enhancing lesion expanding at the supra- and infratentorial convexity, infiltrating and destroying large parts of the skull, and infiltrating the skin. Due to progressive ataxia and dysarthria with proven tumor growth in the posterior fossa in the continuing course, parts of the tumor were resected. A surgical procedure with the aim of complete tumor resection in a curative manner was not possible. Six months after the first operation, due to a new tumor progression, most extensive tumor resection was performed. Due to the aggressive and destructive growth with a high rate of recurrence and tendency of metastases, anaplastic meningiomas can be termed as malignant tumors. The extrinsic growth masks the tumor until they reach a size, which makes these tumors almost unresectable. In the best case scenarios, the five-year survival is about 50%. With the presented case, we would like to show the aggressive behavior of anaplastic meningiomas in a very illustrative way. Chemotherapy, radiotherapy, and surgery reach their limits in this tumor entity.
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Sughrue, Michael E., Martin J. Rutkowski, Derick Aranda, Igor J. Barani, Michael W. McDermott, and Andrew T. Parsa. "Treatment decision making based on the published natural history and growth rate of small meningiomas." Journal of Neurosurgery 113, no. 5 (2010): 1036–42. http://dx.doi.org/10.3171/2010.3.jns091966.
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Object Definitive data allowing clinicians to predict which meningioma patients will fail to respond to conservative management are lacking. To address this need, the authors systematically reviewed the published literature regarding the natural history of small, untreated meningiomas. Methods The authors performed a systematic review of the existing literature on untreated meningiomas that were followed with serial MR imaging. They summarize the published linear rates of tumor growth, and the risk factors for development of new or worsened symptoms during follow-up by using a stratified chi-square test. Results The search methods identified 22 published studies reporting on 675 patients with untreated meningiomas followed by serial MR imaging. Linear growth rates varied significantly: no growth was the most common rate, although reports of more aggressive tumors noted growth rates of up to a 93% linear increase in size per year. The authors found that few patients with initial tumor diameters < 2 cm went on to develop new or worsened symptoms over a median follow-up period of 4.6 years. Patients with initial tumor diameters of 2–2.5 cm demonstrated a marked difference in the rate of symptom progression if their tumors grew > 10% per year, compared with those tumors growing ≤ 10% per year (42% vs 0%; p < 0.001, chi-square test). Patients with tumors between > 2.5 and 3 cm in initial size went on to develop new or worsened symptoms 17% of the time. Conclusions This systematic review of the literature regarding the clinical behavior of untreated meningiomas suggests that most meningiomas ≤ 2.5 cm in diameter do not proceed to cause symptoms in the approximately 5-year period following their discovery. Those that do cause symptoms can usually be predicted with close radiographic follow-up. Based on these findings, the authors suggest the importance of observation in the early course of treatment for small asymptomatic meningiomas, especially those with an initial diameter < 2 cm.
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Gugel, Isabel, Florian Grimm, Christian Teuber, et al. "Management of NF2-associated vestibular schwannomas in children and young adults: influence of surgery and clinical factors on tumor volume and growth rate." Journal of Neurosurgery: Pediatrics 24, no. 5 (2019): 584–92. http://dx.doi.org/10.3171/2019.6.peds1947.
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OBJECTIVEThe authors’ aim was to evaluate the tumor volume and growth rate of neurofibromatosis type 2 (NF2)–associated vestibular schwannomas (VSs) and the clinical factors or type of mutations before and after surgery in children and adults younger than 25 years at the time of diagnosis.METHODSA total of 579 volumetric measurements were performed in 46 operated tumors in 28 NF2 patients, using thin-slice (< 3 mm) T1-weighted contrast-enhanced MRI. The follow-up period ranged from 21 to 167 months (mean 75 months). Growth rate was calculated using a multilinear regression model. Mutation analysis of the NF2 gene was performed in 25 patients.RESULTSSurgery significantly (p = 0.013) slowed the VS growth rate from 0.69 ± 1.30 cm3/yr to 0.23 ± 0.42 cm3/yr. Factors significantly associated with a higher growth rate of VSs were increasing patient age (p < 0.0005), tumor volume (p = 0.006), tumor size (p = 0.001), and constitutional truncating mutations in the NF2 gene (p = 0.018). VS growth rates tended to be higher in patients with spinal ependymomas and in right-sided tumors and lower in the presence of peripheral schwannomas; however, no statistical significance was achieved.CONCLUSIONSDecompression of the internal auditory canal with various degrees of tumor resection decreases the postoperative tumor growth rate in children and young adults with NF2-associated VS. Patients with potential risk factors for accelerated growth (e.g., large volume, truncating mutations) and with increasing age should be monitored more closely before and after surgery.
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Schwartz, Jennifer L., Kent A. Griffith, Lori Lowe, et al. "Features Predicting Sentinel Lymph Node Positivity in Merkel Cell Carcinoma." Journal of Clinical Oncology 29, no. 8 (2011): 1036–41. http://dx.doi.org/10.1200/jco.2010.33.4136.
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Purpose Merkel cell carcinoma (MCC) is a relatively rare, potentially aggressive cutaneous malignancy. We examined the clinical and histologic features of primary MCC that may correlate with the probability of a positive sentinel lymph node (SLN). Methods Ninety-five patients with MCC who underwent SLN biopsy at the University of Michigan were identified. SLN biopsy was performed on 97 primary tumors, and an SLN was identified in 93 instances. These were reviewed for clinical and histologic features and associated SLN positivity. Univariate associations between these characteristics and a positive SLN were tested for by using either the χ2 or the Fisher's exact test. A backward elimination algorithm was used to help create a best multiple variable model to explain a positive SLN. Results SLN positivity was significantly associated with the clinical size of the lesion, greatest horizontal histologic dimension, tumor thickness, mitotic rate, and histologic growth pattern. Two competing multivariate models were generated to predict a positive SLN. The histologic growth pattern was present in both models and combined with either tumor thickness or mitotic rate. Conclusion Increasing clinical size, increasing tumor thickness, increasing mitotic rate, and infiltrative tumor growth pattern were significantly associated with a greater likelihood of a positive SLN. By using the growth pattern and tumor thickness model, no subgroup of patients was predicted to have a lower than 15% to 20% likelihood of a positive SLN. This suggests that all patients presenting with MCC without clinical evidence of regional lymph node disease should be considered for SLN biopsy.
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Schnurman, Zane, Aya Nakamura, Michelle W. McQuinn, John G. Golfinos, J. Thomas Roland, and Douglas Kondziolka. "Volumetric growth rates of untreated vestibular schwannomas." Journal of Neurosurgery 133, no. 3 (2020): 742–48. http://dx.doi.org/10.3171/2019.5.jns1923.
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OBJECTIVEThere remains a large discrepancy among surgeons in expectations of vestibular schwannoma (VS) growth. The anticipated growth rate of a VS and its potential clinical impact are important factors when deciding whether to observe the lesion over time or to intervene. Previous studies of VS natural growth remain limited, mostly confined to linear measurements, often without high-resolution, thin-sequence imaging. The present study comprehensively assessed natural tumor growth rates using volumetric measurements.METHODSBetween 2012 and 2018, 212 treatment-naïve patients diagnosed with a unilateral VS were evaluated. A total of 699 MR images were assessed, with a range of 2–11 MR images per patient. All MR images preceded any intervention, with patients subsequently being observed through completion of data analysis (36%) or treated with stereotactic radiosurgery (32%) or microsurgical resection (32%). To determine precise tumor volumes, the tumor area was outlined on every slice, and the products of the area and slice thickness were summed (99% of scans were ≤ 1-mm slice thickness). A multilevel model with random effects was used to assess the mean volume change over time. Each tumor was categorized as one of the following: growing (volume increase by more than 20% per year), fast growing (volume increase by more than 100% per year), stable (volume change between 20% decrease and 20% increase per year), and shrinking (volume decrease by more than 20% per year).RESULTSThe mean VS volumetric growth rate was 33.5% per year (95% CI 26.9%–40.5%, p < 0.001). When assessing the frequencies of individual tumor annual growth rates, 66% demonstrated growth (30% fast growing), 33% were stable, and 1% exhibited shrinking over an average interval of 25 months. Larger tumors were associated with increased absolute growth, but there was no relationship between tumor size and proportional growth rate. There was also no relationship between patient age and tumor growth rate.CONCLUSIONSThis study comprehensively assessed VS volumetric growth rates using high-resolution images and was conducted in a large and diverse patient sample. The majority of the tumors exhibited growth, with about one-third growing at a rate of 100% per year. These findings may contribute to a consensus understanding of tumor behavior and inform clinical decisions regarding whether to intervene or observe.
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Gugel, Isabel, Julian Zipfel, Philip Hartjen, et al. "Managing NF2-associated vestibular schwannomas in children and young adults: review of an institutional series regarding effects of surgery and bevacizumab on growth rates, tumor volume, and hearing quality." Child's Nervous System 36, no. 10 (2020): 2471–80. http://dx.doi.org/10.1007/s00381-020-04728-x.
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Abstract We reviewed our experience in managing of NF2-associated vestibular schwannoma (VS) in children and young adults regarding the effect of surgery and postoperative bevacizumab treatment. A total of 579 volumetric and hearing data sets were analyzed. The effect of surgery on tumor volume and growth rate was investigated in 46 tumors and on hearing function in 39 tumors. Long-term hearing follow-up behavior was compared with 20 non-operated ears in additional 15 patients. Sixteen operated VS were treated with bevacizumab. Mutation analysis of the NF2 gene was performed in 25 patients. Surgery significantly slowed down VS growth rate. Factors associated with a higher growth rate were increasing patient age, tumor volume, and constitutional truncating mutations. Immediately after surgery, functional hearing was maintained in 82% of ears. Deterioration of hearing was associated with initial hearing quality, larger tumor volumes, and larger resection amounts. Average hearing scores were initially better in the group of non-operated VS. Over time, hearing scores in both groups worsened with a similar dynamic. During bevacizumab treatment of residual tumors, four different patterns of growth were observed. Decompression of the internal auditory canal with various degrees of tumor resection decreases the postoperative tumor growth rates. Carefully tailored BAEP-guided surgery does not cause additional hearing deterioration. Secondary bevacizumab treatment showed heterogenous effects both regarding tumor size and hearing preservation. It seems that postoperative tumor residuals, that grow slower, behave differently to bevacizumab than reported for not-operated faster growing VS.
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Panet-Raymond, Valerie, Kushraw Sabit, George Shenouda, Denis Sirhan, Anthony Zeitouni, and Luis Souhami. "Growth of Pituitary Macroadenomas Postpartial Resection: Implications for Adjuvant Radiotherapy." Journal of Neurological Surgery Part B: Skull Base 80, no. 03 (2018): 323–26. http://dx.doi.org/10.1055/s-0038-1670686.
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Objective To determine the volumetric growth in macroadenomas (MAs) patients with residual postoperative disease and to identify subpopulations with rapid postoperative growth rate that may benefit from early salvage radiotherapy (RT). Methods Patients who had undergone a partial resection for MAs and did not receive immediate postoperative RT were eligible. Residual tissue was contoured on serial magnetic resonance imaging and planimetric and volumetric changes in size were measured. Growth rates were established by a single observer using serial volumetric measurements. Data were analyzed to find a relationship among growth rate, adjuvant treatment, and patient and tumor characteristics. Results Thirty-one patients met the eligibility criteria. Nine patients (29%) required adjuvant treatment because of tumor growth. Volumetric growth was identified 95% of the time compared with 64% planimetrically. Planimetric growth could not be established in 10% of patients showing volumetric changes. Median growth rate was 0.4464 mL/y. Growth rate positively correlated with size of residual postoperative volume (p < 0.001). Receiving salvage treatment positively correlated with growth rate (p = 0.001), particularly at a rate above 2.19 mL/y (p = 0.0064). Five patients (16%) had a growth rate above this level, all of which required salvage treatment. Patients with postoperative residual volume > 3.95 mL were most likely to experience rapid growth rate and require salvage treatment (p = 0.007). Conclusion Volumetric measurement was found to be superior to planimetric measurement in detecting changes in patients with residual tumors. Patients with postoperative residual volume > 3.95 mL should be considered for early treatment with RT.
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Passeri, Thibault, Paolo di Russo, Pierre-Olivier Champagne, et al. "Tumor Growth Rate as a New Predictor of Progression-Free Survival After Chordoma Surgery." Neurosurgery 89, no. 2 (2021): 291–99. http://dx.doi.org/10.1093/neuros/nyab164.
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Abstract BACKGROUND Currently, different postoperative predictors of chordoma recurrence have been identified. Tumor growth rate (TGR) is an image-based calculation that provides quantitative information of tumor's volume changing over time and has been shown to predict progression-free survival (PFS) in other tumor types. OBJECTIVE To explore the usefulness of TGR as a new preoperative radiological marker for chordoma recurrence. METHODS A retrospective single-institution study was carried out including patients reflecting these criteria: confirmed diagnosis of chordoma on pathological analysis, no history of previous radiation, and at least 2 preoperative thin-slice magnetic resonance images available to measure TGR. TGR was calculated for all patients, showing the percentage change in tumor size over 1 mo. RESULTS A total of 32 patients were retained for analysis. Patients with a TGR ≥ 10.12%/m had a statistically significantly lower mean PFS (P &lt; .0001). TGR ≥ 10.12%/m (odds ratio = 26, P = .001) was observed more frequently in recurrent chordoma. In a subgroup analysis, we found that the association of Ki-67 labeling index ≥ 6% and TGR ≥ 10.12%/m was correlated with recurrence (P = .0008). CONCLUSION TGR may be considered as a preoperative radiological indicator of tumor proliferation and seems to preoperatively identify more aggressive tumors with a higher tendency to recur. Our findings suggest that the therapeutic strategy and clinical-radiological follow-up of patients with chordoma can be adapted also according to this new parameter.
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Ruiz-Garcia, Ana, Pasi A. Janne, Keunchil Park, et al. "EGFR status and daily dose: Effect on tumor growth inhibition in cancer patients treated with dacomitinib (PF-00299804)." Journal of Clinical Oncology 30, no. 15_suppl (2012): e18093-e18093. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.e18093.
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e18093 Background: Dacomitinib (D) is a highly selective, irreversible small molecule pan-human epidermal growth factor (EGFR/HER) inhibitor. The effect of mean D daily dose (exposure) on tumor growth dynamics was analyzed using a longitudinal exposure-response tumor growth inhibition model. Methods: Estimated parameters included tumor shrinkage rate (KD), which changes over time as resistance to therapy develops according to an exponential decay function where λ = slope of the dynamic shrinkage rate change; and tumor growth rate constant (KL). eDose, the effect of mean D daily dose changes on tumor shrinkage rate, was tested in the base model to establish the best relationship between tumor shrinkage and drug exposure. Model parameters were estimated using a population (pop) approach. Pop pharmacodynamic analyses included data from 4 clinical trials (3 phase I and 1 phase II) of D (15–45 mg QD) in patients (pts) with advanced solid tumors. Multiple tumor size (SLD) measurements were collected from each pt. Data analysis used nonlinear mixed effects modeling (NONMEM, v 7.1.2). After visual inspection of relationships between covariates (weight, age, creatinine clearance, bilirubin, ALT, baseline ECOG PS, race, sex, EGFR status) and individual parameter estimates of KD; subpopulation analysis was carried out in pts with confirmed EGFR status (mutation [mu] or wild type [WT]) to quantify the potential effect of EGFR status on KD. Results: SLD values over time were collected from 200 pts (47% male). For a typical pt, KL = 0.63 year-1; KD = 1.6 year-1; developed therapy resistance over time (λ) = 13.7 year-1; and eDose = 0.45. Drug-specific parameters affecting tumor shrinkage (KD, λ, eDose) and the disease-specific KL were well estimated with low relative standard errors. Visual inspection of relationships between covariates and individual parameter estimates showed a higher shrinkage rate (KD) for pts with EGFR mu vs those with WT EGFR. Conclusions: D mean daily dose affected tumor growth dynamics. Tumor shrinkage rate at an averaged daily dose below 45 mg QD was lower vs 45 mg QD. EGFR status was a significant covariate affecting tumor shrinkage rate (83% less shrinkage in pts with EGFR WT vs. pts with EGFR mut).
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Kirshtein, Arkadz, Shaya Akbarinejad, Wenrui Hao, et al. "Data Driven Mathematical Model of Colon Cancer Progression." Journal of Clinical Medicine 9, no. 12 (2020): 3947. http://dx.doi.org/10.3390/jcm9123947.
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Every colon cancer has its own unique characteristics, and therefore may respond differently to identical treatments. Here, we develop a data driven mathematical model for the interaction network of key components of immune microenvironment in colon cancer. We estimate the relative abundance of each immune cell from gene expression profiles of tumors, and group patients based on their immune patterns. Then we compare the tumor sensitivity and progression in each of these groups of patients, and observe differences in the patterns of tumor growth between the groups. For instance, in tumors with a smaller density of naive macrophages than activated macrophages, a higher activation rate of macrophages leads to an increase in cancer cell density, demonstrating a negative effect of macrophages. Other tumors however, exhibit an opposite trend, showing a positive effect of macrophages in controlling tumor size. Although the results indicate that for all patients the size of the tumor is sensitive to the parameters related to macrophages, such as their activation and death rate, this research demonstrates that no single biomarker could predict the dynamics of tumors.
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Mehrazin, Reza, Marc C. Smaldone, Alexander Kutikov, et al. "Growth kinetics and outcomes of cT1b renal masses under active surveillance." Journal of Clinical Oncology 32, no. 4_suppl (2014): 440. http://dx.doi.org/10.1200/jco.2014.32.4_suppl.440.
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440 Background: The natural history of untreated T1b renal masses is poorly understood. We assessed the growth kinetics and outcomes of ≥cT1b cortical renal tumors which continue to remain on radiographic AS compared to those who underwent definitive surgery after a period of AS. Methods: Prospectively maintained, renal tumor database was reviewed to identify enhancing solid and cystic masses managed expectantly from 2000-2012. cT1a masses, transitional cell carcinoma or those suspected for metastatic disease were excluded from analysis. Localized tumors > 4.0 cm (≥T1b) that were radiographically followed for > 6 months were included for analysis. Clinical and pathological records were reviewed to determine tumor growth rate and clinical outcomes in those remained on AS or those who underwent delayed intervention. Mean for tumor size on presentation, annual linear tumor growth rate (LGR), Charlson comorbidity index (CCI), and follow-up (FU) were calculated. Chi−square test & Logistic regression were used for uni- and multi-variable analyses. Results: Of 457 pts managed with AS, 67 cT1b tumors (in 63 patients) were identified. 43 pts (67%) were managed solely with AS, while 21 pts (33%) progressed to intervention. The median age at presentation pts managed with AS and intervention was 77 and 60 yrs respectively (p=0.0002), while no difference was observed in median CCI (3 vs. 2, p=0.6). No difference was observed in tumor size at presentation between pts managed with AS and those undergoing delayed intervention (5.9 vs. 5.4 cm, p=0.8). In contrast, the mean LGR significantly differed between pts managed expectantly and pts progressed to intervention (0.37 vs. 0.73 cm/yr; p=0.02). On MVA, age (OR=0.9,CI:0.8−0.98) and LGR (OR=11,CI:1.8−60) were significant predictors of surgical intervention. With a mean FU period of 38.9 ± 24.0 months (6−105), 9 pts died (14%) from other cause and no pt progressed to metastatic disease. Conclusions: Localized cT1b≥ renal masses show comparable growth rates to small tumors managed expectantly with low rates of progression to metastatic disease with short term follow up. An initial period of AS to determine tumor growth kinetics is a reasonable option in select pts with significant competing risks and limited life expectancy.
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Ando, Kei, Shiro Imagama, Zenya Ito, et al. "How do spinal schwannomas progress? The natural progression of spinal schwannomas on MRI." Journal of Neurosurgery: Spine 24, no. 1 (2016): 155–59. http://dx.doi.org/10.3171/2015.3.spine141218.
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OBJECT Little is known about the progression of spinal schwannomas. The aim of this study was to determine the natural progression of spinal schwannomas and establish the risk of tumor growth. METHODS This study retrospectively analyzed data from 23 patients (12 men and 11 women, 40–89 years old) with schwannomas detected by MRI. The mean follow-up period was 5 years (range 2–10 years). The absolute and relative growth rates of the tumors were calculated. RESULTS The average tumor size was 1495 mm3 at the initial visit and 2224 mm3 at the final follow-up. The average absolute growth rate was 139 mm3 per year, and the average relative growth rate was 5.3% per year. Tumors were classified into 3 groups based on enhancement patterns: isointense/hyperintense (iso/high; 11 cases), rim enhancement when enhancement was peripheral (high/rim; 5 cases), and heterogeneous/heterogeneous (hetero/hetero; 7 cases) based on Gd-enhanced T2-weighted MRI. The average absolute growth rates of the 3 lesion groups were 588 mm3, 957 mm3, and 3379 mm3, respectively (p < 0.01). CONCLUSIONS Although the tumors classified as iso/high and high/rim on T2-weighted Gd-enhanced MR images were small and grew very little, most tumors with hetero/hetero classification increased in size. Hetero/hetero-type tumors should be followed closely and may require surgery.
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Hartveit, F., B. O. Mæhle, and K. C. Pettersen. "Size of breast carcinomas at operation related to tumour growth rate." Breast Cancer Research and Treatment 10, no. 1 (1987): 47–50. http://dx.doi.org/10.1007/bf01806134.
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Dhull, A. K., V. Kaushal, R. Dhankhar, R. Atri, H. Singh, and N. Marwah. "The Inside Mystery of Jejunal Gastrointestinal Stromal Tumor: A Rare Case Report and Review of the Literature." Case Reports in Oncological Medicine 2011 (2011): 1–4. http://dx.doi.org/10.1155/2011/985242.
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Gastrointestinal stromal tumors (GISTs) are malignant and rare form of soft tissue sarcoma of the digestive tract. The incidence of gastrointestinal stromal tumors is very low Kramer et al. 2005 Jejunal GISTs are extremely rare. Here we present a rare case of jejunal GIST with unusually large size at presentation. The patient presented with severe abdomen pain, exophytic growth, and dimorphic anemia. Surgical resection of the tumor was carried out, and operative findings revealed a 15 × 10 cm growth, arising from serosal surface of jejunum, at the antimesenteric surface. Diagnosis in this case was made by subjecting the resected specimen to immunohistochemical analysis. In view of large size of the resected tumor, and high-risk histopathological features, imatinib mesylate 400 mg once daily was given as adjuvant chemotherapy. Patient is asymptomatic without any evidence of tumor recurrence after six months of postoperative followup. Imatinib as such is recommended in metastatic, residual or recurrent cases of GISTs or which are surgically not removable; however, recent recommendations suggests the use of imatinib mesylate after radical surgery in high-risk cases, because it has shown a significant decrease in the recurrence rate, and the Food and Drug Administration (FDA) has also approved the use of imatinib as adjuvant therapy after complete resection of localized, primary GIST.
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Delgrange, Etienne, Alexandre Vasiljevic, Anne Wierinckx, et al. "Expression of estrogen receptor alpha is associated with prolactin pituitary tumor prognosis and supports the sex-related difference in tumor growth." European Journal of Endocrinology 172, no. 6 (2015): 791–801. http://dx.doi.org/10.1530/eje-14-0990.
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ContextA sex difference in the progression of prolactin (PRL) tumors has been disputed for years.ObjectiveTo compare tumor characteristics and postoperative clinical course between men and women, and correlate data with estrogen receptor alpha (ERα (ESR1)) expression status.Design, patients, and methodsEighty-nine patients (59 women and 30 men) operated on for a prolactinoma and followed for at least 5 years were selected. Tumors were classified into five grades according to their size, invasion, and proliferation characteristics. The ERα expression was detected by immunohistochemistry and a score (0–12) calculated as the product of the percentage of positive nuclei and the staining intensity.ResultsWe found a significant preponderance of high-grade tumors among men and a lower surgical cure rate in men (23%) than in women (71%). Patients resistant to medical treatment were mainly men (7/8), six of whom showed tumor progression despite postoperative medical treatment, which led to multiple therapies and eventually death in three. The median score for ERα expression was 1 in men (range, 0–8) and 8 in women (range, 0–12) (P<0.0001). The expression of ERα was inversely correlated with tumor size (r=−0.59; P<0.0001) and proliferative activity. All dopamine agonist-resistant tumors and all grade 2b (invasive and proliferative) tumors (from ten men and four women) were characterized by low ERα expression.ConclusionsPRL tumors in men are characterized by lower ERα expression, which is related to higher tumor grades, resistance to treatment, and an overall worse prognosis.
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Maskey, Pukar, Pawan Raj Chalise, Uttam Kumar Sharma, Prem Raj Gyawali, Guna Kumar Shrestha, and Bhola Raj Joshi. "Role of second transurethral resection in determining residual tumor in nonmuscle-invasive bladder cancer." Journal of Society of Surgeons of Nepal 20, no. 2 (2017): 35–42. http://dx.doi.org/10.3126/jssn.v20i2.24379.
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Introduction: Presence of residual tumors is not an uncommon event after transurethral resection of bladder tumor, and no studies from Nepal so far has addressed this issue. We conducted this study to determine the rate of residual tumors after first transurethral resection of nonmuscle-invasive bladder cancer, and to determine the factors associated with the presence of residual tumors and upstaging of nonmuscle-invasive bladder cancer.
 Methods: This was a prospective observational study of 43 patients of bladder cancer who had a diagnosis of nonmuscle-invasive bladder cancer following an initial transurethral resection. Demographic data and data on tumor characteristics were obtained. Patients underwent a second transurethral resection within 2 to 8 weeks. Histopathological findings at first and second resection were compared.
 Results: There were 20 patients with Ta tumor and 23 patiens with T1 tumor at initial resection. Residual tumor was detected in 18 (41.86%) patients overall, 2 in patients with Ta tumor (10%) and 16 in patients with T1 tumor (69.5%). Tumors with T1 stage, high grade, size more than 3 centimeters and sessile growth pattern were seen to have significant association with the presence of residual tumors. Six patients with T1 disease upstaged to T2 disease after second resection (26%), while there were no upstaging with Ta tumors. Tumors with T1 stage, sessile configuration and size more than 3 centimeters were found to be significantly associated with upstaging.
 Conclusion: A second transurethral resection for nonmuscle-invasive bladder cancer should be considered if the initial tumor is T1 stage, high grade, more than 3 centimeters in size and has sessile growth pattern.
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Yang, Weilong, Jiapeng Zhao, Yanyan Han, et al. "Long-term outcomes of facial nerve schwannomas with favorable facial nerve function: tumor growth rate is correlated with initial tumor size." American Journal of Otolaryngology 36, no. 2 (2015): 163–65. http://dx.doi.org/10.1016/j.amjoto.2014.10.019.
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Nakasu, S., and Y. Nakasu. "P09.04 Natural history of meningiomas: review with meta-analyses." Neuro-Oncology 21, Supplement_3 (2019): iii39. http://dx.doi.org/10.1093/neuonc/noz126.136.
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Abstract BACKGROUND A recent investigation using MRI showed 2.5% frequency of meningioma as an incidental finding in the population-based neuroimaging study. Although observation has been a mainstay in asymptomatic meningiomas, it may increase the risk of surgery due to enlargement of the tumors and aging of patients. It is important to characterize tumors that will grow to be symptomatic in order to select appropriate treatments and radiological follow-up. MATERIAL AND METHODS We reviewed 26 studies (3 from the same institute) that analyzed natural courses in asymptomatic or untreated meningiomas. Radiological progression of tumor was redefined as tumor growth by 15% of initial volume or more whenever possible. To adjust the difference of follow-up interval in each study, the percentages of growing tumors in each study were compared with each mean follow-up period. Individual data were extracted from seven studies for univariate or multivariate analyses. Weighted meta-analyses were performed using the 25 studies. RESULTS In time-growth rate analysis, nearly 70% of meningiomas showed radiological progression defined by a volume criteria and the rate approached plateau at 5–6 years. Meta-analyses showed that each radiological progression, growth speed (annual volume change (AVC) or relative growth rate (RGR)) and symptomatic progression had different factors related to their progression. Age, calcification and high intensity on T2 weighted image related to radiological progression and growth speed but not to clinical progression. In individual data analyses, tumor size (diameter 2.6cm (AUC 0.773; specificity 0.759, sensitivity 0.800), volume 5.6cm3 (AUC 0.775, specificity 0.717, sensitivity 0.800)) was a possible marker for symptomatic growth.AVC (>= 2.1cm3/year) was the strongest indicator for clinical progression. In the group of >=2.1cm3/year, Kaplan-Meier analysis showed that progression free rate was 69.3% at 3 years, and reached to 55.4% at 6 years whereas 100% in slower growth group. CONCLUSION Radiological features may not be very much useful for prediction of clinical progression except for perifocal edema. This may be due to dynamic changes of these radiological markers in a long term. Initial quantitative tumor size and growth speed especially AVC were reliable factors for decision of treatment for asymptomatic meningiomas.
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Gonçalves, Vítor Moura, Elisa-Maria Suhm, Vanessa Ries, et al. "Macrophage and Lymphocyte Infiltration Is Associated with Volumetric Tumor Size but Not with Volumetric Growth in the Tübingen Schwannoma Cohort." Cancers 13, no. 3 (2021): 466. http://dx.doi.org/10.3390/cancers13030466.
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Most patients with vestibular schwannomas can be cured with microsurgical resection, or tumor growth can be stabilized by radiotherapy in certain cases. Recurrence is rare but usually difficult to treat. Treatment alternatives to local therapies are not established. There is growing evidence of the role of inflammatory processes in schwannomas, which may be exploitable by targeted innovative therapies. To further define the impact of inflammation with tumor growth in vestibular schwannoma, we performed immunohistochemical analyses of CD3, CD8, CD68 and CD163 to assess lymphocyte and macrophage infiltration in 923 tumor tissue samples of surgically resected vestibular schwannomas. An inflammatory score was compared with tumor size and volumetric growth. We observed a significantly larger preoperative tumor size with increased expression rates of CD3, CD8, CD68 and CD163 (p < 0.0001, p < 0.0001, p = 0.0015 and p < 0.0001, respectively), but no differences in percentual volumetric tumor growth. When all four markers were combined as an inflammatory score, tumors with high inflammatory infiltration showed slower percentual growth in a multivariate analysis, including MIB1 expression (p = 0.0249). We conclude that inflammatory cell infiltration increases with larger tumor size but is associated with slower percentual volumetric tumor growth.
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Peyre, Matthieu, Stéphane Goutagny, Alpha Bah, et al. "Conservative Management of Bilateral Vestibular Schwannomas in Neurofibromatosis Type 2 Patients: Hearing and Tumor Growth Results." Neurosurgery 72, no. 6 (2013): 907–14. http://dx.doi.org/10.1227/neu.0b013e31828bae28.
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Abstract BACKGROUND: As new treatment modalities develop for the management of vestibular schwannomas (VS) in patients with neurofibromatosis type 2, it remains crucial to ascertain the natural history of the disease. OBJECTIVE: To determine the relationship between hearing and tumor growth in patients undergoing conservative VS management. METHODS: Patients harboring bilateral VS with at least 1 year of radiological follow-up were selected. Conservative management was proposed based on the small tumor size and/or serviceable hearing at presentation. Tumor size was calculated by using the 2-component box model and reported as mean tumor diameter. Hearing was evaluated by using pure-tone average and the American Academy of Otololaryngologists and Head and Neck Surgery classification. RESULTS: Forty-six patients harboring 92 VS were included. The mean clinical and radiological follow-up times were 6.0 and 4.2 years, respectively. The mean tumor diameter was 13 mm at presentation and 20 mm at the end of follow-up. Mean tumor growth rate was 1.8 mm/year. During follow-up, 17 patients (37%) underwent surgery for VS. Surgery-free rate for VS was 88% at 5 years. The number of patients with at least 1 serviceable ear was 39 (85%) at presentation and 34 (74%) at the end of follow-up, including 22 (66%) with binaural serviceable hearing maintained. There was no statistical correlation between tumor growth rate and preservation of serviceable hearing. Tumor growth rates and age at presentation were inversely correlated. CONCLUSION: This study illustrates the high variability among neurofibromatosis type 2 patients regarding hearing status and VS growth rate and justifies the choice of initial conservative management in selected cases.
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Lee, Eun Jung, Jeong Hoon Kim, Eun Suk Park, et al. "A novel weighted scoring system for estimating the risk of rapid growth in untreated intracranial meningiomas." Journal of Neurosurgery 127, no. 5 (2017): 971–80. http://dx.doi.org/10.3171/2016.9.jns161669.
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OBJECTIVEAdvances in neuroimaging techniques have led to the increased detection of asymptomatic intracranial meningiomas (IMs). Despite several studies on the natural history of IMs, a comprehensive evaluation method for estimating the growth potential of these tumors, based on the relative weight of each risk factor, has not been developed. The aim of this study was to develop a weighted scoring system that estimates the risk of rapid tumor growth to aid treatment decision making.METHODSThe authors performed a retrospective analysis of 232 patients with presumed IM who had been prospectively followed up in the absence of treatment from 1997 to 2013. Tumor volume was measured by imaging at each follow-up visit, and the growth rate was determined by regression analysis. Predictors of rapid tumor growth (defined as ≥ 2 cm3/year) were identified using a logistic regression model; each factor was awarded a score based on its own coefficient value. The probability (P) of rapid tumor growth was estimated using the following formula:RESULTSFifty-nine tumors (25.4%) showed rapid growth. Tumor size (OR per cm3 1.07, p = 0.000), absence of calcification (OR 3.87, p = 0.004), peritumoral edema (OR 2.74, p = 0.025), and hyperintense or isointense signal on T2-weighted MRI (OR 3.76, p = 0.049) were predictors of tumor growth rate. In the Asan Intracranial Meningioma Scoring System (AIMSS), tumor size was categorized into 3 groups of < 2.5 cm, ≥ 2.5 to < 4.0 cm, and ≥ 4.0 cm in diameter and awarded a score of 0, 3, and 6, respectively; the parameters of calcification and peritumoral edema were categorized into 2 groups based on their presence or absence and given a score of 0 or 2 and 1 or 0, respectively; and the signal on T2-weighted MRI was categorized into 2 groups of hypointense and hyperintense/isointense and given a score of 0 or 2, respectively. The risk of rapid tumor growth was estimated to be < 10% when the total score was 0–2, 10%–50% when the total score was 3–6, and ≥ 50% when the total score was 7–11 (Hosmer-Lemeshow goodness-of-fit test, p = 0.9958). The area under the receiver operating characteristic curve was 0.86.CONCLUSIONSThe authors suggest a weighted scoring system (AIMSS) that predicts the specific probability of rapid tumor growth for patients with untreated IM. This scoring system will aid treatment decision making in clinical settings by screening out patients at high risk for rapid tumor growth.
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Sawamura, Yutaka, Hiroki Shirato, Touru Sakamoto, et al. "Management of vestibular schwannoma by fractionated stereotactic radiotherapy and associated cerebrospinal fluid malabsorption." Journal of Neurosurgery 99, no. 4 (2003): 685–92. http://dx.doi.org/10.3171/jns.2003.99.4.0685.
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Object. The goal of this study was to investigate outcomes in patients with vestibular schwannoma (VS) who were treated with fractionated stereotactic radiotherapy (SRT). Methods. One hundred one patients with VS were treated with fractionated SRT at a radiation level of 40 to 50 Gy administered in 20 to 25 fractions over a 5- to 6-week period. The median tumor size in these patients was 19 mm (range 3–40 mm), and 27 tumors were larger than 25 mm. Patients were consistently followed up using magnetic resonance imaging every 6 months for 5 years in principle. The median follow-up period was 45 months. The actuarial 5-year rate of tumor control (no growth > 2 mm and no requirement for salvage surgery) was 91.4% (95% confidence interval 85.2–97.6%). Three patients with progressive tumors underwent salvage tumor resection. The actuarial 5-year rate of useful hearing preservation (Gardner—Robertson Class I or II) was 71%. The observed complications of fractionated SRT included transient facial nerve palsy (4% of patients), trigeminal neuropathy (14% of patients), and balance disturbance (17% of patients). No new permanent facial weakness occurred after fractionated SRT. Eleven patients (11%) who had progressive communicating hydrocephalus (cerebrospinal fluid malabsorption) and no evidence of tumor growth after fractionated SRT required a shunt. The symptoms of this type of hydrocephalus were similar to those of normal-pressure hydrocephalus and occurred 4 to 20 months (median 12 months) after fractionated SRT. The mean size (± standard deviation) of tumors causing symptomatic hydrocephalus (25.5 ± 7.8 mm) was significantly larger than that of other tumors (18.2 ± 8.7 mm) (p = 0.011). Only four of the 72 patients with tumors smaller than 25 mm in maximum diameter received a shunt. Conclusions. Fractionated SRT resulted in an excellent tumor control rate, even for relatively large tumors, and produced a high rate of hearing preservation that was comparable to the best results of single-fraction radiosurgery. The progression of communicating hydrocephalus should be monitored closely, particularly in patients harboring a large VS.
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Wilkerson, Julia, Laleh Amiri-Kordestani, Ravi A. Madan, et al. "A method for assessing tumor response to therapy and more precisely guiding treatment decisions so as to improve survival." Journal of Clinical Oncology 30, no. 15_suppl (2012): e13122-e13122. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.e13122.
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e13122 Background: The response of tumors to chemotherapy is monitored using imaging data or tumor markers and this quantitative data provides a rich source for an objective response assessment and treatment decisions. Responses are usually assessed as categorical variables based on percentage increase or decrease in tumor size. Methods: We have developed mathematical equations that describe efficacy as a continuous variable, enabling the extraction of the appropriate rate constants for tumor growth and regression (decay), designated g and d, respectively. Both are used to describe the rates of tumor growth and regression for the fraction of tumor that is growing despite treatment and the fraction dying as a result of therapy, respectively. Results: Using data from randomized phase III trials in kidney and breast cancer, multiple myeloma, and medullary thyroid carcinoma; as well as phase II trials in prostate cancer we have shown that: (1) values of g but not those of d are strongly correlated (negatively) with patient survival; (2) g can be discerned early in treatment, before growth is demonstrated clinically, providing an early efficacy measure; (3) g typically does not change over time, even over years, suggesting resistance is intrinsic and predictable and does not worsen over time; (4) effective therapies both increase d, and reduce g; and (5) in every cancer studied, the evidence suggests tumor growth reverts to its pre-treatment rate when chemotherapy is discontinued. Conclusions: The observation that g remains stable allows one to predict the most likely outcome of continued therapy. The evidence indicates that the increase in g occurring after treatment discontinuation is due to a resumption of a pre-treatment growth rate and not a change in biology. Our hypothesis is that if a favorable growth rate that slows tumor growth can be identified, survival might be improved if therapies that achieve this favorable growth rate are continued despite crossing conventional disease progression boundaries. We plan a prospective test of this model to provide a more informed decision and better survival outcome by maximizing the benefit obtained from approved therapies.
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Talts, J. F., G. Wirl, M. Dictor, W. J. Muller, and R. Fassler. "Tenascin-C modulates tumor stroma and monocyte/macrophage recruitment but not tumor growth or metastasis in a mouse strain with spontaneous mammary cancer." Journal of Cell Science 112, no. 12 (1999): 1855–64. http://dx.doi.org/10.1242/jcs.112.12.1855.
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The local growth of tumors and their ability to metastasize are crucially dependent on their interactions with the surrounding extracellular matrix. Tenascin-C (TNC) is an extracellular matrix protein which is highly expressed during development, tissue repair and cancer. Despite the high levels of TNC in the stroma of primary and metastatic tumors, the function of TNC is not known. In the present study we have crossed TNC-null mice with a mouse strain where both female and male mice spontaneously develop mammary tumors followed by metastatic disease in the lungs. We report that the absence of TNC had no effect on the temporal occurrence of mammary tumors and their metastatic dissemination in lungs. Furthermore, the number and size of tumors, the number and size of metastatic foci in the lungs, the proliferation rate and apoptosis of tumor cells and tumor angiogenesis were not altered in the absence of TNC. Histological examination revealed that the tumor organisation, however, was modulated by TNC. In the presence of TNC both primary as well as metastatic tumors were organised in large tumor cell nests surrounded by thick layers of extracellular matrix proteins. In the absence of TNC these tumor cell nests were smaller but still separated from each other by extracellular matrix proteins. In addition, the TNC-null stromal compartment contained significantly more monocytes/macrophages than tumor stroma from TNC wild-type mice. Using in vitro coculture experiments we show that TNC-null tumor cells were still able to activate the TNC gene in fibroblasts which express low basal levels of TNC. Altogether these data indicate that TNC has a very limited role during the spontaneous development and growth of mamary tumors and their metastasis to the lungs.
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Lin, Hongxia, Xiaoping Liu, and Chunnuan He. "Ceramide-Graphene Oxide Nanoparticles Enhance the Cytotoxicity and Reduce the Occurrence and Development of Breast Cancer Xenografts." Journal of Biomaterials and Tissue Engineering 11, no. 11 (2021): 2162–67. http://dx.doi.org/10.1166/jbt.2021.2801.
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Ceramide exerts crucial effect on inducing tumor cell apoptosis, while its insolublility limits the application in treating tumors. In this study, we used NGO-PEG-PEI (NPP) and C6-NPP/Cer (NPP/C) as method to explore NPP/C’s effect and its anti-tumor ability on breast cancer. Confocal microscopy was used to detect the transfection efficiency in tumor cells. Breast cancer cells were treated with C6-NGO-PEG-PEI solution (control group) or NPP/C followed by analysis of cell proliferation and apoptosis by flow cytometry. C6-ceramide solution (control group) or NPP/C was administrated into nude mice with tumor followed by measuring tumor volume and size as well as cell proliferation and apoptosis. NGO-PEG-PEI could significantly enhance cell intake and inhibit cell proliferation and promote apoptosis. In vivo transplantation tumor model experiments showed that NPP/C could decrease tumor growth, slow down the multiplication rate and accelerate apoptosis. In conclusion, Ceramide-graphene oxide can inhibit tumor growth by inhibiting tumor cell growth and promoting cell apoptosis.
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Sughrue, Michael E., Isaac Yang, Derick Aranda, et al. "The natural history of untreated sporadic vestibular schwannomas: a comprehensive review of hearing outcomes." Journal of Neurosurgery 112, no. 1 (2010): 163–67. http://dx.doi.org/10.3171/2009.4.jns08895.
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Object Observation is an important consideration when discussing management options for patients with vestibular schwannoma (VS). Most data regarding clinical outcomes after conservative management come from modestsized series performed at individual centers. The authors performed an analysis of the published literature on the natural history of VSs with respect to hearing outcome. Their objective was to provide a comprehensive and unbiased description of outcomes in patients whose disease was managed conservatively. Methods The authors identified a total of 34 published studies containing hearing outcome data in patients with VSs < 25 mm in largest diameter who underwent observation management. The effects of initial tumor size and tumor growth rate on hearing function at latest follow-up were analyzed. Data from individual and aggregated cases were extracted from each study. Patients with poorer hearing (American Association of Otolaryngology–Head and Neck Surgery Classes C or D, or Gardner-Robertson Classes III, IV, or V) at the time of presentation were excluded. Results A total of 982 patients met the inclusion criteria for this analysis, with a mean initial tumor size of 11.3 ± 0.68 mm. The mean growth rate was 2.9 ± 1.2 mm/year. The length of follow-up for these studies ranged from 26 to 52 months. Patients with preserved hearing at latest follow-up had a statistically larger initial tumor size than those whose hearing declined during the observation period (11.5 ± 2.3 mm vs 9.3 ± 2.7 mm, p < 0.0001), but the 2-mm difference of means was at the limit of imaging resolution and observer reliability. In contrast, patients with lower rates of tumor growth (≤ 2.5 mm/year) had markedly higher rates of hearing preservation (75 vs 32%, p < 0.0001) compared with patients with higher tumor growth rates. Interestingly, the authors' analysis found no difference in the rate of reported intervention for patients in either group (16 vs 18%, p = not significant). Conclusions These data suggest that a growth rate of > 2.5 mm/year is a better predictor of hearing loss than the initial tumor size for patients undergoing observation management of VSs < 25 mm in largest diameter.
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Tian, Li, Lucas Wang, Yang Qiao, et al. "Antitumor Efficacy of Liposome-Encapsulated NVP-BEZ235 Combined with Irreversible Electroporation for Head and Neck Cancer." Molecules 24, no. 19 (2019): 3560. http://dx.doi.org/10.3390/molecules24193560.
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Irreversible electroporation (IRE) kills tumor cells by the delivery of short pulses of strong electric fields. However, the field strength decreases with distance from the treatment center. When IRE cannot eradicate the entire tumor mass, the surviving tumor cells can regrow. NVP-BEZ235 is a dual PI3K/mTOR inhibitor that has been administered orally in clinical trials. However, its hydrophobicity and poor water solubility make NVP-BEZ235 difficult to deliver to target areas. To improve its pharmacokinetics and therapeutic efficacy, we have encapsulated NVP-BEZ235 in a liposome (termed as L-BEZ). Our current study focuses on the long-term antitumor efficacy of IRE and intratumoral injection of L-BEZ in HN5 head and neck cancer xenografts in nude mice. We compared in vitro efficacy, as well as the effect on tumor size and growth rate in vivo, between IRE alone, IRE + oral BEZ, and IRE + L-BEZ over the course of two months. All animals in the control group were sacrificed by day 36, due to excess tumor burden. Tumors treated with IRE alone grew faster and larger than those in the control group. IRE + oral BEZ suppressed tumor growth, but the growth rate increased to that of the controls toward the end of 21 days. Only IRE + L-BEZ eradicated the tumor masses, with no palpable or extractable tumor mass observed after two months. The combination of IRE and L-BEZ could effectively eradicate tumors and prevent recurrence.
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Fujimoto, Masahito, Eiji Yoshino, Norihiko Mizukawa, and Kimiyoshi Hirakawa. "Spontaneous reduction in size of prolactin-producing adenoma after delivery." Journal of Neurosurgery 63, no. 6 (1985): 973–74. http://dx.doi.org/10.3171/jns.1985.63.6.0973.
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✓ The authors describe the case of a pregnant woman with a large prolactin-producing pituitary adenoma that regressed after delivery. The patient's neurological signs and symptoms spontaneously disappeared soon after delivery without treatment. Reduction in tumor size was confirmed on computerized tomography scans. It is hypothesized that the growth rate of a prolactinoma may be accelerated by estrogen.
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Agil, Ahmad, Khemais Benhaj, Miguel Navarro-Alarcon, et al. "Melatonin inhibits growth of B16 melanoma in C57BL/6 mice." Melatonin Research 3, no. 4 (2020): 436–50. http://dx.doi.org/10.32794/mr11250071.
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Melatonin (N-acetyl-5-methoxytryptamine) has oncostatic properties in a wide variety of tumors. In melanoma, melatonin displayed growth suppressive effects in cultured cell lines and tumors. Thus far, however, there is no evidence of orally administrated melatonin reducing melanoma tumor growth. Therefore, the current study investigated the preventive effect of melatonin on C57BL/6 mice injected with B16-F10 murine metastatic melanoma cells. The animals were divided into two groups; control (vehicle) and melatonin pre-treated with oral melatonin in the drinking water (10 mg/kg/day) for 15 days. Grossly, the control animals had a significant exponential increase in tumor size until day 33, and all control animals were dead by day 38; conversely, melatonin pre-treated mice demonstrated delayed tumour appearance as well as decreased tumour volume and increased survival rates. PCNA immunostaining corroborated these data and demonstrated a significant reduction in the number of proliferating cells in the melatonin-treated mice (P < 0.005). Interestingly, histopathological analysis revealed the presence of undifferentiated and pleomorphic cells associated with higher mitotic rate in the control group, while epithelioid-shaped cells, sometimes containing melanin were clearly identified in melatonin-treated animals. Mitochondrial parameters measurement showed greater PTP opening and increased mitochondrial nitrite level associated in melatonin-pretreated animals. Finally, the decreased P-ERK1,2 cytoplasmic expression in melatonin mice compared with the controls supports the conclusion that the MAPK signalling pathway is repressed by melatonin in B16-F10 melanoma. Collectively, these results suggest for the first time that orally-administered melatonin reduces malignant melanoma progression in vivo and increases the percent of survival by lowering tumor cells proliferation due to mitochondrial dependent cytotoxicity and decreased P-ERK1,2 expression. This study demonstrates the chemopreventive potential of melatonin against malignant melanoma in C57BL/6 mice.
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Cohen, Gadi, Parwathy Chandran, Rebecca M. Lorsung, et al. "The Impact of Focused Ultrasound in Two Tumor Models: Temporal Alterations in the Natural History on Tumor Microenvironment and Immune Cell Response." Cancers 12, no. 2 (2020): 350. http://dx.doi.org/10.3390/cancers12020350.
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Image-guided focused ultrasound (FUS) has been successfully employed as an ablative treatment for solid malignancies by exposing immune cells to tumor debris/antigens, consequently inducing an immune response within the tumor microenvironment (TME). To date, immunomodulation effects of non-ablative pulsed-FUS (pFUS) on the TME are poorly understood. In this study, the temporal differences of cytokines, chemokines, and trophic factors (CCTFs) and immune cell populations induced by pFUS were interrogated in murine B16 melanoma or 4T1 breast cancer cells subcutaneously inoculated into C57BL/6 or BALB/c mice. Natural history growth characteristics during the course of 11 days showed a progressive increase in size for both tumors, and proteomic analysis revealed a shift toward an immunosuppressive TME. With respect to tumor natural growth, pFUS applied to tumors on days 1, 5, or 9 demonstrated a decrease in the growth rate 24 h post-sonication. Flow cytometry analysis of tumors, LNs, and Sp, as well as CCTF profiles, relative DNA damage, and adaptive T-cell localization within tumors, demonstrated dynamic innate and adaptive immune-modulation following pFUS in early time points of B16 tumors and in advanced 4T1 tumors. These results provide insight into the temporal dynamics in the treatment-associated TME, which could be used to evaluate an immunomodulatory approach in different tumor types.
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Kerr, Leslie R., Rajinder Hundal, W. André Silva, Joanne T. Emerman, and Joanne Weinberg. "Effects of Social Housing Condition on Chemotherapeutic Efficacy in a Shionogi Carcinoma (SC115) Mouse Tumor Model: Influences of Temporal Factors, Tumor Size, and Tumor Growth Rate." Psychosomatic Medicine 63, no. 6 (2001): 973–84. http://dx.doi.org/10.1097/00006842-200111000-00017.
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Maawy, Ali, Yong Zhang, Michael Bouvet, Robert M. Hoffman, and Ming Zhao. "Salmonella typhimurium A1-R prolongs survival of aggressive pancreatic cancer in orthotopic nude mouse models." Journal of Clinical Oncology 31, no. 15_suppl (2013): e22013-e22013. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.e22013.
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e22013 Background: Salmonella typhimurium A1-R has been previously shown to target multiple tumor types in various mouse models. The aim of this study was to test the efficacy of S. typhimurium A1-R against a high aggressive pancreatic cell line in an orthotopic nude mouse model. Methods: Human MiaPaCa2 pancreatic cancer cells, expressing red fluorescent protein (RFP), were implanted subcutaneously in nude mice. After tumor engraftment, the mice were subjected to intravenous therapy with S. typhimurium A1-R (5×107 CFU) once a week for 3 weeks. The tumors were harvested and weighed after the treatment period. MiaPaCA2-RFP was subsequently surgically implanted orthotopically and S. typhimurium A1-R treatment was initiated 2 weeks later. Mice were treated with intravenous A1-R (5×107CFU) once a week for 6 weeks, after which survival and tumor growth were recorded. Results: In the subcutaneous tumor model, significant decreases in the rate of tumor growth (p = 0.049) and tumor size (p = 0.004) were observed upon termination. In the orthotopic model, a significant decrease in the rate of tumor growth (p = 0.01) and increased survival was observed (p = 0.014). None of the mice showed any adverse events or weight loss from bacterial therapy. Conclusions: The results suggest further investigation S. typhimurium A1-R, including in combination with chemotherapy, with the goal of cure of pancreatic cancer.
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Sughrue, Michael E., Ari J. Kane, Rajwant Kaur, et al. "A prospective study of hearing preservation in untreated vestibular schwannomas." Journal of Neurosurgery 114, no. 2 (2011): 381–85. http://dx.doi.org/10.3171/2010.4.jns091962.
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Object The authors previously published a systematic review of the English language literature regarding the natural history of untreated vestibular schwannomas (VSs). This analysis found that the best predictor of future hearing loss was tumor growth > 2.5 mm/year on serial imaging, a factor that doubled the rate of hearing loss. In this paper the authors present an analysis of prospectively collected outcomes in patients with untreated VS from their institution that confirms their previous findings. Methods Clinical, radiographic, and audiometric data for all patients evaluated for VS at the authors' institution over a 22-year period were prospectively collected in a database. All patients in this database who had serviceable hearing (American Academy of Otolaryngology-Head and Neck Surgery Grade A or B) on initial presentation were selected, and underwent serial observation. Magnetic resonance imaging and audiometric data were analyzed, and the time from presentation until hearing loss was analyzed using Kaplan-Meier analysis. Results Fifty-nine patients with VS who initially presented with serviceable hearing were treated conservatively over this period. Consistent with the authors' previous findings, patients with a tumor growth rate > 2.5 mm/year at any point during follow-up lost their hearing at a much faster rate than those who had slower growing tumors. The median time to hearing loss was 7.0 years in those patients with tumor growth rate > 2.5 mm/year compared to 14.8 years in the other patients (p < 0.0001). The estimated median time to hearing loss in the 3 initial tumor size groups was 11.6 years in the intracanalicular group, 10.3 years in the group with 0.1–1 cm extension into the CPA cistern, and 9.3 years in the group with > 1 cm extension into the CPA cistern (p value nonsignificant). Initial tumor size, age at diagnosis, and neurofibromatosis Type 2 status did not affect the time to loss of serviceable hearing. Interestingly, many patients who were followed up for more than a decade eventually lost their hearing, regardless of whether the tumor displayed any documented interval growth. Conclusion The authors confirmed the findings of their systematic review of the literature using a prospectively followed group of patients with untreated VS. Collectively, these data suggest that the expectation for more rapid hearing loss should be communicated to patients, and the decision for surgical or other intervention should be made in the context of the known risk of continued observation of fast growing tumors.
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Marazuela, M., A. E. Paniagua, M. D. Gahete, et al. "Somatotroph Tumor Progression during Pegvisomant Therapy: A Clinical and Molecular Study." Endocrinology 151, no. 12 (2010): 5974. http://dx.doi.org/10.1210/endo.151.12.9997.
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Context: There is concern that pegvisomant could be associated with a higher risk of tumor growth. The rate and possible determinants of this tumor growth are unknown. Objective: The objective of the study was to investigate the clinical, immunohistological, and molecular factors conditioning tumor growth in patients taking pegvisomant. Design and Setting: This was a cross-sectional study performed from 2004 to 2010 in four university hospitals in Spain. Patients: Seventy-five acromegalic patients with active disease resistant to somatostatin analogs treated with pegvisomant were followed up for a mean of 29 ± 20 months. Main Outcome Measures: Magnetic resonance images before initiation of pegvisomant, at 6 months, and then yearly were examined in all patients. Immunohistological and molecular studies were performed in tumors that grew. Results: A significant increase in tumor size was observed in five patients (6.7%). Absence of previous irradiation (P = 0.014) and shorter duration of prepegvisomant somatostatin analog therapy (P &lt; 0.001) were associated with an increased risk of tumor growth. A stepwise multivariate linear regression analysis (R2 = 0.334, P &lt; 0.001) identified the duration of somatostatin analog therapy prior to pegvisomant (beta = −4.509, P = 0.014) as the only significant predictor of tumor growth. In those tumors that grew, GH expression and insulin receptor expression were higher (P = 0.033 in both cases) than in the control group. Conclusions: No previous radiotherapy, shorter duration of prepegvisomant somatostatin analog therapy, and higher tumor expression of GH and insulin receptor could be risk factors for tumor growth during pegvisomant therapy.
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Malcolm, Joan E., Timothy M. Stearns, Susan D. Airhart, Joel H. Graber, and Carol J. Bult. "Factors that influence response classifications in chemotherapy treated patient-derived xenografts (PDX)." PeerJ 7 (March 28, 2019): e6586. http://dx.doi.org/10.7717/peerj.6586.
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In this study, we investigated the impact of initial tumor volume, rate of tumor growth, cohort size, study duration, and data analysis method on chemotherapy treatment response classifications in patient-derived xenografts (PDXs). The analyses were conducted on cisplatin treatment response data for 70 PDX models representing ten cancer types with up to 28-day study duration and cohort sizes of 3–10 tumor-bearing mice. The results demonstrated that a 21-day dosing study using a cohort size of eight was necessary to reliably detect responsive models (i.e., tumor volume ratio of treated animals to control between 0.1 and 0.42)—independent of analysis method. A cohort of three tumor-bearing animals led to a reliable classification of models that were both highly responsive and highly nonresponsive to cisplatin (i.e., tumor volume ratio of treated animals to control animals less than 0.10). In our set of PDXs, we found that tumor growth rate in the control group impacted treatment response classification more than initial tumor volume. We repeated the study design factors using docetaxel treated PDXs with consistent results. Our results highlight the importance of defining endpoints for PDX dosing studies when deciding the size of cohorts to use in dosing studies and illustrate that response classifications for a study do not differ significantly across the commonly used analysis methods that are based on tumor volume changes in treatment versus control groups.