Continued Tumor Reduction of Metastatic Pheochromocytoma/Paraganglioma Harboring Succinate Dehydrogenase Subunit B Mutations with Cyclical Chemotherapy.

Patients harboring germline mutations in the succinate dehydrogenase complex subunit B (SDHB) gene present with pheochromocytomas and paragangliomas (PPGL) that are more likely malignant and clinically aggressive. The combination chemotherapy cyclophosphamide, vincristine, and dacarbazine (CVD) was retrospectively evaluated in patients with SDHB-associated metastatic PPGL.Query Twelve metastatic PPGL patients harboring SDHB mutations/polymorphisms with undetectable SDHB immunostaining were treated with CVD. CVD therapy consisted of 750 mg/m2 cyclophosphamide with 1.4 mg/m2 vincristine on day 1 and 600 mg/m2 dacarbazine on days 1 and 2, every 21-28 days. Treatment outcome was determined by RECIST criteria as well as determination of response duration and progression-free and overall survivals. A median of 20.5 cycles (range 4-41) was administered. All patients had tumor reduction (12-100% by RECIST). Complete response was seen in two patients, while partial response was observed in 8. The median number of cycles to response was 5.5. Median duration of response was 478 days, with progression-free and overall survivals of 930 and 1190 days, respectively. Serial [18F]-fluorodeoxyglucose positron emission tomography and computed tomography imaging demonstrated continued incremental reduction in maximal standardized uptake values (SUVmax) values in 26/30 lesions. During treatment administration, the median SUV decreased from > 25 to < 6, indicating the efficacy of chemotherapy over a prolonged period of time. Prolonged therapy results in continued incremental tumor reduction, and is consistent with persistent drug sensitivity. CVD chemotherapy is recommended to be considered part of the initial management in patients with metastatic SDHB-related PPGL.

Colorectal Cancer Survival Gains and Novel Treatment Regimens: A Systematic Review and Analysis.

IMPORTANCE: The past 2 decades have witnessed progress in the management of metastatic colorectal cancer (mCRC) with more effective agents and better surgical, medical, and supportive care. While substantial progress has been made, much more must be achieved to prolong the lives of patients. OBJECTIVE: To conduct a systematic review to ascertain what percentage of the life expectancy gain in locally advanced and mCRC over the past 2 decades is due to novel therapies vs improvements in supportive care or secular trends and to thus inform treatment development strategies. EVIDENCE REVIEW: We searched Cochrane Controlled Trials Register, Medline, Embase, CancerLit, and Healthstar electronic databases for trials covering the period 1993 to 2015, scanned reference lists of articles, and searched recent conference abstracts. Ninety-six phase 3 trials and large (>50 patients) phase 2 trials in mCRC were examined. Outcomes evaluated in the experimental arms (EAs) and control arms (CAs) included overall response rate, stable disease, progression-free survival (PFS), and overall survival (OS). FINDINGS: Over the period covered by the studies, the OS in EAs increased at a mean (95% CI) rate of 0.80 (0.67-0.93) mo/y. Importantly, OS in the CAs improved 0.63 (0.51-0.75) mo/y, reflecting in part the use of experimental regimens in subsequent studies. Chemotherapy contributed only partly to the gains in OS, given that (1) mean (95% CI) improvements in PFS were only 0.31 (0.22-0.39) mo/y in the EAs and 0.23 (0.15-0.31) mo/y in CAs; (2) gains in survival not directly attributable to the protocol were greater than gains in PFS (0.46 [0.36-0.57] mo/y in EAs and 0.39 [0.29-0.49] mo/y in CAs; and (3) effects on OS were much lower in second-line trials (median [interquartile range] response rates, 8.6% [0%-11.0%] in EAs and 7.5% [3.8%-12.8%] in CAs) compared with first-line trials (39.5% [24.0%-50.2%] for EAs and 29.4% [16.4%-39.4%] for CAs). CONCLUSIONS AND RELEVANCE: The OS of patients with mCRC has improved gradually over the past 2 decades, with gains from chemotherapy occurring alongside gains from lead-time bias and improved locoregional approaches and supportive care. Gains from first-line therapies have been modest but consistent; however, gains from second-line therapies have been disappointing. We believe that future progress will be greater if emphasis is placed on enrolling patients in experimental trials to explore and develop alternative first-line regimens and better second-line therapies.

Overall survival analysis of adjuvant radiation versus observation in stage I testicular seminoma: a surveillance, epidemiology, and end results (SEER) analysis.

OBJECTIVE: The standard adjuvant treatment for men with stage I testicular seminoma remains controversial within the literature. We analyzed survival rates in men with stage I seminoma who underwent adjuvant radiation therapy (RT) or observation (OB) after orchiectomy. METHODS: Data were obtained from the Surveillance, Epidemiology, and End Results program of the National Cancer Institute from 1973 to 2003. The primary end points were overall survival (OS) and cause-specific survival (CSS). Multivariate Cox regression models were used to study the significance of clinical variables: age at diagnosis, laterality of primary disease, race, and radiation group. RESULTS: Of 6764 patients eligible for analysis, 5265 were treated with RT and 1499 with OB. After a median follow-up of 7.6 years, the 5-, 10-, and 20-year OS rates for the RT versus OB were 97.9 versus 95.0, 94.8 versus 92.2, and 83.5 versus 84.1 (P=0.0047), respectively. The CSS rates for the same time periods were 99.6 versus 98.7, 99.4 versus 98.7, and 99.2 versus 98.7 (P=0.0015), respectively. Adjuvant RT was associated with improved CSS on multivariate analysis with hazard ratio of 0.37 (confidence interval, 0.20-0.70; P=0.0023). CONCLUSIONS: Within this large US population analysis, adjuvant RT was associated with improved OS and CSS compared with OB for men with stage I testicular seminoma. Further studies are needed to determine whether modern RT techniques and field-size reductions may lead to greater improvements in the therapeutic ratio, in light of the trend toward chemotherapy as primary treatment.

Impact of age, race and decade of treatment on overall survival in a critical population analysis of 40,000 multiple myeloma patients.

With the availability of novel agents, the overall survival (OS) in patients diagnosed with multiple myeloma (MM) has improved over the last decade. Data on 40,294 MM patients in the years from 1973 to 2003 were obtained from the Surveillance, Epidemiology, and End Results Program (SEER) of the US National Cancer Institute. Statistical analyses evaluating gender, race, age, and year of diagnosis were performed using univariate and multivariate Cox regression models for the OS endpoint. The mean patient age at diagnosis was 68.3 years. Mean survival was 30 months (median = 19 months). Asian/Pacific Islander race was associated with an improved OS, HR 0.90 (CI 0.86-0.95, P < 0.001). American Indian/Alaska Native race was associated with a decreased OS, HR 1.18 (CI 1.01-1.38, P = 0.040). Multivariate analysis did not reveal statistically significant differences in OS between patients in the white and black race (P = 0.709). Younger age (age <65, and 65-75) was associated with improved OS when compared with patients >75 years of age (all P < 0.001). Recent treatment decades (1983-1992 and 1993-2003) were associated with improved OS on multivariate analysis with HR 0.88 (CI 0.88-0.89, P < 0.001) and HR 0.83 (CI 0.81-0.85, P < 0.001), respectively. As the largest population analysis to date, this study reveals a statistically significant improvement in OS for patients who were treated in more recent decades, even before the availability of novel agents. Patients who were <65 years of age and Asian/Pacific Islander race groups exhibited superior levels of OS, whereas American Indian/Alaska Native groups had decreased OS.