tbuckley/cabot-search huggingface dataset:
Late events audit of sequential studies of seminoma after carboplatin.
Authors: Tim R. D. Oliver
Journal: Journal of Clinical Oncology (2016)

e281 Background: Seminoma is the least malignant subtype of testicular germ cell cancer and has the least risk of metastasis at presentation. Less established compared with its radio-sensitivity, is the fact that it is more chemo-sensitive than non-seminoma. Despite reporting single agent Platinum data in 1982 which supported this concept, most standards of care do not treat seminoma differently from non-seminoma. This abstract reviews personal series some with more than 30 years follow up primarily using email follow up with access to clinical support as required to support this concept. Methods: A total of 97 metastatic seminoma (20 cisplatin, 77 Carboplatin) treated 1980-2006, 167 Stage 1 cases receiving either 1 or two courses of adjuvant therapy treated 1985-2006 and 54 cases receiving chemotherapy as part of testis conservation (12 single agent Platinum and 42 BEP therapy) treated between 1978 and 2006. Prior to 1996 participation was through verbal informed consent and since this time ethical committee approval has been obtained for the ongoing studies. Results: A total of 11 relapses have occurred in patients in 5 studies of carboplatin monotherapy in 264 patients with various stages of seminoma. All have been salvaged by BEP as have 16 relapses after I course carboplatin in the MRC TE19 randomised trial No relapses have occurred after 24 months despite median of 96 months follow-up, 51(19%) &gt; 20 years. Though late malignant and non-malignant events have occurred, the frequency in the cohort followed between 10 and 15 years (n = 93) is not in excess of age matched controls. Conclusions: While in primum non noce does not trump the Sword of Damocles, the lack of any problems to date provide justification for further prospective evaluation of this less toxic option in patient preference studies.
Effect of metformin use on the survival outcomes in diabetic patients with resectable pancreatic cancer: A single-institutional experience and meta-analysis.
Authors: Chenwi Ambe, Amit Mahipal, William J. Fulp, Dung-Tsa Chen, Mokenge Peter Malafa
Journal: Journal of Clinical Oncology (2015)

465 Background: Observational studies have shown that metformin use in diabetic patients decreases both cancer incidence and mortality. The aim of this study was to determine whether metformin use had a survival benefit in patients with resected pancreatic cancer. Methods: All patients with diabetes who underwent pancreatic resections for adenocarcinoma between 12/1/1986 and 4/30/2013 at our institution were identified. Patients were categorized by metformin use. Survival analysis was done using the Kaplan Meier method, with log rank test, and Cox proportional hazards multivariable regression models. The comprehensive Meta-Analysis version 2.2 was used to perform a meta-analysis using data from our study and the only other published study. Results: The study from our institution was comprised of 19 patients receiving treatment with metformin, and 25 patients not receiving metformin. There were no significant differences in major clinical and demographic characteristics between metformin and non-metformin users. The estimated median survival for metformin users was 35.3 months (95% CI 10.7 - not estimable) vs. 20.2 months (95% CI 14.4-58.6) for nonusers. The estimated 2, 3 and 5 year survival rates for non-metformin users were 42% (95% CI 22-62%), 28% (95% CI 7-55%) and 14% (95% CI 1-43%) respectively. Metformin users fared better with corresponding rates of 68% (95% CI 41-84%), 34% (95% CI 12-59%) and 34% (95% CI 12-59%) respectively. Metformin users had a 46% lower risk of death; hazard ratio 0.54 (95% CI 0.16-1.86) in a multivariate analysis, p = 0.3275. For the meta-analysis, there were a total of 111 patients from both studies. There were 46 metformin users and 65 nonusers. Metformin users had a 33% lower risk of death; the HR 0.668 (95 % CI 0.397-1.125), in a multivariate analysis p= 0.129. Conclusions: Although the findings of the current study suggests that metformin use does not significantly impact survival outcomes in diabetic patients with resected pancreatic cancer, there appears to be a clinically meaningful improvement in survival. The potential benefit of metformin should be investigated in adequately powered prospective studies.
The effect of cell cycle progression (CCP) score on treatment decisions in prostate cancer: Results of an ongoing registry trial.
Authors: Ashok J. Kar, Mark Creamer Scholz, Jeffrey E. Fegan, E. David Crawford, Peter T. Scardino, Rajesh R. Kaldate, Michael K. Brawer
Journal: Journal of Clinical Oncology (2014)

277 Background: Improved prognostic markers that provide individual patient risk stratification are a pressing need in prostate cancer. The CCP signature test (Prolaris, Myriad Genetic Laboratories, Inc.) is a novel prognostic assay that has been validated in multiple cohorts and provides accurate risk of prostate cancer-specific disease progression and disease specific mortality risk when combined with standard clinicopathologic parameters. This study evaluated clinicians’ judgment regarding the clinical utility of the CCP test in a prospective registry. Methods: Clinicians ordering the CCP signature test commercially were asked to complete a survey regarding their treatment recommendations before and after they received the CCP test result. In addition, clinicians were asked how influential the CCP test result was in making therapeutic decisions on a 5 point scale (0=None, 5=Very High). Results: Currently, 368 patients have been enrolled and 47 clinicians have completed surveys on the influence of the CCP signature test in 58 cases. In five additional surveys, the therapeutic decision was undecided pre-test, post-test or both. In 77% of cases [95% CI: 65%-86%], there was a change recorded between the therapy initially planned and the therapy actually selected. The table shows the change in intended therapeutic burden from pre-CCP test to post-CCP test. In 30 of 58 cases [52%; 95% CI 39%-64%], clinicians indicated they would reduce the intended therapeutic burden post-CCP test. The CCP signature test influenced treatment selection to a ‘High’ or ‘Very High’ degree in 37 men (62%) and had “Low” or “No” influence in only 3% of cases. Conclusions: Based on the judgment of ordering physicians, the CCP score appears to add meaningful new information to risk assessment for localized prostate cancer patients. Test results led to major changes in treatment decisions with a significant increase in conservative management options, including active surveillance or watchful waiting. [Table: see text]
Defining criteria for Lynch Syndrome/HNPCC in women under 50 with endometrial cancer: Final results of a prospective, multi-center study
Authors: K. H. Lu, J. O. Schorge, K. J. Rodabaugh, C. C. Sun, M. S. Daniels, K. G. White, P. T. Soliman, R. Luthra, R. R. Broaddus
Journal: Journal of Clinical Oncology (2005)

9547 Background: Women with Lynch Syndrome/HNPCC have a 40–60% lifetime risk of endometrial cancer (EC), which equals or exceeds their risk for colon cancer. EC has not been well-characterized in this syndrome; in fact, the recently revised Bethesda criteria do not address young age of onset of EC. The purpose of this study was to define the prevalence of HNPCC germline mutations in an unselected cohort of women under age 50 with EC. The utility of microsatellite instability (MSI) and immunohistochemistry (IHC) for MLH1 and MSH2 was also evaluated. Methods: Women diagnosed with EC ≤ age 50 between 1/00 - 9/04 were prospectively evaluated. Germline mutation testing by full sequencing was performed for MLH1, MSH2 and MSH6. Large rearrangement testing for MLH1 and MSH2 was also conducted. MSI, IHC for MLH1 and MSH2, and MLH1 methylation-specific PCR were performed. Results: Of 100 women enrolled, 9 (9%, CI 4.2–16.4) were found to have mutations: 1 MLH1, 6 MSH2, 1 with both MSH2/MSH6, and 1 MSH6. Additionally, 11 women had MSI-H EC associated with MLH1 methylation but no germline mutation. Median BMI of the mutation and non-mutation carriers was 29.2 and 35.2 (p=0.03). Among the 9 mutation carriers, 7 fulfilled revised Amsterdam criteria, 1 had a single 1st degree relative with colon cancer and 1 had no suggestive family history. For the entire cohort, the PPV+ of having a 1st degree relative with an HNPCC cancer was 32%. The PPV+ of an MSI high tumor was 26%. The PPV+ of absence of expression of MSH2 was 63%. In the entire cohort, 9 women had synchronous EC and ovarian cancers; only 1 had a mutation. Conclusions: The prevalence of Lynch/HNPCC mutations in a prospective, unselected cohort of 100 women ≤ age 50 with EC was 9%. Clinicians caring for women with EC should consider age < 50 as criteria for consideration of Lynch/HNPCC. Having a single 1st degree relative with an HNPCC associated cancer increased the likelihood of identifying a mutation. Among the molecular tests, loss of staining of MSH2 was highly associated with identifying an MSH2 mutation. Because of the high frequency of MSI-H associated with MLH1 methylation, we do not advocate MSI analysis by itself as a means of identifying mutation carriers. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Myriad Genetics
Phase III, double-blind, placebo-controlled, crossover study evaluating a 5HT<sub>3</sub> antagonist plus dexamethasone with or without aprepitant in patients with germ cell tumor receiving 5-day cisplatin combination chemotherapy: A Hoosier Oncology Group (HOG) study.
Authors: M. J. Brames, J. Picus, M. Yu, E. L. Johnston, B. Bottema, C. E. Williams, L. H. Einhorn
Journal: Journal of Clinical Oncology (2011)

9013 Background: Aprepitant, combined with a 5HT3 antagonist plus dexamethasone, is a standard antiemetic therapy for the prevention of single day cisplatin induced nausea and vomiting. There are no data with aprepitant for multiple day cisplatin regimens. A H.O.G. phase III double blind placebo controlled study compared aprepitant to placebo, combined with a 5HT3 antagonist and dexamethasone to assess efficacy. Methods: Germ cell tumor patients receiving 2 identical courses of 5 day cisplatin combination chemotherapy were eligible. Stratification was chemo-naïve versus prior chemotherapy. A 5HT3 antagonist days 1-5 plus dexamethasone 20 mg days 1-2 was utilized in both arms. Patients randomized to either aprepitant 125 mg day 3 and 80 mg days 4-7 or placebo with first course, with crossover to opposite treatment with second course. Blinded dexamethasone 8 mg bid or 4 mg bid days 6-7 for placebo or aprepitant and 4 mg bid day 8 was added. Primary objective was complete response (C.R.) (no emetic episodes or use of rescue medications). Secondary endpoints were nausea based on visual analog scale (VAS) and symptoms measured by M. D. Anderson Symptom Inventory. After 2 cycles, patients stated preferred cycle. Results: 70 patients entered and 68 evaluable. 58 were chemo naive. 60 received bleomycin, etoposide and cisplatin. 35 received aprepitant with first course and 33 placebo. 47% achieved C.R. with aprepitant compared to 19% with placebo (p < 0.0001). 32 (47.1%) had at least 1 emetic episode during placebo cycle versus 11 (16.2%) with aprepitant. 49 of 68 evaluable patients expressed a cycle preference. 38 preferred the aprepitant cycle whereas only 11 preferred placebo (p < 0.0001). There was no statistical difference in VAS for nausea or M. D. Anderson Symptom scores, but numerically improved with aprepitant. There was no observed toxicity with aprepitant compared to placebo. Conclusions: There was a statistically significant improvement in C.R. rate with aprepitant combined with a 5HT3 and dexamethasone. Patient preference strongly favored the aprepitant cycle.
Influence of XPG mRNA levels on the effect of BRCA1 mRNA levels in prognosis of early non-small cell lung cancer (NSCLC)
Authors: R. Bartolucci, M. Botia, P. Mendez, F. Puma, S. Sabatini, S. Catanzani, M. Urbani, P. Saccenti, M. Tarón, R. Rosell
Journal: Journal of Clinical Oncology (2008)

7545 Background: DNA repair genes such as BRCA1 are induced by c-Myc (Menssen and Hermeking, PNAS 2002), and high BRCA1 mRNA levels have been related to poor survival in resected NSCLC (Rosell et al, PLoS One 2007). ERCC1 and RRM1 have also been linked to prognosis. XPG belongs to the flap endonuclease 1 (FEN1) family of nucleases. In the absence of XPG cells without XPG expression survive better than wild-type cells when exposed to a sequence-specific guanine N2 alkylator (Herrero et al, Cancer Res 2006). Methods: BRCA1, ERCC1, RRM1 and XPG transcripts were examined by quantitative PCR in tumors of 54 resected NSCLC patients (p). Median age, 66 years; 51 male; 42 squamous cell carcinomas and 12 adenocarcinomas. Median disease-free survival (DFS) was 40 months (m) for stage IA, not reached for stage IB, and 25 m for stage II. Results: DFS was not reached in p with low ERCC1 or RRM1 levels, while p with high ERCC1 or RRM1 had a DFS of 26 m (P=ns). DFS was not reached in 18 p with low BRCA1 mRNA levels, while 37 p with high BRCA1 mRNA levels had a DFS of 22.4 m (P=0.02). In contrast, p with high XPG had a 51-m DFS, while p with low XPG had a 26-m DFS. When BRCA1 and XPG levels were considered jointly, DFS was not reached for p with low levels of BRCA1 regardless of whether XPG was high (10 p) or low (17 p). However, for p with high BRCA1 levels, DFS was shorter for 10 p with low XPG (16.4 m) than for 17 p with high XPG (26 m) (P=ns). Conclusions: High BRCA1 mRNA expression confers poor prognosis in early NSCLC and the combination of high BRCA1 plus low XPG expression still further increases the risk of shorter DFS. These findings could have important implications for the optimal use of adjuvant chemotherapy. No significant financial relationships to disclose.
Factors affecting survival in elderly patients with non-small cell lung cancer (NSCLC)
Authors: U. Athar, M. Gandhi, S. Lappin, N. Newman, A. Rajan, A. Gajra
Journal: Journal of Clinical Oncology (2008)

17564 Background: Most patients with NSCLC are >65 years and present with stage 3 or 4 disease. Chemotherapy (CT) with supportive care improves quality of life and survival in the elderly but is often associated with increased morbidity. Hence prognostic factors for survival should be evaluated. Methods: A single-institution, retrospective analysis of patients > 65 years with stage 3/4 NSCLC diagnosed between 2000 and 2006 was conducted. The impact of different variables on survival in all patients and in those who received CT was assessed. Variables studied were age, chronic kidney disease, comorbidities using Charlson's weighted index (CCI), total comorbidities (TCM), use of medications, medications based on Beers criteria (inappropriate medications due to ineffectiveness or risk of adverse events), emergency room visits, hospital admissions, treatment [radiation therapy (RT), CT], and performance status (PS). Results: 151 patients with stage 3/4 NSCLC were identified. Median age was 75 years. All patients were male. 66% had stage IV disease. 33% had a PS of 0–1, 23% were on at least one Beer medication, 66% had a CCI of ≥ 2 and 44% had > 5 TCM. Table 1 lists impact of variables on survival. Age did not correlate with survival. In univariate analysis number of medications, TCM and CCI did not correlate with survival. Cox regression analysis for survival showed that total medications (p .05) and Beers medications (p .02) were marginally significant. In patients who received CT the absence of Beers medications was the only variable associated with survival (14.5 versus 9.9 months, p .02). Conclusions: Major determinants of survival in these patients included PS, stage, and treatment with CT and RT. CCI does not predict for survival in these patients. The use of total number of medications and Beers medications correlate with overall survival. If confirmed in larger prospective series number of medications and beers medications could be incorporated into a predictive model for survival in elderly patients with advanced NSCLC. Variable Number of patients Median Survival months P value PS 53 13.57 <.001 0–1 98 4.03 >1 Stage 51 10.50 <.001 3 100 5.36 4 RT 72 4.23 .001 No 76 10 Yes CT 87 3.5 <.001 No 61 12.33 Yes TCM 84 8.27 .33 ≤5 67 5.73 >5 Beers medications 116 7.3 .14 0 35 6.2 1 No significant financial relationships to disclose.
Impact of S-1 as the second-line chemotherapy for patients with relapsing pancreatic cancer.
Authors: K. Ishido, Y. Toyoki, D. Kudo, S. Nrumi, K. Hakamada
Journal: Journal of Clinical Oncology (2011)

e14588 Background: Since the report of CONKO-001, adjuvant chemotherapy with gemcitabine has been the standard treatment for patients who have undergone resection of pancreatic cancer in Japan. However, few reports have described the recommended regimens for patients who have relapsed after the adjuvant chemotherapy. We evaluated, retrospectively, the efficacy and the safety of S-1, an oral fluoropyrimidine derivative, as the second-line chemotherapy for patients who have relapsed after the adjuvant chemotherapy with gemcitabine. Methods: Between 1991 and 2007, 51 patients of pancreatic cancer have relapsed after the curative resection, followed by the adjuvant chemotherapy with gemcitabine. For 26 patients (S-1 group), S-1 was administered orally twice daily meals at a dose of 100 mg/day for body surface areas for 14 consecutive days, followed by 7-day rest. On the other hand, 25 patients (GEM/BSC group) was not administered another anticancer drugs, except the continuation of gemcitabine. Results: During median follow-up time of 35 months, there was a significant difference in over-all survival between the S-1 group and the GEM/BSC group (median OS, 20.9months vs 13.7 months; p=0.031, log-rank test). Furthermore, there was also a significant difference in survival after relapse (SAR) of two groups (median SAR, 11.7 vs 6.02 months; p=0.0026, log-rank test). It was also revealed that second-line chemotherapy with S-1 could prolong the survival time significantly in the patients who had the local recurrences (median OS, 26.9 months vs 17.8 months; p=0.046, log-rank test), not in the patients who had another type of relapse. No increase in grade 3/4 hematologic and nonhematolgic toxicity was seen in the S-1 group. Conclusions: The conbination of second-line chemotherapy with S-1 and adjuvant chemotherapy with gemcitabine could be an efficient strategy, and show a benefit for pancreatic cancer patients.
Efficacy of oral ketamine against opioid-refractory cancer pain due to bone metastases: Four case reports.
Authors: Takeshi Hagihara
Journal: Journal of Clinical Oncology (2012)

161 Background: The use of oral ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, is reported to be effective against opioid-refractory cancer pain. Only a few studies have been performed worldwide so far, and in Japan we have more difficulty evaluating it, as the insurance doesn’t cover the application of ketamine to the tumor pain unlike in some other countries. Here we present the successful treatment of four patients with severe cancer-related pain due to bone metastases, by oral administration of ketamine. Methods: Inclusion criteria were cancer pain refractory to standard opiates. After institutional approval and informed patient consent were obtained, the treatment started with 40mg/day of oral ketamine. The ketamine regimen was adjusted individually based on analgesia and any adverse effects. Results: Self-reported pain significantly improved. In addition, serious adverse effects such as nightmares were not observed. In one case, epidural anesthesia became unnecessary. In another case, base and rescue opiates regimen can decreased. Conclusions: Ketamine is considered one of the World Health Organization essential drugs for the management of refractory pain. By oral administration of ketamine the quality of life can be improved, so we consider that further studies should be performed.
Breast cancer specific mortality in patients with early-stage hormone receptor–positive invasive breast cancer and oncotype DX recurrence score results in the SEER database.
Authors: Steven Shak, Valentina Petkov, Dave P Miller, Nadia Howlader, Nathan Gliner, Will Howe, Nicola C. Schussler, Kathleen Cronin, Frederick L. Baehner, Lynne Penberthy
Journal: Journal of Clinical Oncology (2016)

176 Background: NCI’s SEER Program provides cancer incidence and survival statistics for ~28% of the US. New research models are needed to characterize the use and impact of genomic tests on patient outcomes. Genomic Health and SEER collaborated to electronically supplement SEER registries with Recurrence Score (RS) results, and have evaluated breast cancer specific mortality (BCSM) in early stage hormone receptor (HR)+ HER2- invasive breast cancer. Methods: Pts were eligible for pre-specified node negative (N-) disease analysis if HR+, HER2- (by RT-PCR), no prior malignancy, 40-85 years of age, and diagnosed between Jan 2004 (Oncotype DX available Jan 2004) and Dec 2011 (SEER survival analysis complete through 2012). BCSM was defined as previously described (Howlader et al, JNCI 2010). Additional analyses of BCSM were performed for pts with N+ disease. Results: Of 169,158 eligible N- pts, 38,568 (23%) had a RS, increasing from 2% in 2004 to 35% in 2011. Pts with RS had median age of 57yr, were 99.4% female, 84% white, 29% grade 1 &amp; 54% grade 2, 25% &lt; 1cm &amp; 53% 1-2cm. Median FU was 39mo. 8,239 pts had &gt; 5yrs follow-up. Among RS &lt; 18 (N = 21,023), RS 18-30 (N = 14,494) and RS ≥ 31 (N = 3,051) pts, chemotherapy use was reported in 7%, 34%, &amp; 69%, respectively, and 5yr N- BCSM was 0.4% (95% CI, 0.3-0.6), 1.4% (95% CI, 1.1-1.7) and 4.4% (95% CI,3.4-5.6), respectively. Multivariate showed that RS was significantly associated with BCSM after adjusting for age, grade, and tumor size (p &lt; 0.001), and when stratified by treatment (p &lt; 0.001). BCSM results in additional N- subgroups (e.g., socioeconomic), and in &gt; 60,000 N+ pts will be presented. Conclusions: 5yr survival outcomes are excellent in the over 21,000 N- pts with RS &lt; 18 disease. RS ≥ 31 disease is associated with greater 5yr mortality despite addition of chemotherapy. The large sample size of this population-based observational study provides important information on prospective outcomes in subsets of pts that are often underrepresented in randomized clinical trials.