tbuckley/cabot-search huggingface dataset:
Review of completed and ongoing trials of capecitabine-based adjuvant therapy in patients with early-stage colon cancer.
Authors: J. Cassidy, N. Scotto, E. Diaz-Rubio
Journal: Journal of Clinical Oncology (2011)

495 Background: Capecitabine is an established alternative to 5-FU in gastrointestinal cancers. In metastatic colorectal cancer, capecitabine is non-inferior to 5-FU and capecitabine + oxaliplatin (XELOX) is non-inferior to FOLFOX4. Capecitabine is also an effective adjuvant treatment for early-stage colon cancer. Here we review the evidence available from completed studies of adjuvant capecitabine and describe ongoing trials in this setting. Methods: The X-ACT trial included 1,987 patients (pts) with resected stage III disease receiving either capecitabine (n=1,004) or bolus 5-FU/LV (n=983). NO16968 included 1,886 pts with resected stage III disease receiving either XELOX (n=944) or 5-FU/LV (n=942). The primary efficacy endpoint of both trials was DFS. Other large phase III trials of capecitabine in high-risk stage II/stage III pts include AVANT (XELOX + bevacizumab vs. FOLFOX4 ± bevacizumab), QUASAR2 (capecitabine vs. capecitabine + bevacizumab), SCOT (capecitabine or 5-FU/LV + oxaliplatin 12w vs. 24w), and a Japanese study of single-agent capecitabine. Results: In X- ACT, capecitabine was at least equivalent to 5-FU/LV in terms of DFS (HR=0.88; 95% CI, 0.77–1.01) and OS (HR=0.86; 95% CI, 0.74–1.01). In a preplanned multivariate analysis, capecitabine led to significantly superior DFS (p=0.02) and OS (p=0.02) vs. bolus 5-FU/LV [Twelves et al. WCGIC 2010]. In NO16968, DFS was significantly superior for XELOX vs. 5-FU/LV (HR=0.80; 95% CI, 0.69–0.93; p=0.0045) [Haller et al. ECCO-ESMO 2009]. There was a trend towards improvement in OS with XELOX (HR=0.87; 95% CI, 0.72–1.05; p=0.1486); follow-up is ongoing. Capecitabine-based therapy had an acceptable safety profile in both trials [Twelves et al. NEJM 2005; Schmoll et al. JCO 2007]. Data have yet to be reported from the AVANT, QUASAR2, SCOT and Japanese trials, although results from these trials in over 15,000 pts are awaited with interest. Conclusions: Adjuvant capecitabine is non-inferior to 5-FU/LV when given as monotherapy and superior to 5-FU/LV when given in combination with oxaliplatin. Capecitabine should be considered as a standard component of adjuvant treatment regimens for pts with stage III disease. [Table: see text]
Effects of testosterone deficiency or manipulation on prostate cancer.
Authors: Aksam Yassin, Dany-Jan Yassin, Peter Hammerer
Journal: Journal of Clinical Oncology (2014)

229 Background: There is controversy over whether testosterone replacement therapy is a risk factor for prostate cancer. Herein, we evaluate whether testosterone deficiency (TD), testosterone replacement therapy (TRT) or 5-alpha reductase inhibitor (5-ARI) therapy affect the risk of prostate cancer. Methods: Data were collected from 224 male patients who had an indication for prostate biopsy: Prostate specific antigen (PSA) greater than 4, PSA-Velocity &gt;=0.75 in a year, hypogonadism with PSA &gt;=1.5, positive digital rectal exam (DRE) and/or positive Transrectal Ultrasonography (TRUS) finding. Each patient was then subjected to a TRUS-guided 10 core prostate biopsy. Results: 25% (3 out of 12) of the patients on TRT were found to have prostate cancer via biopsy and 32.1% (68 out of 212) of patients who did not receive TRT were found to have prostate cancer; insignificant with p = 0.757. Seventeen our of 76 (22.4%) of the patients on 5-ARI treatment were found to have prostate cancer and 36.5% (54 out of 148) of the patients who did not receive 5-ARI were found to have prostate cancer; significant with p = 0.03. There was no significant statistical difference in Gleason grades among patients who were on TRT, no TRT, on 5-ARI and no 5-ARI. Conclusions: Our data suggest that TRT is not associated with increased risk of prevalence or Gleason grade of prostate cancer. 5-ARI therapy is associated with lower prevalence of prostate cancer but with no relationship to Gleason grade.
Resection of non-regional lymph node metastasis in patients with colorectal cancer.
Authors: Christina Edwards Bailey, Kamran Idrees, Alexander A. Parikh
Journal: Journal of Clinical Oncology (2016)

664 Background: Approximately 20% of patients with colorectal cancer (CRC) present with metastatic disease-most commonly to the liver or lungs. Successful resection of these metastatic foci leads to significant long-term survival. Less commonly, patients present with isolated metastasis to non-regional lymph nodes (NRLN) and little is known regarding the role of resection in these patients. The primary aim of this study is to evaluate the outcomes of patients with CRC who undergo resection of NRLN metastasis. Methods: A retrospective cohort study of patients diagnosed with CRC and NRLN metastasis was performed using the Surveillance, Epidemiology, and End Results database (2004-2012). Demographic and clinical factors were compared for patients who underwent resection of NRLN metastasis and those who had not. Kaplan-Meier and log-rank analysis was used for survival analysis. Logistic regression analysis was used to assess factors associated with resection of NRLN metastasis. Results: A total of 22,848 patients presented with metastatic CRC and underwent primary tumor resection. Of these, 786 (3.4%) presented with isolated NRLN metastasis and 78 (9.9%) underwent NRLN resection. Patients who underwent resection were more likely to be male, have rectal cancers, and poorly or undifferentiated grade tumors. Median overall survival (OS) was significantly improved for patients who underwent resection compared to those who did not (36 vs. 28 months, p = 0.036). In patients with colon cancer (N = 602), median OS was 33 vs. 21 months (p = 0.042) for those who underwent resection compared to those who did not, whereas in patients with rectal cancer (N = 184), the median OS was 45 vs. 38 months (p = 0.977), respectively. In multivariate analysis, rectal cancer (OR 1.84, 95% CI 1.08 to 3.13) and poorly or undifferentiated grade tumors (OR 1.64, 95% CI 1.01 to 2.66) were associated with increased resection of NRLN. Conclusions: Resection of NRLN metastasis in patients with CRC is associated with an overall survival benefit, particularly among patients with colon cancer. Further studies are needed to identify which specific patient subgroups would best benefit from this resection strategy.
Setting Quality Improvement Priorities for Women Receiving Systemic Therapy for Early-Stage Breast Cancer by Using Population-Level Administrative Data
Authors: Katherine A. Enright, Nathan Taback, Melanie Lynn Powis, Alejandro Gonzalez, Lingsong Yun, Rinku Sutradhar, Maureen E. Trudeau, Christopher M. Booth, Monika K. Krzyzanowska
Journal: Journal of Clinical Oncology (2017)

Purpose Routine evaluation of quality measures (QMs) can drive improvement in cancer systems by highlighting gaps in care. Targeting quality improvement at QMs that demonstrate substantial variation has the potential to make the largest impact at the population level. We developed an approach that uses both variation in performance and number of patients affected by the QM to set priorities for improving the quality of systemic therapy for women with early-stage breast cancer (EBC). Patients and Methods Patients with EBC diagnosed from 2006 to 2010 in Ontario, Canada, were identified in the Ontario Cancer Registry and linked deterministically to multiple health care databases. Individual QMs within a panel of 15 QMs previously developed to assess the quality of systemic therapy across four domains (access, treatment delivery, toxicity, and safety) were ranked on interinstitutional variation in performance (using interquartile range) and the number of patients who were affected; then the two rankings were averaged for a summative priority ranking. Results We identified 28,427 patients with EBC who were treated at 84 institutions. The use of computerized physician electronic order entry for chemotherapy, emergency room visits or hospitalizations during chemotherapy, and timely receipt of chemotherapy were identified as the QMs that had the largest potential to improve quality of care at a system level within this cohort. Conclusion A simple ranking system based on interinstitutional variation in performance and patient volume can be used to identify high-priority areas for quality improvement from a population perspective. This approach is generalizable to other health care systems that use QMs to drive improvement.
Changing treatment paradigms in the era of targeted therapies.
Authors: Philipp Marius Papavassilis, Edwin Herrmann, Laura-Maria Krabbe, Lothar Hertle, Martin Boegemann, Rudolf Moritz, Barbara Thielen
Journal: Journal of Clinical Oncology (2014)

518 Background: Our goal was to describe the change of treatment paradigms for metastatic renal cell carcinoma (mRCC) since targeted therapy became available in 2006. Methods: In this cohort population study we retrospectively investigated all mRCC patients who were treated with targeted therapy between 06/2006 and 06/2012 in the Department of Urology of the University of Münster. To distinguish nominal variables Fisher's exact test was used, in other respects Pearson's χ² test. For metrical variables the Mann-Whitney-U-Test was used. The log-rank test was chosen to derive differences between two or more groups with regard to survival. A p value &lt;0,05 was considered statistically significant. Results: 50/158 (31.6%) patients with a median follow-up of 362 days were initially treated with immunotherapy. The most often used second line treatment after immunotherapy was sorafenib (29 patients, 58.0%). As first line treatment sunitinib was chosen most frequently (68 patients, 63.0%). There was no statistically significant difference in survival between the patients who were treated with immunotherapy and those who were not (572 vs. 554 days, p=0,745). 134 (84.4%) patients received cytoreductive nephrectomy before systemic treatment start. Comparing the survival curves there was a significant survival benefit in favor of nephrectomized patients (632 vs. 169 days, p&lt;0,0001). Conclusions: After introduction of the new agents treatment paradigms have changed substantially. Immunotherapy is used only rarely. Cytoreductve nephrectomy should continue to be regarded as standard treatment.
Association of <i>COMT</i> and <i>TPMT</i> with treatment failure (TF), neuropathy (NTOX), and ototoxicity (OTOX) in patients with testicular cancer (TC) after cisplatin-based chemotherapy (CBCT).
Authors: C. Fung, D. J. Vaughn, N. Mitra, S. Vardhanabhuti, S. L. Ciosek, K. L. Nathanson, P. A. Kanetsky
Journal: Journal of Clinical Oncology (2011)

e15076 Background: Adult TC patients have variable treatment response and risk of NTOX and OTOX after CBCT. COMT and TPMT are important genes for cisplatin metabolism and are associated with OTOX in children after CBCT [Nat Genet, 2009]. We hypothesized that single nucleotide polymorphisms (SNPs) of these genes causing increased cisplatin metabolism may be associated with higher TF and lower risk of NTOX and OTOX in adult TC patients after CBCT. Methods: TC patients who had CBCT, ≥ 1 year of follow-up since diagnosis, and genotyping completed as part of a genome-wide association study were included for analysis. We analyzed 42 SNPs each in COMT and TPMT.TF was defined as incomplete response to or relapse after first-line CBCT. NTOX and OTOX were assessed using surveys adapted from existing questionnaire instruments. For each SNP and outcome, we used a test for trend across ordered groups to determine statistical significance (p ≤ 0.05). Odds ratio (OR) and 95% confidence interval (CI) estimates were determined by logistic regression. Results: Of 118 patients who met eligibility criteria to date, TF status was ascertained on 78 and toxicity surveys were completed by 41. We noted significant associations of TF with 3 SNPs (COMT: rs7287604, rs5993882; TPMT: rs10949476), the strongest of which was a 4-fold (OR=3.9, 95% CI 1.3, 12) increased risk for carriers of the rs5993882 minor allele (dominant model). As expected, we noted inverse associations of NTOX with 3 SNPs (COMT: rs4646316; TPMT: rs12194394, rs1886330) and OTOX with 5 SNPs (COMT: rs12158214, rs7289747, rs887201; TPMT: rs9396834, rs6938294), the strongest of which was a 10-fold (OR=0.13 95% CI 0.03, 0.71) reduced risk of OTOX for carriers of the rs6938294 minor allele. Associations were not confounded by host, tumor or treatment characteristics. Conclusions: Our preliminary results are the first to show associations of genetic variants of COMT and TPMT with TF, NTOX, or OTOX in adult TC patients after CBCT. Requests for completion of the toxicity surveys and review of medical charts is ongoing. These findings may allow us to identify TC patients at risk for these outcomes based on genetic markers.
Potential of surgery and chemotherapy in patients with second metastatic recurrence after R0-resection of colorectal liver metastases.
Authors: Kia Homayounfar, Annalen Bleckmann, Lena Conradi, Thilo Sprenger, Martin Niessner, Thomas Lorf, Heinz Becker, Michael B. Ghadimi, Torsten Liersch
Journal: Journal of Clinical Oncology (2012)

644 Background: Surgical resection is the standard of care for resectable colorectal metastases (CRM). Preoperative chemotherapy allows assessment of tumorbiology and has been shown to convert approximately 30% of unresectable patients into secondary resectability. In patients with second metastatic recurrence (SMR), complete (R0) resection of all metastases seems to be accompanied with a survival benefit. The role of chemotherapy is unclear. Methods: Between 01/2001 and 31/08/2011 R0-resection could be achieved in 178 patients with liver only CRM at our institution. 103 patients developed SMR 10.4 ± 8.9 months after R0-resection of hepatic CRM. Of these, 79 patients had perioperative 5FU-based chemotherapy for treatment of the primary tumor and/or first liver metastases. Median follow-up from diagnosis of SMR was 21 (range 1-80) months. Results: SMR occurred in 80 patients at a single site (48x liver, 18x lung, 14x other) and in 23 patients at multiple sites (11x liver and lung, 7x including lung, 4x including liver, 1x other). 9 patients refused therapy and received best supportive care. 42 patients with single site recurrence were scheduled for primary surgery. R0-resection could be achieved in 26 patients (62%). 52 patients were treated with 8.1 ± 8 cycles of 5FU-based chemotherapy (5x 5FU/FS, 21x FOLFOX, 26x FOLFIRI) extended by the EGFR-antibody cetuximab (n=9) or the VEGF-antibody bevacizumab (n=18). 9 of these patients were scheduled for surgical exploration. R0-resection could be achieved in 5 patients with single site and 2 patients with multiple site recurrence. Morbidity and mortality rates for all operated patients were 16% and 0%, respectively. 5-years DFS rate for R0-resected patients was 20%. 5-years OS rate were 43% for R0-resected patients versus 11% for patients with R1/2 resection and palliative therapy (p&lt;0.001). Conclusions: Surgical resection of SMR offers a survival benefit and became possible even in 7 of 52 patients (13%) initially treated by chemotherapy. Therefore, all therapeutic options should be used in patients with SMR to achieve R0-resection of CRM.
The association between the GOELAMS MCL-PET prognostic index and survival in patients treated with rituximab-hypercvad (R-HyCVAD) or high-dose therapy with autologous stem cell rescue (HDT/ASCT).
Authors: T. Feldman, A. R. Mato, T. Zielonka, S. D. Rowley, S. Goldberg, M. Donato, D. S. D. Siegel, K. Facchin, A. Campaiola, D. H. Vesole, C. Bejot, S. Stives, M. Curtin, M. Miller, H. Agress, D. Panush, P. Lizotte, P. Bhattacharyya, A. Pecora, A. Goy
Journal: Journal of Clinical Oncology (2011)

8050 Background: Prognostic models in MCL are still debated particularly in dose-intensive treatment approaches (R-HyCVAD or HDT/ASCT) since they include both age (med age dx, mid 60s) and performance status. Additional prognostic factors have been looked at including Ki-67 (MIB-1) and more recently PET scan. The GOELAMS group proposed a model to predict OS and PFS in MCL in the 1st-line setting based on a dichotomized SUV max (≤ 6 vs. >6 = 1 point) + IPI score (≤ 2 vs. >2 = 1 point) in 44 heterogeneously treated pts (3 groups: score 0-2). We sought to validate this approach in MCL pts treated in the 1st-line setting. Methods: Single center retrospective study to assess the clinical utility of the GOELAMS MCL-PET prognostic index in newly diagnosed MCL pts treated with R-HCVAD or HDT/ASCT using PFS and OS as 1° endpoints. PET-CT images were centrally reviewed to determine SUV max at diagnosis and response (International Harmonization Project in Lymphoma criteria) by 3 radiologists blinded to outcomes. Results: 83 pts (median age 58, range 35-74) with advanced stage (98% stage IV) MCL treated with 1st line R-HyCVAD (60%) or HDT/ASCT (40%) were indentified for this analysis. Overall treatment response (IWG) was 93% (76% CR + 17% PR). 60 pts had clinical and radiologic data available for the validation study. Median baseline characteristics: WBC 7.75 (range 2.5-918), Ki-67 30% (range 5-90%), IPI 3 (52% ≥3), MIPI 3.5 (40% int+high risk), SUV Max 7.8 (range 2.4-36.7). Estimated 3 year OS and PFS were 82% and 76% (med follow-up 35 months). Using Cox regression and Kaplan Meir survival analyses, the MCL-IPI-PET model did not stratify pts into 3 groups with distinct PFS (HR 1.3, p=.24 LR test) or OS (HR 3.1, p .13 LR test). Baseline SUV max was not an independent predictor of outcome in multivariate analysis (PFS: HR 1.4, p=.71, OS: HR 2.3, p=.29) when added to IPI. Conclusions: The MCL-IPI-PET model was not validated in our series of newly diagnosed MCL pts treated with intensive approaches. This study highlights the need to develop and validate models to identify pts at risk for inferior survival treated with dose-intensive approaches.
Psychosocial well-being assessment in women with breast cancer.
Authors: Rosana Gnanajothy, Jennifer Aileen Correll, Lindsay Leuthen Peterson
Journal: Journal of Clinical Oncology (2016)

207 Background: A breast cancer (BC) diagnosis can affect psychosocial wellbeing. The goal of the current study is to identify the severity of and specific risk factors for depression, anxiety, and quality of life impairment in a sample of BC patients. Early identification of at risk individuals can expedite appropriate referrals and interventions. Methods: Data from 53 female BC patients referred to a Behavioral Medicine service at a large academic medical center in 2013-2015 by medical providers who identified distress at routine clinic visits were analyzed. Patients completed the Center for Epidemiology Studies Depression Scale, State Trait Anxiety Inventory, McGill Pain Questionnaire, and the Short Form 12 Quality of Life Inventory as part of their initial assessment following referral. Demographic factors, disease and treatment related factors were analyzed for correlation with psychosocial wellbeing. Results: Mean age was 52. The majority of the population were Caucasian (79%), and 53% were married. All stages of disease were represented. Significant depression, anxiety and psychological quality of life impairment were seen in 53%, 50%, and 39% of patients respectively. There was a trend towards a significant difference in higher anxiety scores in patients who were not on chemotherapy (M=44.2, SD 5.4) compared to those on chemotherapy at the time of assessment (M=38.54, SD 9.3; t (51) = -1.94 p=0.077). A positive correlation was seen between depression and pain scores (r 0.294, p=0.038). Depression and psychological quality of life scores were negatively correlated (r -0.632 p&lt;0.001), as were pain and physical quality of life scores (r -.343, p 0.024). There was no correlation between higher rates of depression or anxiety with type of surgical intervention or stage of disease. Conclusions: Significant depression, anxiety and quality of life impairment were seen in a large percentage of BC patients referred to Behavioral Medicine for perceived distress, regardless of type of surgery and disease stage. Higher rates of anxiety were seen in patients referred while not on chemotherapy compared to patients who were on chemotherapy at the time of referral. Early referral is the key to proper identification and treatment of high risk individuals.
Osimertinib in Pretreated T790M-Positive Advanced Non–Small-Cell Lung Cancer: AURA Study Phase II Extension Component
Authors: James Chih-Hsin Yang, Myung-Ju Ahn, Dong-Wan Kim, Suresh S. Ramalingam, Lecia V. Sequist, Wu-Chou Su, Sang-We Kim, Joo-Hang Kim, David Planchard, Enriqueta Felip, Fiona Blackhall, Daniel Haggstrom, Kiyotaka Yoh, Silvia Novello, Kathryn Gold, Tomonori Hirashima, Chia-Chi Lin, Helen Mann, Mireille Cantarini, Serban Ghiorghiu, Pasi A. Jänne
Journal: Journal of Clinical Oncology (2017)

Purpose Osimertinib is an irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) selective for both EGFR-TKI sensitizing ( EGFRm) and T790M resistance mutations. AURA (NCT01802632) is a phase I/II clinical trial to determine the dose, safety, and efficacy of osimertinib. This article reports the results from the phase II extension component. Patients and Methods Patients with EGFR-TKI–pretreated EGFRm- and T790M-positive advanced non–small-cell lung cancer (NSCLC) received once-daily osimertinib 80 mg. T790M status was confirmed by central testing from a tumor sample taken after the most recent disease progression. Patients with asymptomatic, stable CNS metastases that did not require corticosteroids were allowed to enroll. The primary end point was objective response rate (ORR) by independent radiology assessment. Secondary end points were disease control rate, duration of response, progression-free survival (PFS), and safety. Patient-reported outcomes comprised an exploratory objective. Results In total, 201 patients received treatment, with a median treatment duration of 13.2 months at the time of data cutoff (November 1, 2015). In evaluable patients (n = 198), ORR was 62% (95% CI, 54% to 68%), and the disease control rate was 90% (95% CI, 85 to 94). Median duration of response in 122 responding patients was 15.2 months (95% CI, 11.3 to not calculable). Median PFS was 12.3 months (95% CI, 9.5 to 13.8). The most common possibly causally related adverse events (investigator assessed) were diarrhea (43%; grade ≥ 3, &lt; 1%) and rash (grouped terms; 40%; grade ≥ 3, &lt; 1%). Interstitial lung disease (grouped terms) was reported in eight patients (4%; grade 1, n = 2; grade 3, n = 3; grade 5, n = 3). Conclusion In patients with EGFRm T790M advanced NSCLC who progress after EGFR-TKI treatment, osimertinib provides a high ORR, encouraging PFS, and durable response.