tbuckley/cabot-search huggingface dataset:
Reproduction rates prior to diagnosis of testicular cancer: Does the testicular dysgenesis syndrome exist?
Authors: M. Cvancarova, J. Oldenburg, M. Sprauten, H. Stensheim, S. D. Fossa
Journal: Journal of Clinical Oncology (2011)

4563 Background: Incidence of testicular cancer (TC) in Norway is approximately three times as high as 50 years ago and the highest world-wide. A “testicular dysgenesis syndrome” (TDS) comprising reduced fertility, cryptorchidism, hypospadias, and ultimately testicular cancer (TC) has been hypothesized. Therefore, rising TC incidence has been considered a “whistle blower” for declining male fertility. According TDS, pre-diagnosis fertility in males developing TC is lower than in the general male population. Methods: Each former TC patient diagnosed in Norway 1967-2007 (n=3.574) was age-matched with five controls from the general population (n=17.865). Complete fatherhood information was retrieved from the Medical Birth Registry. Unadjusted proportions of TC men with 1 child, > 1 child (stratified by seminoma/nonseminoma and unilateral/bilateral TC) were compared to those of the controls by Chi-square tests. Pre-diagnosis fertility rates ratios were calculated with conditional logistic regression, stratified by histology and uni-vs bilaterality thus adjusting for age and diagnostic period. Results: A slightly higher proportion of TC patients (44.4%, n=1,587) as compared to their controls (42.6%, n=7,602) fathered ≥ 1child prior to diagnosis, p=0.041.Overall, the proportions of TC pts having one, two or ≥ 3 children before their diagnosis were always higher compared to their controls, p=0.11. When stratified by histology the rates were OR=1.04, 95%CI [0.97-1.12], p=0.285 and OR=1.05, 95%CI [0.97-1.14], p=0.237 for seminoma and non-seminoma, respectively. For bilateral and unilateral TC the rates were OR=1.05, 95%CI [0.99-1.11], p=0.109 and OR=0.99, 95% CI [0.74-1.31],p=0.923, respectively. Conclusions: Fatherhood was slightly more frequent among men developing TC than in controls. Pre-diagnosis fertility rates of males who developed TC were similar to those of age-matched males from the general population. Interestingly, also males developing TC in both testicles did not have inferior fatherhood rates before diagnosis. These results challenge the appropriateness of the testicular dysgenesis syndrome.
Effect of combined neoadjuvant chemoradiation on overall survival for patients with locally advanced rectal cancer.
Authors: Zhifei Sun, Mohamed A Adam, Jina Kim, Shiao-Wen D Hsu, Manisha Palta, Brian G. Czito, John Migaly, Christopher Mantyh
Journal: Journal of Clinical Oncology (2016)

657 Background: Prospective randomized trials have demonstrated that neoadjuvant chemoradiation improves local control and results in a higher rate of sphincter-sparing surgery for patients with locally advanced rectal cancer. However, neoadjuvant therapy utilization and population-based outcomes are not well defined. Methods: Adults with stage II/III rectal adenocarcinoma within the National Cancer Data Base undergoing surgery between 2006-2012 were analyzed. Patients were grouped by type of neoadjuvant therapy received: no therapy, chemotherapy only, radiotherapy only, or concomitant chemoradiation. Multivariable modeling was used to compare perioperative outcomes and overall survival between groups. Results: Among 32,978 patients included, 9,714 (29.5%) received no neoadjuvant therapy, 890 (2.7%) chemotherapy only, 1,170 (3.5%) radiotherapy only, and 21,204 (64.3%) concomitant chemoradiation. 5-year overall survival among groups was 62%, 69%, 71%, and 74%, respectively. Compared to no therapy, chemotherapy or radiotherapy alone was not associated with any differences in perioperative or oncologic outcomes (all p &gt; 0.05). With adjustment for patient and disease characteristics, neoadjuvant chemoradiation was associated with a lower likelihood of margin positivity (OR 0.74, p &lt; 0.001), need for permanent colostomy (OR 0.77, 95% CI 0.70-0.85, p &lt; 0.001), 30-day mortality (OR 0.67, p = 0.003), and overall survival (HR 0.69, p &lt; 0.001). When compared to chemotherapy or radiotherapy alone, neoadjuvant chemoradiation was still associated with improved overall survival (vs. chemotherapy: HR 0.83, p = 0.04; vs. radiotherapy: HR 0.75, p &lt; 0.001). Conclusions: Neoadjuvant chemoradiation, not chemotherapy or radiotherapy alone, is important for sphincter-preservation and survival for patients with locally advanced rectal cancer. Despite this finding, one third of patients with locally advanced rectal cancer are failing to receive this therapy in the United States.
Risk factors for recurrence of optimally staged/debulked ovarian or tubal cancer patients with adjuvant paclitaxel/carboplatin combination chemotherapy
Authors: T. Kojimahara, K. Nakahara, M. Osakabe, M. Saitoh-Sekiguchi, T. Hayasaka, T. Motoyama, H. Kurachi
Journal: Journal of Clinical Oncology (2008)

16571 Background: This was an exploratory study to find the risk factors for ovarian or tubal cancer recurrence. Methods: Consecutive patients with stage II-IV optimally staged/debulked ovarian or tubal cancer patients with adjuvant paclitaxel/carboplatin combination chemotherapy treated in our department from August 2000 to July 2005 were retrospectively evaluated. The endpoint of this study was disease free survival. Those analyzed as risk factors for recurrence were; age, stage, histological type, residual tumor, interval between operation and first dose of chemotherapy, total course of chemotherapy before recurrence, dose and dose intensity (DI), basal and nadir levels of blood count (white cells, neutrophils, platelets, hemoglobin) and that of albumin. Colony stimulating factor (CSF) usage was also analyzed. Results: There were 25 cases with total of 139 courses of the chemotherapy that met the eligible criteria. There were 16 cases of recurrence. Median follow up for disease free patients was 24 months. Median age was 54 years. There were 4, 19, and 2 cases with stage II, III, and IV. Histological type consists of 11 serous, 4 endometrioid, 2 mucinous, 4 clear cell, 1 undifferentiated, and 3 carcinosarcoma. Median of relative DI of paclitaxel and carboplatin were both 0.85. There were 71 and 45 courses of grade 3 and 4 neutropenia, respectively. There were median of 6.5 days of CSF usage in all but one course. Multivariate analysis with cox proportional hazard model revealed that the prognostic factors for recurrence [hazard ratio; 95% confidence interval] were; neither serous nor endometrioid type histology; mucinous and clear [10.6; 1.98–56.8], undifferentiated and carcinosarcoma [43.0; 5.73–322], nadir neutrophil count fell below 210/mm3 [0.22; 0.06–0.83], and the case more than two-thirds of courses were with further neutropenia despite of CSF usage [0.10; 0.02–0.51]. Conclusion: Within these highly selected cases, the histological type is a prognostic factor. Furthermore, the severity of neutropenia during chemotherapeutic courses is also a prognostic factor that may be controlled by “optimize” dosage of chemotherapeutic agent. No significant financial relationships to disclose.
A phase II study of GM-CSF, IFN alpha and IL-2 in adjuvant setting for high-risk renal cell carcinoma patients
Authors: I. V. Tsimafeyeu, L. V. Demidov, V. Matveev
Journal: Journal of Clinical Oncology (2008)

16123 Background: Patients (pts) with high-risk RCC have a dismal prognosis. To date, no effective adjuvant therapy exists for this pts category. We suppose that combination of granulocyte-macrophage colony-stimulating factor (GM-CSF), IFNa and IL-2 stimulates immune system from dendritic cells to cytotoxic T-lymphocytes and eliminates residuary tumor cells. The primary end-point was median disease-free survival (DFS). Secondary end-points were progression rate, overall survival (OS) and toxicity. Methods: After radical surgery eligible pts with T3b-T4, or N1-N3, or M1 or T3a and tumor grade 3 were supposed to be disease-free. The interval between surgery and protocol therapy was 2–10 weeks. Pts received treatment during 6 months according to scheme: GM-CSF, 1 mcg/kg, 3 tiw, s.c., first week of each 1–6 months; IFN-a2b, 10 MIU, 3 tiw, s.c., second week of 1, 3, 6 months and 5 MIU, 3 tiw, s.c., second-third weeks of 2, 4, 5 months; IL-2, 1 MIU, 3 tiw, i.v. once a day, third week of 1, 3, 6 months. Fourth week of each month was free from treatment. Results: Between 5/2004 and 01/2006, 35 patients (28m/7f; median age = 46, range 21–71; ECOG 0; 12 (34.3%) pts with stage III and 23 (65.7%) pts with stage IV) underwent “radical” surgery and were treated with adjuvant cytokines for 6 planned months. Toxicity was minimal characterized by mainly flu-like syndrome (IFN) and erythema in injection site (GM-CSF). 3 pts (9,4%) had grade 2 hypotension (IL-2). There were neither hematological side effects no toxicity grade 3 or 4. At a median follow-up of 32.4 months, 21 (60%) patients have relapsed. Median DFS was 14.1 months. There was not a significant association between III and IV stages in median DFS (log rank p=0.2). Median OS has not yet been reached. Conclusions: These preliminary data do not demonstrate a marked improvement in DFS over historical controls. Low doses GM-CSF, IFNa and IL-2 during 6 months in adjuvant setting are feasible and tolerable. No significant financial relationships to disclose.
Relationship of pro-angiogenic factor Cyr61to colorectal cancer development and prognosis.
Authors: M. Baek, S. Bae, D. Jeong
Journal: Journal of Clinical Oncology (2011)

446 Background: Angiogenic factorCysteine-rich 61 (Cyr61) is a member of the CCN protein family that has been implicated in diverse biological processes such as cell adhesion, proliferation, angiogenesis, and tumorigenesis. An altered expression of Cyr61 is found to be associated with several human cancers. However, the correlation of expression of Cyr61 protein and clinical features of colorectal cancer remains unknown. Methods: Cyr61 expression in colorectal cancer and normal tissues was evaluated by Western blot analysis. Immunohistochemical staining was carried out using tissue microassay (TMA) to examine the expression status of Cyr61. Correlations of Cyr61 over-expression with various clinicopathologic factors were also determined. Statistical analysis was performed to explore the links between expression of the Cyr61 and clinicopathological parameters. Results: On Western blot analysis Cyr61 up-regulation was observed in colorectal cancer tissues (17/21, 80.9%). In 234 colorectal cancers, tumor tissue microarray revealed significantly up-regulated Cyr61 protein expression in colorectal cancer tissues versus normal tissues adjacent to tumor. Cyr61 expression was high in 136 of 234 cases of colorectal carcinomas (58.1%). Cyr61 over-expression was significantly associated with TNM stage (p=0.012) and regional lymph node involvement (p=0.018). Kaplan-Meier survival analysis showed that over-expression of Cyr61 was related to poor survival of colorectal cancer patients (p=0.031). But significant associations were not found between CYR61 expression versus tumor grade, age and gender. Conclusions: Our results suggest that Cyr61 is highly expressed in colorectal carcinomas and Cyr61 may play a role in the progression of colorectal cancers. Also, Cyr61 might be a new molecular marker to predict the prognosis and serve as valuable targets for therapeutic intervention of patients with colorectal carcinoma. No significant financial relationships to disclose.
Group medical appointments: A novel approach in patient education for adjuvant endocrine therapy.
Authors: Ann Vlahadamis, Melanie Danilak, Krista M. Rawson, Karen M. King, Edith Pituskin
Journal: Journal of Clinical Oncology (2013)

133 Background: Group medical appointments (GMA) are currently practiced for a wide range of medical conditions such as diabetes, hypertension, asthma, and cardiovascular disease. Previously, postmenopausal estrogen receptor positive breast cancer patients (ERBCP) attended individual physician clinic appointments to learn about their options for adjuvant endocrine therapy. This resulted in variable education provided, lengthy medical oncologist (MO) clinic visits and significant wait-lists to attend clinic. Accordingly, we embarked on a pilot program to determine the feasibility and acceptability of GMA in this patient population. Methods: Since 2010, ERBCP requiring endocrine therapy were referred and scheduled in the biweekly GMA program. Education regarding choices, risks, benefits and side effects of endocrine therapy were provided by a nurse practitioner (NP) and/or pharmacist (RX). After questions were solicited from the group, individual ERBCP were provided with prescriptions and scheduled for guideline-based follow-up. Results: Approximately 900 ERBCP have attended GMA, with 100% of MOs referring eligible patients. Surveys indicate high levels of satisfaction with the information provided and the GMA format. Conclusions: GMA provided by NP and/or RX is feasible and acceptable to both ERBCP and MOs. Health system benefits include increased efficiency and reduced cost, with MO clinic reserved for complex patient needs. Patient benefits include timely access to care and high levels of reported satisfaction. Future work will examine the effects of GMA on patient compliance and medication reconciliation with endocrine therapy.
A six-gene panel that predicts survival in men with castration-resistant prostate cancer.
Authors: S. K. Subudhi, G. Heller, A. Anand, D. C. Danila, M. Fleisher, H. I. Scher
Journal: Journal of Clinical Oncology (2011)

4539 Background: Patients with castration-resistant prostate cancer (CRPC) represent a heterogeneous group with survival times ranging from several months to over eight years. Circulating tumor cell (CTC) number is prognostic for survival. While patients with unfavorable (5 or more cells per 7.5 ml blood) counts have inferior survival times, the presence of a low count (4 or less per 7.5 ml blood) does not distinguish the patients who will succumb early to their disease and those who will not. Therefore, we have developed a RNA-based assay to address this issue. Methods: 45 genes from whole blood were evaluated as potential candidates for predicting overall survival in patients. 102 patients with progressive CRPC were identified at Memorial Sloan-Kettering Cancer Center (MSKCC). Whole blood from these patients was collected in PAXgene blood RNA tubes at the time of progression, and RNA was isolated using a PAXgene blood RNA kit (Source MDx). Expression analysis was performed on these samples, and a predictive gene signature for survival time was developed from the L1 penalized partial likelihood derived from the proportional hazards model. Results: Six genes were found to be jointly predictive of survival time. The genes and their relative risk coefficient are presented in the table below. The predictive accuracy of the joint model, characterized by the concordance probability estimate, is equal to 0.71 (standard error = 0.03). Conclusions: We have identified a 6-gene panel that predicts survival in our cohort of patients with CRPC. This panel will require validation in another cohort. Gene BCL2 C1QB CAV2 CD82 GAS1 NFATC2 RR 0.07 -0.46 -0.03 0.01 0.04 0.30
Perioperative chemotherapy in locally advanced gastric cancer in Chile: From evidence to daily practice.
Authors: Bettina G. MÃ¼ller, Carlos Garcia, Jose Antonio Sola, Carlos Benavides, Patrick Werner, Martin Buchholtz, Felipe Reyes Cosmelli, Alejandro Hernan Corvalan
Journal: Journal of Clinical Oncology (2016)

92 Background: Gastric cancer is the leading cause of cancer death in Chile, with mortality rate of 26.7/100.000 in men, placing the country among the highest mortality rates worldwide. For locally advanced gastric cancer, a multimodality treatment is recommended, but in Chile, the treatment covered by the public health insurance, which assists more than 70% of the patients, is surgery alone. We conducted an observational study to assess efficacy and toxicity of perioperative chemotherapy (CT) in public hospitals in Chile (NCT01633203). Methods: Patients with locally advanced, operable gastric carcinoma, defined as presence of invasion of serosa or beyond (cT &gt; 3 AJCC 2002) and/or lymph node metastasis (cN+) without distant metastasis (M0), were offered to receive preoperative CT with Epirubicin+Cisplatin+Capecitabine (ECX) regimen for 3 cycles followed by curative surgery with D2 lymphadenectomy. Staging abdominal CT scan was mandatory, laparoscopy was recommended. Patients with gastric retention, severe dysphagia or contraindications for CT were excluded. All patients signed the IRB approved informed consent form prior to enrolment. Data were collected using the OpenClinica platform. Results: Between August 2010 and March 2013, 110 patients were screened and 61 enrolled. Median age was 62 years (23-76 years) and most patients had good performance status at baseline (ECOG 0: 42, ECOG 1: 19). Tumor site was proximal in 24 (39%), medial in 16 (26%) and distal in 10 patients (16%). All but 4 patients (n = 57, 93%) completed three cycles of preoperative CT as planned. Fifty-five patients were operated and 54 (89%) had curative R0 resection. Of these, 36 (67%) had pT0-2, and 15 (28%) had pN0 tumors. A complete pathological response was found in 2 patients. Two patients were not operated for other reasons (one patient refused surgery and one patient presented a cerebrovascular accident during preoperative CT and died), and 5 patients (8%) progressed. As of September 1, 2015, 32 patients died. Three-year survival rate was 49%. Conclusions: Perioperative CT is feasible in public hospitals in Chile and should be offered as an alternative to primary surgery for patients with locally advanced gastric cancer.
National Comprehensive Cancer Network petitions: Submissions and outcomes.
Authors: Laura Bobolts, Dinah Faith Huff, William J. Hrushesky, Charles Lee Bennett, Kevin Knopf, Michael Baum
Journal: Journal of Clinical Oncology (2016)

248 Background: The National Comprehensive Cancer Network (NCCN) invites petitions to its scientific panels. Most ( &gt; 95%) are from the pharmaceutical industry lobbying to include their products in the NCCN Guidelines. Rarely, physicians request scientific scrutiny of the guidelines. We report the experience of Oncology Analytics (OA) with petition submissions and the possible impact on guidelines. Methods: From 2011-2015, OA made 7 petitions to NCCN. The content of each was tracked into subsequent NCCN Guidelines to ascertain whether any changes resulted. Results: 1) The Survivorship Panel was petitioned to add liposomal doxorubicin to the list of cardiotoxic anthracyclines: No changes were made. 2-3) The NSCLC Panel was asked in 2014 to remove the category 2A listing for trastuzumab and afatinib as HER-2 targeted drugs, and cabozantinib as a RET rearrangement target based on absence of phase I-III full text scientific literature. This was done, however, cabozantinib was reverted to 2A status late 2015 based on abstract-only data. 4) Per FDA approval, the NSCLC Panel was asked to recommend bevacizumab only in combination with carboplatin/paclitaxel for 1st line non-squamous NSCLC based on a survival advantage in ECOG 4599: No changes were made. 5) Given the FDA-approval, the Ovarian Cancer Panel was requested to add doxorubicin: This was done. 6) A 2012 Supportive Care Panel petition pointed out the absence of data supporting palonosetron as the preferred 5-HT3 antagonist with aprepitant for moderate or high emetic risk chemotherapy: No change was made upon request; however, preferred status was removed in 2015 from high emetic risk. 7) Based on a preponderance of evidence, a Supportive Care Panel petition requested re-categorization of the febrile neutropenia risk for carboplatin/paclitaxel from intermediate to low except in patients of Japanese ancestry and/or carboplatin AUC &gt; 6: This was done. Conclusions: Majority of NCCN physician petitions came from OA, yet constituted less than 5% of all petitions submitted. NCCN does not provide direct petitioner feedback, so we cannot say for certain that our petitions led to changes in subsequent guidelines. Not all requests resulted in NCCN changes, despite level one supportive data or accentuating an absence of data.
Outcome of advanced non-small cell lung cancer patients treated in a single institution with first generation platinum doublets. Using a retrospective analysis to help decisions in resource allocation
Authors: C. J. Andrade, C. G. Ferreira, J. L. Pereira, A. L. Porto, E. D. Freitas, H. C. Adriano, C. S. Rocha, E. B. Campos, E. D. Rocha, M. Zukin
Journal: Journal of Clinical Oncology (2005)

7342 Background: The benefit of chemotherapy in advanced NSCLC was established with first generation platinum based schemas. The new platinum doublets improve the tolerability but the magnitude of survival superiority was modest. New technology and drug incorporation in a public health service should be thoughtful for the best use of resources. Methods: We conduct a retrospective analysis of a subset of chemotherapy naive patients from data bank of administrative forms to funding treatments. Patients who receive treatment for advanced nsclc out of clinical trial were evaluated for survival, performance status, age, stage (IIIB vs IV) and type of chemotherapy. Results: We studied 163 patients. The median age was 59y (21 to 85). Median survival was 3,6 months in PS ≥ 2 and 8,5 months in PS < 2 patients (p=0,0001). In Kaplan-Meyer analysis, there were no difference in survival between stage IIIB and IV and age over or under 60 years. Also we do not identify any difference in survival when we combine platinum (CDDP or CDBCA) with VP16 by intravenous or oral route. Neither of these patients received second line chemotherapy. In a Cox analysis, high PS (HR=3.6, p=0,0001) and stage IV (HR=2.24, p=0.012) were independent poor prognostic factors. Conclusion: Although retrospective these data show there were not huge absolute differences in overall survival between the old and new platinum based schemas. In patients with PS 0 and 1 the magnitude of benefit was similar to newest generation doublets. A good selection of patients is critical for this. We believe that in a context of limited resources we should begin incorporating drugs that promote more significant changes in results. We will keep monitoring the results extending the number of evaluations. Economic analysis is on going. No significant financial relationships to disclose.