tbuckley/cabot-search huggingface dataset:
Phenotypic differences among <i>RAS</i> mutational variations in colorectal cancer (CRC): Analysis of 1,001 patients in single institute.
Authors: Eiji Shinozaki, Yoshio Miki, Masashi Ueno, Masahiro Igarashi, Mitsukuni Suenaga, Keisho Chin, Masato Ozaka, Mariko Ogura, Daisuke Takahari, Takashi Ichimura, Takeru Wakatsuki, Nobuyuki Mizunuma
Journal: Journal of Clinical Oncology (2015)

649 Background: RAS mutation has been reported as a predictor of benefit from anti EGFR therapies in the recent sub-analysis of some large prospective trials, PRIME, FIRE-3 and so on. On the other hand, some in vitro experiments had identified the differences of capability of GTP bounding and colony formation according to KRAS mutational variations. It remains unknown whether there are phenotypic differences clinically among RAS mutational variations as potentially negative predictive factors for anti EGFR treatments. This study aimed to reveal the prevalence and the phenotypic differences of these variations in a large cohort. Methods: Consecutive patients of 1,001 CRC from January 2012 to October 2013 were analyzed in this study. Multiplex genotyping of EGFR pathway was performed on archival samples using Luminex Assay (MABGEN and GENOSEARCH Mu-PACK, MBL) for KRAS including codons 61,146 and NRAS. We examined the correlation among mutation variations; KRAS G12D, G12V, G13D and other exon2, exon 3 and 4 and NRAS, and clinical phenotypic features. Statistical analysis was conducted by chi-square test. Results: The incidence of mutations; KRAS G12D, G12V, G13D, other exon2, exon 3 and 4, and NRAS were 16.2%, 10.0%, 6.4%, 7.0%, 4.6% and 3.5%, respectively. So called all RAS mutations were occupied in 47% in this cohort. There was no significant difference of prevalence among mutational variations according to clinical feature as follows; clinical stage, gender, age. In histopathology, moderately differentiated type of G12D was more frequent compared with other type of mutations. The respective proportion of KRAS exon 3 and 4, and NRAS mutations for left sided primary was relatively higher than those for right sided, although the frequency of other mutations were higher in right side. Conclusions: According to our analysis there were not so large phenotypic differences among these RAS mutational variations except histology and localization of primary. Futher follow up of this cohort will provide more information about treatment outcomes in near future.
Patterns of recurrence after resection of intrahepatic cholangiocarcinoma: Results from a multi-institutional cohort of 449 patients.
Authors: Ioannis Hatzaras, Michael A. Choti, Richard D. Schulick, Sorin Alexandrescu, Carlo Pulitano, Bryan M. Clary, Andrew X. Zhu, Irinel Popescu, Hugo Marques, Eduardo Barroso, Cristina Ferrone, Todd W. Bauer, Dustin M Walters, T. Clark Gamblin, Kevin Tri Nguyen, Catherine Hubert, Jean Francois Gigot, Gilles Mentha, Timothy M Pawlik
Journal: Journal of Clinical Oncology (2012)

267 Background: Outcomes following surgical management of intrahepatic cholangiocarcionma (ICC) have largely focused on overall survival. Data on recurrence following surgery for ICC are limited. We sought to investigate rates and patterns of recurrence in patients following curative intent surgery for ICC. Methods: 449 patients who underwent surgery for ICC between 1973 and 2010 were identified from an international multi-institutional database. Clinicopathologic data, recurrence patterns, and recurrence-free survival (RFS) were analyzed. Results: Most patients had a solitary tumor (70%) with a median tumor size of 6.5 cm. The majority of lesions did not have vascular invasion (69%). Surgical treatment was &lt; hemi-hepatectomy (47%), hemi-hepatectomy (26%), or extended hepatectomy (27%). On pathology, 23% patients had lymph node metastasis and 18% had a microscopically positive (R1) margin. A subset of patients received adjuvant chemotherapy (32%) or chemoradiation (39%). While 5-year overall survival was 31%, 351 (78%) patients recurred with a median RFS time of 13.2 months. First recurrence site was intra-hepatic only (54%), extra-hepatic only (24%), intra- and extra-hepatic (22%). There was no difference in RFS based on site of recurrence (intra-hepatic: 11.2 months; extra-hepatic 11.6 months; intra- and extra-hepatic: 9.6 months; P=0.16). An R1 surgical margin (HR: 1.56, p=0.02) and neural invasion (HR: 1.55, p=0.02) were associated with overall recurrence, while male gender (HR: 1.70, p=0.011), &gt;50% liver parenchyma resection HR: 1.97, p=0.03), primary tumor size (1.05, p=.02), and poor differentiation (HR: 1.92, p=0.01, were associated with intrahepatic recurrence. Receipt of adjuvant therapy was not associated with risk of recurrence (P&gt;0.05). Conclusions: Over 75% of patients developed recurrence following curative intent surgery for ICC. The pattern of failure was distributed relatively equally with half of patients recurring with liver only disease while half had an extrahepatic metastatic site of recurrence. Future efforts need to be directed toward identifying more effective adjuvant regimens given the high rate of recurrence.
Does induction chemoradiation effect perioperative mortality and overall survival in patients undergoing pneumonectomy for non-small cell lung cancer?
Authors: J. Oxenberg, T. Li, B. Egleston, M. Goldberg, W. J. Scott
Journal: Journal of Clinical Oncology (2010)

7061 Background: Induction chemoradiation before pneumonectomy allows patients to achieve long term survival, increases resectability rates, and is proven to be safe in previously published studies. Unfortunately, the mortality and morbidity of pneumonectomy after induction chemoradiation is high. This study aims to compare pneumonectomy only with induction chemoradiation and pneumonectomy at our institution, assessing perioperative mortality and overall survival. Methods: Patients with non-small cell lung cancer and prior pneumonectomy at our institution from December 1993 until February 2009 were retrospectively reviewed and their information was entered into a generalized database. Propensity matching and Kaplan Meier Survival curves were used to evaluate perioperative mortality and overall survival. Results: 158 patients were reviewed, 50 patients underwent induction chemoradiation prior to pneumonectomy and 108 patients had only a pneumonectomy. For all patients, 30 and 90 day survival rates were 5.7% and 8.86% respectively. Mortality in the pneumonectomy alone group versus pneumonectomy and induction therapy was 4.63% and 8% respectively at 30 days (p=0.475), and 7.41% and 12% at 90 days (p=0.374). The Propensity Matching Scores showed no significant difference between overall survival of patients with and without induction therapy prior to pneumonectomy, with hazard ratios of 1.125 (unweighted) and 1.312 (weighted). No significant differences were found when Propensity Matching was weighted for mediastinoscopy, side, diabetes, hypertension, coronary artery disease, chronic obstructive pulmonary disease, histology, clinical stage. Conclusions: Although mortality rates for patients with pneumonectomies alone are shown to be lower than those with induction therapy at 30 days, 90 days, and overall, we find no significant difference. In specialized cancer centers such as ours, the overall mortality for pneumonectomies remains low. Additional details with subgroup analyses will be presented at the Meeting. No significant financial relationships to disclose.
Bone health in prostate cancer patients: A survivorship issue requiring intervention.
Authors: George A. Dawson, Anne Greener, Dalila Reyes-Dawson, Sheetal Malhotra, Sarah Weinbrom, Anudh Jain, Sadhana Reddy, Maria D. Kelly
Journal: Journal of Clinical Oncology (2014)

247 Background: In general, men are not routinely screened for bone health. Prostate cancer patients are at an increased risk because of treatment with androgen deprivation therapy (ADT). Unlike other patients diagnosed with a malignancy, they may survive a long time. Some risk factors include inadequate calcium, vitamin D deficiency, tobacco use and alcohol abuse. We implemented a pre-ADT program to mitigate the effects of ADT on bone health. This study evaluates the pre-existing risk factors and bone health by baseline DEXA scans pre-ADT initiation. Methods: We completed a chart review of 182 veterans referred to Radiation Oncology for curative treatment of prostate cancer from 2009 to 2013. Of those, 160 patients underwent baseline DEXA scans. Clinical variables analyzed were demographics, tobacco and alcohol use, vitamin D levels, incidence of AODM (adult onset diabetes mellitus), and calcium or vitamin D intervention. Descriptive statistics and bivariate analysis including Chi Square tests and odds ratios were carried out. Results: The mean age of the study participants was 66.6 years (range 47-82.8 years). Baseline DEXA scans were abnormal in 63% of patients, showing osteoporosis and/or osteopenia. Vitamin D levels were abnormal in 61% of patients- 26% of whom had normal DEXA scans. Twenty percent had a history of alcohol abuse, and 56% used tobacco; 33% had AODM. Smokers with an abnormal Vitamin D level were at increased risk of bone disease as compared to non smokers (OR 3.23, 95% CI 1.35-7.69 p&lt;0.01). Variables significantly impacting bone health were age (OR 1.087, p=0.012, 95% CI 1.018-1.161) and Tobacco use (OR 0.424, p=0.045, 95% CI 0.183-0.980). Almost 90% of the patients in this study had intermediate risk prostate cancer with an expected cancer specific survival of 85 to 90% at 5 to 10 years. Conclusions: Pre-ADT screening confirms the risk of underlying bone disease in this veteran population with an expectation of long term survival. Guidelines for treatment and prevention of bone disease should be implemented in all patients over age of 50. Particular attention should be paid to patients who underwent ADT. This can affect the quality of life in this group of cancer survivors.
Response to second-line chemotherapy (Ctx) in advanced urothelial carcinoma: A pooled retrospective analysis of the correlation between objective response rate (ORR) and progression-free survival (PFS) and overall survival (OS).
Authors: Anuradha Jayaram, MinYuen Teo, Raymond S. McDermott
Journal: Journal of Clinical Oncology (2014)

354 Background: Second-line ctx for advanced urothelial carcinoma (UC) constitutes a substantial unmet need. A commonly used endpoint in phase II studies is ORR, however it is unclear whether this translates to a benefit in OS and PFS. We previously examined pooled OS, PFS, ORR and DCR in second line ctx in advance UC. We now are now determining whether increased ORR correlates with improved PFS and OS. Methods: Published second-line studies were identified from PubMed between 1997- 2012 and were reviewed for data extraction. Pearson correlation coefficient was used to determine correlation between ORR and OS and PFS. Results: 25 prospective studies of second-line ctx for progressive advanced UC were identified (22 non-randomised, 3 randomised) (n= 1,297). The majority of studies (88%) were phase II. 12 studies investigated combination regimens and 13 studies monotherapy. All studies allowed adjuvant and primary chemotherapy as first-line but only 7 studies reported median time from last chemotherapy. The range of reported response rates were 1% - 29%. ORR is moderately correlated to PFS (r= 0.42 {0.01 - 0.71} p = 0.04) and OS (r=0.67 {0.39 - 0.84} p = &lt;0.01) in the entire cohort. When we compared the combination regimens to monotherapy the ORR was 27.7% versus 12.3% (p&lt;0.01). The reported response rate for monotherapy was 8.6% - 27.7% and there was no correlation between ORR and PFS (r=0.26 {-0.37 - 0.72} p=0.42) and OS (r = 0.35 {-0.25 - 0.76} p=0.24). Conversely with combination regimens, response rates were 7% - 60% and ORR strongly correlated to PFS (r= 0.78 {0.40 - 0.93} p =&lt;0.001) and OS (r=0.80 {0.43 - 0.94}, p=&lt;0.001). Conclusions: The analysis revealed that ORR translated to a survival benefit. In second line ctx for advanced UC, responses to combination therapy only yielded a survival benefit. This may be appropriate approach in patients with a good performance status.
Pancreatic cancer and diabetes mellitus: A retrospective cohort study.
Authors: A. Yacoub, E. Siegel, I. Makhoul
Journal: Journal of Clinical Oncology (2011)

4102 Background: Pancreatic cancer (PC) is the fourth leading cause of cancer death in the United States, with PC-related mortality of over 36,000 in 2010. The etiology of PC remains elusive. An association with diabetes mellitus (DM) has been suggested, but due to the inconsistencies of the epidemiologic studies addressing this association, a consensus has not been reached. Evidence is rising for hyperinsulinemia, which exists in Type II DM, as a risk factor for developing PC. We have studied the incidence of PC in two large cohorts of patients with and without Type II DM. Methods: This is a retrospective cohort study utilizing the health-care database maintained by the Veterans Integrated Services Network 16 (VISN16), which consists of 10 Veterans Health Administration (VHA) hospitals in the south-central USA. The two cohorts of the study consisted of a DM cohort of patients diagnosed with Type II DM between October 1st, 1996 and September 30th, 2006, and a control cohort of non-diabetics matched to DM patients by year of birth (YOB), gender, and VHA hospital. After 365 required cancer-free days on study, members of both cohorts were followed for the development of PC. Incidence during follow-up was compared between groups via stratified Cox regression with year of birth, gender, and VHA hospital as the stratification factors. Results: 322,614 subjects met inclusion criteria, including 110,919 DM subjects and 211,695 controls. Cohorts remained well-matched for gender (2.3% females in each) and YOB (medians of 1939 in each). The DM cohort had 124 PCs develop during 0.558 million person-years (MPY) of follow-up (222 PCs/MPY), whereas the control cohort had 140 PCs develop during 1.299 MPY of follow-up (108 PCs/MPY). Stratified Cox regression of PC incidence yielded a hazard ratio (95% CI) of 2.17 (1.70–2.77) for Type II DM compared to controls (chi-square =38.9, DF=1, P<10-9). Conclusions: This is one of the largest studies to examine the incidence of PC in patients with Type II DM. It shows a significantly higher incidence of PC in patients with DM. This study would provide a strong support for the etiologic role of DM II and hyperinsulinemia in the pathogenesis of PC.
In vitro chemotherapy profiling of well-differentiated midgut neuroendocrine tumors (NETs) based on individual patient tumor biomarkers analysis.
Authors: Yi-Zarn Wang, Jean P. Carrasquillo, Alexis Carimi, Elizabeth McCord, Maria M. Chester, Robert Ramirez, J Philip Boudreaux, Eugene Woltering, Daniel Raines, Lowell Brian Anthony
Journal: Journal of Clinical Oncology (2014)

235 Background: Midgut neuroendocrine tumors (NETs) are rare malignancies with indolent clinical courses. In general, they are well differentiated with most tumor cells in the G0 phase of the cell cycle, consistent with the poor response rate of NETs to chemotherapy in vivo. We hypothesize that insults, such as surgery, can drive NET cells from G0 into S phase and that biomarker analysis of individual patient tumors harvested and grown in the lab will provide useful practical guide for future intra and post operative adjuvant therapy. Methods: 97 well-differentiated midgut NET patients underwent cytoreductive surgery at our institution between 5/2012 and 10/2012. 148 surgical specimens were collected and submitted to a single commercial lab for processing. Primary tumors, lymph nodes and liver metastases were harvested and cultured. Their RNAs were then extracted to analyze the expressivity a total of 88 different biomarkers. Based on our patients specific tumor biomarker expressivity and known correlations between 36 anti-neoplastic agents with their linked biomarkers, recommendations were reported as clinically benefit or lacking such benefit. Results: A total of 148 specimens from 97 patients were tested. In four of the 97 patients, no clinically beneficial chemotherapy agent could be identified. Among the remaining 93 patients, the top three agents that are most likely to be clinically beneficial are: Fluorouracil, Cisplatin and Carboplatin. These were reported to be clinically beneficial in 135/148 (91.2%), 103/148 (69.6%), and 103/148 (69.6%) patients respectively. Conclusions: Midgut NETs are slow growing tumors which are chemotherapeutically inert owing to the fact that most of the tumor cells are in G0 cell cycle. Surgical insult drives NET cells into active synthetic phase where they begin to express biomarkers specific to their tumor cells. Analysis of these biomarkers guides further potential beneficial therapy based on the current known associations among biomarkers and chemotherapy agents. These results must then be compared and confirmed against a direct in-vitro chemo sensitivity assessment conducted simultaneously on the same patients.
Incidence of FOLFOX induced amenorrhea in women age 40 and younger with colorectal cancer.
Authors: A. Cercek, D. L. Reidy, L. Saltz
Journal: Journal of Clinical Oncology (2011)

567 Background: The effects of oxaliplatin-based chemotherapy on female fertility are largely unknown. Studies have indicated that the incidence of young women diagnosed with colorectal cancer is on the rise, thus there is an increasing number of female colorectal cancer survivors of child-bearing age. Adjuvant FOLFOX chemotherapy is the most widely used standard treatment for stage III and high- risk stage II colon cancer. The objective of this analysis was to evaluate the incidence of amenorrhea as a crude measure of potential fertility in women age 40 and younger treated with FOLFOX. Methods: A search of computerized pharmacy records identified 45 women age 40 or younger who received adjuvant FOLFOX chemotherapy at Memorial Sloan-Kettering for stage II or III colorectal cancer from January 2002 and January 2009. Fourteen patient s had received pelvic radiation and 3 developed metastatic disease and were thus ineligible. A total of 28 patients were eligible and were mailed an anonymous questionnaire asking their age at time of diagnosis and specific questions regarding their menses pre-, during, and post-chemotherapy. The returned surveys were reviewed and the results tallied. Results: Of the 28 patients that met the eligibility criteria and were mailed the survey 16 (57%) returned the questionnaire. One patient had undergone bilateral oophorectomy and was ineligible. The majority of patients were 31-35 years old (range 21-40). All but one patient had regular pretreatment menses. Of the 15 eligible patients, 7 maintained their usual menses throughout chemo, 3 noted a change in their menses, and 6 lost their cycles. Only 1 (6%) did not regain her menstrual cycle 6 months after stopping chemotherapy. Conclusions: In this small retrospective study, the incidence of amenorrhea in young women treated with FOLFOX chemotherapy is quite low. Prospective studies are planned to more accurately characterize the impact of FOLFOX on female fertility. [Table: see text]
Who chooses palliative chemotherapy when a cure is possible? Results of a risk tolerance survey of laypersons.
Authors: Thomas William LeBlanc, Karen Scherr, Annabel Wang, Monica Lemmon, Peter A. Ubel
Journal: Journal of Clinical Oncology (2016)

35 Background: Many patients with acute myeloid leukemia (AML) face a difficult choice about whether to receive palliative chemotherapy or high-dose, potentially-curative chemotherapy that poses a risk of early death. How people weigh these factors in decision-making is unknown. We hypothesized that the possibility of cure primarily drives decision-making, regardless of treatment risk. Methods: We designed an electronic survey describing two treatment paths: (1) high-dose chemotherapy with possibility of cure but a 10% risk of early death, and (2) palliative chemotherapy with no chance of cure but no risk of early death. We recruited respondents via Amazon MTurk and presented 7 scenarios in random order, varying only the likelihood of cure associated with high-dose chemotherapy. Subjects rated their preferred treatment on a 4-point Likert scale. We assessed numeracy and attitudes toward chemotherapy using validated scales, and employed attention checks for quality assurance. Results: 100 subjects completed the survey (median age 30.5; 52 female, 85 Caucasian). 46 (46%) had at least a bachelor’s degree, and numeracy was generally high (median 4.75 out of 6). Respondents’ preferences for intensive chemotherapy varied with likelihood of cure, however some displayed a fixed preference for either curative or palliative treatment throughout, regardless of benefit level. For example, given a 50% likelihood of cure 20 respondents (20%) still preferred palliative therapy; similarly, with only a 1% likelihood of cure 28 respondents (28%) still preferred high-dose chemotherapy. In a multivariable model, preference for palliative chemotherapy was significantly predicted by subjects’ scores on the attitudes toward chemotherapy scale (p &lt; 0.001), controlling for age, education and numeracy. Conclusions: Contrary to our hypothesis, a significant proportion of subjects preferred palliative chemotherapy, even in scenarios where high-dose chemotherapy conferred a high likelihood of cure. Pre-existing attitudes toward chemotherapy appear to drive patients’ decision-making about even potentially curative treatments. This finding may have significant implications for risk communication in oncology.