tbuckley/cabot-search huggingface dataset:
Prognostic implication of intraoperative radiotherapy for unresectable pancreatic cancer.
Authors: T. Fujii, S. Nagai, Y. Kodera, M. Kanda, T. T. Sahin, H. Sugimoto, S. Nomoto, S. Takeda, S. Morita, A. Nakao
Journal: Journal of Clinical Oncology (2011)

346 Background: There is no established treatment strategy for unresectable pancreatic cancer, and the prognostic effect of intraoperative radiotherapy (IORT) is considered to be limited. Methods: We reviewed 614 surgical cases of pancreatic cancer and selected 198 cases that did not undergo pancreatectomy because of distant metastasis or locally advanced disease, at the Department of Surgery II, between July 1981 and June 2009. Liver metastasis was observed in 70 patients and peritoneal metastasis in 44. Treatment for those who were feasible consisted of IORT and/or postoperative chemotherapy. Overall survival and prognostic factors were evaluated for all patients and for each pattern of disease spread. Results: IORT was performed in 120 patients (61%), and chemotherapy was indicated in 80 (40%). Overall survival in the non-treatment group was significantly inferior to that for IORT alone and IORT plus gemcitabine (GEM)-based chemotherapy (median survival time: 3.2 months vs. 6.1 and 7.9 months; P = 0.0001 and &lt;0.0001, respectively). After multivariate analysis, IORT and GEM-based chemotherapy were identified as independent prognostic factors [hazard ratio (HR) = 0.51, P &lt; 0.001; HR = 0.43, P &lt; 0.001]. IORT was an independent prognostic determinant for patients with peritoneal metastasis (HR = 0.24, P = 0.011), whereas it was not for those with liver metastasis (HR = 0.78, P = 0.381). Conclusions: The prognostic value of IORT is most prominent in the peritoneal disease. IORT followed by GEM-based chemotherapy is possibly one of the most recommended treatment strategies in unresectable pancreatic cancer. No significant financial relationships to disclose.
Ten-year relative suvival for ovarian cancer.
Authors: L. Baldwin, R. Ware, B. Huang, T. Tucker, S. Goodrich, I. Podzielinski, C. P. DeSimone, J. Vannagell, F. Ueland, L. G. Seamon
Journal: Journal of Clinical Oncology (2010)

5113 Background: The overall 5 yr survival rate of ovarian cancer (OC) is 33.5%. Most of the patients alive at five years are alive with disease. Thus, 10 year survival may be a more appropriate endpoint. By definition, the relative survival (RS) rate adjusts for the general survival rate of the population for that race, sex, age, and date at which the diagnosis was coded. The 10 year RS for OC using SEER data has not previously been reported. Our objective was to measure RS in OC over ten years, stratified by stage, classification of residence, and surgery as the first course of treatment. Methods: Using the SEER 1995-2006 database, cases were identified using the International Classification of Diseases code for OC. Inclusion criteria included malignant behavior, first primary, actively followed, and age ≥ 20 years. Exclusion criteria included low malignant potential tumors, as well as death certificate or autopsy only cases. Using the actuarial life table method, RS over ten years was calculated, stratified by stage, classification of residence, and surgery as the first course of treatment. Results: 41,476 pts met inclusion criteria. Stage distribution was 23%, 9%, 41%, and 28% for stages I, II, III, and IV, respectively. The first course of treatment was surgery in 76%. The overall RS was 63%, 45%, and 37% at 2, 5, and 10 yrs, respectively. The largest decline over time was noted in stage III and IV disease. Interestingly, the slope of decline in RS was reduced for years 5-10 as compared with years 1-5 after diagnosis. RS at 5 years was 90%, 68%, 36%, and 17% for stages I, II, III, and IV respectively. The RS at 10 years was 85%, 59%, 24%, and 9 % for stages I, II, III, and IV respectively. RS was comparable for patients living in rural or urban settings. At all stages, patients who underwent surgery as their first course of treatment had better survival than those who did not have surgery. Conclusions: While advanced OC is associated with a poor prognosis, updated data demonstrates that survival rates adjusted for survival in the general population (RS) at 5 years are improved over historic reports and the calculated 10 year RS for stage III is higher than expected. This RS data provides the physician and the patient with more accurate prognostic information, particularly for advanced staged OC. No significant financial relationships to disclose.
When patients decide to stop chemotherapy and choose symptom-focused care: Patients’ perspective and concerns.
Authors: Ilona Fridman, Tanya Nikolova, Paul A. Glare, E. Tory Higgins
Journal: Journal of Clinical Oncology (2015)

28 Background: Patients often continue chemotherapy at the end of life, decreasing their quality of life without prolonging survival. Because humans tend to make emotional choices rather than rational ones when considering unpleasant options, patients are likely to reject hospice and other forms of symptom-focused care (SFC) when it could be beneficial for them. We explored patients’ perspectives on how they choose between continuing cancer treatment and SFC. Methods: Semi-structured interviews with 20 patients recruited from palliative care clinics at Memorial Sloan Kettering Cancer Center (MSKCC). Interviews covered patients’ decision-making process regarding further chemotherapy vs. SFC. Interviewees gave verbal consent, the MSKCC Institutional Review Board granting a waiver. Results: Two key conditions were identified as necessary for patients to choose SFC. First, the patient accepts that further chemotherapy is not going to be beneficial to them. Second, the oncologist endorses the transition to SFC. Preliminary analysis of treatment choices at the time of interview (see Table) also found many of those who expected they would benefit from further treatment experienced negative emotions when SFC was recommended. Conclusions: These data confirm the importance of raising prognostic awareness, and endorsing hospice. Further research should focus on developing communication techniques to recommend SFC in a way that helps patients who continue to want more treatment to calmly understand and consider carefully the advice being offered, rather than simply disliking it and quickly rejecting it. [Table: see text]
Quality of non-small cell lung cancer (NSCLC) care in the Veterans Health Administration (VHA): Impact of patient preference and clinical judgment.
Authors: J. J. Ryoo, B. Kim, D. L. Ordin, S. M. Oishi, S. M. Asch, A. L. M. Antonio, R. He, M. K. Gould, J. Malin
Journal: Journal of Clinical Oncology (2011)

6011 Background: A prior study using administrative data from 2001-2004 suggested VHA patients were less likely to receive cancer-directed therapy for NSCLC. We conducted chart reviews to assess VHA quality of NSCLC care and how often recommended therapy was foregone due to personal preference or clinical judgment. Methods: NSCLC cases diagnosed in 2007 were identified by VHA Central Cancer Registry. Exclusion criteria included death or hospice ≤30 days of diagnosis or clinical trial enrollment. Data were abstracted from medical records to calculate percent of eligible patients fulfilling quality indicator (QI) specifications: (1) resection for Stage I/II, (2) adjuvant chemotherapy for Stage II/IIIA, (3) chemoradiation for unresected Stage III, (4) platinum-based chemotherapy for Stage IV. Criteria for meeting QIs were receipt of recommended treatment, patient refusal, or contraindication – i.e., documented reason why specified care was inappropriate, including poor performance status (PPS). Results: Among 3414 eligible patients nationwide, QI performance was: Stage I/II resection 98%; Stage II/IIIA chemotherapy 80%; Stage III chemoradiation 88%; Stage IV chemotherapy 96%. Of Stage I/II patients, 7% refused surgery and 35% had a contraindication. Of resected Stage II/IIIA patients, 12% refused chemotherapy while 15% of unresected Stage III patients refused treatment and 57% had a contraindication to chemotherapy, radiation, or both. Chemotherapy was documented as inappropriate in 9% of advanced NSCLC patients; <1% refused it. Compared to white patients, higher proportions of black patients refused surgery or had PPS documented as a reason to forego it (p<0.01), though refusal and PPS rates did not differ by race for other treatments. Black patients were more likely to have a contraindication to radiation (p<0.01). Conclusions: VHA performance on NSCLC treatment QIs is higher than previously shown, though a substantial number of patients do not receive therapy due to refusal or reasons why specified care is inappropriate. Racial disparities may be explained, in part, by personal preference and contraindications.
Evaluation of relation between Onco<i>type</i> DX recurrence score and adjuvant chemotherapy administration.
Authors: D. R. Kazzaz, C. Chen, J. Shankleton, M. T. Forsyth, R. Ganesh, M. Sims, D. A. Patt
Journal: Journal of Clinical Oncology (2011)

e11105 Background: The Oncotype DX Recurrence Score (RS) is a clinically validated molecular test that can be used to predict the risk of distant recurrence and the likelihood of chemotherapy benefit among patients with newly diagnosed ER+ early stage breast cancer. By avoiding unnecessary chemotherapy use in patients with low Recurrence Score disease, toxicity and cost could be reduced. By giving chemotherapy to patients with high Recurrence Score disease, recurrences could be reduced. The objective of this investigation was to determine the relation between the RS and adjuvant chemotherapy utilization. Methods: Early stage breast cancer patients who were diagnosed between January 2008 and June 2009 with ER +, LN-, Her 2 non amplified tumors who were evaluated within the USON and registered within the EMR were included. Patients enrolled on clinical trial or treated for another cancer during the study period were excluded. Patients who received RS testing were evaluated utilizing three way contingency tables that evaluated adjuvant chemotherapy administration by age, ECOG PS, tumor size, and grade. Statistical significance of observed associations was evaluated using the Chi-squared, CMH, and Cochran-Armitage trend tests. Homogeneity of association across risk groups were evaluated using the Breslow-Day test. Results: 5,644 patients were included. RS results were obtained for 1,543 (27%) of these patients. 804, 590, and 149 patients had low, intermediate, and high RS respectively. 7.5%, 45%, and 86% of patients in the low, intermediate, and high RS groups received adjuvant chemotherapy, respectively. Three way contingency tables demonstrate chemotherapy administration for each category is higher among patients who are younger, have better PS, and have larger and higher grade tumors. Conclusions: Recurrence Score values were strongly associated with adjuvant chemotherapy administration. Chemotherapy administration was also higher among patients who had independent risk factors for recurrence including younger age, larger tumor size and higher grade tumors and among patients with better performance status.
Analysis of PTEN in patients with advanced colorectal cancer (CRC) receiving capecitabine alone or in combination with bevacizumab with or without mitomycin C in the phase III AGITG MAX trial.
Authors: Timothy Jay Price, Jenny Hardingham, Chee Lee, Joe Wrin, Amanda Rose Townsend, Kate Wilson, Andrew James Weickhardt, John Simes, Carmel Murone, Niall Christopher Tebbutt
Journal: Journal of Clinical Oncology (2012)

3534 Background: There is an urgent need for potential biomarkers for anti-VEGF therapies. The tumour suppressor gene PTEN is thought to have a potential role as a biomarker for anti-EGFR therapy in CRC, but there is also evidence that decreased levels of PTEN leads to increased expression of VEGF suggesting a potential relationship to outcome with anti-VEGF therapy*. The prognostic value of PTEN also remains controversial. Methods: Patients enrolled in the Phase III MAX trial of capecitabine (C) +/- bevacizumab (B) (+/- mitomycin C (M)) with available tissue were analysed for PTEN expression (loss v no loss) as assessed using a Taqman copy number assay to measure copy number variation at the PTEN locus. PTEN status was correlated with progression-free survival (PFS) and overall survival (OS) outcomes. The predictive value of PTEN status for bevacizumab efficacy was also examined. Results: Of the original 471 patients enrolled in the trial, tissue from 302 (64.1%) patients were analysed. Baseline characteristics of those with and without tissue were comparable. PTEN loss was observed in 38.7% of patients. There was no relationship between PTEN loss and KRAS or BRAF mutation. Patients with PTEN loss were more likely to have rectal primary (p=0.01) and less likely to have lung metastasis (p=0.03). By using the comparison of C v CB+CBM, PTEN status was not significantly predictive of the effectiveness of B for PFS or OS (Table). PTEN status is also not prognostic for PFS or OS in multivariate analyses adjusting for other baseline factors (Table). Conclusions: PTEN status did not significantly predict different benefit with anti-VEGF therapy. PTEN status was also not prognostic for survival in advanced colorectal cancer. [Table: see text]
Comparison of abiraterone acetate (Abi) versus ketoconazole (Keto) in patients (pts) with metastatic castration resistant prostate cancer (mCRPC) refractory to docetaxel (D).
Authors: Avivit Peer, Maya Ish-Shalom, Natalie Maimon, Maya Gottfried, Ben Boursi, Raya Leibowitz-Amit, Raanan Berger, Avivit Neumann, Svetlana Kovel, Avishay Sella, Roberto Pili, Hans J. Hammers, Victoria J. Sinibaldi, Michael Anthony Carducci, Mario A. Eisenberger, Daniel Keizman
Journal: Journal of Clinical Oncology (2013)

e16068 Background: Abi is a standard treatment (tx) in pts with mCRPC refractory to D. It is a potent and selective CYP 17 inhibitor, that blocks the synthesis of androgens in the testis, adrenal glands, and prostate. However, in many countries where abi has not been approved yet, keto is used as an alternative CYP 17 inhibitor. Although preclinical data suggests that keto is a less specific and potent inhibitor of CYP 17, there are limited clinical data comparing both agents. Aims: To compare the clinical effectiveness of abi vs keto in pts with mCRPC refractory to D. Methods: Records from 156 mCRPC pts treated with keto 200 - 400 mg 3x day, in 4 centers across the US and Israel, were reviewed retrospectively. 26 pts treated post D were individually matched by clinicopathologic factors to pts treated with abi (selected from a multicenter Israeli database, n=120). We compared the PSA response (decrease ≥50% from baseline), biochemical and radiological progression free survival, and overall survival between the groups. Progression free survival and overall survival were determined by Cox regression. Results: The groups were matched by Gleason score, pre-tx disease extent (limited-axial skeleton and/or nodal vs extensive- appendicular skeleton and/or visceral), ECOG PS, pre-tx risk category (favorable, intermediate, poor; Keizman, Oncologist 2012). Furthermore, they were balanced regarding median age (71 abi vs 69 keto), time from primary tx to disease relapse, time to progression on prior GnRH-a and antiandrogen, PSA response and time to progression on prior D, pre-tx pain score/alkaline phosphatase/hemoglobin/neutrophil to lymphocyte ratio/PSADT/PSA. In the groups of abi vs keto, PSA response was 46% vs 19% (OR 4.4, p=0.043), median biochemical PFS 7 vs 2 months (HR 0.65, p=0.02), median radiological PFS 6 vs 2.5 months (HR 0.63, p=0.016), median overall survival 17 vs 12 months (HR 0.53, p=0.79), and tx interruption d/t adverse events 12% vs 23% (0R 0.6, p=0.023). Conclusions: In mCRPC refractory to D, the outcome of pts treated with abiraterone was superior to ketoconazole.
Tandem mass technology: A helpful tool for proteomic research in breast cancer?
Authors: E. Ruckhäberle, T. Karn, L. Hanker, P. Schulz-Knappe, J. Schwarz, K. Engels, R. Gaetje, U. Holtrich, A. Rody, M. Kaufmann
Journal: Journal of Clinical Oncology (2010)

e21074 Background: Proteomic analyses has become a valuable tool in cancer research. The new tandem mass tag (TMT) technology was evaluated in breast cancer. Methods: Proteomic analysis was used to compare ER- positive and ER-negative samples. The results of the proteomic approach were validated by gene expression analysis and immunohistochemistry. Results: 18 proteins with significant differences in expression were identified. 14 proteins (e.g., TP, GSTP1, 14-3-3-protein, calreticulin, nucleolin, alpha-enolase, phosphoglycerakinase 3, thymosin-beta-like 3, rap-1b, transaldolase, thymosin-beta-10, actin cytoplasmic and protein-disulfid- isomerase) were overexpressed in ER-negative tumors and 4 proteins (e.g. decorin, mimecan, biglycan, ASPN) were overexpressed in ER-positive samples. All those proteins were characterized by relative high cellular abundance. Subsequently we validated our proteomic results on the level of mRNA expression in an independent microarray dataset (n = 119). We confirmed the significant higher expression for 12 out of 14 proteins in ER-negative samples and two of four proteins in ER-positive samples. Conclusions: The gel-free TMTduplex approach allows the quantification of differences in protein expression levels. Further improvement of the sensitivity by subfractionation of tissues should allow also the identification of low abundance proteins and might lead to a broader use in breast cancer research. No significant financial relationships to disclose.
Treatment and outcomes of neuroendocrine malignancies (NEMs) of the rectum.
Authors: Erica Tsang, Caroline Speers, Hagen F. Kennecke
Journal: Journal of Clinical Oncology (2014)

594 Background: NEMs of the rectum are rare and standard therapy is not well defined. We sought to characterize the clinicopathologic features, locoregional, and systemic management of a series of rectal NEMs and correlated these with outcomes. Methods: Patients referred to the BC Cancer Agency with rectal NEMs between 2005-2011 were included. Well-differentiated tumors with a Ki67 ≤20% and/or mitotic count ≤ 20 per high power field were classified as neuroendocrine tumors (NETs) while poorly differentiated tumors with higher Ki67 and/or mitotic count were classified as neuroendocrine carcinomas (NECs). Results: Of 28 NEMs, 18 (64%) NETs, and 9 (36%) NECs were identified with a median age of 56 and 59, respectively. Of 15 patients with stage I-III NETs, 13 underwent local excision, 2 had a surgical resection and none received pelvic radiation. Univariate analysis demonstrated an association between tumor size (&lt; 1cm, 1-2 cm, &gt; 2cm) and T stage (χ 2 = 10.7, p = 0.03). One of 15 NETs developed distant relapse 8.9 months after surgical resection of a T1bN1 tumor. Of 9 NECs, only 2 presented with stage I-III tumors and were treated with radiation (1) or surgery (1). One patient developed distant relapse 4.8 months after radiation. Among all NEMs, liver was the most common site of metastasis (n = 10) followed by bone (n = 3). Median overall survival was 46.5 and 4.8 months for NETs and NECs (p &lt; 0.01), respectively. Conclusions: Rectal NEMs comprise a rare subgroup of rectal tumors and may be classified as NETs or NECs. NETs generally present with early stage disease and are associated with good outcomes with local excision and without pelvic radiation. Rectal NECs frequently present with advanced disease and are associated with poor outcomes.
Early clinical adoption of next-generation sequencing panels for diagnosis of hereditary cancer susceptibility: A single commercial laboratory experience.
Authors: Neil M. Barth, Aaron Stuenkel, Elizabeth Chao
Journal: Journal of Clinical Oncology (2012)

37 Background: Genetic risk assessment and testing for patients suspected of inherited cancer susceptibility has become a standard of care in oncology services. Advances in molecular sequencing technology have facilitated the development of multi-gene hereditary cancer testing panels utilizing next-generation sequencing (NGS) methods. Appropriate utilization of these NGS panels by practitioners has been raised as a potential issue. In addition, patient stratification, safety and value-based resource allocation have been cited as possible areas of concern. In 2010, ASCO published updated guidelines for clinical utilization of genetic testing that included ordering based on appropriate risk stratification, informed patient consent, ordering by knowledgeable professionals, testing by a licensed laboratory, and results interpretation supported by counseling with qualified professionals. Methods: 467 patient samples submitted to a single commercial genetics laboratory for hereditary cancer testing by NGS panels were analyzed for compliance with guidelines based on information supplied with samples. Results: All samples were accompanied by an informed consent as part of the requisition. All samples originated from a licensed medical facility and all except one came from the domestic United States. Only 13.1% of providers ordering cancer predisposition testing utilized the NGS panels while 25.1% of organizations ordering cancer predisposition testing utilized the NGS panels. Genetic counselors were involved in 71.5% of the NGS panel orders, medical oncologists were involved with 32.5% of orders, and 24.8% of tests were ordered from practitioners of unknown clinical specialty. Samples from non-Caucasian minorities were under-represented based on national census demographics. Of the NGS samples from breast cancer patients, 90% were reportedly BRCA1/2-negative and median age at diagnosis was 42 years old. Conclusions: Early analysis of the clinical samples received by a single commercial laboratory for NGS hereditary cancer screening demonstrated conservative utilization with general adherence to recommended clinical adoption criteria.