tbuckley/cabot-search huggingface dataset:
Impacts of toxicity on patient treatment choices for metastatic breast cancer.
Authors: Carol B. White, Mary Lou Smith, Oyewale O. Abidoye, Deepa Lalla
Journal: Journal of Clinical Oncology (2012)

18 Background: Most patients with metastatic breast cancer (MBC) are treated with chemotherapy and/or targeted therapy with varying toxicity profiles. Experience with adverse events (AE) may vary and factor into subsequent treatment decisions. As newer agents and combinations become available, it becomes increasingly important to understand which AEs impact treatment decisions. Methods: The objective was to assess patient experience with AEs and preferences for future treatments. Following focus groups and pretests, an online survey was released by breast cancer organizations to recruit patients with MBC. The survey assessed the impact of experiences on future treatment choices and measured preferences via conjoint analysis (CA). Results: A total of 551 respondents completed the online survey. Among the AEs studied to assess their impact on either treatment stops or breaks, neutropenia topped the list, particularly for a required break. Fatigue, hand and foot syndrome, diarrhea, joint pain and peripheral neuropathy (PN) were high for chosen stops. Five AEs (fatigue, alopecia, diarrhea, PN, neutropenia) were studied extensively. Almost all respondents report experiencing fatigue, ~80% experienced alopecia, and ~66% each of the other 3 AEs. For each AE, the majority of respondents reported their prior experience would not impact a future decision involving the same AE; about 1/3 report they’d be more likely to take a treatment with the same AE; 8% to 18% would be less likely to take a treatment with the same AE. CA was also used to assess influence of the 5 AEs on future decisions. Within the tested ranges of likelihood, severity and duration, alopecia had the highest impact; PN, diarrhea, and neutropenia were in the middle; and fatigue was lowest. Further analysis is ongoing and final results will include differences in patient subgroups. Conclusions: This information informs priorities for development of new therapies allowing additional attention on AEs that matter most to patients. In addition, these results may generate discussion and consideration of patient preferences in conversations about care and treatment selection.
Interpretation of an online surgeon scorecard by the general public and its effect on adults changing cancer surgeons even when presented with complication rates that are statistically equivalent.
Authors: Christopher J. Weight, Lucas Labine, Isaac Palma, Colby Dixon
Journal: Journal of Clinical Oncology (2016)

83 Background: Recently Pro-Publica, an independent, non-profit newsroom, created a surgeon scorecard. This scorecard reports calculated death and complication rates for surgeons performing elective procedures in Medicare patients, including radical prostatectomy. We wanted to understand how the general population would interpret these data and whether it would influence surgeon choice. Methods: 265 adults at the Minnesota State Fair were recruited to participate in a survey requiring interpretation of a representative output graphic from the Pro-Publica website surgeon scorecard ( https://projects.propublica.org/surgeons ). The complication point estimate and 95% confidence intervals (CI) of a hypothetical surgeon, with whom survey participants were to assume that cancer surgery was already scheduled, were presented. They were also shown a graphic with 13 other surgeons point-estimate, complication rates, all of which fell within the index surgeon’s complication rate CI. Another surgeon, with a 0.6% lower point estimate, but statistically equivalent complication rate to the first surgeon, was indicated on the graphic. Participants were asked, based on this graphic alone, would they recommend switching surgeons? Results: The surveyed population was educated with 89% having attended, or graduated from college or higher (n = 235). Median age of participants was 50 years (Range 20-74). There were 179 females (68%) and 86 males (32%). Participants were from 136 different zip codes predominantly in the upper Midwest. 124 or 46.8% (95% CI 41-53) of respondents would recommend switching surgeons based on this single graphic. Conclusions: Nearly half of adults surveyed would recommend switching cancer surgeons for genitourinary malignancies based on data graphically presented on an online website, even though the point estimates between the two surgeons are not statically significantly different. This type of data display may lead to changes in medical decision-making based on random error of measurement of true complication rates not true differences in surgeon quality.
CD133 status influences in prognosis of patients with metastatic colorectal cancer receiving cetuximab.
Authors: Dai Inoue, Satoshi Matsusaka, Noriko Yamamoto, Mitsukuni Suenaga, Yuji Mishima, Eiji Shinozaki, Yasuhito Terui, Nobuyuki Mizunuma, Yuichi Ishikawa, Kiyohiko Hatake
Journal: Journal of Clinical Oncology (2012)

509 Background: Recently, the cancer stem cell (CSC) theory has been proposed, and CD133 has been suggested as a potential marker of CSCs in metastatic colorectal cancer (mCRC). Cetuximab, an IgG1 anti-EGFR chimeric mouse/human monoclonal antibody, has been approved for the treatment of mCRC. The purpose of this study is to evaluate the prognostic significance of CD133 expression in mCRC treated with cetuximab in combination with chemotherapy. Methods: We evaluated the prognosis of pts with mCRC treated with cetuximab retrospectively, and performed immunohistochemical staining to analyze the CD133 status. Non-parametric statistics, univariate and multivariate analysis were used. Results: From October 2008 to June 2009, 56 pts with measurable metastatic colorectal cancer were received cetuximab and 43 were evaluable. Patients characteristics were as follows : median age : 59.6 years (range 28-80) , PS 0/1 : 30/13 , colon/rectum : 28/15 , metastatic site (liver +/- : 35/8 , lung +/- : 32/11 , bone +/- : 6/37 , peritoneum +/- : 6/37 , lymph node +/- : 11/32 , local +/- : 3/40), best response rate was 9.3% (CR/PR/SD/PD : 1/3/19/11). Compared with CD133- pts with colorectal cancer , the progression-free survival (PFS) of CD133+ pts was significantly better (5.5 month; 95% CI, 4.4-6.7,p=0.026), and median overall survival (OS) was also significantly better (11.0 month; 95% CI, 5.4-16.5, p=0.002). In univariate analysis, liver metastasis, lung metastasis, peritoneal metastasis, lymph node metastasis, age, and CD133 at the baseline predicted PFS, and age, gender, liver metastasis, lung metastasis, bone metastasis, peritoneal metastasis, lymph node metastasis at the baseline, the presence of skin rash, and CD133 predicted OS. In order to evaluate the independent predictive effect of chemotherapy, multivariate Cox regression analysis was carried out. It showed that CD133 was the strongest predictor. Conclusions: CD133 status at the baseline was correlated with the prognosis of patients treated with cetuximab, suggesting that CD133 status might play a role to estimate the prognosis.
A preliminary report of irinotecan and carboplatin combination chemotherapy in extensive-disease small-cell lung cancer
Authors: H. J. Choi
Journal: Journal of Clinical Oncology (2005)

7283 Purpose: The combination chemotherapy of irinotecan and cisplatin has been previously reported to be effective in the treatment of extensive-disease small-cell lung cancer (ED-SCLC). We conducted a phase II trial of the combination chemotherapy of irinotecan and carboplatin in replace of cisplatin in untreated ED-SCLC to evaluate the efficacy and toxicities. Methods: From Jan. 2003 to Aug. 2004, 24 patients (pts) with previously untreated ED-SCLC were enrolled. Pts were treated with irinotecan (50mg/m2 i.v. on day 1, 8 and 15) and carboplatin (target AUC=5 i.v. on day 1) every 4 weeks for up to 6 cycles. Results: The pts characteristics were as follows: median age 63 yrs (range, 39–72 yrs), ECOG PS 0–1/2 13/9, male/female 22/2. Median 5 cycles of chemotherapy (range, 1–6 cycles) and total 105 cycles was given to pts. Twenty one pts were assessable for response and toxicity. The median follow-up duration was 8months (range, 4–23 months). By intent-to-treat analysis the overall response rate was 75% (1 CR, 17 PR and 3 PD). The median time to progression was 6 months (95% CI: 4–7months). The median response duration and overall survival time was not reached. Major toxicityis was myelosuppression. G3/G4 neutropenia and thrombocytopenia occurred in 12.4% and 6%, respectively. G3/4 non-hematoloic toxicities included diarrhea (3%), infection (2%) and nausea (3%). There was one treatment-related death because of superimposed infection on bronchopleural fistula. Conclusion: The combination chemotherapy of irinotecan and carboplatin was effective and tolerable in ED-SCLC. No significant financial relationships to disclose.
Exploratory <i>RAS</i> analysis of the phase Ib/II 20060447 trial of rilotumumab (R) or ganitumab (G) plus panitumumab (pmab) versus pmab alone in patients (pts) with previously treated metastatic colorectal cancer (mCRC).
Authors: Cathy Eng, Eric Van Cutsem, Elzbieta Nowara, Anna Swieboda-Sadlej, Niall C. Tebbutt, Edith P. Mitchell, Irina Davidenko, Oliver Lee, Kelly Smith Oliner, Marco Schupp, Elwyn Loh, Roger Sidhu, Josep Tabernero
Journal: Journal of Clinical Oncology (2015)

694 Background: Pmab, R, and G are fully human monoclonal antibodies that target EGFR, HGF, and IGF-1R, respectively. In part 2 of this 3-part study in previously treated pts with wild-type (WT) KRAS mCRC, pmab+R met the pre-specified criterion for improvement in objective response rate (ORR) whereas pmab+G did not. We report an exploratory analysis of the treatment effect of pmab, R, and G in pts with activating RAS mutations beyond KRAS exon 2. Methods: Part 2 was a phase II, randomized, double-blinded trial of pmab+R or pmab+G vs. pmab+placebo, administered Q2W until disease progression or intolerance. The primary endpoint was ORR. Secondary endpoints included overall survival (OS), progression-free survival (PFS), and safety. Mutations in KRAS exon 3 (codons 59/61) and exon 4 (codons 117/146); NRAS exon 2 (codons 12/13), exon 3 (codons 59/61), and exon 4 (codons 117/146); and BRAF exon 15 (codon 600) were detected by bidirectional Sanger sequencing. Results: Of 142 pts randomized, 92 (65%) were evaluable for RAS. Of 92 evaluable pts, 79 (86%) were WT RAS (WT in KRAS and NRAS exons 2, 3, and 4) and 13 (14%) had RAS mutations beyond KRAS exon 2 (mutant in any KRAS exon 3 or 4 or NRAS exon 2, 3, or 4). None of the pts with RAS mutations had an objective response (Table). Of 93 pts evaluable for BRAF, 7 (8%) had V600E mutations (all 7 were WT RAS). Two pts with BRAF V600E tumors had a partial response and were in the pmab+R arm (n=3). No new safety signals were identified. Conclusions: In this small, retrospective study, ORR, PFS and OS were similar between the arms of R or G plus pmab vs pmab alone in pts with WT RAS mCRC tumors. Our findings indicate that RAS mutations beyond KRAS exon 2 impact ORR, PFS, and OS. Clinical trial information: NCT00788957. [Table: see text]
EGFR mutation status and survival after diagnosis of brain metastasis in non-small cell lung cancer.
Authors: A. F. Eichler, K. T. Kahle, D. L. Wang, V. A. Joshi, J. A. Engelman, L. V. Sequist
Journal: Journal of Clinical Oncology (2010)

7542 Background: Non-small cell lung cancer (NSCLC) is the most frequent site of origin for brain metastases (BM), which affect 30%-40% of pts with advanced disease. A small subset of pts with NSCLC harbor mutations in the epidermal growth factor receptor (EGFR) that predict unique sensitivity to EGFR tyroskine kinase inhibitors (TKIs). The characteristics and behavior of BM in this population have not been well described. Methods: From August ‘04 to November ‘08, 373 NSCLC pts underwent EGFR mutation screening at our center; 93 of these developed BM at some time during their course. Clinical and treatment variables were collected by chart review. Survival was estimated using the Kaplan-Meier method and log-rank test. Multivariate predictors were assessed via Cox proportional hazards models. Results: Among the 93 pts with BM, 41 (44%) had an EGFR mutation, including 13 exon 19 del and 12 L858R. Brain was the first site of metastasis in 55/93 pts (59%) and the proportion did not differ by mutation status. 83% of pts with BM were treated initially with whole brain radiation, either alone (53%) or in combination with surgery (22%) or stereotactic radiosurgery (8%). 6 pts were treated with TKIs alone; all but 1 were EGFR mutant. Median survival from the time of BM was 10.5 mo. On univariate analysis, EGFR-mutated pts had prolonged survival after BM (12.0 mo vs. 7.3 mo, p = 0.05). Additional predictors of survival included age, performance status, number of BM and status of extracranial disease. On multivariate analysis, EGFR mutation status (HR 0.36, 95% CI 0.20- 0.63), age (HR 1.03, 95% CI 1.01-1.06) and active extracranial disease (HR 3.72, 95% CI 1.84-1.75) remained strong independent predictors of survival. The rate of development of leptomeningeal disease (7%) did not vary by EGFR mutation status, nor did the rate of intracranial recurrence. Cause of death was isolated intracranial progression in 9%; combined intra- and extracranial in 31%; and isolated extracranial in 38%. Conclusions: EGFR mutation status is a strong prognostic factor in NSCLC pts developing BM, independent of known prognostic factors including age, functional status, extracranial disease status and number of BM. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Gatekeeper Biogen Idec, Bristol-Myers Squibb, Daiichi Sankyo, GlaxoSmithKline, MedImmune, Millennium, Roche, Schering-Plough, Telik Novartis
Fibroblast growth factor receptor 1 (FGFR1) expression and activation in clear cell renal cell carcinoma (ccRCC).
Authors: T. H. Ho, F. Wang, A. Hoang, P. Tamboli, E. Jonasch
Journal: Journal of Clinical Oncology (2011)

e15015 Background: The fibroblast growth factor (FGF) family is involved in proliferation and angiogenesis and aberrant activation of the pathway is associated with tumor neovascularization. FGF pathway activation may also provide a compensatory mechanism for angiogenesis in the setting of vascular endothelial growth factor (VEGF) blockade. However, the prognostic impact of FGF pathway activation is unknown in ccRCC. Methods: A tissue microarray representing 40 untreated ccRCC specimens was constructed with unaffected kidney parenchyma controls and analyzed by immunohistochemistry (IHC). The Ariol imaging platform was used to stratify the specimens based on intensity of staining for FGF and HIF biomarkers (FGFR1, pFRS2, HIF1 and HIF2). Progression-free survival (PFS) was defined as the number of months from chemotherapy start until death or disease progression. The relationship between marker levels and PFS was analyzed using Cox proportional hazards regression methods. All p-values were 2-tailed and considered significant at alpha < 0.05. Analyses were conducted using SAS for Windows. Results: We identified that FGFR1 expression showed a significant association with PFS using a univariate model of Cox proportional hazards regression. FGFR1 was significantly associated with PFS, with the hazard of progression greater for patients who had tumors that were FGFR1 level 3 or 4 (HR 4.56, 95% CI 1.25 to 16.66, p = 0.0218) or FGFR1 level 2 (HR 3.54, 95% CI 1.02 to 12.29, p = 0.0463) relative to the hazard among patients who had tumors with FGFR1 level 1. Conclusions: Our data indicates that the subset of ccRCC tumors with increased expression of FGFR1 is associated with a shorter PFS. These results may be used to build predictive models that identify patients that would benefit from therapeutic strategies that target both VEGF and FGF signaling.
Circadian rhythm of breakthrough cancer pain.
Authors: A. Saini, M. Tucci, K. Bouraouia, P. Ghio, M. Tampellini, P. M. Furlan, L. Ostacoli, L. Dogliotti, A. Berruti
Journal: Journal of Clinical Oncology (2011)

e19529 Background: breakthrough pain (BTP) is a transitory flare of pain that occurs on a background of well controlled baseline pain. BTP is highly prevalent among patients with cancer pain treated with major opioids. The events of BTP are considered unpredictable, although some studies have provided preliminary data suggesting a possible circadian pattern of such events; the results are however contrasting. The aim of the present investigation was to assess the diurnal variation of BTP in two separate consecutive patient series. Methods: from December 2009 to February 2010, and from April 2010 to June 2010, two groups of consecutive patients attending a Medical Oncology Day Hospital, suffering from severe chronic pain and treated with major opioids were enrolled in the study. To each patient were administered a general pain questionnaire and the “diary of BTP”, consisting in a table in which the patient could record every event of BTP, if present, for the duration of seven days, by crossing the corresponding box of day and hour. Results: In group 1 were included 47 patients, 23 M and 24 F while in group 2, 76 patients, 37 M and 39 F. The primary malignancies mostly represented were breast, colon-rectum and prostate, while the main sites of metastases were bone, liver and lymph nodes. BTP was found in 41/47 patients in group 1 and 45/76 patients in group 2. At Cosinor analysis BTP events in group 1 showed a circadian pattern, with an acrophase at 13.45. (p<0.01). In group 2 similarly a circadian pattern emerged, with an acrophase at 10.45. (p<0.001). By dividing into two subgroups, for presence or absence of bone metastases, the circadian pattern was conserved: in group 1 patients with bone metastases had an acrophase at 11.55 (p<0.05), while those without bone metastases had an acrophase at 14.30 (p<0.05); in group 2 patients with bone metastases had an acrophase at 10.45 (p<0.01), while those without bone metastases had an acrophase at 10.15 (p<0.001). Conclusions: BTP showed a circadian pattern with peak in the same phase of the day in both pilot and validation series of patients. These results suggest that BTP events may be relatively predictable, and provide a rationale for testing the efficacy of boosting doses of immediate release opioid to prevent this event.
Long-term survivors (LS) of malignant pleural mesothelioma (MPM): An effort to gain knowledge of this uncommon biology.
Authors: F. Grosso, A. Roveta, T. Bensi, N. F. Trincheri, R. Libener, M. Pavesi, L. Giaretto, E. Piccolini, M. Botta, G. Bottero, D. Mirabelli, P. G. Betta
Journal: Journal of Clinical Oncology (2011)

e21033 Background: The median overall survival (OS) of MPM patients (pts) is 10-month. However a small number of pts survive beyond 24 months (mos) and are considered LS. Here we report on the clinical features of a series of LS MPM patients from an highly asbestos-polluted geographic area. Meanwhile, as part of a new work in progress, we are trying to identify some biological and molecular characteristics possibly associated with this favourable behaviour. Methods: We went through our MESO database of 397 cases diagnosed between march 2003 and december 2009 at Alessandria and Casale Monferrato Hospitals and screened 32 MPM pts whose survival was at least 24 mos (LS). These data were born out by the Piedmont mesothelioma registry. Paraffin embedded tumor tissue is available for immunohistochemistry and molecular studies (programmed necrosis and apoptosis, PDGFR and EGFR signalling pathways) in 25 pts. Moreover blood derivatives and primary cell lines from 9 and 6 pts respectively, are stored in the Alessandria MPM Biobank and are available for biological studies. (i.e. VEGF). Results: Median age at diagnosis was 60 years (range 43-79), histology was epithelioid in 30, sarcomatoid in 1 and biphasic in 1. 11 pts underwent EPP and 5 pleurectomy. 11 pts received neoadjuvant/adjuvant chemotherapy. 11 pts underwent radiotherapy. All pts but 1 received palliative chemotherapy (pCT), median number of pCT lines was 2 (range 0-6), best response to first pCT line was PD in 31% (10), SD in 40% (13), PR in 13% (4) and 16% were not evaluable (5). With a median follow-up of 51 mos the median OS was 38 mos (range 24-69). Conclusions: In these 32 LS MPM pts, except from epithelioid histology, we failed to identify any clinical feature that could stimulate further investigation. Though the small number does not allow any conclusion, it is intriguing that response to first line pCT seems to be lower than that reported in literature. This once more suggests that dimensional response is not the best surrogate for favourable outcome and prompts us to look for alternative prognostic factors. Tumor samples and fluid specimens from most of these pts are available. Molecular and biological studies are ongoing, and results thereof will be presented.
Timing of testing for <i>K-ras</i> mutational status in metastatic colorectal cancer (mCRC).
Authors: Mitra Corral, Michelle Sotak, Benjamin Chastek, John R. Penrod, Jessica Cairns, David A. Williams
Journal: Journal of Clinical Oncology (2012)

441 Background: The objective of this study was to examine physician perspectives on K-ras testing in mCRC at two time points: diagnosis of mCRC and after treatment failure. Methods: Interviews were conducted with 16 oncologists experienced in treating mCRC to obtain information on treatment patterns. Based upon the interview data, a two-round Delphi panel web survey was then used to obtain consensus on specific percentages of patients in a separate sample of 25 oncologists. Both samples were asked to respond to two scenarios: at metastatic diagnosis and after treatment failure. Results: The majority of interviewed physicians reported that they primarily test at diagnosis of mCRC versus later in treatment. Both the interviewed physicians and Delphi respondents said most patients have a tissue sample available at metastatic diagnosis for K-ras testing (Delphi median 90%, mean 81.2% at diagnosis, 78.8% after treatment failure). For patients without tissue, it was stated that a tissue sample would be obtainable in most patients (Delphi median 90%, mean 87.8% at diagnosis, 85.8% after treatment failure). Of patients with K-ras wild-type mCRC, the Delphi panel estimated that 75-80% would receive an EGFR inhibitor (mean 75.5% at diagnosis, 81.5% after treatment failure, median 80%) while only 0-5% of patients with K-ras mutated mCRC would receive an EGFR inhibitor (mean 4.6% at diagnosis, 5.3% at EGFR decision, median 0%). For a scenario where K-ras information is unknown, the Delphi panel estimated that a small percentage of patients may receive EGFR inhibitors (at diagnosis: mean 12.2%, median 5%; after treatment failure: mean 14.1%, median 0%) although it was noted this is uncommon and many insurers will not cover EGFR inhibitors without K-ras status. Conclusions: Current guidelines for mCRC recommend that K-ras testing be conducted as part of the diagnostic workup. In this study, two samples of oncologists reported that the majority of patients they treat are tested for K-ras mutations at metastatic diagnosis rather than later in therapy. Both samples reported minimal use of EGFR inhibitors in patients with K-ras mutated mCRC or patients with unknown K-ras status, consistent with clinical guidelines and many insurance policies.