tbuckley/cabot-search huggingface dataset:
Effect of dose-escalation of IMRT for unresectable pancreatic cancer 1 cm away from the luminal mucosa on long-term survival.
Authors: Christopher H. Crane, Awalpreet Singh Chanda, Eugene Jon Koay, Gauri R. Varadhachary, Prajnan Das, Milind M. Javle, Yelin Suh, Robert A. Wolff, Jason B. Fleming, Matthew H. G. Katz, David R. Fogelman, Rachna T. Shroff, Jeffrey Edwin Lee, Sunil Krishnan
Journal: Journal of Clinical Oncology (2015)

354 Background: The use of chemoradiation (CXRT) for locally advanced pancreatic cancer (LAPC) is controversial. Delivery of high doses of RT capable of leading to local tumor control is challenging. We reviewed outcomes of treatement with dose-escalated IMRT with curative intent. Methods: Of 211 patients treated from 5/2006 to 8/2014 with CXRT for LAPC, 49(23%) had tumors &gt; 1 cm from the luminal organs ere selected for dose-escalated IMRT using integrated boost (SIB) technique, inspiration breath hold, and computed tomographic (CT) image guidance. Fractionation was optimized for coverage of gross tumor (GTV,Table 1). A 2-5mm margin on the GTV, was treated as an SIB within a microscopic dose. Forty-seven (96%) patients received a median of 4.0 months of induction chemotherapy and 45 (92%) received concurrent capecitabine or gemcitabine. Results: Mean GTV coverage was 86% (95% CI 78% to 94%). Median FU was 32 mo. Median OS and 1, 2, 3 and 5 year OS rates were 22.6mo (95% CI 16.4 to 43.9mo), 83%, 49%,38%, and 18% from the date of diagnosis and 17.8mo, 63%, 38%, 33%, and 18% from the start of RT. Degree of GTV coverage and Biological Equivalent Dose (BED) did not appear to affect outcome. Freedom from progression at 3 y were 40.6% (local) and 37.1% (distant). Acute toxicity was uncommon: grade 2 pain, diarrhea, anorexia, nausea or fatigue in 18 (37%), and grade 3 diarrhea in one patient (2%). Four patients (13%) required transfusion for anemia. One patient had a GI bleed possibly related to treatment. Conclusions: Dose-escalated IMRT across a BED range of 70-100Gy for inoperable patients selected with induction chemotherapy appears well tolerated and may improve the likelihood of long term survival. These results are similar to the best outcomes reported for patients after surgical resection. Incomplete high-dose GTV coverage does not appear to be detrimental. A randomized phase II trial is testing IMRT (RTOG 1201, 63Gy/28fx, with stratification by SMAD4 expression). [Table: see text]
Phase II study of i.v. vinflunine as second line in patients with metastatic breast cancer after anthracycline-taxane failure
Authors: P. Fumoleau, M. Campone, D. Vorobiof, M. Casado, P. Ruff, S. Khoo Kei, H. Cortes-Funes, S. Khalfallah, I. Caroff, C. Colin
Journal: Journal of Clinical Oncology (2004)

542 Background: The aim of this study was to assess efficacy and safety of vinflunine (Javlor), a novel semi-synthetic vinca alkaloid, in patients with metastatic breast cancer who have progressed on or after anthracycline-taxane based regimens. Methods: So far, from 60 patients enrolled, for this analysis, 52 patients have been evaluated for safety and 45 patients for efficacy. Median age was 55 years [33–75], median Karnofsky's Performance Status was 90% [70–100]. Visceral involvement was present in 45 patients (86.5%), and 38 patients (73.1%) had liver metastases. VFL was administered intravenously at 320 mg/m2 every 21 days.Results: A total of 228 cycles with a median of 6 cycles [1–12] were analysed. Dose reduction was required in 11.4% cycles (36.5% patients). Relative dose intensity was 96.3%[50.4–104.7]. Safety: Grade ≥ 3 main related toxicities were: neutropenia 37.1% cycles (63.5% patients), neutropenic infection 1.3% cycles (5.8% patients), constipation 5.7% cycles (19.2% patients), abdominal pain 3.5% cycles (13.5% patients), nausea 2.2% cycles (9.6% pts), vomiting 2.2% cycles (7.7% patients). No grade ≥3 related peripheral neuropathy was observed. Efficacy: Partial response (PR) confirmed by independent review was obtained in 16 out of 45 evaluable patients (35.6%) [CI95%22—50], and stable disease in 15 patients (33.3%). By an intent to treat analysis PR was 30.8% and median progression free survival was 4.2 months [2.8–4.8]. From 16 out of 45 patients with a progression free interval < 3 months after taxane exposure, 7 patients (43.8%) achieved a partial response. Conclusions: Vinflunine has a high level of activity after anthracycline-taxane exposure, even in patients considered taxane-refractory (progression free interval after < 3 months). Its toxicity was manageable and reversible. Further phase III development is planned. Updated results and PK data will be presented. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pierre Fabre Aventis Aventis Pierre Fabre
<sup>18</sup>F-Fluorodeoxyglucose positron emission tomography (FDG-PET) as a prognostic and predictive biomarker in metastatic colorectal cancer (mCRC)
Authors: P. A. Philip, S. Gupta, L. Heilbrun, D. Smith, B. El-Rayes, A. Shields
Journal: Journal of Clinical Oncology (2009)

e15037 Background: Information on the prognostic and predictive role of FDG-PET in the management of patients (pts) with mCRC is limited. The growing complexity of current therapies and the increasing number of agents to be tested in this disease warrants better understanding of the role of FDG-PET in earlier treatment decisions. Methods: Consecutive pts with 2 or more serial FDG-PET scans at baseline and during the treatment course were studied. Tumor standardized uptake value (SUV) and its percentage change (%ΔSUV) were each studied for their potential association with time to progression (TTP) via univariate Cox models to estimate the hazard ratio (HR) for progression. Results: 27 pts (median age 58.2 yrs) with mCRC were studied. 85% of pts were treated in the first line setting. 44% had received prior adjuvant therapy. 63%, 26% and 11% received oxaliplatin based, irinotecan based and fluropyrimidine only regimens, respectively. 85% received concurrent bevacizumab. Median pretreatment SUV was 9.0 (range 1.7 - 46.0); Median post treatment SUV was 3.4 (0–13.5); median %ΔSUV was -77.2 (range -10% to -100%). Mean interval between scans was 4.1 months. Ten (37%) patients had no tumor uptake on post treatment scans. 56% and 37% of pts had partial response and stable disease (RECIST criteria), respectively. Median TTP was 13.0 months (90% CI: 10.9 - 16.3 mos), with a median follow-up time for progression of 7.8 months. The HRs for baseline SUV and %ΔSUV were 0.972 (90% CI: 0.901 - 1.048, p=0.534) and 1.018 (90% CI: 1.003 - 1.033, p=0.049), respectively. The median TTP of patients whose post-treatment SUV reached zero was 13.8 months vs. 10.9 months (p=0.17) for pts whose post-treatment SUV did not reach zero. Conclusions: Systemic therapy significantly decreased the SUV on follow up PET scans in pts treated for mCRC. However, no significant association was seen between either baseline SUV or %ΔSUV and TTP. There may be a very weak statistical association of decreasing SUV with decreasing risk of progression. Further work is needed to optimize and standardize evaluation of tumor response in mCRC patients with FDG-PET. No significant financial relationships to disclose.
Association of gender, age, and ethnicity with survival in patients with pancreas cancer
Authors: M. Ottochian, D. Yang, A. El-Khoueiry, S. Iqbal, A. Pohl, W. Zhang, Y. Ning, H. J. Lenz
Journal: Journal of Clinical Oncology (2009)

e15587 Background: Pancreatic cancer (PC) is the fourth leading cause of cancer death in the United States. However little is still known about factors that influence its development and progression. Recent data suggest that PC is, at least in part, an estrogen- dependent disease; there is growing epidemiological evidence that aspects of reproductive history and hormonal exposure are associated with risk of this disease. It was shown that age at menarche of &lt;13 is associated with less risk of PC. However no data are available whether gender is associated with outcome in patients with PC. The purpose of this study was to test whether age, gender or ethnicity influence the outcome in PC. Methods: The data of the 50,302 adults diagnosed with PC between 1988 and 2004 were extracted from the Surveillance Epidemiology and End Results public use database. These included 24,240 patients diagnosed with localized pancreatic cancer (LPC) and 26,062 patients with metastatic pancreatic cancer (MPC). Demographic, clinical variables and survival time were retrieved. The primary endpoint was overall survival. We constructed Cox proportional hazards models to evaluate association between patient characteristics and survival in LPC and MPC separately. Pair interactions were also tested. Results: On multivariate analysis gender, age, race, marital status, tumor size, grade, histology, type of treatment and lymph node involvement were found to be independent predictors of survival. Females had a significant longer survival, with an HR of 0.959 (95% CI: 0.932–0.987) among patients with LPC and an HR of 0.918 (95%CI: 0.894–0.942) among patients with MPC. Each age group displayed a significant longer survival than its correspondent older age group. When we combined age and gender in the analysis, females had a longer survival than males in each single age group in the MPC group. In the LPC group the longer survival of female patients was only observed in the youngest age group. Conclusions: This is the first and largest study to address gender and outcome in PC. Our data suggest that the estrogen pathway may play an important prognostic role in patient with this disease. These data also warrant further in vitro and in vivo investigations on the mechanisms of estrogen and pancreas progression. No significant financial relationships to disclose.
Clinical efficacy of capecitabine as first-line chemotherapy in metastatic breast cancer
Authors: Y. Yap, A. Kendall, U. Banerji, G. Walsh, I. E. Smith
Journal: Journal of Clinical Oncology (2006)

10727 Background: Capecitabine is commonly used in metastatic breast cancer (MBC), but there are limited data on its efficacy in the first-line setting. The clinical efficacy of capecitabine monotherapy was evaluated in our institution. Methods: Patients who received capecitabine monotherapy (starting dose 1 g/m 2 twice daily every 2 out of 3 weeks) between April 2001 and April 2005 as first-line treatment for advanced disease were retrospectively identified from our prospectively maintained database. Endpoints included response rate (RR), response duration, time to progression (TTP) and overall survival (OS). Results: 63 patients were evaluated. The median age was 57 (30–79) years. The sites of disease were soft tissue and/or bone only in 24 (38%) patients, and involved visceral sites in 39 (62%) patients. 45 (71%) patients had previously received adjuvant or neoadjuvant chemotherapy. The median number of cycles administered was 5 (1–40). 48 (76%) had measurable disease with a RR of 29% (14/48). Chemotherapy-naive patients with measurable disease had a RR of 33% (5/15), while patients previously exposed to neoadjuvant or adjuvant chemotherapy had a RR of 27% (9/33). The median response duration was 24(9–68) weeks. The median TTP was 18 (range 2–122) weeks. However 12(19%) had a TTP of 9 months or more, including 7 (11%) with a TTP of &gt;1 year (14–28 months). Of these, 6/7 were oestrogen receptor +ve and 5/7 had bone and/or soft tissue disease only. 21 (33%) patients developed disease progression on treatment, and response was not evaluable in 4 (6%) patients who stopped capecitabine after 2 or fewer cycles due to medical co-morbidities. Conclusions: These audit results on first line capecitabine monotherapy in MBC are consistent with a previously published study (1) . The overall RR may be less than for anthracyclines and taxanes (generally 30–50%) in this setting, but for a subgroup of patients with predominantly soft tissue/bone disease capecitabine can result in prolonged TTP with minimal toxicity. This should be evaluated further in a randomized clinical trial. References 1. O’Shaughnessey JA et al. Ann Oncol 2001 Sept; 12 (9): 1247–54. [Table: see text]
Molecular markers to differentiate between pancreatic cancer and normal pancreas/chronic pancreatitis: Gene expression profiling study
Authors: M. Jarzab, M. Olakowski, M. Oczko-Wojciechowska, M. Kowalska, K. Fujarewicz, E. Chmielik, D. Lange, A. Świerniak, B. Jarz'ab, P. Lampe
Journal: Journal of Clinical Oncology (2007)

21150 Background: The aim of the study was to analyze the gene expression profile of pancreatic cancer by multivariate methods of class prediction. Methods: The snap-frozen or RNA-later preserved samples of 18 pancreatic adenocarcinomas, 9 chronic pancreatitis cases and 6 specimens collected from microscopically unchanged pancreas (N/CP) were analyzed by HG-U133 Plus 2.0 oligonucleotide microarrays (Affymetrix). The obtained dataset was pre-processed using GC-RMA method, gene selection was carried out both by class comparison methods (Welch test with Benjamini-Hochberg correction, False Discovery Rate FDR&lt;5%) and by our own algorithms of class prediction, based on Support Vector Machines technique (Recurrent Feature Replacement and Bootstrap-Based Feature Ranking). Real- time quantitative PCR (Q-PCR) was carried out on Applied Biosystems 7900 HT machine, with Universal Probe Library (Roche) fluorescent probes and normalization by three reference genes index (geNorm, Vandesompele et al.). Results: We compared gene expression profiles between pancreatic cancer samples and N/CP specimens. 23850 probesets significantly differentiated between these three classes (FDR&lt;5%). No ideal discrimination between cancer and N/CP samples was possible by any of single markers. We selected the optimal multi- gene classifier by Support Vector Machines, using Bootstrap-Based Feature Ranking method. The smallest classifier resulting in 100% accuracy consisted of three genes, 45 genes were included in more than half of the diagnostic genesets obtained during bootstrapping process. 14 genes were selected for Q-PCR validation, again none of them ideally discriminated between cancer and normal specimens, with the area under the receiver-operating-characteristic curve ranging from 0.82–0.93. Three-gene combinations allowed for proper classification of all samples. Conclusions: The multi-gene classifier, derived both by microarray technique and Q-PCR analysis, is properly discriminating between pancreatic cancer and chronic pancreatitis/normal pancreas. At least three genes must be included in the classifier to obtain satisfying accuracy. MO and MJ equally contributed to the study. No significant financial relationships to disclose.
Use of modified PCV chemotherapy as principal therapy for adults with incompletely resected or recurrent low-grade glioma: A retrospective review
Authors: E. B. Arenson, J. Bank, M. Pierick, C. Greenwald, J. McVicker, J. P. Elliott, J. D. Day, T. M. Fullagar
Journal: Journal of Clinical Oncology (2006)

1571 Background: In order to assess outcomes of patients treated with chemotherapy versus a more standard approach of radiotherapy (RT), we reviewed 48 patients with newly diagnosed, partially resected or recurrent low-grade glioma (LGG) treated between 1996 and the present. Methods: Patients were divisible into three groups: those treated with chemotherapy ± RT before (Group A, 28 patients) or after (Group B, 13 patients) radiographic progression, and those with recurrences after treatment with RT (Group C, 7 patients). Diagnoses included astrocytoma (23%), oligodendroglioma (48%) and mixed glioma (29%). 39 patients were treated with chemotherapy alone and 9 received post-chemotherapy RT. Chemotherapy consisted of PCV in one case; all other patients received modified PCV (MPCV) which variably included addition of carboplatin (200–360 mg/m 2 ) and etoposide (150 mg/m 2 ) and substitution of temozolomide (150 mg/m 2 × 5 doses) for procarbazine. The intent was to treat monthly for one year. Results: Patients received a mean of 10 courses of MPCV; 481 cycles were given. There were no deaths or admissions during chemotherapy. Grade III/IV toxicities occurred in 108 cycles (25 patients), 107 hem. and 1 GI. Late events included 1 case of MDS and 1 AML. There were no cases of disease progression during chemotherapy. Two patients stopped MPCV early, one because of worsening seizures (2 cycles) and one by personal preference (1 cycle); both died of disease. With median follow-up of 46 months (range 4–120) from initiation of chemotherapy, overall survival and progression-free survival were 89% and 79% for Group A, 91% and 83% for Group B, and 100% and 86% for Group C. Of 7 patients (15%) who recurred after completing chemotherapy, 2 have died; both had received post-chemotherapy RT and had clinical features of GBM. Four patients are either lost to follow-up (2) or alive with stable disease (2) following additional treatment. Conclusions: 1. MPCV is a tolerable regimen which can be given more aggressively than standard PCV. 2. There is minimal risk of early disease progression with MPCV. 3. Results support a prospective trial comparing MPCV to RT in patients with progressive unresectable LGG, and use of MPCV as salvage therapy for patients who fail RT. No significant financial relationships to disclose.
Point-of-care clinical decision support for cancer symptom management: Results of a group randomized trial.
Authors: Mary E. Cooley, Traci Blonquist, Paul Catalano, David Lobach, Ilana Braun, Barbara Halpenny, Ruth McCorkle, Michael Rabin, Ellis Johns, Kathleen Finn, Janet Abrahm, Donna Lynn Berry
Journal: Journal of Clinical Oncology (2014)

1 Background: Integration of palliative care into oncology is recommended for quality care. Clinicians may benefit from assistance in assessing and managing multiple symptoms. Palliative care clinicians have the expertise but may not be available or are not consulted early in the course of a patient’s disease. Clinical decision support (CDS) offers an innovative way to deliver symptom management and trigger palliative care referrals at the point-of-care. Methods: Twenty clinicians and their patients were randomized to usual care (UC) or CDS using the symptom assessment and management intervention (SAMI), which provided tailored suggestions for pain, fatigue, depression, anxiety and/or dyspnea. One-hundred seventy-nine patients completed a Web-based symptom assessment prior to each visit for 6 months. A tailored report provided a longitudinal symptom report and suggestions for management were provided to clinicians in the SAMI arm prior to the visit. Standardized questionnaires were administered to patients at baseline, 2, 4 and 6 months later to measure communication about symptoms and health-related quality of life (HR-QOL). The treatment outcome index (TOI) was the primary outcome for HR-QOL. Management of the target symptoms was assessed through chart review. Linear mixed models and logistic regression were used for analyses. Results: Patient characteristics were: mean age of 63 years, 58% female, 88% white, and 32% had &lt; HS education. No differences were noted in communication between patients and their clinicians. Significant differences were noted in physical well-being (p = 0.007, 0.08 adjusted for baseline) and a clinically significant difference in the TOI (62 vs. 68) at 4 months in SAMI as compared to UC. The odds of managing depression (1.6, 90% CI, 1.0-2.5), anxiety (1.7, 90% CI, 1.0-3.0) and fatigue (1.6, 90% CI, 1.1-2.5) were higher in SAMI as compared to UC. The odds of palliative care consults for pain (3.2, 90% CI, 0.7-13.4) appear to be higher in SAMI as compared to UC. Conclusions: Enhanced HR-QOL was noted among patients in the SAMI arm at 4 months. SAMI increased management of depression, fatigue and anxiety and appeared to increase palliative care consults for pain. Clinical trial information: NCT00852462.
Complications and effectiveness of combination chemotherapy in metastatic colorectal cancer (MCRC) with unresected primary (UP)
Authors: S. Abdal Raheem, B. Gupta, W. Tan, G. Wilding, J. Smith, G. Yang, A. Rajput, K. Bullard Dunn, M. G. Fakih
Journal: Journal of Clinical Oncology (2007)

14537 Background: The outcome of patients (pts) with MCRC and unresected primary (UP) has not been studied systematically in the modern era of targeted and combination chemotherapy. We conducted a single institute retrospective study to determine the rate and nature of complications in this population. Methods: MCRC-UP pts treated at Roswell Park Cancer Institute between 2002 and 2006 were identified. Demographic, toxicity, efficacy, and palliative intervention data were collected. Primary tumor related complications including obstructive symptoms, bleeding, perforation, and fistulas were assessed. Results: 24 pts with colonic UP were identified. 14/24 were treated with bevacizumab-based chemotherapy (11 FOLFOX, 3 capecitabine), 7/24 with FOLFOX, 2 with capecitabine, and 1 with FOLFIRI. No perforations, hemorrhagic events, or arterial events were noted. None of the 24 pts required palliative surgical intervention secondary to the UP. Only 2 pts developed obstructive symptoms and 1 pt developed an entero-cutaneous fistula; all 3 events were attributed to peritoneal carcinomatosis. 10 pts with rectal UP were identified. 1 pt received upfront chemoradiation followed by 5-FU/bevacizumab. 9/10 pts were treated with upfront systemic chemotherapy (6 bevacizumab-based [5 FOLFOX, 1 capecitabine], 3 FOLFOX). Of these 9 pts, 4 required subsequent palliative radiation therapy for obstructive symptoms (3 pts) or pain (1pt) while 5 continue on systemic chemotherapy (median 1 st line chemotherapy duration &gt; 7 months). No perforations, bleeding requiring transfusion, or arterial events were noted among the rectal cancer population. 1 pt required a diverting colostomy for obstruction despite palliative CRT. Median time to progression on first line chemotherapy was 7.4 months for colon cancer and 8 months for rectal cancer. The median overall survival was 13.6 months for colon cancer and has not been reached for rectal cancer (exceeded 13 months). Conclusion: Treatment of MCRC with UP is feasible and is rarely associated with complications related to the primary tumor. Rectal cancer with UP can be managed with upfront chemotherapy. Subsequent palliative RT is needed in about 50% of these pts. No significant financial relationships to disclose.
Gemcitabine in combination with intraperitoneal cisplatin in advanced hepatobiliary cancers
Authors: W. Liu, H. Zhang, D. Liu, Y. Xue, Y. Huang, X. Si
Journal: Journal of Clinical Oncology (2009)

e15666 Background: Standard chemotherapy for advanced hepatobiliary cancers remains undefined. This study was to observe the therapeutic effect of gemcitabine combined with intraperitoneal cisplatin for the treatment of advanced hepatobiliary cancers and analyze their toxicities. Methods: Patients with measurable hepatobiliary cancers were unrandomized into gemcitabine (GEM) + cisplatin (DDP) (GEM group) and epirubicin (EPI) + DDP (EPI group). GEM was used intravenously by infusion for 30 min with the dose to 1,000 mg/m 2 on day 1 and 8; cisplatin was infused intraperitoneal with a dose of 25mg/m 2 on day1, 3 and 5. Twenty-one days counted as one cycle. After 2 cycles, treatment efficacy and adverse events were evaluated according to WHO criteria. Results: A total of 76 patients were enrolled from May 2004 to May 2006, with 30 patients for EPI group and 46 patients for GEM group, and all the patients were eligible for effectiveness analysis. Among GEM group patients, there was no complete response. The partial response rate was 32.61% and clinical benefit response (CR+ PR +SD) was 67.39%. All those data mentioned above were significantly higher than that of EPI group. The main adverse re-ction was hematologic toxicity, while nonhematologic toxicity was mild. Conclusions: This study demonstrated that combination gemcitabine with intraperitoneal infusion of cisplatin was an effective and safety treatment for the patients with advanced hepatobiliary cancers. No significant financial relationships to disclose.