bluuebunny/crossref_metadata_2025_split huggingface dataset:
CA19-9 and surgical margin status (SMS) associations with local-regional (LRF) and distant failure (DF) in patients (Pts) with pancreatic cancer: RTOG 9704 secondary analysis.
Authors: Regine William , Winter Kathryn A. , Kessel Ivan , Chen Yuhchyau , Fugazzi James A. , Donnelly Eric Donald , DiPetrillo Thomas A. , Narayan Samir , Plastaras John Peter , Gaur Rakesh , Delouya Guila , Suh John H. , Meyer Joshua E. , Haddock Michael G. , Didolkar Mukund S. , Padula Gilbert D. A. , Johnson David B , Hoffman John Parker , Crane Christopher H. 
Published: February 2017

347 Background: 9,704 was the first phase 3 pancreatic cancer trial to validate the prognostic value of postresection CA19-9 for overall survival (OS), with values > 90/180 associated with worse OS. All pts received adjuvant gemcitabine or 5-FU and chemo-radiotherapy (RT). This analysis evaluates patterns of disease failure. Methods: SMS was negative, positive, or unknown. CA19-9 was analyzed at cut points 90, 180 and continuously. LRF and DF were estimated by cumulative incidence and Gray’s test compared. Cox hazard models were used for multivariate analyses (MVA) and included treatment, tumor site, size and nodal status. To adjust for multiple comparisons a p-value < 0.01 is statistically significant and 0.01 to < 0.05 a trend. Results: 538 pts accrued, with 451 eligible and analyzable for SMS and 385 for CA19-9. For CA19-9, 132 (34%) were Lewis Antigen negative (no CA19-9 expression), 200 (52%) < 90 and 220 (57%) < 180. 188 (42%) had negative margins, 152 (34%) positive and 111 (25%) unknown (i.e., no margin comment in path report; shown to have outcomes similar to negative margin pts). Pts with CA19-9 ≥ 180 were more likely to have tumors ≥ 3 cm and pts with positive SMS more likely to have KPS 60 - 80, T3/T4, or N1 disease. On univariate analysis (UVA) CA19-9 cut at 90 was associated with significant increases in both LRF (trend) and DF; in the gemcitabine arm this was seen in DF, not in LRF; in the 5-FU arm it was seen in both. Results were similar at the 180 cut point and continuously. SMS on UVA was not associated with increase in LRF/DF; see Table. On MVA, CA19-9 > 90 was significantly associated with LRF and DF; positive SMS showed only a trend for DF. Conclusions: Postresection CA19-9 has significant association with both LRF and DF not seen with SMS. These findings support continued use of RT in trials and consideration of dose intensification among pts with elevated postresection CA19-9. Grants: NCI U10, CA21661, CA37422, CA180868, CA180822. Clinical trial information: 0000000. [Table: see text]
Do recurrent and de novo metastatic biliary tract cancer patients have the same outcome on treatment?
Authors: McNamara Mairead G , Aneja Priya , Maganti Manjula , Horgan Anne M. , Cleary Sean P. , Knox Jennifer J. 
Published: February 2017

351 Background: Biliary tract cancers (BTCs) include cholangiocarcinoma, which refers to cancers arising in the intrahepatic, perihilar or distal biliary tree, ampulla of vater and gallbladder carcinoma. Even after complete surgical resection, a large number of BTC patients develop recurrence. Whether recurrence after surgery and de novo metastatic BTC should have comparable stratification in first-line palliative systemic therapy clinical studies is unknown. Methods: 480 patients who received palliative chemotherapy as first-line treatment for advanced BTC between January 1987 and May 2014 in Princess Margaret Cancer Centre, Toronto were reviewed. Probability of overall survival (OS) was estimated using the Kaplan-Meier method, and independent prognostic factors for OS were identified using the multivariable Cox proportional hazard model. Results: There were 171 recurrent and 309 de novo metastatic patients. Median age at diagnosis was 62 years, performance status<2; 436 (91%) patients, male; 262 (55%). In the recurrent group, 91 (53%) had indwelling stents, ampulla of vater; 50 (29%), gallbladder; 29 (17%), cholangiocarcinoma; 92 (54%). In the de novo metastatic group, 185 (60%) had indwelling stents, primary site was ampulla of vater; 16 (5%), gallbladder; 94 (30%), cholangiocarcinoma; 199 (65%). Systemic treatment received was gemcitabine/platinum doublet in 134 (28%), gemcitabine/5-FU doublet; 186 (39%), gemcitabine; 97 (20%), other; 63 (20%). Median OS for the recurrent group who received first-line palliative chemotherapy was 15.6 months (95% confidence interval [CI] 13.5-18.0) and 14.4 months (95% CI 12.0-16.0) in the de novo metastatic group. Multivariable analysis for OS revealed that gallbladder as the primary site (P=0.03) and ECOG performance status ≥2 (P=0.001) were prognostic for worse OS. De novo metastatic status was not prognostic for worse OS compared with recurrent status (Hazard ratio 1.1, 95% CI 0.82-1.50, P=0.51). Conclusions: Similar treatment of patients with recurrent disease after surgery and de novo metastatic BTC, with first-line palliative chemotherapy is acceptable.
Chemotherapy for surgically resected intrahepatic cholangiocarcinoma: Influence of lymph node status on treatment efficacy.
Authors: Miura John Thomas , Johnston Fabian McCartney , Tsai Susan , George Ben , Thomas James P. , Christians Kathleen K. , Turaga Kiran , Pawlik Timothy M. , Gamblin T. Clark 
Published: February 2017

353 Background: High rates of recurrence following surgery (S) for intrahepatic cholangiocarcinoma (ICC) have prompted treatment strategies that incorporate chemotherapy (CT). However the benefit of CT remains poorly defined. The present study sought to determine the survival impact of CT for surgically resected ICC. Methods: Patients with non-metastatic ICC that underwent curative intent surgery (R0) were identified from the National Cancer Database (1998-2011) and stratified by receipt of CT. Log rank tests and cox proportional hazards models were used to examine overall survival (OS). Results: A total of 1,729 patients were identified (median age: 66 years, 53% female); 520 (30.1%) received CT. Patients receiving CT were younger (61 vs 66 years, p<0.01), had larger tumors (>5cm: 47 vs 40%, p<0.01), and had a higher frequency of lymph node metastasis (23 vs 12%, p<0.01). However, lymph node evaluation was not conducted in 30% (n=519) of the collective cohort. In the entire series, there was no difference in unadjusted median OS between patients receiving CT compared to S alone (30 vs 32 months, p=0.31). In multivariate models, advanced tumor stage and lymph node status (p<0.05) were associated with shorter OS. When stratified by lymph node status, CT demonstrated a significant improvement in median OS among N1 patients (HR: 0.47, 95%CI: 0.25-0.87; p=0.02). In contrast, patients with N0 disease derived no benefit from CT (HR: 0.95, 95%CI: 0.65-1.39; p=0.80). Conclusions: The use of CT was associated with a survival benefit only for ICC patients with nodal metastasis. Assessment of lymph nodes at the time of surgical resection is critical when attempting to identify a subgroup of patients best suited for CT.
Effect of dose-escalation of IMRT for unresectable pancreatic cancer 1 cm away from the luminal mucosa on long-term survival.
Authors: Crane Christopher H. , Chanda Awalpreet Singh , Koay Eugene Jon , Varadhachary Gauri R. , Das Prajnan , Javle Milind M. , Suh Yelin , Wolff Robert A. , Fleming Jason B. , Katz Matthew H. G. , Fogelman David R. , Shroff Rachna T. , Lee Jeffrey Edwin , Krishnan Sunil 
Published: February 2017

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 > 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]
Patient-reported outcomes after treatment for cancers of the pancreas and biliary tract.
Authors: Metz James M. , Vachani Carolyn , Hampshire Margaret K. , Hill-Kayser Christine E. 
Published: February 2017

375 Background: Pancreas and biliary (PBT) cancers are generally associated with poor overall prognosis, despite aggressive, multimodality therapy. The population of cancer survivors after these diagnoses may be largely ignored, despite risk of late effects. This Internet-based study seeks to evaluate patient-reported outcomes and survivorship care patterns after treatment of PBT cancers. Methods: Patient-reported data were gathered via a convenience sample frame from PBT survivors voluntarily utilizing a publically available Internet-based tool for creation of survivorship care plans. Available through the OncoLinkwebsite, the tool asks survivors to enter data regarding diagnosis, demographics, and treatments, and provides customized guidelines for future care. During use of the tool, PBT survivors are queried regarding late effects associated with specific treatments. Results: 134 PBT survivors utilized the tool from 2010-2014, 67% with pancreas cancer, 20% biliary, and 12% liver. Of the entire group, 59% were female and 81% Caucasian. Median diagnosis age was 59 and median current age 61. Average time since diagnosis was 2 years (range <1-8). Most reported having had multimodality therapy - 71% surgery, 78% chemotherapy, and 46% radiation. Most patients (70%) reported not receiving continued care from an oncologist, and >90% had never received previous survivorship information. Of 35 patients queried, 6 had metastatic disease and 7 had recurrent disease. When the entire group was queried regarding possible side effects of treatment, 44% reported persistent neuropathy, 24% chronic diarrhea, 21% bowel stricture or obstruction, and 15% chronic skin changes in the radiation portal. Conclusions: Although the prognosis after PBT cancers remains relatively poor, a population of long-term survivors exists. Survivors using this tool have generally not received survivorship information and most are no longer followed by an oncologist despite having received multimodality treatment. Neuropathy and gastrointestinal side effects appear to be the most bothersome to this group. This tool represents a potential way to provide information to underrepresented survivorship groups such as PBT survivors in the future.
Adjuvant therapy (Adj) in intraductal papillary mucinous neoplasm cancer (IPMN-Ca) versus pancreatic ductal adenocarcinoma (PDAC): Comparison of survival analyses.
Authors: Krishna Kavya , Krishna Somashekar Gopala , Bloomston Mark , Muscarella Peter , Schmidt Carl Richard , Conwell Darwin , Bekaii-Saab Tanios S. 
Published: February 2017

385 Background: Incidence of IPMN-Ca is increasing and due to lack of large prospective trials to evaluate optimal management of IPMN-Ca following resection, benefit of Adj is unknown. Methods: Retrospective review of patients (pts) who underwent pancreatic resection for invasive cancer from 2004 to 2012 at a single institution. Univariate and multivariate Cox regression models were used to determine association between different characteristics and survival. Results: From a total of 225 pancreatic resections (IPMN-Ca = 39, PDAC = 186), data regarding Adj was available in 179 pts (IPMN-Ca = 30, PDAC = 149). As shown in the Table, IPMN-Ca pts were less likely to receive Adj than PDAC (53% vs. 85% p = <0.001). There was no significant difference in tumor stage (stg) (early T vs advanced T) and Nodal stg (N0 vs. N1) distribution between pts who received Adj with IPMN-Ca or PDAC. Univariable survival analysis (SA): In PDAC, Adj improved overall survival (OS) (Hazard ratio [HR]: 0.46, 95% CI 0.28, 0.77), but there was no improvement in OS in IPMN-Ca pts with Adj (HR: 1.6, 95% CI 0.56, 4.64). Multivariable SA adjusting for age, Adj, resection margin, T, N stg: For PDACs, Adj was singularly associated with improved OS (HR 0.50, 95% CI 0.30, 0.82). In contrast, SA for IPMN-Ca did not reveal any significant contributing variable. For all pancreatic cancers, multivariable SA adjusting for IPMN-Ca vs. PDAC, age, Adj, resection margin, T, N stg revealed that a diagnosis of IPMN-Ca (HR: 0.52, 95% CI 0.30, 0.91) and a negative resection margin (HR: 0.65, 95% CI 0.43, 0.96) were significantly associated with better OS. Conclusions: Post resection, although pts with IPMN-Ca have better OS than PDACs, Adj fails to influence OS in IPMN-Ca pts. Larger studies are needed to confirm these findings. [Table: see text]
Octreotide LAR dosage and survival among elderly patients with distant-stage neuroendocrine tumors.
Authors: Shen Chan , Shih Ya-Chen T. , Xu Ying , Yao James C. 
Published: February 2017

392 Background: Octreotide long-acting repeatable (LAR) is approved for the management of symptoms due to carcinoid syndrome and may delay tumor progression among patients with neuroendocrine tumors (NETs). It is unknown whether dosage of octreotide LAR has an impact on survival. The current analysis evaluates the impact of initial octreotide LAR dosage on survival of elderly patients with NETs. Methods: Distant stage NET patients diagnosed between 1/1999 and 12/2009 who had received octreotide LAR treatment within 12 months of diagnosis were identified from the SEER-Medicare database. Those under age 65, enrolled in HMOs, or without continuous enrollment in Medicare Parts A and B were excluded. We compared the five-year survival of NET patients based on dose per 28 days averaged over the initial 3 months: Group A, <= 20 mg; B, 21 to 30 mg; C, > 30 mg. Kaplan-Meier estimations and Cox proportional hazard modeling were used to examine the association between octreotide LAR dose and survival. Results: Among 214 distant stage patients (mean and median age at 74 years old) with octreotide LAR treatment, 73 (34%) received <= 20 mg, 82 (38%) received 21 – 30 mg, while 59 (28%) received >30 mg. Median survival for patients who received low, medium and high dosage levels were 20.8 (95% CI: 13.2 – 31.5), 32.6 (95% CI: 20.5 – 51.1), and 36.3 (95% CI: 24.8 – N/A) months respectively. The log rank test had a p-value of 0.006. Multivariate analyses showed that higher octreotide LAR dosage levels were associated with significant survival improvement for distant stage patients. Compared to patients with the low dosage level, patients with medium dosage (HR=0.52, P=0.002) and patients with high dosage (HR=0.48, P=0.004) had better five-year survival. The difference in survival between Groups B and C was not statistically significant. Conclusions: This population-based study suggests potential survival benefits for octreotide LAR 30 mg dosage level among elderly distant stage NET patients.
Quality of life in RCT of pasireotide to reduce pancreatic complications following resection.
Authors: Eaton Anne , Gonen Mithat , Karanicolas Paul Jack , D'Angelica Michael Ian , DeMatteo Ronald P. , Kingham T. Peter , Jarnagin William R. , Allen Peter J. 
Published: February 2017

393 Background: A recent trial demonstrated that prophylactic pasireotide reduces pancreatic complication (PC) rates (primary objective). In this secondary analysis, we describe quality of life (QoL) in this population before and after resection using a standard instrument (the EORTC QLQ-C30) and the EORTC pancreatic cancer module (PAN26), which was recently developed to address the unmet need for QoL assessment in this subpopulation. Also of interest is assessing the association between PC and QoL and testing the hypothesis that pasireotide improves QoL. Methods: We conducted a randomized, double-blind, placebo-controlled trial of preoperative subcutaneous pasireotide in 300 patients undergoing pancreaticoduodenectomy or distal pancreatectomy. Participants completed the C30 and PAN26 preoperatively and on postoperative days 14 and 60. Scores were compared using paired t-tests. Results: All patients completed at least one questionnaire and 87% of patients completed all three. No major differences in QoL were seen between treatment groups so pooled results were reported. A significant worsening of function at 14 days was detected on all PAN26 and C30 function scales except hepatic and emotional functioning (EF), and all C30 symptom scales (all p<.01). These effects lessened by 60 days, but scores remained significantly worse than baseline with the exception of the sexuality, cognitive functioning, nausea and vomiting, insomnia and constipation scales, which returned to near baseline, and EF, which was significantly better than baseline (p=0.03). PC occurred in 45 patients and was associated with worse body image, dyspnea, financial difficulties and physical, role, emotional and social functioning at 14 and 60 days (all p<.05). Conclusions: During the first 14 days following resection, patients can be expected to have a significant decline in QoL. Many symptoms abate by 60 days, and EF improves. Although pasireotide effectively reduced PC, its effect did not appear to translate to improved QoL based on this sample of 300 patients. While PC was associated with worse QoL, most patients in both pasireotide and placebo groups did not experience PC, which may explain why no significant difference in QoL was observed. Clinical trial information: NCT00994110.
Characterization of unresectable cholangiocarcinoma patients treated with or without chemoradiation.
Authors: Rogers Jane Elizabeth , Nguyen Van , Nogueras-Gonzalez Graciela M. , Crane Christopher H. , Das Prajnan , Krishnan Sunil , Law Lindsey , Javle Milind M. , Kaseb Ahmed Omar , Shroff Rachna T. 
Published: February 2017

403 Background: Curative treatment for cholangiocarcinoma (CC) is surgical resection. Unfortunately, most CC patients (pts) present with unresectable disease in which gemcitabine plus platinum (GEM-P) chemotherapy is the mainstay of treatment (tx). Advanced CC has a dismal prognosis with 5-year survival reported at 5-10 %. Data regarding chemoradiation (CRT) in pts with unresectable CC (uCC) remains limited. Methods: We retrospectively reviewed uCC pts from 1/1/2009 to 7/31/2013. Primary objective: to evaluate the percentage of pts treated with CRT and the median number of chemotherapy cycles given prior to CRT. Secondary objectives: response to first-line tx, progression free survival (PFS) with or without CRT, overall survival (OS) with or without CRT, and duration of CRT control. Inclusion criteria: uCC diagnosis, received tx, and had follow-up at our institution. Exclusion criteria: pts who received liver-directed therapy other than CRT, mixed histology tumors, and a history of other malignancies. Results: 114 pts were included with 62% having intrahepatic CC. Disease control (DC) (response + stable disease) with first-line tx was 75% with 71% receiving GEM-P +/- erlotinib first-line. 65% of pts received CRT with a median of 6 chemotherapy cycles given prior to CRT. DC after CRT was 62% with a median duration of radiation control of 6.4 mths. Median PFS and OS for all pts were 13.4 mths and 27.8 mths, respectively. Median PFS in the CRT group was 14.5 mths versus 11.4 mths in the no CRT group (p = 0.105). Median OS in the CRT cohort was 29.4 mths, while median OS without CRT was 22.4 mths (p = 0.005). Median OS and PFS after CRT for pts with DC on first-line tx were 32.0 months (95% CI = 24-44 mths) and 15.7 mths (95% CI =13.5-18.8 mths), respectively. Pts who progressed on first-line tx and received CRT had a median OS of 23.8 mths (95% CI = 7-30 months) and median PFS of 4.2 mths (95% CI = 2.3-9 mths). Conclusions: Our retrospective review reveals a significant improvement in median OS with CRT in uCC pts. Those with DC on first-line tx showed improvement in PFS and OS with CRT. Patient selection is key with the benefit being highest in pts with DC with first-line tx. Our results warrant further investigation of the role of CRT in uCC.
Factors associated with increased incidence of toxicities following administration of yttrium-90 resin microspheres.
Authors: Roberson John , McDonald Andrew M. , Baden Craig Joseph , Jacob Rojymon , Burnett Omer L. 
Published: February 2017

409 Background: To further define factors associated with increased incidences of hepatic, constitutional, and gastrointestinal toxicities following administration of yttrium-90 (90Y) microspheres in a sequential cohort of heterogeneous patients. Methods: Fifty-seven patients who underwent 76 treatments were assessed for toxicity incidence following 90Y administration. Post-treatment clinical and liver function test (LFT) toxicities were assessed using Common Terminology Criteria for Adverse Events version 4.03. Binary logistic regression was used to evaluate the univariate effect of factors on toxicity incidences. A multivariate binary logistic regression model was performed for each toxicity using all factors with a p < 0.10 on univariate analysis. Results: Hepatic toxicities, including LFT toxicities, were present following 46.1% of treatments, while gastrointestinal and constitutional toxicities were present following 57.3% and 55.3%, respectively. Multivariate analyses revealed that colorectal adenocarcinoma, age at time of treatment, intraprocedural stasis, decreased Karnofsky Performance Status, increased body mass index (BMI), and decreased lung shunt were statistically significant (p < 0.05) predictors for increased incidence of toxicities most prevalent among our cohort. Increased pre-treatment laboratory values including albumin, alkaline phosphatase, total bilirubin, and white blood cells were also statistically significant predictors. Conclusions: Colorectal adenocarcinoma, declining functional status, decreased lung shunt, and increased pre-treatment laboratory values should be given more clinical attention when attempting to limit toxicities and improve the quality of life in patients following 90Y treatment. Specific constitutional, gastrointestinal, and hepatic toxicities including weakness, loss of appetite, and laboratory abnormalities are also associated with patients’ age, increased BMI, and intraprocedural stasis.