bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of adjuvant chemotherapy, chemoradiation, and chemotherapy followed by chemoradiation for resected stage I-II pancreatic cancer.
Authors: Ma Sung Jun , Hermann Gregory , Prezzano Kavitha M , Serra Lucas M , Iovoli Austin J , Singh Anurag K 
Published: January 2019

372 Background: Prior National Cancer Database (NCDB) studies have demonstrated an overall survival (OS) benefit for adjuvant concurrent chemoradiation (CRT) compared to chemotherapy alone. Given the more recent adoption of postoperative chemotherapy followed by concurrent chemoradiation (C+CRT), this NCDB analysis evaluates the clinical outcomes of C+CRT compared to CRT alone or adjuvant chemotherapy alone (C) for resected pancreatic cancer. Methods: The NCDB was queried for primary stage I-II, cT1-3N0-1M0, resected pancreatic adenocarcinoma treated with adjuvant C, CRT, or C+CRT (2004-2015). Patients treated with C+CRT were compared with those treated with C (cohort C) or with CRT (cohort CRT). The primary endpoint was overall survival (OS). Baseline patient, tumor, and treatment characteristics were examined. Kaplan-Meier analysis, multivariable Cox proportional hazards method, forest plot, and propensity score matching were used. Results: Among 5667 patients (n = 3031 for C, n = 1307 for CRT, n = 1329 for C+CRT), median follow-up was 34.7 months, 45.2 months, and 39.7 months for the C, CRT, and C+CRT cohorts, respectively. In the multivariable analysis for all patients, C (HR 1.31, p < 0.001) and CRT (HR 1.24, p < 0.001) were associated with worse mortality compared to C+CRT. Treatment interactions were seen among pathologically node positive disease. C+CRT was favored in 1-3 (HR 0.74, p < 0.001) and 4+ (HR 0.75, p < 0.001) positive lymph node disease when compared to C or CRT alone, but none of the treatment options were significantly favored in node negative disease (HR 0.96, p = 0.67). Using 1:1 propensity score matching, 2152 patients for cohort C and 1774 patients for cohort CRT were matched. C+CRT remained significant for improved OS for both cohort C (median OS 23.3 vs 20.0 months, p < 0.001) and cohort CRT (median OS 23.4 vs 20.8 months, p < 0.001). Conclusions: This NCDB study using propensity score matched analysis demonstrates an OS benefit for C+CRT compared to C or CRT alone following surgical resection of pancreatic cancer. Most of this benefit is in patients with positive lymph nodes.
Duodenal neuroendocrine tumors: Somewhere between the pancreas and small bowel?
Authors: Gamboa Adriana Carolina , Liu Yuan , Zaidi Mohammad Yahya , Lee Rachel M , Russell Maria C. , Cardona Kenneth , Maithel Shishir K. 
Published: January 2019

377 Background: While small sub-2 cm pancreatic neuroendocrine tumors (NETs) are often observed given their indolent behavior, small bowel NETs are routinely resected with a regional lymphadenectomy regardless of size given their malignant potential. Considering this variability, our aim was to define the natural history of duodenal (D-NETs) and determine the role of resection. Secondary aim was to define clinicopathologic factors associated with overall survival (OS) in pts who undergo resection. Methods: All pts in the National Cancer Database (2004-14) diagnosed with non-metastatic, non-functional D-NETs were included. Local resection (LR) was defined as local excision, polypectomy, or excisional biopsy. Anatomic resection (AR) was defined as removal with radical surgery. Tumor size was divided into three categories (< 1 cm, 1-2 cm, ≥ 2 cm). Propensity score weighting analysis was used to create balanced cohorts between resection and no-resection pts; this was maintained in all three size categories. Primary endpoint was OS. Results: Among 5,502 pts, median age was 65 yrs; 52% were male. Median f/u was 51 mos. Median tumor size was 0.8 cm. Resection was performed in 72% (n = 3954) of which 61% were LR and 39% were AR. At least one lymph node (LN) was retrieved in 25% of pts, of which 44% had LN metastasis. 74% had negative margins. Resection and no-resection cohorts were propensity score weighted for age, gender, race, Charlson-Deyo score, and tumor grade, all of which were independently associated with OS on MV Cox regression analysis, thus creating balanced cohorts. Resection was associated with improved median OS compared to no-resection (MNR vs 94 mos, p < 0.01); this persisted for all three size categories (< 1 cm: MNR vs 194 mos; 1-2 cm: MNR vs 56 mos; > 2 cm: MNR vs 90 mos; all p < 0.01). Subset analysis of each size cohort who underwent resection showed that neither type of resection, LN retrieval, LN positivity, or margin status was associated with OS (all p > 0.05). Conclusions: All pts with non-metastatic non-functional D-NETs should be considered for resection regardless of tumor size. Given their lack of prognostic value, the type of resection and extent of LN retrieval should be tailored to the patient’s clinical picture and safety profile.
Second-line chemotherapy in advanced biliary tract cancer: Who may benefit?
Authors: Salati Massimiliano , Caputo Francesco , Marcheselli Luigi , Rimini Margherita , Spallanzani Andrea , Gelsomino Fabio , Andrikou Kalliopi , Zironi Sandra , Di Emidio Katia , Clo' Vera , Luppi Gabriele , Cascinu Stefano 
Published: January 2019

381 Background: No established second-line treatment (2L) is available for patients (pts) with advanced biliary tract cancer (ABC) failing gemcitabine/platinum first-line chemotherapy (CT). However, 20-40% of pts are offered 2L CT in daily practice. We evaluated the impact of clinical and biochemical parameters on survival of ABC in order to identify factors aiding in 2L treatment selection. Methods: Medical records of consecutive ABC pts treated with 2L CT between 2005 and 2018 at the Modena Cancer Centre were reviewed. Log-rank test and multiple Cox proportional hazard regression were performed to assess the prognostic significance of covariates on OS. A prognostic score was developed from the multivariate model. Results: A total of 98 pts were identified and included in the analysis. Median (m) age was 63 years, 52% of pts were female, 75% had ECOG PS of 1-2. 72% of pts received first-line gemcitabine/platinum combination. In the 2L setting, 70% of pts received a doublet and the most common regimen was FOLFIRI (26%), followed by FOLFOX (20%) and fluoropyrimidine monotherapy (19%). Disease control rate was 39%, with 7% of objective responses. mOS and mPFS were 7.2 months and 3.5 months, respectively. At both univariate and multivariate analysis ECOG PS > 0 ( P= 0.002), peritoneum involvement ( P< 0.001), LDH > 430 UI/L ( P< 0.001), albumin < 3.5 g/dL ( P= 0.001), gamma-GT > 100 UI/L ( P= 0.001), PFS to first-line < 6 months ( P= 0.025), Na+ < 140 mEq/L ( P= 0.010), absolute lymphocyte count < 1000/uL ( P= 0.030) were significantly associated with shorter OS. By assigning to each of the 8 variables weight = 1, three different risk groups were identified: low-risk group (0-2 factors), intermediate-risk group (3-4 factors) and high-risk group (5-8 factors). mOS was 18, 9.4, and 2.9 months in the low-, intermediate-, and high-risk group, respectively ( P< 0.001). Conclusions: Our 2L study confirms the prognostic value of ECOG PS, PFS to first-line and peritoneal carcinomatosis, identifies novel biochemical prognosticators and proposes a readily-available and inexpensive score to risk stratify patients both in daily practice and clinical trials.
Efficacy and tolerability of sorafenib in unresectable/advanced hepatocellular carcinoma patients: Real-life experience in a Hong Kong tertiary liver cancer institute.
Authors: Yau Thomas Cheung , Tang Vikki , Leung Roland Ching-Yu , Kwok Gin Wai , Chiu Joanne Wing-Yan , Cheung Tan To 
Published: January 2019

382 Background: To evaluate the pattern and outcomes of sorafenib use in unresectable/advanced HCC in a real life setting in a tertiary Hong Kong liver cancer centre. Methods: A retrospective review of unresectable or advanced HCC patients treated with sorafenib at Queen Mary Hospital, Hong Kong from 2010-2015 was conducted. The objectives were to evaluate the sorafenib efficacy in overall treated population as well as different subgroups; and also reviewed the tolerability of sorafenib, especially its impact on liver function. Results: During the study period, 504 consecutive cases were identified and 493 cases with sufficient clinical data were analyzed. Consistent with Asia-Pacific etiologies, 79.3% patients had chronic hepatitis B. Sorafenib was mainly used in patients with high tumor burden (75.1% BCLC-C, 68.6% MVI or/and EHS). Two-third patients (68.2%) were pretreated, mostly with loco-regional therapies . While 70.2% patients had good baseline PS 0, one-quarter (26.6%) had Child-Pugh B/C cirrhosis state. The overall survival (OS) was 8.15 months, with no difference between HBV and non-HBV subgroups. Patients had Child-Pugh A(CP-A) had significantly better OS compared with those at CP-B/C (11.1m vs 3.29m vs 3.34m). About 36.1% patients received subsequent therapies. Safety profile was essentially consistent with literature with hand-foot-skin reaction (HFSR) being the most common AE (30.7% all-grade). Interestingly, the onset of HFSR was associated with significantly better OS (median: 14.59 vs 5.59 months, p <0.001). Notably, there was no significant change in the on-treatment levels of liver function in terms of bilirubin and plasma albumin level. Conclusions: Our study confirms the efficacy and safety in using sorafenib to treat unresectable or advanced HCC patients in the real life setting. Our results are s comparable with those reported in literature. In addition, we found that 1) similar efficacy in treating HCC regardless of HBV status, 2) positive association of OS with HFSR onset, and 3) no compromised liver function during sorafenib therapy.
Evaluation of safety and tolerability of durvalumab (D) with or without tremelimumab (T) in patients (pts) with biliary tract cancer (BTC).
Authors: Ioka Tatsuya , Ueno Makoto , Oh Do-Youn , Fujiwara Yutaka , Chen Jen-Shi , Doki Yuichiro , Mizuno Nobumasa , Park Keunchil , Asagi Akinori , Hayama Manabu , Nii Masahiro , Komuro Keiko , Sugimoto Mariko , Vlahovic Gordana , Ikeda Masafumi 
Published: January 2019

387 Background: This Phase 1 study (NCT01938612) evaluated D (anti-PD-L1 mAb) and T (anti-CTLA-4 mAb) in Asian pts, in whom optimal dosing of D and T is undetermined. No dose-limiting toxicities were observed, and durable responses were seen in a dose escalation phase evaluating various D doses and regimens in Japanese pts (Iguchi, ASCO 2015). The study was subsequently expanded to larger cohorts of Asian pts with advanced solid tumors including BTC. Methods: Two regimens were selected for the expansion phase: D monotherapy (10 mg/kg q2w) and D+T (D 20 mg/kg + T 1.0 mg/kg q4w). One cohort of pts with advanced BTC was enrolled to receive D monotherapy followed by a separate cohort that received D+T with additional pts enrolled if efficacy was observed. Safety, response, and survival endpoints were based on investigator assessment. Results: Pts were enrolled to D (N = 42) or D+T (N = 65). Median age was 64 years for the D cohort and 62 years for the D+T cohort, the majority were male, and ECOG PS was 0 or 1: 64% and 36% for pts in the D cohort and 49% and 51% for pts in the D+T cohort, respectively. Median number of prior chemotherapy regimens was 2 for both cohorts. Treatment-related adverse events (trAE) of any grade occurred in 64% and 82% of pts in the D and D+T cohorts. Grade ≥ 3 trAEs occurred in 19% and 23% of pts in the D and D+T cohorts. trAEs led to discontinuation in 2 pts in the D cohort and 5 pts in the D+T cohort. A death due to trAE (drug-induced liver injury) was reported in the D+T cohort, none in the D cohort. In the D cohort, 2 pts had a partial response (PR) and 7 pts had a PR in the D+T cohort; disease control rate at 12 weeks was 16.7% and 32.2%, respectively. Median duration of response for the D cohort was 9.7 months and 8.5 months for the D+T cohort. Median overall survival was 8.1 (95% CI, 5.6-10.1) months and 10.1 (95% CI, 6.2-11.4) months for the D and D+T cohorts, respectively. Conclusions: Both D monotherapy and D+T combination therapy were tolerable for Asian pts with BTC, and no unexpected toxicities were observed with either regimen. Promising clinical benefit was observed with both D and D+T therapy. This study provides valuable information regarding these therapeutic regimens for future studies in pts with BTC. Clinical trial information: NCT01938612.
Incidence of gastroesophageal junction cancer continues to rise: Analysis of Surveillance, Epidemiology, and End Results (SEER) database.
Authors: Bartel Michael , Brahmbhatt Bhaumik , Bhurwal Abhishek 
Published: January 2019

40 Background: Gastroesophageal junction (GEJ) cancer can be endoscopically resected and/or ablated in its early tumor stage. Despite significant effort to address the epidemiology and populations at risk for distal esoaphgeal cancer, very limited effort has been undertaken to assess such in GEJ cancer. Methods: A SEER database analysis was performed for the study period 1973 – 2013. Inclusion criteria were GEJ cancer (microscopically confirmed primary site of malignancy with ICD-O-3 histology of adenocarcinoma). Data was stratified by years 1973-82, 1983-92, 1993-2002 and 2003-2012, patient age, gender, and race. A Kaplan-Meier curve for the 5-year survival analysis of GEJ cancer was calculation. Further, GEJ cancer data was compared with the epidemiology of distal esophageal cancer (ICD-10). Results: 32,073 patients with GEJ cancer were included in the SEER database between 1973 and 2015 (female 19%, Caucasian race 88.7%). The incidence of GEJ cancer increased significantly over the four decades between 1973 and 2013, 15.7%, 25.3%, 26.9% and 32% (p = 0.001). The rising prevalence was particularly accounted in the patient age cohorts 65-74 years and 75+ years and in white male patients followed by black male patients. The 5-year survival analysis showed a median survival during the four analyzed decades of 8, 10, 11, and 14 months, respectively (Log rank test p < 0.001). During the last decades (1993-2002 and 2003-2012) GEJ cancer and distal esophageal cancer had comparable incidences. Conclusions: GEJ cancer incidence is rising over the last four decades and is in fact comparable with the incidence of distal esophageal cancer. This is particularly true for white male patients and patients older than 65 years. Given that early GEJ cancer is endoscopically treatable, more effort is warranted to address its risk factors and to identify populations at risk who could benefit from early cancer detection programs.
Treatment sequencing in MPC, insights from a 3˚ care center.
Authors: Barrera Ivan , Ranger Jill , Roofigari Nooshin , Dalfen Richard , Batist Gerald , Kavan Petr 
Published: January 2019

400 Background: Since 2011, options for treatment of metastatic pancreatic cancer (mPC) have improved with the use of nab-paclitaxel plus gemcitabine (n-PGEM) or FOLFIRINOX (FFX) as first line treatments (1LTx). In 2016, Nanoliposomal irinotecan plus 5FU (nal-IRI-5FU) demonstrated efficacy in 2LTx. Yet, optimal sequential Tx has not been established. Methods: We evaluated oncologist-selected Tx algorithms and resultant progression free & overall survival (PFS, OS) for pts with mPC from 2010 and 2018 at the Jewish General Hospital, Montreal, QC. This retrospective study included 203 pts with mPC (33 to 89 years, 54% male). Results: 1LTx included 66 pts on FFX, 60 pts on n-PGEM, and 66 pts on single-agent GEM. The remaining pts received Capecitabine (CAP) or another Tx (N = 11). Mean PFS in FFX, n-PGEM, and GEM groups was 5.07, 5.52, and 4.10 months, respectively (progression was 1˚ or 2˚ disease progression or a change of Tx due to adverse events or intolerance). Only the FFX and GEM groups were significant when compared (p = 0.049). Only 43.8% of pts (N = 89/203) advanced to 2LTx most receiving GEM (N = 27), n-PGEM (N = 21), or FFX (N = 11), PFS 3.87, 7.04, and 2.30 months, respectively. FFX and n-PGEM groups were significant when compared (p=0.011). CAP and nal-IRI-5FU were 2LTx options for 25.8% (N=23/89) and 7.9% (N = 7/89) of pts, respectively. For 30 pts in 3LTx, Txs included: nal-IRI-5FU (N = 8), clinical trials (CT) (N = 7), GEM (N = 5), FFX (N = 4), n-PGEM (N = 2), CAP (N = 2) and Irinotecan (IRI) (N = 2). Only 7 pts received 4LTx: GEM (N = 3), CAP (N = 2), CT (N = 1), and IRI (N = 1). Median OS from start of 1LTx for pts in FFX (N = 60), n-PGEM (N = 41), and GEM (N = 60) groups was 11.42, 9.50, and 6.23 months, respectively. (Excluding pts on ongoing tx and other censored data points). GEM tx was a significant prognostic factor for shorter OS, GEM verus FFX, HR 1.673 (1.165 to 2.402, p = 0.0053), GEM versus n-PGEM, HR 1.511 (1.012 to 2.258, p = 0.0437). No difference in survival was seen between FFX and n-PGEM groups, HR 0.903 (95% CI 0.605-1.349, p = 0.6196). Conclusions: Though FFX and n-PGEM are considered mainstays of 1LTx, GEM was chosen by physicians in ~1/3 of cases despite reduced PFS. Pts on FFX or n-PGEM had better OS compared to GEM alone, as expected. Further investigation into Tx sequencing in this and larger cohorts, is needed.
Outcomes of stereotactic body radiotherapy for unresectable hepatocellular carcinoma.
Authors: Zhao Yizhou , Dunne Emma , Ma Roy , Liu Mitchell , Beaton Laura , Yeung Rosanna , Lund Chad R. , Schellenberg Devin 
Published: January 2019

401 Background: Stereotactic body radiotherapy (SBRT) is an emerging curative treatment for hepatocellular carcinoma (HCC). We report toxicity and efficacy of all patients treated in British Columbia, one of the largest series to date. Methods: From 2011 to Jan 2018, 99 patients underwent SBRT to 128 HCCs. Fiducials were placed and 4D CT (78.4%) and respiratory gating (19.6%) were used for motion management. Local control (LC), progression-free survival (PFS) and overall survival (OS) were analyzed by Kaplan-Meier. Cox regression identified outcome predictors. Results: Median Child-Pugh Score (CPS) was A5 (65% A5, 18% A6, 12% B7, 5% B8, 1% B9) and median Albumin-Bilirubin (ALBI) score was -2.55, grade 2 (48% gr1, 45% gr2, 6% gr3). Most (87.7%) had either Hepatitis B or C and 73.7% had prior HCC treatment, with 47.5% going on to further HCC treatment post SBRT and 42.4% deceased at the time of analysis. The median tumor size was 2.8 cm (range 0.8 – 11). The median prescribed biologically effective dose (BED10) was 112.5 Gy, with 45 Gy in 3 fractions (BED10112.5 Gy) in 56.9% of cases and 45 Gy in 5 fractions (BED10 85.5 Gy) in 30.4%. Median follow-up was 18.5 months (range 2.2 – 73.5). At 3 months, 12 (11.8%) patients had a rise in CPS of ≥ 2, and 26 (25.5%) patients had increased ALBI grade (median change in score of +0.16). Excluding laboratory findings, 14 (14.1%) patients developed CTCAE V5 grade 3 / 4 toxicities (ascites n = 12, hepatic failure n = 4, hepatic pain n = 1, nausea n = 1, GI bleed n = 1). The 1-, 2- and 3-year LC were 94.3%, 86.6% and 80.2%. The median PFS was 14.8 months, respectively 53.7%, 39.5% and 23.8% at 1, 2 and 3 years. The median OS was 41.1 months, respectively 80.3%, 63.5% and 55.2% at 1, 2 and 3 years. Univariate factors predicting improved LC were mean dose (Dmean) ≥ BED10 100 Gy to GTV (p < 0.01) and PTV (p = 0.03). Predictors of improved OS were prescription dose ≥ BED10 100 Gy (p = 0.02), GTV Dmean ≥ BED10 100 Gy (p < 0.01), lower CPS (p = 0.04) and lower ALBI score pre-SBRT (p < 0.01), smaller tumor size (p < 0.01), no liver directed therapy post-SBRT (p < 0.01), younger age (p = 0.03) and favorable ECOG (p = 0.01). Conclusions: SBRT achieves excellent LC, with low rates of toxicity and can be included with or without other therapies in HCC treatment.
Prognostic factors and disease course in patients enrolled onto clinical trials of second-line therapy for hepatocellular carcinoma.
Authors: Personeni Nicola , Pressiani Tiziana , D'Alessio Antonio , Prete Maria Giuseppina , Bozzarelli Silvia , Smiroldo Valeria , Simonelli Matteo , Giordano Laura , Santoro Armando , Rimassa Lorenza 
Published: January 2019

406 Background: Prognostic factors of survival and disease course in patients with hepatocellular carcinoma (HCC) and preserved liver reserves, enrolled onto clinical trials of second-line treatments after sorafenib, are unclear. Methods: This single-center database analysis included all patients with Child-Pugh A score and ECOG performance status (PS) 0 - 1 participating between 2012 and 2017 in clinical trials of second-line systemic treatments for advanced HCC. Patients received first-line sorafenib and experienced either disease progression (PD) to sorafenib or were sorafenib-intolerant. Their clinicopathologic characteristics were correlated with overall survival (OS, calculated from the first day of second-line treatment to death or last visit available), and post-treatment survival (PTS, calculated from the date of end-of-treatment to death or last follow-up). Results: Ninety-nine patients (21 sorafenib-intolerant, 78 progressors) were enrolled onto trials of checkpoint inhibitors (CPI, 23 patients), tyrosine kinase inhibitors (TKI, 44 patients) versus best supportive care (BSC, 24 patients), open-label TKI (8 patients). Overall, median OS was 9.4 months (9.6, 9.8, and 8.0 months for CPI, TKI and BSC, respectively; p = 0.493). Median time-to-treatment failure was 3.5, 4.4, 3.7 months for CPI, TKI and BSC, respectively (p = 0.561). In multivariable analyses, worse OS was linked to high neutrophil/lymphocyte ratio (Hazard Ratio, HR = 1.13; p = 0.005) and macrovascular invasion [(MVI), HR = 2.59; p < 0.001]. Second-line treatment discontinuation due to liver failure independently conferred worse PTS than adverse events (HR = 2.32; p = 0.111) or PD (HR = 3.44; p = 0.002), as did ECOG PS > 1 at EOT (HR = 3.05; p = 0.002). Death rate within 30 days of end-of-treatment was 4.2% on placebo versus 10.5% on IO versus 22.9% on TKI. Conclusions: In this homogeneous cohort of compensated HCC patients pre-treated with sorafenib, MVI and NLR at start of second-line clinical trial are prognostic factors of OS. Besides ECOG PS and liver failure, further predictors of subsequent PTS to inform treatment options beyond second-line were not identified.