bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patient-reported outcomes (PROs) in pancreatic cancer clinical trials (CTs).
Authors: Grewal Udhayvir Singh , Ahmed Danya , Dhaliwal Lovekirat Singh , Laheru Daniel A. , Lou Emil , Beg Muhammad Shaalan , Nipp Ryan David , Gupta Arjun 
Published: January 2022

534 Background: Incorporating PROs into CTs is critical for patients with pancreatic cancer, as these individuals often experience a high symptom burden and prioritize maximizing quality of life (QOL). Methods: We reviewed protocols of completed U.S. CTs listed on ClinicalTrials.gov that investigated curative/palliative interventions in pancreatic cancer from 1995-2020. We assessed up to August 2021 if CT publications reported PRO results through linked publications and an independent search through PubMed/MEDLINE. We extracted CT details (funding, eligibility, etc), and if PROs (outcome directly reported by patients) were listed as an endpoint (primary/secondary/exploratory). We classified interventions as cancer-directed (e.g. chemotherapy), supportive care (e.g. neurolysis), or other (e.g. curcumin). Results: We reviewed 619 protocols and included 379 in the analysis. Most CTs investigated cancer-directed interventions (317, 83.6%). Only 43 (11.4%) included PROs as endpoints (Table). In these, most of the PROs assessed QOL (34, 79.1%) and pain (15, 34.9%). For the 33/43 (76.7%) protocols that listed a specific PRO instrument, EORTC-QLQ C30 (11/33, 33.3%) was the most common. Only 6 (18.2%) protocols included pancreatic cancer-specific PROs, such as QLQ-PAN26. Supportive care CTs were more likely to assess PROs than cancer-directed CTs (odds ratio, OR= 62.6, 95% CI 16.7-234.3, p<0.0001). Protocols listed PROs as a primary, secondary, and exploratory endpoint in 15 (34.9%), 25 (58.1%), and 3 (6.9%) CTs respectively. Most CTs (13/15, 86.7%) with PROs as a primary endpoint evaluated supportive care interventions. Of 15 CTs with PROs as a primary endpoint, 10 (66.7%) had results published. Of 28 CTs assessing PROs as a secondary/exploratory outcome, 20 (71.4%) had published results and 12 (42.9%) included PRO data. Conclusions: From 1995-2020, only 11.4% of pancreatic cancer CTs incorporated PROs as endpoints. Supportive care CTs were more likely to include PROs than cancer-directed CTs. Our findings underscore the need to improve efforts to incorporate PROs into CTs for patients with pancreatic cancer. Data as number (%).[Table: see text]
Cost-effectiveness of universal screening for germline BRCA mutations in metastatic pancreatic cancer.
Authors: Ingram Myles , Pumpalova Yoanna S , Park Jiheum , Lim Francesca , Ferris Jennifer S. , Bates Susan Elaine , Manji Gulam Abbas , Kong Chung Yin , Hur Chin 
Published: January 2022

536 Background: Germline BRCA1/2 mutations (gBRCAm) increase the risk of pancreatic ductal adenocarcinoma (PDAC). The NCCN 2020 guidelines recommend testing for gBRCAm in metastatic PDAC patients if the patients have a personal history and/or familial history of PDAC (current standard-of-care). However, given the advances made in genetic testing, universal gBRCAm testing for metastatic PDAC patients can be considered. The cost-effectiveness of universal gBRCAm screening has yet to be compared to the current standard-of-care. The purpose of our study was to explore the cost-effectiveness, treatment outcomes, costs, and quality-of-life impact of universal gBRCAm screening. Methods: We developed a decision-analytic mathematical model comparing the cost and health outcomes of universal gBRCAm screening against the current standard-of-care. Inputs for the model were estimated using clinical trial data and published literature. No intervention was used as a comparator. The primary endpoint was incremental cost-effectiveness ratios (ICERs) with a willingness-to-pay (WTP) threshold of $100,000 per quality-adjusted-life-year (QALY). Secondary endpoints included overall survival (OS), progression-free survival (PFS), life-years (LYs) and total cost of care (USD). Results: Universal gBRCAm screening was the cost-effective strategy, totaling incremental QALYs of 1.61 at a cost of $73,682 per QALY when compared to no intervention. A one-way sensitivity analysis found that the standard-of-care becomes the cost-effective strategy when the prevalence of gBRCAm is lowered to 2% of the base case. Conclusions: Our model found that universal gBRCAm screening is cost-effective and even cost-savings for patients with metastatic PDAC. Additional clinical trial data with sufficient follow-up are needed to confirm our findings.[Table: see text]
Differences in pretreatment frailty across gastrointestinal (GI) cancers in older adults: Results from the Cancer and Aging Resilience Evaluation (CARE) registry.
Authors: Arora Sankalp , Fowler Mackenzie , Harmon Christian , Al-Obaidi Mustafa , Outlaw Darryl Alan , Hollis Robert , Gbolahan Olumide B. , Khushman Moh'd M. , Giri Smith , Williams Grant Richard 
Published: January 2022

542 Background: Frailty is an independent predictor of mortality in older adults and has been used to predict surgical complications and chemotherapy toxicities in GI cancers. How frailty differs between GI cancer types is unknown and could explain disparities in cancer outcomes. Our goal was to examine differences in pre-treatment frailty and geriatric assessment (GA) domain impairments between pancreatic, hepatobiliary, and colorectal cancers (CRC). We hypothesized that patients with more aggressive cancers (such as pancreatic cancer) would have increased frailty and more GA impairments, even prior to initiation of treatment. Methods: Our study included older adults age ≥60 years with cancer enrolled in the CARE Registry at the University of Alabama at Birmingham (UAB) who underwent a patient-reported GA during their initial visit with a GI medical oncologist. The GA was performed prior to any cancer-directed therapy. Frailty was defined using the 44-item CARE frailty index constructed based on principles of deficit accumulation described by Rockwood et al. We evaluated differences in frailty and GA domains between patients with CRC, pancreatic, and hepatobiliary cancers. Lastly, using a multivariable model we examined the adjusted odds ratio (aOR) of frailty by GI cancer type (reference CRC), adjusted for age, sex, race, cancer stage, and comorbidities. Results: Our study included 505 patients; 211 (41.8%) with CRC, 178 (35.2%) with pancreatic, and 116 (23.0%) with hepatobiliary cancers. Mean age of 70 years (standard deviation of 7) and 59% male. Cancer types did not differ by age, race, or sex. Patients with pancreatic and hepatobiliary cancers had more advanced cancer stage at time of assessment (stage IV 36.2% for CRC, 44.9% for pancreatic, and 45.2 for hepatobiliary; p=0.007). Older adults with pancreatic cancer had the highest prevalence of frailty (23.3% for CRC, 40.6% for pancreatic, and 34.3% for hepatobiliary; p=0.001), instrumental activities of daily living limitations (50.2% for CRC, 64.3% for pancreatic, and 52.7% for hepatobiliary; p=0.018), and malnutrition (40.8% for CRC, 70.3% for pancreatic, and 45.4% for hepatobiliary; p< 0.001). In multivariable analyses, older patients with pancreatic cancer had a 2.0 times higher odds of frailty in comparison to patients with CRC (aOR 2.0 95% CI 1.2-3.3, p=0.007). Conclusions: Older adults with pancreatic cancer had a higher prevalence of pre-treatment frailty, malnutrition, and functional impairments compared to CRC and hepatobiliary cancers. A focus on early intervention in these patients with optimization of nutrition and targeted physical/occupational therapy prior to and during treatment may help mitigate these factors and potentially improve outcomes.
Potential serum protein biomarkers of cancer cachexia, muscle atrophy, and survival in pancreatic ductal adenocarcinoma.
Authors: Cameron Miles , Judge Sarah , Judge Andrew 
Published: January 2022

545 Background: Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of death in the United States. Treatment is difficult and often complicated by the presence of cachexia, a systemic wasting condition affecting most PDAC patients at diagnosis. Skeletal muscle atrophy is a hallmark of cachexia and predicts outcomes after surgery and chemotherapy. In this study, we sought to identify possible serum biomarkers of cachexia, which correlates with changes to lean body mass and survival, using an aptamer-based platform in patients with PDAC. We hypothesize that unique proteins associate with cachexia and survival measures. Methods: Using SomaScan we measured the serum levels of 4,006 proteins in 21 patients with PDAC undergoing curative surgery. Clinical data and anthropometric measurements derived from pre-operative CT imaging were compared to protein levels with Spearman correlational analyses and logistic regression. We then queried DAVID Bioinformatics database to identify enriched functional protein categories. Results: Mean age was 66.9 ± 8.91 years, and mean body-weight loss in the six months preceding diagnosis was 12.6 ± 8.80%. Using consensus guidelines considering percent weight loss and skeletal muscle mass and radiation attenuation, 10 subjects (46.7%) were defined as “cachectic.” We found 241 proteins significantly correlated to Cancer Weight Loss Grade (a composite measure of percent body weight loss and body mass index). High IDUA, CTLA4 and USE1, in particular, predicted the worst weight loss grade with 75% sensitivity and 92% specificity (AUC = 0.8894, odds ratio: 36, p = 0.0068). Four additional proteins significantly correlated with skeletal muscle index (CK-MM, CK-MB, PCOC2 and ADH4) while 13 proteins significantly correlated with muscle radiation attenuation. Lastly, we identified 18 proteins that significantly correlated with survival quartile. Of these, we found that elevated HS6ST2 and DEPP significantly predicted early recurrence and death compared to those with lower levels (medial survival: 177 days v. 850 days, p = 0.0049). Of the correlative proteins, enriched gene ontology terms included signal peptide (28.2), cytokine (6.86), negative regulation of endopeptidase activity (3.39), and immunoglobulin domain (3.24). Conclusions: Cancer cachexia in PDAC and various gastrointestinal malignancies remains a key clinical issue. While there are no definitive biomarkers currently in use to diagnose and manage cachexia preemptively, we present several potential candidates in a small cohort of patients. Ultimately, such assays may better elucidate common cachexia-inducing pathways, a shared spectrum of biomarkers and allow for the development of more specific therapies targeting cachexia.
Adjuvant gemcitabine (GEM) versus gemcitabine plus capecitabine (GEMCAP) in resected pancreatic adenocarcinoma: A retrospective analysis.
Authors: Kang Sora , Yoo Changhoon , Lee So Heun , Chang Heung-Moon , Jeong Jae Ho , Kim Kyu-Pyo , Ryoo Baek-Yeol 
Published: January 2022

547 Background: For patients who underwent curative-intent upfront surgery, adjuvant chemotherapy is the current standard of care. The previous, randomized phase 3 ESPAC-4 study showed significantly improved overall survival (OS) with GEMCAP compared to GEM. However, this study was conducted in European countries and its implication in Asian patients has not been explored yet. We conducted a retrospective analysis to evaluate the efficacy and safety of GEMCAP compared to GEM regimen. Methods: Between January 2017 and December 2020, a total of 292 patients who received adjuvant GEM or GEMCAP after curative-intent surgery in Asan Medical Center, Seoul, Korea, were included in this retrospective analysis. Results: Adjuvant GEM and GEMCAP were administered in 161 patients (55.1%) and 131 patients (44.8 %), respectively. Compared the GEMCAP group, age of patients were significantly older in the GEM group (median 66 vs 63 yo, p = 0.025); otherwise, there was no significant difference in baseline characteristics between two groups. With the median follow-up duration of 39.4 months (95% CI 36.9 - 45.0 months) in GEM group and 39.4 months (95% CI 34.7-41.6 months) in GEMCAP group, the median OS was 36.8 months (95% CI 29.7-43.5 months) and 46.1 months (95% CI 31.5 months – not reached) in the GEM group and GEMCAP group, respectively (unadjusted HR 0.72, 95% CI 0.51-1.02, p = 0.065). The median recurrence-free survival was 14.3 months (95% CI, 12.9-17.7 months) and 17.0 months (95% CI, 13.3-28.8 months) in the GEM group and GEMCAP group, respectively (p = 0.52). In the GEMCAP group, hand-foot skin reaction (any grade, 15.27 % vs 0.62 %, p < 0.001), neutropenia (78.6% vs 67.7%, p=0.037) and thrombocytopenia (30.53% vs 20.5%, p=0.035) were more common in the GEMCAP group compared to the GEM group. In multivariate analysis, adjuvant GEMCAP was significantly associated with better OS compared to adjuvant GEM (adjusted HR 0.64, 95% CI, 0.44-0.91, p = 0.014). Otherwise, moderate or poor histologic grade, lymph node positive, positive resection margin, and elevated CA 19-9 levels (> median) were significantly associated with poorer OS. Conclusions: In this retrospective analysis for Korean patients, adjuvant GEMCAP showed consistent clinical outcomes shown in the ESPAC-4 trial. As mFOLFIRINOX is the new standard of care for medically fit patients with resected pancreatic adenocarcinoma, further evaluation of optimal adjuvant chemotherapy in daily practice is warranted.
Nal-IRI+5-FU/LV vs 5-FU/LV in metastatic pancreatic cancer: Additional safety report of randomized Japanese phase 2 trial.
Authors: Okusaka Takuji , Ikeda Masafumi , Ioka Tatsuya , Ueno Makoto , Teng Zhaoyang , Furuya Momoko , Furuse Junji 
Published: January 2022

549 Background: Based on a phase II study conducted in Japanese metastatic pancreatic cancer (NCT02697058) and a global phase III study, nal-IRI obtained market authorization in March 2020 in Japan for "Unresectable pancreatic cancer after disease progression following cancer chemotherapy". After one year of practice, physicians have a sense that some of the safety profile of nal-IRI to be slightly different from conventional irinotecan. The purpose of this report is to explore additional points of the nal-IRI safety in the Japanese study. Methods: This analysis with the safety population of nal-IRI+5-FU/ l-LV group was done for the incidence, time to first onset (TTO), and time to resolution (TTR) for the events associated with 12 identified risks in the Risk Management Plan (RMP)(Table) and other selected GI toxicities. Prophylaxis used were also analyzed. Results: Myelosuppression (82.6%), diarrhoea (58.7%) and hepatic dysfunction (41.3%) were commonly reported of the 12 identified risks. The median (m) TTO of these TEAEs was 16 days (range: 6, 73), 9 days (1, 61), and 22days (2,325) respectively. As for the mTTR, it was 8.0 days (95% CI: 8.00, 9.00), 4.0 days (4.00, 8.00), and 40.0 days (9.00, -) respectively. For the myelosuppression, there were 4 patients who received G-CSF for the treatment of ≥ grade 3 myelosuppression. The 8 patients who experienced diarrhoea leading to dose reduction had no recurrence of ≥grade3 diarrhoea after intervention. For other GI toxicities, anorexia occurred in 28/46 patients (60.9%) with mTTO 4.0 days (range: 2, 132) and mTTR 12.0 days (95% CI: 6.00, 26.00). Summary of TTO for the events associated with identified risks in the RMP. * Intestinal obstruction, enteritis, disseminated intravascular coagulation, interstitial lung disease, ventricular extrasystoles are also included in the RMP but not observed. Discussion: This is the first report of nal-IRI safety profile details such as timing in Japanese patients. It is interesting to note that some TEAEs appear different in practice regarding TTR in comparison with conventional irinotecan. This difference can be due to the unique PK profile of nal-IRI as a result of utilizing liposomal technology but needs to be further elucidated. Conclusions: Although the TEAEs occurred with nal-IRI+5-FU/ l-LV were controllable with proper management in Japanese patients, some with prolonged toxicities should be carefully managed. Clinical trial information: NCT02697058. [Table: see text]
Outcomes of anlotinib plus nab-paclitaxel/gemcitabine as first-line treatment for patients with advanced pancreatic adenocarcinoma: A retrospective analysis in China.
Authors: Wu Hongyang , Huang Nana , Zhao Chenchen 
Published: January 2022

556 Background: Anlotinib, a novel small molecule multi-target tyrosine kinase inhibitor that can effectively inhibit VEGFR, PDGFR, FGFR, C-KIT et al, is proved to have anti-tumor angiogenesis and tumor growth inhibition effects. However, Anlotinib exploration on advanced pancreatic adenocarcinoma (PDAC) is still limited. The motivation of this work is to evaluate the efficacy and safety of anlotinib combined with nab-paclitaxel/gemcitabine in the first-line treatment of patients with advanced PDAC, and provide some evidence for the treatment regimens of advanced PDAC. Methods: This was a retrospective study in patients with advanced PDAC performed from Aug 17, 2019 to Apr 3, 2021. Patients who received anlotinib plus nab-paclitaxel/gemcitabine treatment were defined as Group 1, and patients who received nab-paclitaxel/gemcitabine as Group 2. The study was approved by the Ethics Committee of the First Affiliated Hospital of Anhui Medical University (P2021-13-21). The response to treatment was evaluated according to RECIST version 1.1. In addition, adverse events were evaluated by CTCAE v5.0. Results: In this work, 33 patients were included, with 17 cases in Group 1 and 16 cases in Group 2. The median PFS (mPFS) of Group 1 and Group 2 were 5.0 (95% Cl, 4.97-5.94) months and 2.7 (95% Cl, 2.4-3.3) months, respectively ( P = 0.0220). The median OS (mOS) of Group 1 and Group 2 were 9.0 (95% Cl, 6.55-11.45) months and 6.0 (95% Cl, 1.08-10.92) months, respectively ( P=0.006). The PFS rate in 3 and 6 months and the OS rate in 6 and 12 months of Group 1 were significantly higher than that of Group 2. The most common grade 3 treatment related AEs (trAEs) were hematological toxicity, with 35.29% in Group1 and 31.25% in Group 2. Non-hematological toxicity were hypertension, hand-foot syndrome and diarrhea. No grade 3 or higher non-hematologic toxicity was observed in all patients. Conclusions: Anlotinib plus nab-paclitaxel/gemcitabine as first-line treatment demonstrates encouraging efficacy and manageable AE in patients with advanced PDAC. Clinical outcomes are improved with longer PFS and OS in anlotinib plus chemotherapy group. More data are needed to confirm the long-term efficacy and safety of anlotinib plus nab-paclitaxel/gemcitabine in advanced PDAC patients.
A phase I study of pharmacokinetic (PK)-driven sequential dosing of rucaparib (RUB) with irinotecan liposome (nal-IRI) and fluorouracil (5FU) in metastatic gastrointestinal (mGI) and pancreas (PANC) cancers.
Authors: Ma Wen Wee , Zemla Tyler J. , Walden Daniel , McWilliams Robert R. , Shaib Walid Labib , Ahn Daniel H. , El-Rayes Bassel F. , Halfdanarson Thorvardur Ragnar , Hobday Timothy J. , Bruggeman Sarah , Jaszewski Brandy L. , Ou Fang-Shu , Wu Christina , Bekaii-Saab Tanios S. 
Published: January 2022

563 Background: RUB is an oral PARP1,2,3 inhibitor that demonstrated efficacy in patients (pts) with ovarian and prostate cancers harboring deleterious BRCA mutations. RUB exerts synergistic anti-tumor effect with IRI preclinically though the combination has overlapping toxicities. We previously published on the population PK of nal-IRI (Adiwijaya, Ma et al, Clin Pharm Ther 2017). We conducted a phase I study to evaluate a novel sequential dosing of RUB with nal-IRI/5FU in mGI cancer pts. Methods: Eligible pts had incurable mGI cancer previously received > 1 line of therapy (rx), ECOG PS 0-1, had RECIST measurable disease, adequate organ reserves and not received IRI for metastatic disease. Previous PARPi rx was excluded. The endpoints included dose limiting toxicity (DLT), maximum tolerated dose (MTD) and toxicity profile. The dose escalation utilized the 3+3 design. RUB was given oral bid on Day 4 to 13 and 18 to 27 with nal-IRI i.v. and 5FU i.v. 2400 mg/m2 over 46 hr on Day 1 and 15, every 28 day. Planned dose levels were RUB 400 mg/nal-IRI 50 mg/m2 (DL1), 400 mg/70 mg/m2 (DL2) and 600 mg/70 mg/m2 (DL3). Adverse events (AEs) were scored per CTCAE v4.03. Molecular profile was evaluated by CLIA-certified NGS testing. Results: Eighteen pts including 11 colorectal (CRC), 6 PANC, 1 gastroesophageal (GE) were enrolled and 12 were evaluable for DLTs. DL2 was not tolerable (DLT: G3 diarrhea, nausea and vomiting) and DL2A was added (RUB 600 mg/nal-IRI 50 mg/m2). DL2A enrolled 6 pts with no DLT and was determined as the MTD. Of DLT-evaluable pts, G3 and worse treatment-related AEs from all cycles were diarrhea (33%), fatigue (25%), leukopenia (25%), neutropenia (25%), anemia (8%) and nausea (8%). Four of 12 response evaluable pts had partial response: 2 CRC (1 had ATM mut), 1 PANC ( ATM mut), 1 GE ( BRCA2 mut) whilst 3 responders previously had platinum (PLA). Five pts had stable disease beyond 16 weeks (range 18.9 to 100.7 weeks), and all had prior PLA. Conclusions: The study successfully determined the MTD of RUB in combination with nal-IRI and 5FU. Encouraging efficacy was observed in PLA-treated mGI cancers including responses in those harboring ATM and BRCA alterations. The study is proceeding to evaluate the efficacy of the combination in metastatic pancreas cancer pts with and without BRCA1/2 or PALB2 alterations. Clinical trial information: NCT03337087.
Phase II study of SHR-1701 combined with famitinib in the treatment of advanced pancreatic cancer or biliary tract cancer.
Authors: Xie Jing , Meng Zhiqiang , Chen Lianyu , Hua Yongqiang , Li Huajun 
Published: January 2022

568 Background: Pancreatic cancer (PC) and biliary tract cancer (BTC) are highly malignant cancers with limited treatment (tx) options. SHR-1701 is a novel bifunctional anti-PD-L1/TGF-βRII agent. Famitinib is a multitargeted tyrosine kinase inhibitor (TKI). Many studies have proved the mutually enhanced effect of anti-angiogenesis and ICI therapy in multiple tumours. Herein, we reported the safety and efficacy of SHR-1701 in combination with famitinib in advanced PC and BTC patients (pts) who have failed previous standard tx. Methods: This is an ongoing single-site, exploratory phase II study. PC or BTC pts who have failed ≥1 prior therapy would be enrolled into PC or BTC cohort, and received SHR-1701 plus famitinib until disease progression or unacceptable toxicity. SHR1701 would be intravenously given at a fixed dose of 30mg/kg q3w. Famitinib was initially given at a dose of 20mg/d. Dose reduction of famitinib to 15mg was allowed if it was intolerable. The primary endpoint was objective response rate (ORR) as per RECIST v1.1. Simon’s two-stage minimax design was used in this trial. For each cohort, if ≥2 responses are observed among 15 patients in stage I, the study will proceed to full accrual. Results: Up to 15 Sep 2021, 15 pts and 9 pts were enrolled in PC and BTC cohorts respectively. The baseline data are shown in the table. Of 15 evaluable pts in PC cohort, one had complete response, one had partial response (PR), 6 pts had stable disease (SD). The ORR and DCR were 13% and 53%, respectively. The first stage of PC cohort had a sufficient response rate to meet full enrollment. Among 8 evaluable pts in BTC cohort, one had PR (tumor shrinkage > 80%), 4 had SD. The ORR and DCR were 13% and 63%, respectively. 22 pts (92%) experienced treatment-related adverse events (TRAEs). The most frequently reported TRAEs (any grade) were proteinuria (58%), hypertension (42%), and blood urine present (42%). The incidence of Grade 3 TRAEs was 33%, among which the most common ones were hypertension (8%), and bilirubin conjugated increased (8%). No grade 4/5 TRAEs were reported. Conclusions: SHR-1701 plus famitinib showed encouraging activity with manageable safety in pts with advanced PC or BTC. Enrollment is ongoing and updated data will be presented. Clinical trial information: ChiCTR2000037927.[Table: see text]