bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between post-treatment (tx) alpha-fetoprotein (AFP) reduction and outcomes in real-world (rw) U.S. patients (pts) with advanced HCC (aHCC).
Authors: Wang Xiaoliang , Magee Kelly , Gossai Anala , Parrinello Christina M. , Miksad Rebecca A. , Kim Richard D. , Abou-Alfa Ghassan K. 
Published: January 2021

341 Background: A decrease in post-tx AFP may be associated with improved outcomes in clinical trials. However, the impact of AFP reduction after initiation of a first-line (1L) tyrosine kinase inhibitor (TKI) therapy on outcomes is unclear among pts with aHCC treated in routine clinical practice. Methods: This analysis utilized data from the nationwide Flatiron Health electronic health record (EHR)-derived de-identified database and included pts with aHCC with ≥2 visits between 1/1/2011-7/31/2019 who received 1L TKI. Pts with a baseline serum AFP value (closest to 1L initiation within -30 to +7 days) and a post-tx AFP value (closest to 8 weeks after 1L initiation within ±2 weeks) were included. Post-tx AFP reduction was defined as a ≥20% decrease from baseline AFP, and no reduction as a <20% decrease or any increase. Rw overall survival (rwOS) was defined as time from post-tx AFP measurement to death (censored at last EHR activity). Rw progression-free survival (rwPFS) was based on clinician documentation and defined as the first progression event or death after post-tx AFP measurement (censored at last clinic note date). Adjusted hazard ratios (aHR) for reduction vs no reduction (reference) were estimated using multivariable Cox proportional hazards models adjusted for potential confounders and baseline AFP. Effect modification was assessed by conducting tests for interactions with analyses stratified by HCC risk factors. Results: 441 pts were included in the study. 8% had documented history (hx) of hepatitis B (HBV), 52% hepatitis C (HCV), 47% obesity/diabetes (DM), 42% heavy alcohol use, and 11% no documented risk factor. Median baseline AFP was 210 ng/mL (IQR 237 - 2981) and 150 ng/mL (IQR 17 - 1311) among pts with reduction (N = 150) and no reduction (N = 291). There was a 35% decrease in hazard of death for pts with reduction vs no reduction (median rwOS 10.3 vs 6.7 months; Table). Similarly, a 35% decrease in hazard of rw progression or death was observed for pts with reduction vs no reduction (aHR=0.65; 95% CI: 0.52-0.81; median rwPFS 4.4 vs 2.4 months). Reduction (vs no) was associated with better rwOS among pts with hx of HCV, obesity/DM or alcohol use vs without the respective risk factor, however, no statistically significant interactions were observed (Table). Conclusions: Results show post-tx AFP reduction may be prognostic for rwPFS and rwOS in pts with aHCC treated with 1L TKI. Further research may clarify if prognostic value differs by HCC risk factor profile. [Table: see text]
Radiomic signatures to predict survival in patients with advanced hepatocellular carcinoma (HCC) treated with sorafenib +/- doxorubicin: Correlative science from CALGB 80802 (Alliance).
Authors: Dercle Laurent , Geyer Susan Michelle , Nixon Andrew B. , Innocenti Federico , Shi Qian , Jacobson Sawyer B. , Luk Lyndon , Liu Andrew , Yang Hao , Wen Yujia , Zhao Binsheng , Bertagnolli Monica M. , Meyerhardt Jeffrey A. , O'Reilly Eileen Mary , Venook Alan P. , Schwartz Lawrence Howard , Abou-Alfa Ghassan K. 
Published: January 2021

343 Background: Alliance/CALGB 80802, a randomized phase III trial, evaluated sorafenib plus doxorubicin vs. doxorubicin in pts with HCC and showed no improvement in median overall survival (OS) (HR[95CI] 1.05[0.83-1.31]) or PFS (HR[95CI] 0.93[0.75-1.16]). In HCC surrogacy of tumor response with OS remains controversial, in part due to varying criteria used for response evaluation (e.g., RECIST1.1 and mRECIST). We evaluated the performance of several models to predict OS using pretreatment clinical and radiomic variables. Methods: In CALBG 80802, we segmented all measurable tumor lesions on sequential CT scans. A lesion’s imaging phenotype was deciphered with 23 uncorrelated quantitative imaging features measured at baseline and week (wk) 10 (first follow-up). An OS landmark survival analysis was conducted at wk 10. Patients were randomly assigned (3:1) to training (n = 92) and validation (n = 37) sets. In a training set, 6 random forest predictive models (6 signatures) used features that best predicted OS using 3 sets of variables: radiomics only (n = 23), clinical only (n = 9), radiomics and clinical (n = 32). Two time points (baseline only or baseline + wk 10) were assessed. Each signature's output was an individualized prediction and a continuous value ranging from 0 to 1 (from most to least favorable predicted OS). The primary endpoint was to compare these models' performance to predict OS using error rate (Harrell's concordance-index) in the validation set. Results: Of the 6 training signatures evaluated, the one achieving the highest performance in the validation set was an 8-feature signature combining radiomics and clinical variables measured at two time points (baseline + wk 10) with an error rate of 35.6%. The variables [rank of importance] (table) selected by the signature included baseline clinical features (albumin[1], AFP[2], Child-Pugh[4]), baseline radiomics features (component 17[3], component 1[5], component 9[7], tumor volume[8]) and wk 10 radiomics features (delta tumor volume[6]). Variable delta tumor volume [6] used a more enhanced estimation of tumor burden at baseline and a delta tumor volumetric measurement; compared to RECIST1.1 measurement of percentage change in unidimensional measurement of a subset of target lesions. The four quartiles of the signature were significantly associated with OS (Log-Rank, P < 0.0001). Conclusions: The selected combined radiomic and clinical composite signature provided the best prediction for OS in the 80802 study patients’ population. It is a suggested way forward to go beyond single anatomic measurement techniques such as RECIST or mRECIST. [Table: see text]
Factors influencing adjuvant treatment decision making among Chinese patients with hepatocellular carcinoma (HCC): Results of a patient survey.
Authors: Sun Hui-Chuan , Zhu Xiao-Dong , Xu Li , Shen Ying-Hao , Huang Cheng , Zhou Jian , Fan Jia 
Published: January 2021

346 Background: This study aimed to understand patient decision-making factors for post-operative adjuvant treatment after resection of hepatocellular carcinoma (HCC) in China. Methods: Patients who had received surgical resection of HCC in the last 2 years at 27 hospitals in China were surveyed using a questionnaire (https://pro.wenjuan.com/t/jUZFU). Feedback was collected by telephone or online. The survey covered three domains: adjuvant treatment decision making, selection of treatment regimen and the influence of recurrence risk on willingness to receive adjuvant treatment. For each domain, participants were asked to identify decision makers and to score decision-making factors from 1 (no influence) to 7 (high influence). All factors with an average score of 6 or 7 points were considered impactful, and those with scores ≤5 were not considered impactful. Descriptive statistics were used to summarize the findings. This study was approved by the ethics committee of Zhongshan hospital and patients provided informed consent. Results: In total, 2,220 valid responses were collected (2,183 patients from Zhongshan Hospital, 37 from 26 other hospitals); 75% of respondents were male, 60% were aged 50-70 years, and 50% had a monthly family income ≤5,000 Chinese Yuan (~$740 USD). Among respondents, 62% had received adjuvant treatment: 56% received systemic therapy (chemotherapy, tyrosine kinase inhibitors, immune therapy and traditional Chinese medicine), 27% transarterial chemoembolization (TACE) plus systemic therapy and 17% TACE alone. The majority of respondents (75%) identified physicians as the decision makers for use of adjuvant therapy and selection of treatment regimen. Of the 38% of respondents who did not receive adjuvant treatment, 90% gave ‘physician recommendation’ as the reason. When patients were the decision makers, factors influencing decisions to use adjuvant treatment and selection of treatment regimen, ranked from most to least influential, were efficacy (for prevention of tumor recurrence), reimbursement status, treatment side effects and cost. Patient willingness to receive adjuvant treatment was influenced by predicted risk of recurrence; among respondents with an estimated 2-year recurrence risk > 10% and > 30%, 40% and 56%, respectively, believed they should receive adjuvant therapy. Conclusions: A majority of patients surveyed received adjuvant therapy, the most common of which were systemic therapy and TACE. Patients who underwent resection had a strong desire to reduce postoperative recurrence by using adjuvant therapy. Physician opinion was identified as the most important factor in treatment decision making, followed by economic factors. When patients were the decision maker, the most influential factors were treatment effectiveness followed by reimbursement status.
Defining optimal selection criteria to improve prognosis and avoid futility in surgical resection of colorectal peritoneal metastases.
Authors: Bijelic Lana , Ramos Isabel , Sabia Domenico , Crusellas Oriol , Martin Montse , Barrios Pedro 
Published: January 2021

36 Background: Surgical resection of peritoneal metastases of colorectal cancer (CRC PM) may benefit some patients similar to hepatic metastases. This approach remains controversial in part due to inconsistent selection criteria and reported outcomes. The impact of preoperative clinical characteristics and tumor molecular profiles on survival among surgically treated patients is incompletely understood. The aim of this study was to investigate the relationship between possible predictive variables and survival in a large cohort of patients treated on a standardized clinical pathway and to develop a clinically useful patient selection tool. Methods: This retrospective cohort study utilized the database of the Catalonian peritoneal metastases regional program, established in 2006. The program provides treatment for all PM patients within an autonomous region with a population of 7.5 million and includes a single dedicated high volume surgical unit. We included all adult patients with surgically resected CRC PM. The clinical pathway includes the administration of perioperative (neoadjuvant and adjuvant) systemic chemotherapy and has historically included a dose of heated intraoperative intraperitoneal chemotherapy (HIPEC) at the time of surgery. Demographic and clinical data was analyzed with descriptive statistics. Survival and the associated predictors were analyzed with the Cox proportional hazard model with HRs used to create a predictive nomogram. Results: A total of 538 patients (mean age 59) have been treated with surgery and a complete resection (CC0) was achieved in 94% of cases. Planned preoperative systemic chemotherapy was delivered in 95% of cases, consistent with the clinical pathway. Surgical morbidity was low (urgent reoperation 6.1%, postoperative return to the ICU 2.4%, 30-day readmission 4.3%) as was 30-day mortality (0.4%). After a median follow up of 27.5 months, the median overall survival (OS) was 43.1 months. It varied considerably by subgroup: patients with low peritoneal tumor burden had the highest OS (median 49 months) and those with signet ring cell subtype the lowest (median 19 months). Factors independently associated with survival were: N stage at diagnosis, histological subtype, quantified peritoneal tumor burden (PCI score) and presence of visceral involvement. A selection tool and predictive nomogram were designed incorporating the results of the multivariable analysis. Conclusions: A set of clinical variables can be identified that independently influences patient survival after surgical resection of CRC PM that should be used as selection criteria when considering surgery. With optimized patient selection and treatment within a specialized center, excellent survival and low morbidity can be anticipated following surgery for CRC PM.
A clinical score (CS) for patients with well-differentiated neuroendocrine tumors (WD NETs) under consideration for peptide receptor radionuclide therapy (PRRT) with Lu 177-dotatate.
Authors: Das Satya , Du Liping , Schad Aimee , Jain Shikha , Jessop Aaron , Shah Chirayu , Eisner David , Cardin Dana Backlund , Ciombor Kristen Keon , Goff Laura Williams , Bradshaw Marques , Delbeke Dominique , Sandler Martin P. , Berlin Jordan 
Published: January 2021

363 Background: Despite the benefit of PRRT for patients with WD NETs, questions remain regarding sequencing and optimal patient selection for the treatment. We developed a CS at Vanderbilt Ingram Cancer Center (VICC) that we hoped would predict outcomes for patients with WD NETs receiving PRRT. Methods: Patients with progressive WD NETs (N = 146) under consideration for PRRT with Lu 177-dotatate between 3/1/2016-3/17/2020 at VICC (N = 122) and Rush Medical Center (RMC) (N = 24) were scored. The CS included 5 categories: available non-PRRT treatments for tumor type, prior systemic treatments, patient symptoms, tumor burden in critical organs and peritoneal carcinomatosis presence. All categories were scored from 0-2 except the peritoneal carcinomatosis category which was scored from 0-1; scoring criteria were determined by the VICC NET tumor board. All patients at VICC were prospectively scored, while patients from RMC were scored retrospectively with the investigator blinded to patient outcomes. The primary outcome, progression-free survival (PFS) was estimated by the Kaplan‐Meier method; a Cox proportional‐hazards model adjusting primary tumor site, tumor grade and number of PRRT doses administered (none, 1-2 doses or 3-4 doses) was used to analyze effect of CS. Results: Median patient age was 62.7 while median CS was 5 (range 1-8); the most common primary tumor sites were small intestinal (N = 81) and pancreatic (N = 37). A total of 101 patients and 31 patients received 3-4 doses and no doses of PRRT, respectively. On multivariable analysis, in patients treated with 3-4 doses of PRRT, for each 2-point increase in CS, the estimated hazard ratio (HR) for PFS was 3.26 (95% confidence interval (CI) 2.05-5.19). On multivariable analysis, in patients who received no doses of PRRT, for each 2-point increase in CS, the estimated HR for PFS was 1.37 (95% CI .78-2.41). Conclusions: Among patients treated with 3-4 doses PRRT, those with lower CS had better PFS with the treatment compared to patients with higher CS. This PFS difference, based upon CS, was not observed in patients who did not receive PRRT, suggesting the predictive utility of the CS for patients with WD NETs receiving PRRT with Lu 177-dotatate. Though the CS needs to be validated, it is the first of its kind reported.
Treatment response and clinical outcomes of well-differentiated high-grade neuroendocrine tumors to 177Lu-DOTATATE.
Authors: Coffman Kelley Lauren , Bodei Lisa , Le Tiffany , Choi Ye , Chou Joanne F. , Capanu Marinela , Dunphy Mark , Fox Josef J. , Grewal Ravinder K , Reddy Ryan , Riedl Christopher , Schöder Heiko , Reidy Diane Lauren , Raj Nitya Prabhakar 
Published: January 2021

368 Background: 177Lu-DOTATATE is an approved therapy for somatostatin receptor (sstr) positive gastroenteropancreatic neuroendocrine tumors (NETs). There are little data available on response and outcomes for well differentiated (WD) high grade (HG) NETs treated with 177Lu-DOTATATE. Methods: Pts with WD HGNETs treated with 177Lu-DOTATATE at MSK from 2018-2020 were identified. Demographics, response to treatment, and progression-free survival (PFS) were determined. In pts with archival tumor tissue, next-generation sequencing (NGS) was performed through an institutional platform (MSK-IMPACT). Results: 19 pts were identified (mean age 54, 63% female). Site of tumor origin included: pancreas (14/19, 74%), small bowel (2/19, 10.5%), rectal (2/19, 10.5%), lung (1/19, 5%). Average tumor Ki-67 was 34.8 (range 22-56). All tumors were sstr avid on pre-treatment Ga68-DOTATATE PET/CT; none of the patients had sstr negative lesions detected. Median number of prior treatments (systemic and/or liver-directed) was 4 (range 2-7). All pts had progressive disease prior to initiation of 177Lu-DOTATATE. 13 pts (68%) completed all four treatment cycles; treatment was incomplete in 6 pts due to treatment-related toxicities (n = 3) and clinical progression (n = 3). Best response by radiographic report was available in 16 patients (84%):10/16 (63%) with partial response, 1/16 (6%) with stable disease, 5/16 (31%) with disease progression. One pt with stable disease as best response received two additional cycles of 177Lu-DOTATATE at progression. Median PFS (from date of first treatment with 177Lu-DOTATATE until progression/death) was 11.1 months (95% CI 10.6 to NA). Five pts (26%) experienced dose modifying toxicity with 177Lu-DOTATATE. The most common treatment-related toxicities were thrombocytopenia (9 pts, 47%; G3/4 in 1 pt, 5%), anemia (7 pts, 37%; G3/4 in 2 pts, 10.5%), leukopenia (6 pts, 32%; G3/4 in 0 pts), and AST/ALT elevation (4 pts, 21%; G3/4 in 0 pts). NGS results were available in the tumor tissue of 13 pts (68%). The most commonly observed alterations were in MEN1 (6/13, 46%) and DAXX (4/13, 31%). No RB1 alterations were identified. Conclusions: We observed a meaningful disease control rate of 69% during treatment of WD HGNETs with 177Lu-DOTATATE. In this heavily pre-treated population, more than half of pts received all four treatment cycles with treatment-related toxicities largely bone-marrow related, as expected, based on historical data. As would be expected in sstr avid tumors, the vast majority had alterations in chromatin remodeling genes (MEN1, DAXX) consistent with WD NETs, with no RB1 alterations identified.
Efficacy of ipilimumab and nivolumab in patients with high-grade neuroendocrine neoplasms.
Authors: Al-Toubah Taymeyah E. , Gile Jennifer , Strosberg Jonathan R. , Halfdanarson Thorvardur Ragnar 
Published: January 2021

370 Background: Dual checkpoint inhibitor therapy with anti-PD-1 and ant-CTLA-4 therapy has shown promising results in patients with high-grade NENs, demonstrating varying response rates of 9 – 44%. More data are needed to evaluate the true response in a real-world cohort of patients. Methods: Retrospective study of all patients with high-grade neuroendocrine neoplasms treated at the Moffitt Cancer Center and Mayo Clinic between 9/2017 and 7/2020 who received combination therapy with ipilimumab and nivolumab. Primary endpoint was objective response rate. Results: 34 patients met eligibility criteria for evaluation. Patients had received an average of 2 lines of therapy prior to treatment with ipilimumab/nivolumab, including at least one cytotoxic chemotherapy regimen. 27 (79.4%) of patients had poorly differentiated NECs and 7 (20.6%) had well-differentiated high grade NETs. The most common primary site (10, 29.4%) was pancreas; other primary sites of disease included unknown primary (n = 9), colon (n = 5), uterus (n = 3), anorectum (n = 2), esophagus (n = 2), cervix (n = 1), stomach (n = 1), and small intestine (n = 1). 5 patients (14.7%) exhibited a best response of PR per RECIST 1.1 criteria, 9 (26.5%) SD, and 17 (50%) PD: 3 patients did not have a follow-up scan and discontinued treatment shortly after initiation due to clinical progression. ORR was 14.7% and DCR was 41.2%. Median PFS was 1 month (95% CI, 0.45 – 1.55); median OS from time of treatment initiation was 5.0 months (95% CI, 3.42 – 6.59) and median OS from diagnosis was 14.0 months (95% CI, 1.49 – 26.51). Median duration on treatment was 1 month (range 0 – 10 months). 26 patients discontinued treatment for progression, 4 patients for toxicity, and 4 remain on treatment at the time of data cut off. 12 patients (35%) experienced grade 3 and 4 treatment-emergent toxicities: liver transaminitis, elevated blood bilirubin, arthralgia, myalgia, peripheral sensory neuropathy, lower extremity edema, confusion, diarrhea, encephalopathy, acute kidney injury, rhabdomyolysis, myocarditis, and colitis. Conclusions: The ipilimumab and nivolumab regimen has modest activity in aggressive and heavily pretreated high-grade NENs who have progressed on prior cytotoxic chemotherapy. Use of this regimen may be considered in patients with particularly aggressive, refractory high-grade NENs.
Alliance A021501: Preoperative mFOLFIRINOX or mFOLFIRINOX plus hypofractionated radiation therapy (RT) for borderline resectable (BR) adenocarcinoma of the pancreas.
Authors: Katz Matthew H. G. , Shi Qian , Meyers Jeffrey P. , Herman Joseph M. , Choung Michael , Wolpin Brian M. , Ahmad Syed , Marsh Robert de Wilton , Schwartz Lawrence Howard , Behr Spencer , Frankel Wendy L. , Collisson Eric Andrew , Leenstra James Lewis , Williams Terence Marques , Vaccaro Gina M. , Venook Alan P. , Meyerhardt Jeffrey A , O'Reilly Eileen Mary 
Published: January 2021

377 Background: Neoadjuvant therapy has been associated with a median overall survival (OS) of 18 – 23 months (mo) in patients (pts) with BR pancreatic ductal adenocarcinoma (PDAC). To establish reference regimens to which novel treatments can be compared in future studies, we evaluated neoadjuvant mFOLFIRINOX with or without RT in BR PDAC in a phase II National Clinical Trials Network (NCTN) trial. Methods: Pts with ECOG PS 0-1 and BR PDAC confirmed by central real-time radiographic review after pre-registration were randomized to either arm A: 8 cycles of neoadjuvant mFOLFIRINOX (oxaliplatin 85 mg/m2, irinotecan 180 mg/m2, leucovorin 400 mg/m2 and infusional 5-fluorouracil 2400 mg/m2 over 46 hours), or arm B: 7 cycles of mFOLFIRINOX followed by stereotactic body RT (SBRT, 33-40 Gy in 5 fractions [fx]) or hypofractionated image guided RT (HIGRT, 25 Gy in 5 fx). Pts in either arm without disease progression underwent pancreatectomy, then 4 cycles of adjuvant mFOLFOX6 (oxaliplatin 85 mg/m2, leucovorin 400 mg/m2 and infusional 5-fluorouracil 2400 mg/m2 over 46 hours). The primary endpoint, 18-mo OS rate, of each arm was compared to a historical control of 50%. Planned interim analysis mandated closure of either arm in which <11 of first 30 accrued pts underwent R0 resection. Results: 155 pts pre-registered and 126 pts were enrolled to arm A (N=70; 54 randomized, 16 following closure of arm B) or arm B (N=56; closed at interim analysis, all pts randomized prior to closure). Median age (A: 63y, B: 67y), median CA 19-9 level (A: 171 U/ml, B: 248 U/ml) and ECOG PS (A: 51% PS 0, B: 57% PS 0) of registered pts were similar between arms (p > 0.05). Treatment detailed in Table. The 18-mo OS rate based on Kaplan Meier estimates was 67.9% (95%CI: 54.6 – 78.0) in arm A and 47.3% (95%CI: 33.7 – 59.7) in arm B. Among pts who underwent pancreatectomy, 18-mo OS rate was 93.1% (95%CI: 84.3 – 100) and 78.9% (95%CI: 62.6 – 99.6) in arm A and B, respectively. With median follow-up of 27 and 31 mo, median OS was 31.0 (95%CI: 22.2 – NE) mo and 17.1 (95%CI: 12.8 – 24.4) mo in arm A and B, respectively. Conclusions: Neoadjuvant mFOLFIRINOX was associated with favorable OS relative to historical data in pts with BL PDAC in this phase II NCTN trial. mFOLFIRINOX with hypofractionated RT did not improve OS compared to historical data. mFOLFIRINOX represents a reference regimen in this setting and a backbone on which to add novel agents. Support: U10CA180821, U10CA180882, U24CA196171; https://acknowledgments.alliancefound.org Clinical trial information: NCT02839343. [Table: see text]