bluuebunny/crossref_metadata_2025 huggingface dataset:
A randomized phase III trial comparing primary tumor resection plus chemotherapy with chemotherapy alone in incurable stage IV colorectal cancer: JCOG1007 study (iPACS).
Authors: Kanemitsu Yukihide , Shitara Kohei , Mizusawa Junki , Hamaguchi Tetsuya , Shida Dai , Komori Koji , Ikeda Satoshi , Ojima Hitoshi , Hasegawa Seiji , Shiomi Akio , Watanabe Jun , Takii Yasumasa , Yamaguchi Takashi , Katsumata Kenji , Ito Masaaki , Okuda Jyunji , Hyakudomi Ryoji , Shimada Yasuhiro , Katayama Hiroshi , Fukuda Haruhiko
Published: February 2020

7

Background: It is still controversial whether primary tumor resection (PTR) before chemotherapy (CTX) improves overall survival (OS) of colorectal cancer (CRC) patients (pts) with synchronous unresectable metastases. There are several retrospective analyses suggesting better outcomes in pts who underwent PTR compared to pts without it, but no prospective studies confirming these results. We conducted a randomized controlled trial to confirm the superiority of PTR plus CTX to CTX alone in asymptomatic unresectable stage IV CRC patients. Methods: Eligibility criteria included histologically proven colon and upper rectal adenocarcinoma, cT1-4 without involvement of other organs, presence of three or less unresectable factors confined to either liver, lungs, distant lymph nodes, or peritoneum, aged 20-74, no symptoms due to primary tumor and PS 0-1. Eligible patients were randomized to either PTR followed by CTX or CTX alone. CTX regimens were declared before study entry; options included mFOLFOX6 plus bevacizumab or CapeOX plus bevacizumab. The primary endpoint was the OS. The planned sample size was 140 pts per arm, with one-sided alpha of 5%, and 70% power detecting a median OS difference of 8 months (24 months vs. 32 months). Results: Between Jun 2012 and Apr 2019, 160 patients were randomized. 78 pts were allocated to PTR plus CTX, and 82 pts to CTX alone. When the first interim analysis was performed in Sep 2019, with 50% (114/227) of the expected events observed, the DSMC recommended the early termination of the trial based on its futility. With a median follow-up period of 22.0 months for 160 patients, median OS was25.9 months (95% CI 19.9 – 31.5) with PTR plus CTX and 26.7(21.9 – 32.5) with CTX alone (hazard ratio 1.10 [0.76 – 1.59], one-sided p = 0.69). Median PFS was 10.4 (8.6-13.4) with PTR plus CTX and 12.1 (9.4 – 13.2) with CTX alone (hazard ratio 1.08 [0.77 – 1.50]). There were three treatment related deaths following PTR due to postoperative complications. Conclusions: PTR followed by CTX has no survival benefit over CTX alone. PTR is not recommended for CRC patients with asymptomatic primary tumor and synchronous unresectable metastases. Clinical trial information: UMIN000008147.
Does nutritional status affect treatment tolarability, response, and survival in metastatic colorectal cancer patients? Results of prospective multicenter study.
Authors: Karabulut Senem , Dogan İzzet , Afşar Çiğdem Usul , Karabulut Mehmet , Karaman Sule , Ferhatoglu Ferhat , Tastekin Didem
Published: February 2020

70

Background: The efficacy and tolerability of modern cytotoxic chemotherapy regimens used in malnourished metastatic colorectal cancer patients is uncertain. The aim of this study was to investigate the effect of malnutrition on efficacy and tolerability of cytotoxic chemotherapy and overall survival in mCRC patients. Methods: In this multicenter study, demographic, oncologic and nutritional data were collected prospectively from mCRC patients. Nutritional status were evaluated on the basis of NRI, BMI and WL before the first chemotherapy, after the first and second chemotherapy. To determine the inter-treatment weight loss toxicity assessment was included to theese parameters after each chemotherapy. NRIs were examined in 3 categories as ‘no malnutrition’ (NRI >97.5), ‘moderate malnutrition’ (97.5 ≥ NRI ≥83.5) or ‘severe malnutrition’ (NRI <83.5). Response to treatment and drug-induced toxicities were assessed based on RECIST 1.1 and CTCAE version 4.0 respectively. Results: 137 mCRC patients were prospectively included. Median age was 48 (range 18-83). Primary location was colon in 66% of patients, 84% of them source was left colon. Malnutrition was detected in 39% of the cases. Response rate to treatment was 24 %. Moderate / severe malnutrition was associated with multipl site of metastases, WHO PS of 1, over the median value of CEA/CA 19-9 levels (p=0.003, p=0.03, p<0.001, and p=0.02; respectively). Hypoalbuminemia and moderate/severe malnutrition were associated with all types of toxicity (p<0.001 and p<0.001). Moderate/severe malnutrition was associated with thrombocytopenia, and diarrhea following chemotherapy predominately, (p=0.02 and p=0.04; respectively). In moderate/severe malnutrition group median overall survival was prominently shorter than those with no malnutrition [6.6 moths (95 %CI, 5.6-7.6) vs 11.9 moths (95 % CI, 11.1-12.7) respectively, p<0.001]. Conclusions: Our study showed that moderate/severe malnutrition in mCRC patients was associated with decreased overall survival and increased chemotherapy toxicity.
Radiation as a single modality treatment in localized pancreatic cancer.
Authors: Shaib Walid Labib , Zakka Katerina Mary , Shahin Asser , Yared Fares , Switchenko Jeffrey M. , Wu Christina , Akce Mehmet , Alese Olatunji B. , Patel Pretesh R. , McDonald Mark William , El-Rayes Bassel F.
Published: February 2020

703

Background: Locally advanced pancreatic cancer (LAPC) is managed with multimodality therapy. A subset of patients with LAPC are not good candidates for aggressive treatment. The aim here is to evaluate the outcomes of single modality radiation therapy for LAPC using the National Cancer Database (NCDB). Methods: Data was obtained between years 2004 and 2013. Pancreatic ductal adenocarcinoma (PDAC) patients with unresectable local disease were identified excluding patients who received chemotherapy or surgery. Univariate and multivariable analyses identified factors associated with patient outcome. Kaplan-Meier analysis and Cox proportional hazards models were used for patient characteristics and overall survival (OS). Results: A total of 6,590 patients were included; 480 (6.9%) received radiation therapy only and 6470 (93.1%) received no treatment. Mean age was 73.5 (range, 28‐90) years, with the majority being White (N = 5685; 83.2%) and female (N = 3779; 54.4%). Poorly differentiated histology and tumors ≥ 4 cm ( > T3 stage) accounted for 47.8% and 52.7%, respectively. The median dose of radiation was 39.6 Gy. Stereotactic body radiation (SBRT) was given in 64 patients and external-beam/Intensity modulated radiotherapy (IMRT) in 416 patients. Charlson-Deyo score of +1 was seen in 34.4% of patients who received no treatment, 32.8% of patients who received SBRT and in 29.8% of patients who received external-beam IMRT. Radiation therapy was associated with improved OS compared to no treatment in univariate and multivariable analyses controlling for sex, Charlson-Deyo score, age, tumor size, amongst other covariates. Median OS for patients who received SBRT, external-beam/IMRT or no radiation was 8.6, 6.7 and 3.4 months; respectively (P < 0.001). There is a significant difference in 12-month OS for the SBRT cohort (31.9%; 95% CI 20.9%-43.5%) compared to patients who received no radiation (15.1%; 95% CI 14.2%-16.0%), similarly seen on multivariable analysis (HR 0.50; 95% CI 0.38-0.65; P < 0.001). Conclusions: The current study is the first to evaluate the efficacy of radiation as single modality therapy in LAPC. The results suggest a potential benefit for radiation therapy alone, in comparison to no treatment.
Phase III, international, randomized trial of adjuvant nab-paclitaxel plus gemcitabine (nab-P + G) versus gemcitabine (G) for resected pancreatic cancer (APACT): Recurrence patterns.
Authors: Sahai Vaibhav , Tabernero Josep , Van Cutsem Eric , Reni Michele , Tempero Margaret A. , O'Reilly Eileen Mary , Berlin Jordan , Riess Hanno , Goldstein David , Li Mingyu , Lu Brian , Ferrara Stefano , Philip Philip Agop
Published: February 2020

704

Background: APACT did not meet the primary endpoint of independently assessed disease-free survival (DFS) with nab-P + G vs G; overall survival showed a nominal improvement. Here, we report recurrence patterns by resection status. Methods: A total of 866 treatment-naive patients (pts) with histologically confirmed pancreatic cancer, R0/R1 resection, CA19-9 < 100 U/mL, and ECOG PS ≤ 1 received 6 cycles of nab-P + G or G on days 1, 8, and 15 Q28 days. Stratification: resection (R0/R1); lymph node status (LN+/−); geographic region. Disease recurrence was per investigator review of CT/MRI scans. Results: Of 571 (66%) pts with investigator-assessed DFS events (median follow up, 35.4 mo), 543 had radiographic progression with 764 recurrent lesions (≥ 20 events: liver, 271; unspecified abdominal organ, 152; lung, 130; surgical bed, 70; mesenteric nodes, 54). Most pts (73%) had only abdominal, 61% had only distant, and 10% had only local recurrence (Table). Although more pts with R1 vs R0 status had recurrence (72% vs 60%), patterns were generally similar, and local recurrence was similarly low. Conclusions: Most recurrences in APACT were distant and in abdomen (liver). Recurrence patterns were generally similar in pts with R0 and R1 status, with low rates of local recurrence. These data may help make more informed pt management decisions. Additional data on patterns by baseline characteristics will be presented. Clinical trial information: NCT01964430 . [Table: see text]
Comparing total cost of care for Medicare FFS patients with pancreatic cancer by chemotherapy regimen.
Authors: Hirsch Jared , Dieguez Gabriela , Cockrum Paul
Published: February 2020

721

Background: To analyze total cost of care for patients with pancreatic cancer by FDA-Approved/NCCN Category 1 regimen. Methods: Cancer episodes were identified using a methodology similar to the Medicare Oncology Care Model (OCM) in the 2014-2016 100% Medicare Limited Data Set (LDS) claims files. Index dates were established for chemotherapy claims that did not occur within 6 months of another chemotherapy claim for all Medicare fee-for-service beneficiaries. Cancer episodes were defined as the 6-month period following an index date. Each episode was assigned a cancer type based on the plurality of cancer ICD 9/10 diagnosis codes that occurred on chemotherapy claims in the episode. Episode costs were calculated from claim paid amounts, and DME and other Part B spending was estimated using episodes created in the 5% Medicare LDS files using the same methodology. We analyzed total episode costs for three FDA-Approved/NCCN Category 1 pancreatic cancer regimens: gemcitabine plus nab-paclitaxel (gem-nab), FOLFIRINOX (FFX), and liposomal irinotecan (nal-IRI). Results: We identified 110,618 cancer episodes in 2016, of which 4,018 were for pancreatic cancer (average age at index: 71.3 years). Pancreatic cancer patients in these episodes were treated with gem-nab (45% of episodes), FFX (14%), and nal-IRI (4%). The main cost drivers across all regimens were Part B chemotherapy, other Part B drugs and inpatient services. Episode costs were $41,749, $42,086, and $45,851 for patients receiving gem-nab, FFX, and nal-IRI, respectively. Part B chemotherapy costs were $13,065 (gem-nab), $3,095 (FFX), and $18,472 (nal-IRI); other Part B drug costs were $7,343 (gem-nab), $17,013 (FFX), and $10,479 (nal-IRI); and inpatient service costs were $9,044 (gem-nab), $9,069 (FFX), and $5,108 (nal-IRI). Conclusions: Total episode costs for pancreatic cancer care were similar among three FDA-Approved/NCCN Category 1 regimens, but the components of cost varied. Episodes with Nal-IRI had the largest Part B chemotherapy costs and the lowest inpatient service costs. Episodes with FFX and gem-nab had similar inpatient service costs, which were higher than episodes with nal-IRI. Episodes with FFX had the highest other Part B drug costs.
DNA-damage repair deficiency (dDDR) and response to nanoliposomal irinotecan (nal-IRI) in metastatic pancreatic ductal adenocarcinoma (mPDAC).
Authors: Rau Sameeha , Espejo Freire Andrea P. , Terrero Gretel , Patel Manisha Jayandra , Rush Benjamin Woodress , Rocha Lima Caio Max Sao Pedro , Hosein Peter Joel
Published: February 2020

731

Background: Chemotherapy is the standard of care for patients with mPDAC but there are no biomarkers to aid in treatment selection. Nal-IRI with 5-fluorouracil/folinic acid (FUFA) improves survival over FUFA in the second-line treatment of mPDAC. Nal-IRI is a topoisomerase inhibitor and its action produces DNA damage leading to cell death. We hypothesize that tumors with dDDR, a process that is altered in a subset of patients with PDAC, may be more sensitive to the effects of nal-IRI. Methods: Utilizing the IRB-approved pancreas cancer databases at the University of Miami and Wake Forest University, we identified patients with mPDAC treated with nal-IRI and FUFA who had germline and/or somatic mutation testing. We conducted a retrospective chart review to extract demographic and clinical characteristics including treatments received, response, and survival. Results: Among 31 patients identified, the median age was 66y and 47% were female. Nine patients had a DDR mutation; 6 germline and 3 somatic. Median progression-free survival (PFS) in patients with any germline or somatic DDR mutation was 3.2m vs 3.9m for those without (log-rank p = 0.7). When restricted to germline DDR mutations only, the median PFS was not reached with germline dDDR vs 4m for those without (log-rank p = 0.22). Presence of dDDR was associated with a higher clinical benefit rate (CBR = partial response + stable disease); a DDR mutation was present in 36% of patients who showed clinical benefit vs 15% in those without clinical benefit (p = 0.21). Conclusions: DDR mutations appear to define a subset of patients with mPDAC who may be more sensitive to nal-IRI and FUFA. The PFS and CBR were numerically but not statistically superior, especially in patients with germline DDR mutations. Larger data sets and longer follow-up are needed to confirm this trend.
Gray areas and evidence gaps in the management of rectal cancer as revealed by the comparison of recommendations from national and international clinical guidelines.
Authors: Bregni Giacomo , Akin Telli Tugba , Camera Silvia , Baratelli Chiara , Shaza Leila , Deleporte Amélie , Moretti Luigi , Liberale Gabriel , Hendlisz Alain , Sclafani Francesco
Published: February 2020

74

Background: While the management of nonmetastatic and oligometastatic rectal cancer has rapidly evolved over the last few decades, many grey areas and highly debated topics remain that foster significant variation in clinical practice. We aimed to identify controversial points and evidence gaps in this disease setting by systematically comparing recommendations from national and international clinical guidelines. Methods: Twenty-six clinical questions reflecting practical challenges in the routine management of nonmetastatic and oligometastatic rectal cancer patients were selected. Recommendations from the ESMO, NCCN, JSCCR, Australian and Ontario guidelines were extrapolated and compared using a 4-tier classification system (i.e., identical/very similar, similar, slightly different, different). Overall agreement between guidelines (i.e., substantial/complete disagreement, partial disagreement, partial agreement, substantial/complete agreement) was assessed for each clinical question and compared against the highest level of available evidence according to the Oxford CEBM Levels of Evidence guidelines by using the χ2 statistic test. Results: Guidelines were in substantial/complete agreement, partial agreement, partial disagreement, and substantial/complete disagreement for 8 (30.8%), 2 (7.7%), 7 (26.9%), and 9 (34.6%) clinical questions, respectively. High level of evidence supported clinical recommendations in 2/10 cases (20%) where guidelines were in agreement and in 10/16 cases (62.5%) where guidelines were in disagreement (χ2 = 4.4726, p = 0.034). Agreement was frequently reached for questions regarding diagnosis, staging, and radiology/pathology pro-forma reporting, while disagreement characterised most of the treatment-related topics. Conclusions: Substantial variation exists across national and international clinical guidelines in the recommendations for the management of nonmetastatic and oligometastatic rectal cancer. This variation is only partly explained by the lack of supporting, high-level evidence.
Clinical significance of MUC4 isoforms in pancreatic cancer patients.
Authors: Thompson Christopher M , Cannon Andrew , Kshirsagar Prakash , Bhatia Rakesh , Batra Surinder , Kumar Sushil
Published: February 2020

742

Background: Pancreatic adenocarcinoma (PC) is a highly aggressive cancer with a 5-year survival rate around 9% with majority of patients diagnosed at advanced stage. Prior studies describe transcriptomic alterations during tumorigenesis, of which novel and progressive expression of mucins are significant. Mucins are large secreted or membrane-tethered glycoproteins that have been shown to be of pathogenic importance in PC. Methods: We explored differential expression and survival outcomes based on mucin expression using TCGA PC patients (n = 150). RNA-Seq. reads were realigned to all known mucin splice variant (SV) sequences. Hazard ratios (HR) were calculated for all SVs (n = 123), and SVs with significant HRs were plotted on Kaplan-Maier survival curves comparing expression about the median. The MUC4 SV (MUC4Δ6) was selected for validation in patient tumor samples (n = 17) due to PC tumor cell-specific expression and in-frame deletion of a single exon. After discovery of significant mucin SVs, we designed a gold-nanoparticle (GNP) assay to specifically detect MUC4Δ6 in circulation from PC patient plasma. Results: In the absence of significant mucin-based survival differences, we expanded our analysis to include mucin SV transcripts. Through hazard and survival analyses, we identified 3 MUC1 SVs with better survival (SV1 HR = .61, p = .033; SV2 HR = .64, p = .05; SV3 HR = .62, p = .04), and one each of MUC4 (HR = 1.93, p = .028) and MUC16 (HR = 1.90, p = .027) with worse prognosis. In a validation cohort, we found 10 samples had a high cellularity (HC) gene signature. Expression of MUC4Δ6 was 4804.7 copies/100,000 GPI copies in the HC population and expressors above the median had a median survival of 397 days compared to1964.5 days (p = .191) in low expressors. Our novel GNP assay detected MUC4∆6 transcripts at minimum concentrations of 100 fM with a synthetic RNA. Uniquely, our assay detects the MUC4∆6 SV but not wild-type variant. Conclusions: We were able to determine that expression of specific mucin SV are prognostic in PC patients. We developed technology to detect MUC4Δ6 transcript in circulation using a novel GNP assay. Future studies will seek to stabilize the nanoparticles and modify them for potential diagnostic purposes in a clinical setting.
CEACAM6 as a candidate biomarker for pelareorep sensitivity in pancreatic adenocarcinoma (PDAC).
Authors: Noonan Anne M. , Yount Jacob , David Jason , Hoang Mindy , Stets Colin W. , Bekaii-Saab Tanios S. , Huang Ying , Frankel Wendy L. , Timmers Cynthia Dawn , Hays John L. , Chen James Lin
Published: February 2020

746

Background: Pelareorep is a proprietary formulation of live, replication-competent, naturally occurring Reovirus Type 3 Dearing strain. A randomized phase II trial of pelareorep in combination with carboplatin and paclitaxel in first-line treatment of metastatic PDAC (NCT01280058) was performed. Although pelareorep did not improve the primary endpoint of progression-free survival compared to carboplatin and paclitaxel alone, impressive durable responses were seen in the pelareorep arm in some patients (pts). Further, prior studies have noted the immunomodulatory carcinoembryonic antigen-related cell adhesion molecule (CEACAM6/CD66c) as a receptor for specific viral subtypes. We thus speculated that altered CEACAM6 levels may be predictive for pelareorep sensitivity. Methods: Pre-treatment tissue biopsies were collected prior enrolment for all 73 pts on study. Evaluable pts with transcriptomic data was available for only 31 pts. RNA was purified from FFPE tissue and gene expression analysis was performed using SensationPlus FFPE Amplification and WT labelling kit and the Human Transcriptome Array 2.0. CEACAM6 protein expression was determined by immunohistochemistry. Differential gene expression and survival analysis using were performed in R/Bioconductor. Appropriate corrections for multiplicity were performed. Results: When comparing extraordinary responders in the pelareorep treated arm to those with poor outcomes, low levels of CEACAM6 mRNA expression were associated with prolonged PFS in pelareorep-treated pts (adjusted p = 0.05). This effect was not seen in non-pelareorep treated pts. The luminal, but not the cytoplasmic immunohistochemistry score, was highly correlated with mRNA expression levels of CEACAM6, p = 0.001. Modulation of CEACAM6 in vitro and in vivo are underway. Conclusions: CEACAM6 may be a candidate biomarker of sensitivity to pelareorep and, in theory, could improve viral trafficking of this compound in tumor cells. Clinical trial information: NCT01280058 . [Table: see text]
The relationship between perioperative markers of the systemic inflammatory response and postoperative complications in patients undergoing curative resection of colon cancer.
Authors: Knight Katrina , Choong Jia Xun , Roxburgh Campbell SD , Horgan Paul G. , McMillan Donald C.
Published: February 2020

75

Background: Surgical resection remains the mainstay of treatment for patients with potentially curable colorectal cancer (CRC). However, it can be associated with the development of postoperative complications (POC), which are associated with an increased cancer recurrence risk. Neutrophils are important in innate immunity, especially in the immediate postoperative period as part of the systemic inflammatory response (SIR). We aimed to assess the use of perioperative SIR markers as predictors of POC. Methods: Patients undergoing elective curative CRC surgery at one institution between March 2008 and June 2015 were identified from a prospective database. Demographics and clinicopathological data were extracted from medical records. Logistic regression was used to assess the relationship between perioperative blood counts, clinicopathological variables and POCs. Results: Of 443 cases, most were aged 65 years or older (n = 314, 71%), male (n = 245, 55%), smokers (n = 229, 52%), overweight or obese (n = 263, 59%) and had ASA score of 2 or less (n = 267, 60%). The majority underwent open resection (n = 288, 65%). Preoperative factors associated with the development of POC were: ASA grade > 2 (OR 1.48, 95% CI 0.99-2.18, p = 0.05), smoking history (OR 1.99, 95% CI 1.35 – 2.93, p < 0.001), neutrophil count > 7.5x109/L (OR 3.40, 95% CI 1.82-6.36, p < 0.001) and CRP > 10mg/L (OR 1.70, 95%CI 1.12-2.59, p = 0.013). Postoperative factors associated with the development of POC were open surgery (OR 0.47, 95%CI 0.31-0.72, p < 0.001), neutrophil count > 7.5x109/L (OR 2.67, 95%CI 1.75-4.07, p < 0.001) and CRP > 150mg/L (OR 3.97, 95%CI 2.61-6.02, p < 0.001) on postoperative day 3 (POD3). On multivariate analysis, a preoperative neutrophil count > 7.5x109/L (OR 3.65, 95%CI 1.68-7.90, p < 0.001), a neutrophil count > 7.5 x109/L on POD3 (OR 1.69, 95%CI 1.05-2.72, p = 0.029) and CRP > 150mg/L on POD3 (OR 3.66, 95%CI 2.29-5.87, p < 0.001) were related to POC, independent of smoking, ASA and operative approach. Conclusions: Neutrophil count complements the prognostic value of pre and post-operative CRP to predict POC. Further validation work is required.
Association of SMAD4 loss with response to neoadjuvant chemotherapy with the autophagy inhibitor hydroxychloroquine in patients with pancreatic adenocarcinoma.
Authors: Fei Naomi , Wen Sijin , Rao Pavan , Ramanathan Rajesh , Hogg Melissa E. , Zureikat Amer H. , Lotze Michael T. , Bahary Nathan , Singhi Aatur D. , Zeh Herbert , Boone Brian A.
Published: February 2020

761

Background: SMAD4, a tumor suppressor gene, is inactivated or deleted in 60-90% of pancreatic adenocarcinomas (PDA). Loss of SMAD4 allows tumor progression by limiting cell cycle arrest and apoptosis and increasing metastases. SMAD4 deficient PDA cells are resistant to radiotherapy by upregulation of autophagy, a cell survival mechanism that allows intracellular recycling of macromolecules and organelles. Hydroxychloroquine (HCQ) is a known autophagy inhibitor, suggesting that HCQ treatment in SMAD4 deficient PDA may prevent therapeutic resistance induced by autophagy upregulation. Methods: We retrospectively analyzed the SMAD4 status of PDA patients enrolled in two prospective clinical trials evaluating preoperative HCQ. The first dose escalation trial demonstrated the safety of preoperative gemcitabine with HCQ ( NCT01128296 ). More recently, a randomized trial of gemcitabine/nab-paclitaxel +/- HCQ evaluated Evans Grade histopathologic response ( NCT01978184 ). Immunohistochemistry of resected specimens for SMAD4 was previously performed. Patients not treated at the max HCQ dose (n = 5), not resected (n = 2) or with SMAD4 staining unavailable were excluded (n = 10). The effect of SMAD4 loss on response to HCQ and chemotherapy was studied for association with clinical outcome. Fisher’s exact test and log-rank test were used to assess response and survival. Results: 52 patients receiving HCQ with neoadjuvant chemotherapy and 24 patients receiving neoadjuvant chemotherapy alone were studied. Of the HCQ group, 25 patients had SMAD4 loss (48%), compared with 15 control patients (63%, p = 0.32). 76% of HCQ treated patients with SMAD4 loss obtained a histopathologic response ≥2A, compared to only 37% with SMAD4 intact (p = 0.006). In the control group, loss of SMAD4 was associated with a nonsignificant detriment in 3 year OS (25% vs. 78%, p = 0.3) that was less apparent in patients treated with HCQ (46% vs. 47%, p = 0.18). Conclusions: The addition of HCQ to neoadjuvant chemotherapy in PDA may improve treatment response in patients with SMAD4 loss. Further study of the relationship between SMAD4, autophagy and treatment outcomes in PDA is warranted.
Impact of surveillance among patients with resected pancreatic cancer following adjuvant chemotherapy.
Authors: Wong Selina , Gondara Lovedeep , Renouf Daniel John , Lim Howard John , Gill Sharlene
Published: February 2020

768

Background: Pancreatic adenocarcinoma carries a poor prognosis and high risk of recurrence even after surgery and adjuvant chemotherapy (AC). Guidelines recommend against routine surveillance imaging due to lack of evidence supporting a survival benefit. With current first-line chemotherapy options, it is unclear whether surveillance scans allow for early detection of asymptomatic disease and therefore an opportunity to offer fit patients chemotherapy. We describe the patterns of surveillance in patients followed at a Canadian provincial cancer agency and determine whether routine imaging after AC is associated with receipt of palliative chemotherapy (PC). Methods: A retrospective review was completed to identify patients treated at British Columbia (BC) Cancer centres between January 1, 2010 and December 31, 2016 who had undergone curative intent resection and received at least one cycle of AC. Baseline characteristics, number of scans done after completing AC to recurrence, and PC were collected. Logistic regression analysis was performed. Results: A total of 151 patients followed at BC Cancer were identified. Patients who recurred within 28 days after AC were excluded, leaving 142 patients, of which 115 patients had recurrence. We defined 2 cohorts based on number of scans done between completion of AC and recurrence: those with 0-1 scans were “symptomatic” recurrences (22 patients, median age 68y, 64% female, and 91% node-positive) and those with > 1 scan were “surveillance” recurrences (93 patients, median age 64y, 43% female, and 81% node-positive). Patients who underwent surveillance scans were more likely to receive PC at time of recurrence, though statistical significance was not reached (OR 2.11, 95% CI 0.75-6.58, p = 0.17). Conclusions: Despite guidelines, the majority of patients treated in BC underwent surveillance imaging. Within the limits of our sample size, we demonstrated a trend towards increased likelihood of receiving PC in patients who receive surveillance scans following AC. With efficacious PC options available, studies to determine whether receipt of PC in asymptomatic recurrences detected on imaging translates into improved survival and/or quality of life are warranted.
Timing and location of palliative care consultation in metastatic pancreatic cancer: A retrospective, single-center observational study.
Authors: Patel Timil , Miccio Joseph Anthony , Srikumar Thejal , Prsic Elizabeth Horn , Adelson Kerin B. , Kozhevnikov Dmitry , Patel Komal , Lacy Jill , Cecchini Michael
Published: February 2020

770

Background: Patients (pts) receiving treatment for metastatic pancreatic cancer (MPC) experience significant symptoms, treatment related side effects and psychosocial burdens. The ASCO guidelines recommend early palliative care consultation (PCC) to improve quality of life and survival. However, limited real-world data is available regarding the timing of PCC, hospice enrollment and location of death (LOD) in pts with MPC. Methods: We conducted a retrospective observational analysis of pts treated with chemotherapy for MPC at the Yale Smilow Cancer Hospital and affiliated community care centers (CCC) from January 2011 to April 2019. Patient demographics, treatment dates, initial PCC, enrollment of hospice at the time of death and LOD were manually abstracted from the electronic medical record. Univariate and multivariable logistic regression analyses were conducted to predict for PCC and death outside the hospital. Results: Of 363 pts identified with MPC who received chemotherapy, 38% (138) had a PCC. 67% (93) of patients’ initial PCC was in the hospital versus 33% (45) in the outpatient setting. The median time from the start of first-line chemotherapy to the first PCC was 5.2 months (interquartile range [IQR] 1.2 – 12.9). The median time from the first PCC to death was 1.5 months (IQR 0.5 – 4.42). At the time of our analysis, 300 pts had died and of those 76% (229) were enrolled on hospice at the time of death while 24% (71) were not. With respect to LOD, 47% (139) of pts died at home with hospice, 31% (94) at an inpatient hospice facility and 22% (67) died in the hospital. Female gender was associated with an increased likelihood of a PCC (HR 1.78, 95% CI 1.07-2.94, P = 0.026). Pts treated at a CCC were less likely to have a PCC (HR 0.21, 95% CI 0.12-0.36, P < 0.001). A PCC was not associated with a higher likelihood of death outside the hospital (HR 1.31, 95% CI 0.75-2.29, P = 0.346). Conclusions: Although most pts with MPC enroll in hospice, PCC is generally underutilized. In fact, many pts receive PCC near the end of life and in the hospital. Further studies are warranted to determine how best to incorporate early PCC to maximize supportive care for pts with MPC.
Prognostic value (PV) of pathologic response (PR) to neoadjuvant chemotherapy (NC) alone in resected pancreatic cancer (PDAC): Initial analysis.
Authors: Picozzi Vincent J. , Mandelson Margaret T. , Lin Bruce Shih-Li , Biehl Thomas R , Alseidi Adnan , Rocha Flavio G. , Helton Scott
Published: February 2020

771

Background: As neoadjuvant Rx for resected PDAC often includes chemoradiation, the PV of PR includes its impact. We began analysis of the impact of NC alone in this setting. Methods: Patients (pts) were identified from the Virginia Mason Pancreaticobiliary Cancer Database. Inclusion criteria: 1) Dx 1/2010 - 3/2019; 2) Path dx PDAC stage I-III; 3) NC ( any type) as sole neoadjuvant Rx; 4) complete surg path data; 5) longitudinal OS known. Exclusion criteria: 1) neoadjuvant chemoradiation; 2) unknown NC (outside providers only). Histologic response was scored as follows: ( 0=complete response, 1 ≥95% response, 2=50-95% response, 3<50% response). Results: Results for 134 pts are in Table. Median (med) f/u was 33 months (mo). In univariate analysis, all path features examined were statistically significant re med/5-yr OS. In multivariate analysis, risk increased with tumor size (HR 1.9, 95% CI 1.1-3.2) and tumor differentiation (HR 1.8, 95% CI 1.1-3.1 ) independent of other variables. Conclusions: 1) In univariate analysis, all PR features after NC had PV for med/5-yr OS, especially tumor size and histologic response score. NC type was not significant. 2) In multivariate analysis, risk increased with tumor size and tumor differentiation.3) This data needs extension to a bigger pt base/correlation with other variables (Ca 19.9, postop Rx, recurrence pattern etc.) for greater utility ( now underway). 4) This approach may aid postop Rx decision -making in this setting. [Table: see text]
Nonoperative management (NOM) in rectal cancer: Physician perspectives on offering NOM as standard of care.
Authors: Covelli Andrea Marie , Quereshy Fayez A. , Kennedy Erin Diane , Chadi Sami A. , Wright Frances Catriona
Published: February 2020

79

Background: 20% of rectal cancer patients will have a complete clinical response (cCR) following neoadjuvant chemoradiotherapy. Non-operative management (NOM) with close surveillance can spare patients proctectomy and avoid the sequelae of surgery. Patients are interested in and advocate for NOM, whereas oncologists appear to be reluctant to offer this option. We wished to identify the perceptions and barriers that oncologists face when considering NOM. Methods: This qualitative study explored oncologists’ experiences treating rectal cancer and identified their perceptions and values around NOM. Purposive and snowball sampling identified medical, radiation and surgical oncologists’ who treat a high volume of rectal cancer across Canada. Oncologists varied in length/location of practice and gender. Data were collected via semi-structured interviews. Constant comparative analysis identified key concepts. Results: Data saturation was achieved after 40 interviews: 20 surgeons, 12 radiation and 8 medical oncologists. The dominant theme was “NOM is not ready for prime time’. Most oncologists felt that there is insufficient long-term data around NOM and single center studies appear ‘too good to be true’. Physicians voiced concerns about worsening oncologic outcomes in the setting of regrowth, the challenges in determining a cCR and apprehension around patient compliance to surveillance. Some oncologists felt that NOM is limited to a very select population and voiced reluctance in offering it to younger patients or patients with more advanced disease. There was little consideration to improved functional outcomes with NOM. Overall the majority of participants felt that NOM is ‘ trading the benefit of saving the rectum for the uncertainty of an inferior oncologic outcome’. Conclusions: Oncologists felt that NOM should not be offered as a standard of care option following a cCR. Most felt that there is insufficient data supporting NOM and are concerned around worse oncologic outcomes. Patient views of NOM are critically needed to assess if patients value the same outcomes. Additional research is needed to address barriers should patients wish to consider NOM as a treatment option in the setting of a cCR.
Pattern of recurrence after curative resection of stage I-III duodenal adenocarcinoma.
Authors: Colina Andreina , Raghav Kanwal Pratap Singh , Katz Matthew H. G. , Das Prajnan , Ikoma Naruhiko , Koay Eugene Jon , Thomas Jane V , Tzeng Ching-Wei David , Wolff Robert A. , Overman Michael J.
Published: February 2020

794

Background: Duodenal adenocarcinoma (DA) is a rare cancer with limited data regarding the pattern of disease recurrence following resection. Methods: A retrospective review of 115 patients with Stage I-III DA from 3/1994 to 6/2018, at a single high-volume cancer center was conducted. Only patients (pts) who underwent a potentially curative surgical resection (R0/R1 margins) and had a postoperative follow-up radiographic evaluation were included. Periampullary adenocarcinomas were excluded. Clinicopathologic features and patterns of recurrence were compared across cohorts. Results: Of 76 patients who met inclusion criteria, 7 (9%) were stage I, 25 (33%) stage II, and 44 (57%) stage III. Histologic grade was moderate in 58% and poor in 38%. Median age was 63 years (range, 29-84), 38% were female, and R0 resection was 97%. Neoadjuvant therapy was given to 14% and adjuvant therapy to 61%. Radiation therapy (XRT) as either adjuvant/neoadjuvant therapy was used in 27%. Median follow-up was 44 (6-293) months. Median time to recurrence was 11mo, with 84% of recurrences occurring within 2 years. Median time to local recurrence (LR) vs. distant recurrence (DR) was 11mo vs. 12mo, respectively, p = 0.42. Stage impacted recurrence rate: 0% in stage 1 vs. 50% stage 2 vs. 71% stage 3 (p = 0.002). Median time to recurrence was 16mo for stage II and 11mo for stage III (p = 0.04). In total, 4 (5%) pts had LR only, 8 (10%) had LR concurrent with DR, and 32 (42%) had DR only. Recurrence distribution was similar across stage II (LR 8%, LR+DR 15%, DR 77%) and stage III (LR 10%, LR+DR 19%, DR 71%). LR was similar in patients that received XRT (10%) compared to those who did not (9%). Most common sites of DR were peritoneal (38%), liver (33%), distant lymph nodes (12%), and lung (10%). Conclusions: The recurrence pattern for resected DA is predominantly distant metastatic disease with the majority of recurrences occurring within the first two years. Future therapies should focus on improved systemic therapy, and surveillance should be most intensive in the first two years.
Pilot study to test safety and efficacy of avelumab in small bowel adenocarcinoma (SBA).
Authors: Cardin Dana Backlund , Whisenant Jennifer , Ayers G. Dan , Gilbert Jill , Dahlman Kimberly Brown , Shi Chanjuan , Berlin Jordan
Published: February 2020

797

Background: SBA is rare and often grouped with, and treated like, large intestinal adenocarcinomas. However, SBA has a very different microenvironment and could respond differently to the same therapies, potentially lowering efficacy. Also no standard treatments exist due to the lack of prospective randomized trials. We presented data at GI ASCO 2016 that suggested SBAs might benefit from targeting the PD-1/PD-L1 axis based on strong PD-L1 staining in ~50% of SBAs tested. Thus, we designed a pilot phase 2 trial to study safety and efficacy of avelumab in SBA. Methods: Patients (pts) with advanced (not amenable to surgery) or metastatic disease were eligible; ampullary tumors were considered part of the duodenum and allowed. Pts with prior PD-1/PD-L1 were excluded. Avelumab (10 mg/kg) was given every 2 weeks in 14-day cycles, and imaging was performed every 8 weeks. Primary endpoint was response rate (RR). Enrollment of 25 pts were planned, and avelumab would be considered active if ≥4 responses (RR≥16%) were observed (80% power, a = 5%). Secondary endpoints included disease-control rate (DCR) and progression-free survival (PFS). Results: Eight SBA pts (5 small intestine; 3 ampullary) were enrolled, with a majority (88%) being male and a median age of 61 years. Median time on treatment was 3.4 months; 1 patient is still on study with an ongoing partial response (PR). Of 7 efficacy-evaluable patients, 2 had a PR for a RR of 29%; DCR was 71% (5/7). Median PFS was 8.0 months. Most frequent, related adverse events were fatigue (38%), elevated alkaline phosphatase (25%), and infusion related reaction (25%), all ≤G2; a G3 (not serious) hypokalemia and a G4 (serious) diabetic ketoacidosis occurred in 1 pt each. Conclusions: Avelumab was considered safe, and antitumor activity was observed as evidenced by a 29% RR and 71% DCR. Despite this benefit, accrual was slower than expected and the study was closed early due to feasibility. A general clinical observation is that more pts are receiving immunotherapy off-label as the availability of these agents increases. This was a likely contributor to slow accrual, in addition to disease rarity. Analysis of PD-L1 expression, MSI status, and other immune cell markers is planned and will be compared to response. Clinical trial information: NCT03000179 .
Clinical outcomes of patient migration in locally advanced rectal cancer from community cancer centers: An analysis of the National Cancer Database.
Authors: Kumar Rohit , Bhandari Shruti , Ngo Phuong , Singh Sunny R K , Malapati Sindhu Janarthanam , Rojan Adam
Published: February 2020

81

Background: With cancer care changing at a rapid pace, patients are becoming increasingly involved with their management and oftentimes migrating to a different facility to seek better care. Our study evaluated the characteristics of such patients who were initially diagnosed at a community cancer center (CCC) and how this affects clinical outcomes. Methods: The National Cancer Database identified 11,977 patients with stage II/III rectal cancer initially diagnosed at a CCC between 2005 and 2015. Clinical characteristics and outcomes between patients who received all of their treatments at the CCC versus those who received part or all of their treatments elsewhere were compared using rank-sum and X2 tests where appropriate. Cox model was used for survival analysis. Results: Of the total population, 51% were stage II and 49% were stage III. Gender and ethnic distributions were similar between the groups. Approximately 44 % of patients received all their treatment at the CCC and 56% had part or all of their care elsewhere. Patients who migrated were younger (63 vs 65 years, p<0.001) and had govt insurance (43.5 vs 35.8%, p<0.001). On multivariate analysis, age <65 years (OR 1.12, 95% CI 1.02-1.24), govt insurance (OR 1.17, 95% CI 1.06-1.29), Charlson/Deyo comorbid score <2 (OR 1.29, 95% CI 1.11-1.49), higher income (OR 1.21, 95% CI 1.16-1.27) and Stage III (OR 1.15, 95% CI 1.07-1.24) were associated with higher probability of migration. The treatment characteristics and outcomes are shown in Table. The 5y-OS rate was better in patients who received part or all of their treatment at other institutions (adjusted HR 0.80, 95% CI 0.74-0.86, p<0.001). Conclusions: Further studies are needed to provide direction for future strategies to reduce the apparent survival disparities in patients who migrate from CCC.

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Survivorship care engagement with American Indian and Alaska Native survivors of gastrointestinal (GI) cancers.
Authors: Hill-Kayser Christine E. , Vachani Carolyn , Amaniera Isabella , Bach Christina , Arnold-Korzeniowski Karen , Hampshire Margaret K. , Metz James M.
Published: February 2020

814

Background: American Indian and Alaska Native (AI/AN) survivors are at significant risk for GI cancers, and also represent an underserved medical population. Gastrointestinal cancers represent the third most commonly diagnosed cancers in the AI/AN population and are a leading cause of death. Survivorship resources tailored for the AI/AN population are sparse and patterns of survivorship care poorly understood. Methods: The OncoLife survivorship care plan has been through the OncoLink website since 2007. The tool is free and publically available. It asks survivors to enter data regarding diagnosis, demographics, and treatments, and provides customized guidelines for future care. All research is IRB approved. Results: Over the past 12 years, the OncoLife tool has been utilized by >85,000 persons, with survivors of GI cancer representing 10-12% of users each year. Most users are women (75%) and Caucasian (80%). American Indian and Alaska Native survivors represent <1% of users since the launch of the tool. Of 519 AI/AN users, median age was 54 years, and 76% identified as female. Of plans created for AI/AN survivors, 13% were for survivors of GI cancers, with the most common GI diagnosis being colorectal cancer (74%), followed by pancreas (11%) and anal (6%). Most plans (73%) were created by HCP, with the remainder by survivors themselves; 20% of AI/ AN users completing plans requested information on smoking cessation as part of their care plan. Conclusions: American Indian and Alaska Native survivors represent a very small minority of survivors utilizing this free Internet-based tool, with most plans for this population being created by healthcare providers and not by survivors themselves. Future efforts should be directed at supporting this underserved population with survivorship information, particularly given high risk of morbidity and mortality related to GI cancers.
Comprehensive genomic profiling for chemotherapy-naïve advanced gastrointestinal malignancies.
Authors: Kondo Tomohiro , Pham Nguyen Quy , Matsubara Junichi , Fukuyama Keita , Nomura Motoo , Funakoshi Taro , Funakoshi Mari , Sakamoto Hitomi , Ashida Kanami , Mukai Kumi , Uemoto Shinji , Sakai Yoshiharu , Seno Hiroshi , Minamiguchi Sachiko , Haga Hironori , Kosugi Shinji , Kanai Masashi , Matsumoto Shigemi , Muto Manabu
Published: February 2020

832

Background: From June, 2019, two comprehensive genomic profiling (CGP) assays, "FoundationOne CDx" and “OncoGuide NCC Oncopanel”, were reimbursed by the national insurance system in Japan for patients who were refractory to standard chemotherapy. However, their clinical utility for chemotherapy-naïve cancer patients is unknown. Methods: We conducted a single institutional prospective observational study to evaluate the clinical utility of FoundationOne CDx assay (Cambridge, MA, USA) for the patients with chemotherapy-naïve advanced gastrointestinal malignancies. Patients with adequate H.E. sample were registered in this study. Primary outcome was the detection rate of at least one actionable/druggable cancer genomic alterations. The evidence levels were classified according to clinical practice guidance for next-generation sequencing in cancer diagnosis and treatment (Edition 1.0) (Sunami K. Cancer Sci. 2018). Results: From October 2018 to June 2019, a total of 238 patients were screened and the following 158 patients were registered: colorectal cancer (n = 60), gastric cancer (n = 19), esophageal cancer (n = 23), pancreatic cancer (n = 30), biliary tract cancer (n = 11), rare gastrointestinal malignancies (n = 15). The CGP data were obtained for 113 patients . Median turn-around time was 14 days (range 10-247 days). Actionable/druggable cancer genomic alterations were observed in 113 patients (100%)/ 65 patients (57.5%), respectively. Clinically relevant biomarkers and genomic alterations were identified in 22 patients (19.5%); BRCA2 (n = 4), ERBB2 (n = 4) , BRAF (n = 3) , EGFR (n = 3), FGFR2 (n = 2), MET (n = 2), NTRK (n = 2) , MSI-H (n = 2 ), TMB-high (n = 2), ALK (n = 1) , KIT (n = 1) and ROS1 (n = 1). Of note, novel biomarkers such as ROS1- GOPC fusion and PALB2 rearrangement were obtained in the patients with esophageal squamous cell carcinoma. Conclusions: This is the first study to evaluate the clinical utility of CGP in patient with chemotherapy-naïve advanced gastrointestinal malignancies. Our result indicated that CGP might provide a chance of potentially effective drugs as a novel approach in precision cancer medicine. Clinical trial information: UMIN000034830.