bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of ICD codes and phecodes for the identification of pancreatic cancer in a large genomic database.
Authors: Isom Chelsea Anne , Gamazon Eric R. , Tan Marcus Chuan Beng 
Published: February 2020

642 Background: Large genomic databases linked to electronic health records promise to shed light on molecular mechanisms underlying rare diseases, such as pancreatic cancer. However, accurately identifying patients with the desired phenotype can be challenging. This is particularly the case for pancreatic tumors, since ICD codes do not distinguish between pancreatic adenocarcinoma (PDAC) and pancreatic neuroendocrine tumors (pNET). Previous studies have shown that ICD codes aggregated by phenotype, known as “phecodes”, have a higher accuracy in identifying specific phenotypes than ICD codes themselves; however, their performance in identifying cancers of the pancreas has not been studied. Methods: From a large deidentified genomic database, two queries were performed to identify all adults with pancreatic cancer for a GWAS study, one using ICD-9/10 codes and the other using phecodes. The medical records for all patients identified from both queries were then reviewed to confirm the presence and histologic type of pancreatic cancer. Results: Of the 91,985 genotyped adults in the database, ICD-9/10 codes identified 1,247 patients with pancreatic cancer, compared with only 422 patients identified by the phecode query. All patients in the phecode cohort were also found in the ICD cohort. Of the 1,247 patients in the ICD cohort, 760 were confirmed to have pancreatic cancer on review of the health records (594 with PDAC, 166 with pNET) whereas in the phecode cohort, only 251 were confirmed to have pancreatic cancer (159 with PDAC, 92 pNET). The positive predictive value (PPV) for PDAC in the ICD query was 47%, compared with 38% for the phecode cohort. The ICD and phecode cohorts had similarly low numbers of pre-malignant cystic tumors (5% in each cohort) and other periampullary cancers (3%). Conclusions: In this large genomic database, the use of ICD-9/10 codes for pancreatic cancer was able to identify nearly three times as many patients with pancreatic cancer and had a higher PPV compared to using phecodes. Therefore, ICD codes, rather than phecodes, should be used to identify patients with pancreatic cancer for subsequent genotyping analysis, though caution is required because the PPV is still low.
Detection of circulating tumor DNA in pancreas cancer.
Authors: King Daniel , Alizadeh Ash A. , Fisher George A. 
Published: February 2020

645 Background: Pancreas cancer remains a leading cause of cancer-related death. Improved detection of early relapse or early failure of chemotherapy also has the potential to further improve outcomes. Exploring circulating tumor DNA (ctDNA) in this setting is an area of active investigation. Methods: We previously developed an approach, CAPP-Seq, combining high-depth sequencing with several strategies of error-suppression to identify minute amounts of circulating tumor DNA. We then trained and validated a new capture panel for pancreas cancer from 640 tumors from three data sources (TCGA, ICGC, UTSW), targeting 265 kb of the genome. We enrolled two cohorts of patients with pancreatic cancers at Stanford Cancer Center: (1) patients with localized tumors undergoing resection with curative intent, and (2) patients with unresectable or metastatic disease undergoing systemic therapy. Results: As of August 2019, we recruited 131 patients with at least one blood collection, with 63% having resectable disease and 27% having advanced disease; 59 patients had 2 or more blood collections. Stage distribution included 34% stage I, 33% stage II, 18% III, 16% IV disease. Approximately 15% had normal CA19-9 levels. Deep sequencing (4,000x unique depth) of an initial set of resected pancreatic tumors and matched germline specimens identified 1-6 non-synonymous coding mutations per case (median=3, n=14), with the most frequently mutated genes involving KRAS (79%), TP53 (50%), SMAD4 (29%). Among newly diagnosed treatment-naïve patients with resectable adenocarcinoma (n=9), we detected ctDNA in 4 patients (44%) prior to surgery including with AFs ranging from 0.27% - 0.88%. Subsequent sequencing will compare patients with and without neoadjuvant therapy prior to resection, selection of unresectable patients across a larger range of tumor burden and across multiple timepoints, and integration of large-scale copy number variant detection using low-pass whole-genome sequencing. Conclusions: Circulating tumor DNA monitoring with CAPP-Seq shows promise for improved detection of PDAC. Two key applications include early detection of minimal residual disease after resection and early assessment of response to chemotherapy.
Survival outcomes based on sequence of therapy using FOLFIRINOX and nab-paclitaxel + gemcitabine in metastatic pancreatic ductal adenocarcinoma.
Authors: Baron Kelsey , Nevala-Plagemann Christopher Duane , Moser Justin , Haaland Benjamin , Wang Xuechen , Garrido-Laguna Ignacio 
Published: February 2020

657 Background: Optimal sequence of therapy for patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) is unknown. FOLFIRINOX (FFX) and Gemcitabine + Nab-paclitaxel (AG) are standard first line (1L) therapies. They have never been prospectively compared. Therefore, we retrospectively compared the overall survival (OS) of patients treated with 1L AG and second line (2L) FFX compared to those treated with 1L FFX and 2L AG. Methods: Patients with mPDAC treated with 1L FFX followed by 2L AG, or vice versa were identified using the Flatiron Health EHR-derived nationwide database. To avoid immortal time bias, patients who received no 2L were included. OS from the initiation of 1L was compared with Kaplan Meier curves and log rank analysis. A cox model, stratified by deciles of propensity score (PS), was used to estimate the effect of treatment on OS with adjustment for differences between the groups. Results: 3,042 patients were identified. 2001 patients received 1L AG. Among these patients, 1446 received 2L FFX, and 555 received no 2L. 1041 patients received 1L FFX. Among these patients, 496 received 2L AG, and 545 received no 2L. Median OS and 1-year OS for those treated with 1L AG followed by 2L FFX or no therapy was 6.1 months (95% CI:5.6 – 6.5) and 25% (95% CI: 0.23 – 0.28). Median OS and 1-year OS for patients treated with 1L FFX followed by AG or no therapy was 8.7 months (95% CI: 7.9 – 9.2) and 36% (95% CI: 0.33 – 0.39). The propensity stratified hazard ratio between these two groups was 0.76 (95% CI: 0.69 – 0.83), favoring 1L FFX. Median OS for patients treated with 1L FFX and 2L AG versus 1L AG and 2L FFX was not significantly different (12.0 m vs. 12.5 m; HR 1.04; 95% CI: 0.90 - 1.20). Conclusions: In this analysis of real-world data, 1L FFX was associated with increased OS in propensity analysis. For patients who received both FFX and AG, median OS was similar, regardless of the sequence.
Effects of duration of initial treatment on postoperative complications in pancreatic cancer.
Authors: Takeda Naoya , Yamada Suguru , Takami Hideki , Sonohara Fuminori , Hayashi Masamichi , Yoshioka Isaku , Shibuya Kazuto , Matsui Koshi , Hirano Katsuhisa , Watanabe Toru , Tohmatsu Yuuko , Kimura Nana , Hojo Shozo , Sawada Shigeaki , Okumura Tomoyuki , Nagata Takuya , Kodera Yasuhiro , Fujii Tsutomu 
Published: February 2020

658 Background: Early studies raised concerns over whether preoperative treatment led to postoperative complications or even death. In contrast, recent studies have reported that initial treatment (IT) prior to resection of pancreatic ductal adenocarcinoma (PDAC) is safe, with no significant increase in overall morbidity or mortality, despite evidence for more advanced disease. In this study, we analyzed the clinical impact of chemotherapy or chemoradiotherapy as IT, focusing on treatment duration, on morbidity and mortality in patients with resected PDAC. Methods: We enrolled 509 consecutive patients, with 417 in the upfront surgery group and 92 in the IT group. The IT group was subdivided into 72 patients treated for < 8 months and 20 treated ≥8 months. We compared rates of postoperative Clavien–Dindo grade ≥III complications between the groups. Multivariate logistic regression analysis was used to find independent predictors of complications. Results: The upfront surgery and IT groups did not significantly differ in overall postsurgical complications. The rate of postoperative pancreatic fistula was significantly less in the IT group. Rates of other complications did not significantly differ, except for severe infection and delayed gastric emptying. Initiation of adjuvant chemotherapy was later in the IT group than in the upfront surgery group (43.2 vs 57.8 days, P < 0.001). In contrast, rates of overall complications significantly differed between the < 8 months and ≥8 months IT groups, although their background clinical factors did not differ. In multivariate analysis, operative procedure (distal pancreatectomy and distal pancreatectomy with celiac axis resection) (odds ratio [OR] 6.950, P = 0.0416) and IT ≥8 months (OR: 4.508, 95%, P = 0.0156) were independent predictive factors for postoperative complications. Conclusions: The incidence of postoperative complication was similar between the upfront surgery group and the IT group, however, it was significantly higher in the ≥8 months IT group in patients who underwent PDAC resection.
The role of neoadjuvant chemotherapy in elderly patients with borderline or locally advanced pancreatic cancer: Is it safe and feasible?
Authors: Oba Atsushi , Lieu Christopher Hanyoung , Meguid Cheryl Lauren , Davis Sarah Lindsey , Leal Alexis Diane , Purcell Tom , King Gentry Teng , Goodman Karyn A. , Schefter Tracey E. , Gleisner Ana Luiza , Ahrendt Steven Arthur , Leong Stephen , Messersmith Wells A. , Shulick Richard D. , Del Chiaro Marco 
Published: February 2020

685 Background: For borderline resectable (BRPC) or locally advanced pancreatic cancer (LAPC), neoadjuvant (NAT) FOLFIRINOX or gemcitabine plus nab-paclitaxel (GnP) are standard treatment options and these regimens have shown a survival advantage over single-agent gemcitabine. However, the role of these modern therapeutic regimens in elderly patients is debatable. In this analysis, we evaluated the outcomes of neoadjuvant treatment (NAT) with combination chemotherapy in elderly patients. Methods: 230 consecutive patients who underwent neoadjuvant treatment for BRPC/LAPC discussed and planned for NAT at the University of Colorado Cancer Center from January 2011 to March 2019 were reviewed. 214 patients who received FOLFIRINOX (n = 143) or GnP (n = 71) were eligible for analysis. We divided all patients into three groups ( < 70, 70-74, ≥75 years) and compared the short-term and long-term outcomes. Results: Of 214 patients, patients < 70 (n = 147) received FOLFIRINOX more frequently than the other groups (p < 0.001): FOLFIRINOX: 115 cases, GnP: 32 cases, 70-74 years (n = 33): FOLFIRINOX: 15 cases, GnP: 18 cases, and ≥75 years (n = 34): FOLFIRINOX: 13 cases, GnP: 21 cases. Resection rates were not statistically different between three groups ( < 70: 62%, 70-74: 70%, ≥75 years: 56%, p = 0.504). There was a slight trend towards worse survival in the two older groups (Median Survival Time [MST]: < 70: 23.2 mo., 70-74: 19.5 mo., ≥75 years: 17.6 mo., p = 0.075) The FOLFIRINOX group was superior to GnP group in all three groups (MST: < 70: 25.6 vs 18.2 mo., p = 0.017; 70-74: 33.2 vs 16.1mo., p = 0.029; ≥75 years: not reached vs 16.1 mo., p = 0.135). There were no toxic deaths or 30 day mortality after pancreatectomy in the study population. Conclusions: Neoadjuvant combination chemotherapy regimens were safe and feasible for elderly patients. Neoadjuvant therapy with FOLFIRINOX was associated with a survival advantage vs GnP and is an good option for fit and elderly patients ≥75 years.
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.