bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical implications of peritoneal cytology evaluated by staging laparoscopy for potentially resectable pancreatic cancer.
Authors: Tanaka Haruyoshi , Fukasawa Mina , Igarashi Takamichi , Watanabe Toru , Saeki Shiori , Itoh Ayaka , Shibuya Kazuto , Kimura Nana , Hirano Katsuhisa , Nagamori Masakazu , Mori Kosuke , Takeda Naoya , Miwa Takeshi , Hashimoto Isaya , Hojo Shozo , Matsui Koshi , Yoshioka Isaku , Okumura Tomoyuki , Fujii Tsutomu 
Published: January 2023

674 Background: Positive peritoneal cytology has been reported to indicate a poor prognosis in patients with pancreatic cancer even if the primary tumor is surgically resected. This study investigated the clinical implications of peritoneal cytology by staging laparoscopy for patients with potentially resectable pancreatic cancer for whom initial treatment will be started. Methods: We retrospectively reviewed 113 consecutive patients with pancreatic cancer diagnosed as resectable by computed tomography in whom peritoneal cytology was evaluated by staging laparoscopy between December 2018 and August 2022. Patients with positive cytology received induction chemotherapy, and those in whom cytology converted to negative underwent surgical resection as needed when possible. We set best tumor marker cutoff values for predicting positive cytology by maximizing the Youden index. Results: Seventy-three patients were men and the mean age was 72 years. Thirty patients (26.5%) had positive cytology at initial staging laparoscopy. Minimal peritoneal metastases were detected in seven of these patients and liver metastases in two. Larger tumor diameter ( > 30 mm), location in the pancreatic body or tail, an elevated CA19-9 level ( > 138.5 U/ml), an elevated CA125 level ( > 13.5 U/ml), and an elevated CEA level ( > 5.1 ng/ml) were associated with a significantly increased risk of positive cytology (odds ratio 4.71 [confidence interval 1.87–12.2] P = 0.001, 2.49 [1.07–6.05] P = 0.038, 2.95 [1.26–7.12] P = 0.014, 3.89 [1.57-10.7] P = 0.005, and 3.52 [1.23–10.2] P = 0.018, respectively). Eighteen patients (60%) who received induction chemotherapy converted from positive to negative cytology; seven (38%) of these patients underwent surgery and all remain alive without recurrence. Interestingly, median overall survival in patients with negative cytology was not necessarily inferior to that in those with positive cytology (23.4 months vs. 24.2 months, P = 0.33). Conclusions: Over a quarter of patients with pancreatic cancer that is diagnosed as resectable by computed tomography may have positive peritoneal cytology at the initial assessment. These patients tend to have higher CA19-9, CA125, and CEA levels, larger tumors, and tumors located in the body or tail of the pancreas. A more favorable prognosis may be achieved by administering induction chemotherapy until cytology converts to negative than by upfront surgery.
Adult BMI change over time and risk of colorectal adenoma.
Authors: Holum Parker Jayce , Palmer Chelsea , Sun Xiangqing , Venkatesh Samyukta , Devall Matthew , Cooper Gregory , Powell Steven M. , Yoshida Cynthia , Li Li 
Published: January 2023

68 Background: Obesity and adult weigh gain are established risk factors for colorectal cancer (CRC). Few studies have investigated the association between adult body weight change over time and risk of colorectal adenoma. We hypothesize adult BMI change over time is associated with risk in the development of colorectal adenomas. Methods: We tested this hypothesis in 2,993 patients undergoing screening colonoscopy from 2007–2017. Weight at age 20, 30, 40, and 50 were self-reported via computer assisted personal interviews. Height and weight at recruitment were measured at the time of colonoscopy exam. BMI (kg/m2) change was calculated as the difference of BMI at recruitment from the BMI estimate for each of the age periods. Results: Of the 2,993 patients, 984 had pathologically confirmed diagnosis of colon adenoma. Multivariate logistic regression adjusted for potential confounders and BMI at recruitment showed statistically significant increase of risk of adenoma with increase of BMI since age 30, age 40, and age 50. Compared to those with BMI change of less than 5, the ORs for those with BMI gain of 5-10 and ≥10 were: 1) 1.16 (0.92-1.46) and 1.48 (1.08-2.03) respectively for change from age 30 (ptrend = 0.05); 2) 1.11 (0.87-1.43) and 1.60 (1.09-2.35) respectively for change from age 40 (ptrend = 0.05); and 3) 1.36 (0.95-1.94) and 2.95 (1.33-6.90) respectively for change from age 50 (ptrend = 0.01). Stratified analysis did not reveal noticeable gender differences. Conclusions: Large adult weight gain over time is an independent risk factor for colorectal adenoma. Our results suggest maintaining healthy body weight throughout adulthood is an important preventive measure against the development of early colorectal neoplasia. [Table: see text]
Phase I study of proton therapy in adjuvant pancreatic cancer (PROTON-PANC).
Authors: Weinberg Benjamin Adam , Wang Hongkun , Noel Marcus Smith , He Aiwu Ruth , Marshall John , Weiner Louis M. , Fishbein Thomas M. , Winslow Emily R. , Jackson Patrick G. , Guerra Juan F. , Aguila Francisco , Unger Keith Robert 
Published: January 2023

709 Background: Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, with a 5-year survival rate of 10%. The current standard of care for patients with resectable disease is surgical resection followed by 6 months of adjuvant mFOLFIRINOX (mFFX) chemotherapy. As survival outcomes and distant recurrence rates improve with the use of mFFX, locoregional recurrence remains a significant cause of morbidity and mortality. We sought to integrate short-course proton radiation therapy (PRT) to the operative bed between cycles of adjuvant chemotherapy in patients with resected PDAC of the pancreatic head. Methods: Between 2019 and 2022, patients with resected PDAC with an R0 or R1 resection on adjuvant mFFX were enrolled in a phase I trial using a 3+3 dose-escalation schema (NCT03885284). Patients received mFFX as used in the PRODIGE 24 study and also received short-course PRT delivered over 1 week in 5 fractions (5 GyE each) between cycles 6 and 7 of mFFX. In dose level 1 (DL1), patients received PRT on days 15-19 in a 28-day cycle before starting cycle 7, and in dose level 2 (DL2) patients received PRT on days 8-12 in a 21-day cycle before starting cycle 7. Results: Nine patients were enrolled on the trial, median age 66 (range 52-78). Five had R0 resections, 4 had R1 resections, and 5 had node-positive disease. No patients received preoperative therapy, and none underwent vein reconstruction. Three patients were enrolled on DL1 and 6 patients on DL2. One dose limiting toxicity (DLT) occurred at DL2 (prolonged grade 3 neutropenia resulting in discontinuation of mFFX after cycle 7). No other DLTs were observed. Four patients completed the planned 12 cycles of mFFX (range 7-12, median 11). None of the patients have had local recurrence. Five of 9 patients had recurrence: 3 in the liver, 1 in the peritoneum, and 1 in the bone. Six patients are still alive, 4 of whom are recurrence free. With a median follow up from date of chemotherapy start of 12.5 months, median time to disease recurrence was 12 months (95% confidence interval [CI] 4-not reached [NR]), and median overall survival has not been reached (95% CI 6-NR, 2-year survival rate 57%). Conclusions: PRT integrated within adjuvant mFFX was well-tolerated and no local recurrence was observed for patients with resected PDAC. These findings warrant being confirmed in a phase II trial. Clinical trial information: NCT03885284 .
Metronomic oral cyclophosphamide as maintenance therapy in metastatic pancreatic ductal adenocarcinoma.
Authors: Reni Michele , Orsi Giulia , Peretti Umberto , Macchini Marina , Militello Anna Maria , Falconi Massimo , Cascinu Stefano 
Published: January 2023

716 Background: Metastatic Pancreatic Ductal Adenocarcinoma (mPDAC) has a grim prognosis, with limited therapeutic options. In this context, treating patients (pts) with chemotherapy (CT) till progression is not supported by scientific evidence and must be weighed against quality of life impairment and cumulative toxicity. Therefore, we explored the role of metronomic oral cyclophosphamide (mCTX) as maintenance therapy (MT) in mPDAC pts. Methods: Any age mPDAC pts, with Karnofsky performance status >60 and wild-type germline BRCA1-2, who were progression-free after at least 6 months of any regimen and line CT and received mCTX (50 mg/die) MT between August 2020 and July 2022, were included in the analysis. An historical cohort (HC) of mPDAC pts, who were progression-free after 6 months of 1st-line platinum-based combination CT and did not receive MT between 2000 and 2016, was considered for exploratory comparison. Progression-free and Overall Survival (PFS and OS) were calculated from last CT administration for both cohorts. Results: 41 and 122 pts were included in mCTX and HC, respectively. Median PFS was 4.1 (range 1.5-18.4) and 3.1 (1-141) months for mCTX and HC, respectively (p= 0.003). PFS rates at 6 and 12 months were 34.7% and 11.1% in the mCTX cohort, 18.9% and 6.6% in the HC. Median OS was not reached (range 1.5-25) and 10.2 (1.3-142) months for mCTX and HC, respectively (p= 0.002). OS rates at 6 and 12 months were 96.9% and 74.6% in the mCTX cohort, 74.5% and 46.9% in the HC. Factors associated with longer PFS in the mCTX cohort were normal CA19.9 at CT start (p= 0.006), female gender (p= 0.036), no liver metastases (p= 0.01), normalized CA19.9 after CT (p= 0.01). Only 2 pts receiving mCTX had Grade 3 toxicity. Conclusions: mCTX MT extends PFS and OS of mPDAC pts not progressing after at least 6 months of CT with unremarkable toxicity in our exploratory non-randomized analysis.[Table: see text]
Multiagent neoadjuvant chemotherapy compared to upfront surgery in pancreatic cancer of the body and tail using the National Cancer Database.
Authors: Franklin Oskar , Sugawara Toshitaka , Rodriguez Franco Salvador , Schulick Richard D. , Del Chiaro Marco 
Published: January 2023

722 Background: While neoadjuvant chemotherapy is increasingly being using in pancreatic cancer treatment, it is unclear whether it is beneficial in treatment of body and tail tumors. Randomized controlled trials are lacking and previous observational studies have not demonstrated any benefit. We aimed to assess survival associations, trends over time and patient selection associations for multiagent neoadjuvant chemotherapy treated pancreatic cancer of the body and tail using data from the National Cancer Database (NCDB). Methods: We queried the NCDB for pancreatic adenocarcinoma in the body or tail diagnosed between 2010 – 2018 that received multiagent neoadjuvant chemotherapy and/or a distal pancreatectomy. Patients with clinical M1, clinical T4 and surgery other than partial pancreatectomy were excluded. Survival was compared with Kaplan-Meier estimates and multivariable Cox Proportional Hazard Estimates. Results: Between 2010 – 2018, the use of multiagent neoadjuvant chemotherapy increased from 5.7% to 31.8%. In total, 1951 patients were included with n = 384 receiving multiagent neoadjuvant chemotherapy (cases) and n = 1567 undergoing upfront surgery (controls). Neoadjuvant chemotherapy was associated with younger age, tumor in the pancreatic body, clinical N1-2 and with Ca 19-9 ≥98 U/mL. Neoadjuvant chemotherapy was associated with a decreased mortality rate in multivariable Cox regression models adjusting for preoperatively assessed variables (HR 0.65, 95% CI 0.53 – 0.81, p < 0.001) and results were significant in both clinical T1-2 and T3 tumors. Patients treated with upfront surgery had higher rates of adjuvant chemotherapy receipt after resection (41.4% vs 70.6%) but there was no difference in R1 resection rates or 90-day postoperative mortality between the groups. The addition of neoadjuvant radiotherapy was not associated with improved survival in patients receiving neoadjuvant chemotherapy. Conclusions: Multiagent neoadjuvant chemotherapy is increasingly being used in the treatment of pancreatic cancer of the body and tail, especially in younger patients and patients with more aggressive tumor characteristics. Multiagent neoadjuvant chemotherapy is associated with improved survival but randomized trials are needed to establish causal relationships.
Cost effectiveness of liquid biopsy for colorectal cancer screening.
Authors: Aziz Zainab , Wagner Sophie , Agyekum Alice , Prest Matthew , Pumpalova Yoanna S , Hur Chin 
Published: January 2023

73 Background: Despite established screening guidelines, adherence to colonoscopy is approximately 60%. Blood-based screening tests, or Liquid Biopsies (LB), have the potential to close this screening gap. Our aim was to determine the cost-effectiveness of LB tests for CRC screening in the US. Methods: We developed a Markov model to compare four CRC screening strategies: no screening, or natural history (NH), colonoscopy (Colo) only, LB only, and colonoscopy to LB hybrid (C-LB). US SEER CRC incidence and mortality data were used to develop and validate the model. Many LB tests are in development awaiting validation; we used the preliminary performance characteristics for CRC screening of 82% sensitivity and 99.5% specificity (base case) from the Galleri multi-cancer early detection test (GRAIL). Screening ran from age 45 to 75; polyp surveillance ended at 85. We assumed 60.6% of the US population would undergo a screening colonoscopy, and 100% adherence for LB. In Colo, nonadherent patients were not offered other screening; in C-LB those who refused colonoscopy underwent LB. Primary outcomes were overall survival, total cost, incremental cost-effectiveness ratio (ICER), number of CRCs, and CRC deaths. Results: In the NH strategy, 5.2% of the population developed CRC and 1.8% died from CRC, with a cost of $7,802.15/individual. Compared to NH, in Colo, 40% of CRCs and 44% of CRC deaths were prevented, at a cost of $10,610.43/individual. In C-LB, 42% of CRCs and 50% of CRC deaths were prevented compared to NH, costing $13,762.61/individual. LB only prevented 2.0% of CRCs and 11% of CRC deaths compared to NH, and cost $34,339.85/individual. While LB showed an incremental benefit of 0.01 life years gained compared to NH, the ICER compared to NH is $2,653,770. Colo was most cost-effective with an ICER of $30,191.04. Although C-LB prevented the greatest number of CRCs, this strategy had an ICER of $457,057.64, above the accepted US willingness to pay threshold of $100,000/life year. We performed sensitivity analysis around base case estimates for LB. At both 70% and 90% test sensitivity, all outcomes remained largely constant. Conclusions: CRC screening with LB alone or with LB in conjunction with colonoscopy among nonadherent patients is not cost-effective in the US context. At this time, LB is unable to detect pre-cancerous colon polyps, which may limit its effectiveness as a CRC screening strategy. [Table: see text]
Effects of gene expression in 5-FU metabolic pathways in a phase III trial evaluating adjuvant S-1 therapy compared to surgery alone following curative resection for biliary tract cancer (JCOG1202A1).
Authors: Mitsunaga Shuichi , Ikeda Masafumi , Nomura Shogo , Morizane Chigusa , Todaka Akiko , Kamei Keiko , Yanagibashi Hiroo , Mizuno Nobumasa , Gotoh Kunihito , Kawamoto Yasuyuki , Shirakawa Hirofumi , Okano Naohiro , Nomura Tatsuya , Takahashi Amane , Makino Isamu , Anbo Yoshiyasu , Ohta Koji , Katayama Hiroshi , Konishi Masaru , Ueno Makoto 
Published: January 2023

732 Background: S-1, an oral fluoropyrimidine derivative, is standard adjuvant therapy in Japanese patients with resected biliary tract cancer (BTC), based on the results of JCOG1202, a phase III trial evaluating adjuvant S-1 following curative resection for BTC compared to surgery alone. The efficacy of 5-FU-based therapy is related to the expression of enzymes involved in 5-FU metabolic pathways, such as thymidylate synthase (TS), thymidine phosphorylase (TP), orotate phosphoribosyltransferase (OPRT) and dihydropyrimidine dehydrogenase (DPD). The aim of this study was to evaluate the impact of messenger RNA (mRNA) levels of the four 5-FU metabolic pathway genes on the outcomes of patients enrolled in JCOG1202. Methods: Tumor cell RNA was isolated from formalin-fixed paraffin-embedded primary BTC specimens resected in 264 of 440 randomized patients in JCOG1202. The four 5-FU metabolic pathway genes were measured in 183 patients (surgery alone: n = 94; adjuvant S-1: n = 89) who were randomly divided to training (n = 96) or validation set (n = 87). The endpoints of interest were the predictive values of the four genes for the efficacy of adjuvant S-1 on overall survival and relapse-free survival (RFS), and we here report the results regarding RFS. Cut-off levels for mRNA expression were selected in the training set which minimized the bootstrap p-values (2,000 samples) of an interaction term of treatment (surgery alone or S-1) and mRNA expression in a Cox regression model. Results: There were no obvious differences in each mRNA level and clinical characteristics between surgery alone and adjuvant S-1 groups. RFS tended to be better with adjuvant S-1 (hazard ratio [HR] = 0.790, [95% confidence interval: 0.524-1.192]) compared to surgery alone, which was maintained in the low DPD population (HR = 0.440 [0.216-0.898] in training set and 0.748 [0.334-1.675] in validation set), in the low TP population (HR = 0.709 [0.388-1.296] and 0.602 [0.287-1.262]), and in the high OPRT population (HR = 0.520 [0.152-1.779] and 0.609 [0.161-2.304]). Conclusions: The efficacy of adjuvant S-1 on RFS was representative in BTC patients with intratumoral gene expressions of low DPD, low TP, and high OPRT, which was disappeared in the population with high DPD, high TP, and low OPRT. These biomarkers might be useful to predict therapeutic benefits with S-1 containing chemotherapy for BTC.
Comparison of precursor neoplasms at colonoscopic diagnosis of early-onset and later-onset colon cancer.
Authors: Emiloju Oluwadunni Eunice , Saberzadeh Ardestani Bahar , Sinicrope Frank A. 
Published: January 2023

74 Background: Colorectal cancer (CRC) incidence has steadily increased in adults younger than 50 years (EO-CRC) since the 1990s, with a reported higher prevalence in the left colon and rectum. Established precursor lesions of CRCs are adenomas, including advanced adenomas, and sessile serrated polyps. We hypothesized that patients at diagnosis of early-onset colon cancer (EO-CC) would have fewer adenomas compared to patients with later-onset colon cancer (LO-CC). Methods: We performed a retrospective review of electronic health records and identified 58 patients diagnosed with EO-CC who had colonoscopy at Mayo Clinic or Mayo Health System who were then matched with 58 LO-CC patients based on gender and procedure indication (diagnostic in 76%, surveillance 16%, screening 8%)[2012 to 2021]. At colonoscopy where colon cancer was diagnosed, we recorded findings of adenomas, advanced adenomas (≥ 1 cm, villous histology, and/or high-grade dysplasia) and sessile serrated polyps. On CCs, limited molecular data were available [mismatch repair (MMR); BRAFV600E, KRAS]. Results: Among 116 patients included in the EO-CC and LO-CC study arms, the median age at cancer diagnosis were 42 and 74 years, respectively. No significant differences were found between study arms and risk factors for CRC including tobacco, alcohol, BMI, genetic syndromes, family history of CRC, and MMR, BRAFV600E or KRAS status (all p> 0.05). While no difference was found for polyp number by arm, patients with EO-CC had larger polyps (median of 10 mm vs 6 mm, p=0.001) compared with LO-CC. At least 1 adenoma was found in 50% and 52% of patients with EO-CC and LO-CC, respectively. Importantly, advanced adenomas were significantly more common in the EO-CC group compared with the LO-CC group (41% and 21%, p=0.027). Sidedness of all adenomas did not differ significantly for EO-CC vs LO-CCs. Conclusions: Patients found to have a primary EO-CC had a significantly higher likelihood of a synchronous advanced adenoma in the colon compared to those with a primary LO-CRC. Together, these data suggest accelerated carcinogenesis throughout the colorectum with increased risk of synchronous and metachronous patients with EO-CC. [Table: see text]
ATM or CHEK2 alterations: Potential biomarkers of improved outcomes with irinotecan-containing chemotherapy in advanced pancreatic ductal adenocarcinoma.
Authors: Mehdi Maahum , Thapa Bicky , Szabo Aniko , Ahmed Gulrayz , Shreenivas Aditya V. , Thomas James P. , Sriram Deepika , Evans Douglas B. , Tsai Susan , Christians Kathleen K. , Erickson Beth , Hall William A. , McFall Thomas , Patrick Steve , George Ben , Kurzrock Razelle , Kamgar Mandana 
Published: January 2023

754 Background: ATM and CHEK2 mutations are linked to homologous recombination DNA repair deficiency, with the potential for improved therapeutic response to DNA damaging agents. To investigate our clinical observation of improved outcomes with irinotecan (IRI) based chemotherapy in advanced/metastatic pancreatic ductal adenocarcinoma (PDAC) patients (pts) with somatic or germline ATM/ CHEK2 mutations, we examined our institutional real world experience. Methods: Between 2015-2021, 33 pts with ATM or CHEK2 mutations treated with chemotherapy were identified, of which 16 pts had advanced/metastatic disease. Progression-free survival (PFS) was calculated and compared (Kaplan Meier, log-rank test) in several ways to assess the impact of IRI vs platinum or other regimens. The event for PFS was progression (or death), and pts without progression were censored at treatment end, or at last follow up if treatment was ongoing. Results: Among 16 pts with advanced/metastatic PDAC, 8 (50%) had ATM (5 germline, 3 somatic) and 8 (50%), CHEK2 alterations (4 germline, 4 somatic). Overall, pts received 48 lines of chemotherapy (platinum-based-(No-IRI) N=14; IRI-based-(No-Platinum) N=8; both N=4; none N=22). For best-PFS among pts analysis, median line of best-PFS therapy for IRI-Ever (N=9 pts) was 2nd line (range 1-7) and for IRI-Never (N=7 pts) was 1st (range, 1-1); median PFS was 13 vs 3 months (mo) (IRI-Ever vs IRI-Never; p=0.0076). For PFS analysis within lines of treatment of each pt, median therapy line for both IRI-containing and No-IRI lines was 2nd line (range 1-7); median PFS for IRI-containing (N=12 lines of therapy) vs No-IRI (N=36) was 12.1 vs 3 mo (p<0.001). Median PFS for best IRI-based-(No-Platinum) line (N=7) was 13 mo; for best platinum-based-(No-IRI) line (N=9) was 2.8 mo; and for best treatment containing no IRI or platinum (N=13) was 5.1 mo (P= 0.003) (median therapy line for each was 3, 2 and 1.5, respectively). Conclusions: Irinotecan is a topoisomerase 1 inhibitor that induces DNA strand breaks, potentially causing synthetic lethality in tumors with DNA damage repair deficits due to ATM or CHEK2 alterations. IRI-containing therapy out-performed other treatment types, including platinum-containing regimens, in pts with ATM or CHEK2-mutated advanced/metastatic PDAC. Prospective trials are warranted.