bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lifestyle factors, viral hepatitis, and hepatocellular carcinoma in Uganda.
Authors: Assefa Redeat , Aizire Jim , Nsibirwa Sara , Ocama Ponsiano , Kirk Gregory 
Published: January 2024

571 Background: The effect of lifestyle factors, namely alcohol use, cigarette smoking, and other forms of tobacco use on hepatocellular carcinoma (HCC) remains unclear. We assessed the independent associations of lifestyle factors with HCC among individuals with and without viral hepatitis. Methods: In a hospital-based case-control study recruiting from Mulago and Lacor hospitals in Uganda from March 2015 to August 2021, HCC cases were confirmed by clinical and ultrasound criteria, with biochemical and pathology confirmation on a subset. Controls were frequency matched by age and sex and from the same hospitals. Demographic, clinical and lifestyle data were collected using standardized instruments. Alcohol content of local drinks was standardized, and intensity categorized as light, moderate, or heavy based on CDC definitions. We analyzed alcohol (use status (current, former, never), duration (years), frequency (drinks/week)), cigarette smoking (status (current, former, never), cumulative (pack‐years), duration (years), intensity (cigarettes/day), and time since cessation), other tobacco use (tobacco chewing and pipe-smoking), and viral hepatitis (HBV surface antigen (HBsAg) and HCV antibody (HCVAb)). We used logistic regression models (Stata 18.0) to estimate adjusted odds ratios (aOR) and 95% confidence intervals (CIs) controlling for age, sex, family history of HCC, socioeconomic status, and Schistosomiasis (urine Circulating Cathodic Antigen (CCA)). Stratified analyses were performed separately by HBV and HCV status. Results: Among 596 HCC cases and 1,277 controls, the median age (IQR) was 43 (32-56) and 45 (31-54) years, 410 (68.8%) and 832 (65.0%) were males, 460 (24.6%) and 442 (23.7%) current or former alcohol users, 96 (5.1%) and 251 (13.4%) current or former cigarette smokers, and 177 (9.45%) and other tobacco users, respectively. Other tobacco users were more likely to be heavy (⩾10 pack-years) cigarette smokers (aOR=5.10; 95% CI: 2.41-10.79), heavy (>14 drinks/week for males and >7 drinks/week for females) alcohol drinkers (aOR=5.25; 95% CI: 2.84-9.68), farmers (aOR=1.61; 95% CI: 1.01-2.57) and lower socioeconomic status (aOR=3.23; 95% CI: 1.76-5.94). HCC risk was associated with HBV (aOR=18.66; 95% CI: 12.96-27.88), HCV (aOR= 4.03; 95% CI:2.31-7.02), and other tobacco use (aOR=1.86; 95%CI: 1.13-3.08). The observed HCC risk with other tobacco use, and the null associations with heavy alcohol use (aOR= 0.89; 95% CI: 0.60-1.31) and heavy cigarette smoking (aOR=0.74, 95% CI:0.34-1.60), were homogenous by HCV status (positive versus negative), and similarly by HBV status. Conclusions: Viral hepatitis (HBV and HCV), and lifestyle factors (tobacco chewing and pipe-smoking) were strongly associated with HCC. Further research should explore the role of tobacco chewing and pipe-smoking in HCC risk in Uganda and similar settings in Sub-Saharan Africa.
Survival benefit and clinical characteristics of patients with metastatic colorectal cancer (mCRC) receiving pulmonary metastasectomy.
Authors: Soto Alsar Javier , Jiménez Rodríguez Roberto , Bringas Beranek Marianela , Gutiérrez Alonso Natalia , Martín Lozano Rocío , Gonzalez Caraballo Irene , Pérez Pérez Sara , González Casaurrán Guillermo , Muñoz Andrés , Ortega Morán Laura , Calvo Aitana , Torres Pérez-Solero Gabriela , Martin Miguel , Simón Adiego Carlos María , Garcia-Alfonso Pilar 
Published: January 2024

59 Background: The role of lung metastasectomy in mCRC remains a topic of particular controversy, being uncertain which patients benefit more from it and whether it leads to better survival outcomes. Our aim was to identify clinical and molecular differences and survival data in a cohort from a tertiary care hospital. Methods: We retrospectively analyzed 115 patients with lung metastases from colorectal cancer (CRC) in a tumor registry from 2015 to 2021, analyzing clinical and molecular characteristics, as well as overall survival (OS) data of patients who received lung metastasectomy versus patients who did not. Results: Among all patients, 36 (31.3%) received pulmonary metastases surgery. Patients undergoing metastases resection had more frequently ECOG 0 (51.4% vs 20.8%, p = 0.0011), resected primary tumor (100% vs 78.5%, p = 0.0026), metachronous metastatic disease (75% vs 46.8%, p = 0.0048) and a single metastatic location (79.4% vs 41%, p = 0.0002). In addition, none of them had BRAF mutation (0% vs 17.1%, p = 0.04); however, no statistically significant differences were found regarding KRAS, NRAS, PI3K, HER2 or presence of microsatellite instability (MSI). Patients who received lung metastasectomy had higher BMI (26.1 vs 24.4, p = 0.037) and lower mean levels of CEA (19.5 vs 142.9, p = 0.007), CA 19.9 (30.6 vs 244.9, p = 0.011) and LDH (159 vs 211.9, p = 0.018). We found an OS benefit in patients undergoing metastatic surgery (median not reached (NR) vs 41.4 months, HR for death 0.27, 95% CI, 0.14 - 0.53, p < 0.000); a multivariate analysis confirmed that this benefit was independent from the characteristics mentioned above. The median progression-free survival (PFS) after metastases resection was 53.3 months. Conclusions: In our study, patients who were more likely to receive lung metastasectomy were those with ECOG 0, resected primary tumor, metachronous disseminated disease, a single metastatic location, native BRAF mutation status and low CEA, CA 19.9 and LDH levels, with a significant OS benefit associated.
Quality of surveillance in patients with completely resected gastroenteropancreatic neuroendocrine tumors.
Authors: Moffat Gordon Taylor , Mesci Aruz , Chadi Sami A. , Jang Raymond Woo-Jun , Avery Lisa , Moulton Carol-Anne , Nathan Paul C. , Krzyzanowska Monika K. 
Published: January 2024

591 Background: The incidence and prevalence of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are increasing worldwide. Surgery remains the only curative modality. Because of limited data on patterns of recurrence, real-world surveillance practices and duration vary widely. In 2018, the Commonwealth Neuroendocrine Tumour Research Collaboration (CommNETs) published consensus surveillance guidelines for patients with completely resected GEP-NETs. Our aim was to assess adherence to the CommNETs guidelines for surveillance practices for this patient population at our center. Methods: We conducted a retrospective cohort study of patients with GEP-NETs seen for a new patient appointment at Princess Margaret Cancer Centre (PMCC) from 2019-2022. Patients were included if they had a completely resected GEP-NET and followed on surveillance at our center. Demographic and tumor characteristics, surveillance practices, and clinical outcomes were abstracted. Summary statistics and a descriptive comparison of surveillance practices were completed. Results: Out of the 374 new patient appointments, 87 met the inclusion criteria. The main reasons for exclusion were metastatic disease at presentation (n=128), primary tumor not resected (n=58), and patients not followed at PMCC (n=49) so their surveillance practices cannot be determined from our records. The primary tumor sites were pancreatic (n=50, 57%), appendiceal (n=15, 17%), small bowel (n=11, 13%), rectal (n=10, 12%), and colon (n=1, 1%). Thirty-eight patients (44%) had stage 1 disease, 21 patients (24%) had stage 2, and 28 patients (32%) had stage 3. Forty-six patients (53%) had a WHO tumor grade of 1, 36 patients (41%) had grade 2, and 5 patients (6%) had grade 3. The median duration of follow-up was 18.2 months. Adherence to ordering the recommended surveillance investigations was 23% (20/87). Within the adherent cases, there was a higher number of appendiceal, WHO grade 1, and stage 1 tumors. Sixty-six patients (76%) had at least one test that was not recommended by the guidelines. The most frequent unnecessary tests were CT chest in all patient groups and CT pelvis in pancreatic NETs (Table). Six patients were lost to follow up and none discharged from surveillance. Conclusions: Adherence to the CommNETs consensus guidelines was low at our center, suggesting the guidelines had a minor impact on surveillance practices and providing an area for improvement in process of care and resource utilization. [Table: see text]
Prognostic value of O6-methylguanine-DNA methyltransferase (MGMT) status in pancreatic neuroendrocrine tumors with capecitabine and temozolomide (CAPTEM).
Authors: Terán Brage Eduardo , Feito Pérez Jorge , Navarro Martín Luis Miguel , Escala Cornejo Roberto Andrés , Abad Hernández María Mar , Del Carmen Sofía , López Gutiérrez Álvaro , Cigarral García Belén , Vidal Tocino Rosario , Lozano Rebeca , Fonseca Sánchez Emilio 
Published: January 2024

598 Background: Loss of MGMT expression has been suggested as a predictor of response to alkylating agents in pancreatic neuroendocrine tumors (pNET), however, its determination is controversial. We aim to analyze the prognostic value of MGMT status assessed by immunohistochemistry (IHC) or pyrosequencing (PSQ) in patients with pNET receiving CAPTEM. Methods: Retrospective and unicentric analysis in patients (p) with pNET treated with CAPTEM from April 2008 to February 2023. MGMTdeficiency was determined by IHC and MGMT promoter methylation by PSQ. We analyzed patients’ characteristics, progression-free survival (PFS) and overall survival (OS) according to MGMT status. Results: 20p were included. Age (median): 62 [46-77]. Males (45%). Tumor grade (G): G1 (15%), G2 (55%) and G3 (20%). MGMT deficiency was detected in 12p (60%) and promoter methylation in 10p (50%). Results by IHC were consistent with PSQ in 10p (50%), with mismatches in 4p (methylated MGMT and positive IHC) and 6p (unmethylated MGMT and negative IHC). We reported a higher response rate in MGMT-deficient and MGMT-methylated p (Table) . In MGMT-deficient p we observed significantly better PFS (88m vs 11.1m; p=0.02, HR=0.21) and OS (141.9m vs 35.8m; p=0.03, HR=0.20). Also, in MGMT-methylated p we detected better PFS (88m vs 17.7m; p=0.20, HR=0.44) and OS (188.7m vs 141.9m; p=0.11, HR=0.28). A subanalysis was performed based on G, showing better PFS (88m vs 6.2m; p=0.03, HR=0.11) and OS (188.7m vs 35.8m; p<0.01, HR=0.06) in those with G2 vs G3. There was a strong negative correlation between G and MGMT by PSQ; the higher G, the lower probability of promoter methylation r(16)= -0.62, p<0.01. Conclusions: Our results support MGMT status, deficiency by IHC or promoter methylation by PSQ, as a potential prognostic biomarker in pNET treated with alkylating agents. However, it is necessary to evaluate its prognostic value in prospective studies. [Table: see text]
Clinical characteristics and survival analysis in patients with isolated pulmonary metastases from colorectal cancer (CRC).
Authors: Soto Alsar Javier , Jiménez Rodríguez Roberto , Gutiérrez Alonso Natalia , Bringas Beranek Marianela , Martín Lozano Rocío , López Jiménez Carlos , Gonzalez Caraballo Irene , Juliao Caamaño David Salomon , Gutierrez Ana , Muñoz Andrés , Ortega Morán Laura , Calvo Ferrandiz Pilar Aitana , Torres Pérez-Solero Gabriela , Martin Miguel , Garcia-Alfonso Pilar 
Published: January 2024

60 Background: Recent studies seem to indicate that patients with metastatic colorectal cancer (mCRC) with exclusive pulmonary metastatic disease have better outcomes than those with other metastatic sites. The aim of this study is to identify differences in clinical and survival characteristics between the two groups in a cohort of a third level hospital. Methods: We retrospectively analyzed a sample of 569 patients with mCRC in a tumor registry from 2015 to 2021, studying clinical and molecular characteristics, as well as overall survival data of patients with isolated pulmonary metastases, versus the rest of patients. Results: Of the total sample analyzed, 61 patients (10.7%) had isolated pulmonary metastases. In these patients, several clinical characteristics were more frequent: primary rectal tumor (52.5% vs 23.4%, p < 0.000), resected primary tumor (95.1% vs 78.9%, p = 0.0026), metachronous metastatic disease (62.3% vs 42%, p = 0.0025) and complete response rate to the first line of treatment (19.3% vs 9.9%, p = 0.026). Furthermore, analytically, these patients were more likely to have normal CEA (75% vs 38.3%, p < 0.000), CA 19.9 (84.3% vs 57.7%, p = 0.0002) and LDH (91.1% vs 66.5%, p = 0.0007) levels. In our cohort, we found no statistically significant differences in tumor mutational status (KRAS, NRAS, BRAF, PI3K and HER2). There were no patients with exclusive pulmonary metastatic disease and microsatellite instability (MSI). 70.3% of patients with isolated pulmonary metastases received lung metastasectomy, and up to 58.3% received a second metastases surgery. We also found a numerical benefit in terms of overall survival (OS) in patients with exclusive metastatic lung disease, although it did not reach statistical signification (median OS 77.3 vs 58.1 months, HR for death 0.70, 95% CI, 0.49 – 1.01, p = 0.083). Conclusions: In our cohort, patients with isolated pulmonary metastases were more likely to have rectal tumors, primary tumor resection, metachronous metastatic disease, higher rate of complete responses and normal CEA, CA 19.9 and LDH levels, with a possible benefit in terms of OS.
Clinical impact of KRAS mutations in metastatic pancreatic ductal adenocarcinoma (PDAC).
Authors: Norton Carter , Smith Jarrod , Rubnitz Zach , Tan Grace H. , Nevala-Plagemann Christopher Duane , Soares Heloisa P. , Garrido-Laguna Ignacio , Florou Vaia 
Published: January 2024

619 Background: Mutations in the KRAS oncogene occur in most PDAC and lead to the activation of the KRAS protein. Little is known about the differential impact of KRAS mutations on the outcomes of patients receiving standard of care cytotoxic treatments for metastatic disease. KRAS inhibitors are emerging as promising options for this disease and understanding the impact of distinct KRAS mutations in patient outcomes is needed. Methods: This study used the nationwide Flatiron Health electronic health record (EHR)-derived de-identified database from 5,369 patients. Adult patients with diagnosis of metastatic PDAC who received at least one line of systemic therapy and had sufficient data available were included in this analysis. Median time to next treatment (TTNT) and overall survival (OS) time were calculated for three common first-line treatments and KRAS mutations. TTNT and OS were calculated for each permutation of treatment and each KRAS mutation. Hazard ratios (HR) were generated for each KRAS mutation and treatment, accounting for potentially confounding variables. Results: Of the 5,369 patients, 2,472 met the inclusion/exclusion criteria. G12C had the shortest median OS (7.5 mo) and G12R had the longest (9.1 mo). Overall, KRAS mutation-positive patients had a median OS of 8.6 mo, compared to 11.7 mo for KRAS Wild Type (WT) patients. A Cox Proportional Hazard analysis of OS across KRAS mutation status found that G12C, G12V, G12D, and Other Non G12/13 KRAS had significantly higher HR than KRAS WT. A comparison of the three common first-line interventions for metastatic PDAC showed that FOLFIRINOX had the longest median TTNT (5.3 mo) and the longest OS (10.2 mo), while Gemcitabine had the shortest TTNT (2.6 mo) and OS (5.9 mo). A Cox Proportional Hazard analysis of OS across all patients found that Gemcitabine and Gemcitabine with Nabpaclitaxel had significantly higher HR than FOLFIRINOX. FOLFIRINOX had the longest TTNT in the G12C, G12V, G12D, G12R, and other non-G12/G13 KRAS groups (see table). Conclusions: Our data suggest that FOLFIRINOX has a longer TTNT than other first-line regimens for KRAS G12C, G12V, G12D, and G12R. KRAS G12C was associated with the shortest OS among common KRAS mutations.[Table: see text]
Optimising utility of selective internal radiation therapy in metastatic pancreatic adenocarcinoma.
Authors: Cooray Prasad , Muralidharan Vijayaragavan , Spanger Manfred , Page Patrick , Fox Adrian , Mackay Sean , Thang Sue , Miller Lisa , Poh Ashleigh , Le Caroline 
Published: January 2024

622 Background: Selective internal radiation therapy (SIRT) using Yttrium-90 containing microspheres has established benefit for a number of cancers but there is limited data available on the utility of SIRT for the treatment of metastatic pancreatic ductal adenocarcinoma (PDAC). Methods: In this retrospective audit we identified 32 patients who received SIRT using Yttrium-90 microspheres for metastatic PDAC in 2 treatment centres. All patients received SIRT in combination with chemotherapy. Data was analysed from electronic medical records. Results: Thirty two patients with metastatic PDAC who had SIRT were identified. Patients received SIRT (median activity 1.6 GBq) in combination with chemotherapy (platinum-based; n = 23, non-platinum-based; n = 9). Three patients remain alive and 29 patients were included in the survival analysis. For the entire group, the median OS was 15 months (range 4-49), median survival from time of SIRT was 9 months (range 1-48) and median PFS from time of SIRT was 4 months (range 1-25). Median PFS (6 vs 2 months, p=0.0011) and OS (13 vs 4 months, p=0.0004) from SIRT was significantly better when SIRT was given with 1st-line therapy vs with 2nd-line and beyond. Median PFS from SIRT was significantly better (10 vs 2 months, p=0.0020) when combined with 1st line platinum-based chemotherapy (n=14) vs non-platinum based treatment (n=6). 18 month survival was 40% (n=13) with 9/13 patients having had SIRT with 1st line with platinum-based therapy. 24 month survival was 22% (n=7) with 7/7 patients having had SIRT with 1st line with platinum-based therapy. SIRT was well-tolerated with no associated 30-day all-cause mortality. Grade 3 adverse events were liver abscess (7%, n = 2), gastritis (7%, n = 2) and duodenitis (7%, n=2). Conclusions: This is the first report to analyse optimum utility of SIRT with chemotherapy in metastatic PDAC. Our data suggest SIRT in combination with 1st-line platinum agents contribute to the best outcomes in the setting and warrants further study.
Prognostic value of the CRM status in pancreatic ductal adenocarcinoma: Data from a regional cancer registry.
Authors: Morakis Philipp , Surovtsova Irina , Schuhbaur Jasmin , Kokh Daria , Winzler Claudia , Szotyori-Artz Gertrud , Schütz Juliane , Uhl Waldemar , Tannapfel Andrea , Seufferlein Thomas 
Published: January 2024

632 Background: Ductal pancreatic adenocarcinoma (PDAC) still has a dismal prognosis even when deemed resectable. A cancer free resection margin (R0) is associated with a more favourable prognosis than the presence of tumour cells at resection margin (R1). However, the precise definition of the R0 status is still a matter of debate in PDAC. For a more accurate determination of R0 in PDAC the concept of circumferential resection margins (CRM) has been introduced. However, an international standardized nomenclature of CRM is still missing, and the clinical value of the CRM concept is not yet fully established. Here we evaluate whether the CRM status as defined in the national German S3 guideline is an independent prognostic factor in PDAC using data from the regional cancer registry of the State of Baden Württemberg in Germany. Methods: Data from the cancer registry of the State of Baden-Württemberg, Germany were collected, using documented patients diagnosed with invasive ductal adenocarcinoma of the pancreas between 2015 and 2020. The R-status was assessed according to the national German S3 guideline with R0 wide/CRM- when CRM is > 1mm, R0 narrow/CRM+ when CRM is £ 1 mm from the tumour and R1 when tumour cells are found at the resection margin. Progression free survival (PFS) as well as 3-year overall survival (OS) were assessed using Kaplan-Meier statistics and multivariable Cox regression models (adjusted for age, pN stage, primary tumor location and systemic treatment). Results: In total we identified 1098 cases surgically treated for pancreatic cancer and fulfilling the inclusion criteria. 340 patients had an R0 wide/CRM- resection, 410 patients an R0 narrow/CRM+ resection, and 348 patients an R1 resection. The R0 wide/CRM- status was associated with a significantly increased median 3-year OS rate compared to the other two groups (51,5%, 37,4% and 26,7% for R0 wide/CRM-, R0 narrow/CRM+ and R1, respectively). mPFS was also longer in the R0 wide/CRM- group. These findings were robust with regards to grading. 5-FU based adjuvant treatment was mainly mFOLFIRINOX and show better outcome as compared to gemcitabine-based treatments. Conclusions: The present study was performed using real world data reflecting actual clinical settings. The results obtained are in good agreement with data from clinical trials, including the prognostic role of the R- and N- Status as well as the efficacy of adjuvant chemotherapy protocols used.
Intra-operative radiation for pancreatic cancer: Initial experience at the Hadassah Medical Center.
Authors: Cornejo Gianella , Blumenfeld Philip , Hubert Ayala 
Published: January 2024

634 Background: Prognosis following surgery for pancreatic cancer (PC) remains poor. Local recurrence is common and negatively impacts survival rate. In an effort to improve local control and potentially improve survival, we have adopted a strategy of adding intra-operative electron radiation therapy (IOeRT) to selected patients undergoing pancreatic resection (PR) for PC. Here we report our initial experience with this treatment modality. Methods: 14 patients (10 male, 4 female), age between 44 - 81 years (mean 66.17), who underwent PR (Head 7, Body7) between 1/2021-1/2023 were included in this analysis. Patients selected for IOeRT included patients that according to surgeon assessment were at risk not to achieve satisfactory resection margins by surgery alone. All had resectable or borderline resectable disease according to standard criteria. 8 patients underwent pre-op chemotherapy followed by stereotactic body radiotherapy (SBRT) to a dose of 25-40 Gy in 5 fractions to the tumor and regional lymphatics followed by PR (5 Whipple, 3 distal pancreatectomy) and IOeRT, 3 patients received preop SBRT followed by PR (3 distal pancreatectomy) + IOeRT, 2 patients underwent PR (whipple 1, distal pancreatectomy 1) + IoeRT, and 1 received neoadjuvant chemotherapy followed by SBRT only and did not undergo surgery due to tumor progression. Immediately following resection, mobile IOeRT accelerator using a 40-80mm applicator with a level of 0-15 degrees was directed at the tumor bed deemed at high risk for recurrence. 10-20 Gy was delivered using 6-8 MeV electrons to the 90% isodose line at the discretion of the treating radiation oncologist. Data including serial imaging, genomic analysis, radiation protocol, complications, pathological results and outcome was collected for analysis. Results: Mean follow up was 9.7 months (2-21). 8 patients are alive: 7 pts with no evidence of disease and 1 pt with liver metastases. 6 patients died: 4 with distant metastatic disease, 1 from disease progression prior to surgery and 1 from early post-op sepsis. Negative surgical margins were achieved in 10 patients of which 2 mutated BRCA gene carriers showed complete pathological response (both who received combined neoadjuvant chemotherapy followed by SBRT). Post-operative complications possibly attributed to RT included hepatic artery occlusion (1 pt), portal vein stenosis (1 pt) and prolonged GI tract dysfunction (1pt). Conclusions: Combining RT with resection appears feasible and safe. Our data possibly show a reduction in local recurrence following resection of PC, however, longer follow up is necessary. Refinements in patient selection and treatment protocol may further improve outcomes. Larger scale studies are required to determine the benefit of this modality.