bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of complete pathological response outcome in Latin American patients with rectal cancer.
Authors: Calderillo Ruiz German , Diaz Dr. Consuelo , Herrera Marytere , Ruiz-Garcia Erika , Miyagui-Adame Sayako Mariana , Carbajal Berenice , Albarrán-García Alejandra , Murguía-Guzmán Zugeyth Emireth 
Published: January 2023

58 Background: Rectal cancer is one of the leading cancer-related causes of death worldwide. Nevertheless, complete pathological response (pCR) to neoadjuvant treatment has been associated with a decrease in local recurrence and distant disease, and therefore an improvement in disease-free survival (DFS) and overall survival (OS). The aim of this study was to evaluate the impact of pCR in DFS and OS Mexican patients with rectal cancer. Methods: Retrospective, observational study. Included patients with rectal adenocarcinoma treated with neoadjuvant chemo-radiotherapy between 1998 and 2021. Statistical analysis: X2 and t-test, Kaplan Meier, Log Rank, and Cox Regression. Statistical significance p <0.05 bilaterally. Results: A total of 707 patients were included in the analysis. 52.3% were male with a median age of 57 (18 – 86) years. According to clinicopathological features, moderate-grade was the most prevalent at 66%, 38.5% were low-rectum and 32% of patients reported an ACE<10mg/dL. Patients were divided into 2 groups: pCR (n=155) and non-pCR (n=552) for the analysis. According to surgical margins, 89%(n=491) non-pCR-patients reported R0 (p=0.003). Recurrence rate was 12.9%(n=20) versus 35.7%(n=197) in pCR and non-pCR respectively (p<0.001). Regarding DFS analysis, pCR-patients median-DFS was Not Reached (NR), while non-pCR-patients median-DFS was 154 months (p<0.001; HR:0.32, 95%CI:0.20-0.51). At OS analysis, pCR-patients median-OS was NR, non-pCR-patients median-OS was 166 months (p<0.001; HR:0.41,95%CI 0.26-0.65). At DFS-multivariate analysis, location (p<0.001; HR:1.47, 95%CI:1.20-1.80) and rPC (p=0.013; HR:0.48,95%CI:0.27-0.85) remained predictive factors of DFS. At OS-multivariate analysis, ACE (p=0.047; HR:1.37, 95%CI:1.00-1.89) and pCR (p=0.009; HR:0.45, 95%CI:0.24-0.81) remained as predictive factors of OS. Conclusions: The pCR rate in our population is similar of what is reported in the literature. Our study demonstrates that pCR significantly impacts DFS and OS, rectal cancer patients. Total neoadjuvant chemo-radiotherapy, short-scheme-radiotherapy, and immunotherapy in selected populations can achieve doubling the percentage of pCR. [Table: see text]
Genomic profiling to provide new treatment opportunities in ampullary carcinoma.
Authors: Fabregat Franco Carles , Castet Florian , Saoudi Gonzalez Nadia , Castillo Gloria , Acosta Eyzaguirre Daniel , Salcedo Maria Teresa , Verdaguer Helena , Macarulla Teresa 
Published: January 2023

582 Background: Ampullary carcinoma (AC) is a rare heterogeneous group of diseases with an abysmal prognosis. Treatment options are limited, and the molecular landscape of this disease and its therapeutic implications have been incompletely explored. Here, we aim to provide a clinical and genomic characterization of AC and explore opportunities for precision oncology. Methods: Patients diagnosed with AC and treated at a single tertiary institution between 2010 and 2022 were reviewed. Molecular profiles were analyzed by applying an in-house exome-targeted panel or the FoundationOne CDx panel. Gene mutations were categorized into molecular pathways and potentially targetable alterations were classified according to the ESCAT scale. Overall survival (OS) and disease-free survival (DFS) were estimated by using the Kaplan-Meier method. Results: We included 64 patients with a median age of 66 years, 51.6% were women, most were classified as pancreatobiliary tumours (PB, 58.3%), followed by intestinal (INT, 33.3%) and mixed histologies (8.3%). 18.8%, 23.4%, 32.8% and 25.0% of the patients were diagnosed at stage I, II, III and IV, respectively. 81.2% of the patients were treated with surgery. The INT subtype was enriched in WNT pathway alterations (28.6 vs 6.2%, p=0.02) and showed a non-significant enrichment in the apoptotic pathway (57.1 vs 34.4%, p=0.08). Conversely, BP showed a non-significant enrichment in HRR pathway alterations (16.7 vs 54.5%, p=0.3). The frequency of KRAS mutations were similar in both subtypes (38.1 vs 37.5%). Potentially actionable molecular alterations were found in 46.7% of the patients (9 ERBB2, 8 HRD, 8 PI3KCA, 2 MSI, 2 BRAF, 2 PTEN and 1 KRAS G12C). Importantly, KRASwt tumours were enriched in potentially targetable alterations (ESCAT I-IIIA), including 20% ERBB2 amplification/mutations, 6% MSI and 3% BRCA1. 6 patients received matched targeted therapies during their disease course, 66% of which responded and 100% stable disease, with a median TTD of 7 months. Conclusions: More than 45% of AC harbor potentially targetable genomic alterations that may provide novel therapeutic opportunities and enhance personalized medicine in this rare disease entity.
Genetic heterogeneity of intrahepatic cholangiocarcinoma: Implications for outcome.
Authors: Song Yi , Boerner Thomas , Drill Esther N. , Shin Paul , Cercek Andrea , Kemeny Nancy E. , Abou-Alfa Ghassan K. , Iacobuzio-Donahue Christine A , Schultz Nikolaus , Walch Henry S. , Sigel Carlie S. , Kingham T. Peter , Soares Kevin , Wei Alice Chia-chi , D'Angelica Michael Ian , Drebin Jeffrey A. , Chandwani Rohit , Harding James J. , Jarnagin William R. 
Published: January 2023

595 Background: Intrahepatic cholangiocarcinoma (IHC) is characterized by marked clinical heterogeneity, likely the result of multiple cells of origin and variable driver gene alterations. The hidden-genome classifier is a statistical algorithm that classifies tumors by integrating multi-level genomic features. In this study, we trained the hidden-genome classifier with extrahepatic cholangiocarcinoma (EHC), gallbladder cancer (GBC) and hepatocellular carcinoma (HCC) as extremes of a spectrum to quantify the genetic heterogeneity of IHC with a view toward improved tumor classification. Methods: An IRB approved retrospective review of patients with biopsy confirmed IHC, EHC, GBC and HCC was conducted. All tumors were subjected to MSK-IMPACT to determine the mutational profile. A two-class model was built and internally validated with the genomic data of EHC/GBC as one class and HCC as the other class. IHC tumors were analyzed in the model and classified into three groups based on their proportional genetic resemblance to EHC/GBC (Biliary Class) or HCC (HCC Class), with the remainder as Intermediate Class. The classification thresholds were 90% resemblance to EHC/GBC or HCC and were determined by the inflection point of predicted survival. The survivals of the three groups were analyzed and compared. Results: A total of 1497 patients were included: IHC (733), EHC (208), GBC (258) and HCC (298). 527 IHC tumors with complete metagenetic information were analyzed in the model, showing a continuous spectrum of alterations, ranging from Biliary Class (122 tumors), Intermediate Class (375 tumors) to HCC Class (30 tumor). The biliary-class IHC was characterized by frequent alterations of IDH1 R132C, KRAS, SMAD4, ERBB2 gain, MDM2 gain, and CKDN2A loss, while the HCC-class IHC was primarily characterized by TERT alterations. In patients with unresected IHCs, the median survival ranged from 1 year (CI 0.77, 1.5) in Biliary Class, 1.8 years (CI 1.5, 2.0) in Intermediate Class, to 2 years (CI 0.93, NR) in HCC Class. In patients subjected to resection, the median survival of Biliary Class (2.4 years, CI 2.1, NR) was lower than both the Intermediate Class (5.1 years, CI 4.8, 6.9) and the HCC Class (3.4 years, CI 2.7, NR). Conclusions: By integrating multi-level genomic features, we leveraged the mutational heterogeneity to classify IHC based on its resemblance to EHC/GBC or HCC tumors. We found that the survival in IHC patients appeared to decline with increasing genomic similarity to Biliary Class. The results support a genomic basis for IHC’s variable clinical behavior and point to a role of mutational testing to guide clinical intervention. [Table: see text]
The efficacy of immune checkpoint inhibitors in biliary tract cancer with KRAS mutation.
Authors: Jeong Sun Young , Kim Seung Tae , Jang Jae Yeon 
Published: January 2023

598 Background: Biliary tract cancer (BTC) is rare cancer but has a poor prognosis with only 10% of 5-year overall survival (OS). The treatment of advanced BTC remains challenging with limited standard options. With a 15% of incidence, KRAS is one of the most common mutations in BTC. The immune checkpoint inhibitor as salvage therapy has modest activity in BTC. Methods: We conducted molecular profiling including tumor mutational burden in BTC patients with immune checkpoint inhibitors (ICI) as salvage therapy. Programmed death ligand 1 (PD-L1) expression on tumor cells and on tumor-infiltrating lymphocytes (TIL) was also assessed. Results: Between 2020 to 2022, a total of 62 patients were analyzed. The median age was 68 (58.0-73.0). 47 patients (75.8%) received pembrolizumab and 15 (24.2%) received nivolumab as salvage therapy. All patients received gemcitabine plus cisplatin as the frontline therapy, and 53.2% had fluoropyrimidine plus oxaliplatin (FOLFOX) before ICIs. The median lines of prior chemotherapy were 2.5 (2.0-3.0). KRAS mutation was found in 14 patients (22.6%). 28 patients (45.2%) were positive for PD-L1. There was no statistical correlation between KRAS mutation and PD-L1 expression. The median OS and PFS of patients were 5.2 and 3.5 months respectively. There were no statistically significant differences in PFS according to the status of KRAS mutation (Mutant type vs. Wild type) and PD-L1 expression (Positive vs Negative). In subgroup analysis, patients with KRAS mutation and PD-L1 positivity had longer PFS as compared to patients with KRAS mutation and PD-L1 negative (6.5 vs 2.6 months, p=0.047). This finding was not shown in patients without KRAS mutation. Conclusions: The PD-L1 expression might be a novel biomarker for ICIs in BTC patients with KRAS mutation but not in those with the wild type of KRAS.
Do nonoperative modality (NOM) treatments of rectal cancer compromise the chance of cure? Final surgical salvage results from OPERA phase 3 randomised trial (NCT02505750).
Authors: Sun Myint Arthur 
Published: January 2023

6 Background: Watch and wait strategy without surgery for rectal cancer is gaining popularity as it avoids a stoma. We set up an OPERA trial to evaluate the role of radiation dose escalation using Contact X-ray brachytherapy [CXB] (Papillon). We report on the final surgical salvage results for local failures of non-surgical approach. Methods: OPERA is a European phase 3 randomised trial between (Arm A-standard arm)EBCRT 45Gy/25/5weeks with oral capecitabine 825mg/m2 and EBRT boost of 9Gy/5/5 days randomised against experimental arm (Arm B) EBCRT followed by CXB boost (90 Gy/3/4 weeks). Patients were assessed at 14, 20 and 24 weeks. Watch & wait policy was adopted for patients with cCR and surgery (TME or local excision) offered for residual disease or recurrence after cCR. Results: From July 2015 –June 2020, 148 patients were randomised of which 141 were evaluable. Median age was 68 years and 88 (61%) patients were males. There were 69 patients in Arm A (standard of care with EBRT boost) and 72 patients in Arm B (experimental with CXB boost). All patients received the protocol stratified radiation dose. Median follow-up was 38.2 months (95% CI:34.2-42.5). Clinical complete response (cCR) was observed in 44/69 (64%) in Arm A and 66/72 (92%) in Arm B at 24 weeks (p< 0.001). Surgery was carried out in 66/141 (47%) with suspected residual tumour or local regrowth after achieving cCR. Total 39/66 (59%) patients had TME surgery. Local excision was carried out in 27 /49(41%). Our primary endpoint of organ preservation (OP) rate was 59% (95% CI: 48-72) in Arm A vs. 81% (95% CI: 72-91) in Arm B (HR 0.36, 95% CI: 0.19-0.70; P= 0.0026). When comparing A1(<3cm) vs. B1(<3cm), OP rate was 63% vs. 97% respectively (HR: 0.072, 95% CI 0.0093-0.57; P= 0.0123]). Overall TME free overall survival was 57% for Arm A and 79% for Arm B (HR 0.37,95% CI 0.2-0.71; P=0.0026). Conclusions: OPERA data at 38 months suggest that non-surgical treatment for cT2-cT3a-b rectal cancer is feasible and those who needed surgery for local failures can be salvaged without compromising their chance of cure. There is significant improvement in OP rate for rectal cancer <3cm to start with CXB followed by EBCRT. This option should be discussed with patients wishing to avoid surgery and a stoma as an initial treatment. Clinical trial information: NCT02505750 . [Table: see text]
Comprehensive molecular profiling in patients with advanced biliary tract cancers (BTC) in a Latinx-rich cohort.
Authors: Kapoor Vidit , Keiser Sylvia , Liu Qianqian , Michalek Joel , Arora Sukeshi Patel 
Published: January 2023

605 Background: BTC are genetically diverse and heterogeneous. Despite knowledge of molecular subtypes of BTC, the distribution of molecular aberrations in the Latinx population has been understudied. These may have prognostic and/or predictive implications. Therefore, we analyzed our cohort of Latinx-rich patients with advanced BTC. Methods: We analyzed patients with advanced BTC, who were seen at the Mays Cancer Center from Jan 2018-Dec 2021. Tumor samples profiled by Next Generation Sequencing (NGS) were identified retrospectively. Associations between demographics, clinical characteristics, and genetic alterations were identified. Results: 88 patients with locally advanced/metastatic BTC were identified. 50 (56.2%) were Latinx. 42 (47.7%) had intrahepatic CA (IHCA), 14 (15.9%) had extrahepatic CA (EHCA), 16 (18.2%) had Gall Bladder Carcinoma (GBC) and 16 (18.2%) had Ampullary/Periampullary Carcinoma (APC). 49 (56%) had NGS on their tumors out of which 30 (61.2%) were Latinx and 19 (38.8%) were non-Latinx. The most commonly altered genes were TP53 (34.7%), KRAS (24.5%), ARID1A (16.3%), BRCA-2 (12.2%), PDL-1 (12.2%), FGFR (12.2%), MET (10.2%), PTEN (10.2%) and HER-2 (8.2%). 14.3% patients had no identifiable mutations. There was no significant difference observed in the rates of different molecular mutations between Latinx and non-Latinx (p=1) and among different histologies of IHCA, EHCA, GBC and APC (p=1). The Median Overall Survival (OS) for Latinx population was 16.1 months (95% CI 12.3-28.2) which was similar to the median OS for non-Latinx population of 15.5 months (95% CI 11.6-28.6) (p=0.69). The median OS was not different due to the presence or absence of any one mutation (p values ranged from 0.04 to 0.9). Conclusions: BTCs are genetically diverse. Somatic alterations were identified in 85% patients who were tested. Only 56 % had molecular testing, when it should be 100% in advanced BTC, per NCCN guidelines. This may be due to inadequate tissue, lack of funding, use of alternate ctDNA, or the patient may have died before getting to testing/repeat biopsy. The likelihood of having a genetic alteration was similar between Latinx and non-Latinx patients and among different sites of disease. Latinx and Non Latinx with advanced BTC had similar survival rates. Survival rate was not different due to the presence or absence of any one mutation. Future studies should prospectively investigate implementation programs for NGS in tumor and blood in all patients with BTCs.
A glimpse into the future of hepatocellular carcinoma (HCC): Predicting the future incidence based on the current epidemiological data.
Authors: Tella Sri Harsha , Wieczorek Mikolaj , Hodge David , Mahipal Amit 
Published: January 2023

615 Background: Accounting for 90% of primary liver cancers, HCC is the fourth-most common cause of cancer-related deaths in the United States. While the vaccination against hepatitis B and awareness on hepatitis C transmission possibly decreased the incidence of HCC in Eastern World, there was an uptrend in the HCC incidence the Western World over the past few years possibly related to metabolic causes. With this changing paradigm of hepatocellular carcinoma, it is important to estimate its future burden stratified based on the age, sex, and race, that could possibly help plan prevention, control, and treatment strategies for this cancer. Methods: We obtained histologically confirmed cases of HCC (ICD-0-3 Site: C220 and 228; codes: 8170-8175) from National Cancer Institute (NCI) Surveillance, Epidemiology, and End Results (SEER) 18 registries between 2000 to 2017 and predicted the incidence between the years 2018-2029. We applied age-period-cohort models to estimate future HCC incidence rates (per 100, 000) and the estimated disease burden by multiplying incidence forecasts by corresponding US Census population projections. Results: A total of 76029 patients with HCC were included in the final analysis. The median age was 62 (range: 20-79) years with male predominance (70%). The overall observed age-adjusted incidence of HCC between 2000-2017 was 6.22, which is predicted to increase to 9.03 by 2029 with a predominant increase in incidence rate observed in the age groups 70-79 and White males. Interestingly, we noticed a progressive decrease in incidence rate in Asian cohort (both males and females) and Black males. Incidence rates by sub-groups based on the age, sex, and race are summarized in the Table. Conclusions: We predict an overall increased incidence of hepatocellular carcinoma over the next decade in the United States, predominantly in 70-79 years age group irrespective sex and race, with an exception to Asian cohort probably representing differential risk factors. Further epidemiological studies are needed to determine the etiological factors contributing to predicted increase in incidence rate.[Table: see text]
Molecular genetic sequencing of neuroendocrine tumors of the gastrointestinal tract.
Authors: Androsova Alexandra , Orlova Rashida , Gordiev Marat , Ivanova Anastasia , Belyak Natalia P. , Kutukova Svetlana 
Published: January 2023

651 Background: The objective of this work was to evaluate the molecular and genetic features of the NET gastrointestinal tract. Genomic sequencing of 30 tumor samples of the latest generation was carried out and the data obtained were evaluated. Methods: In total, 30 tumor blocks of patients with gastrointestinal NET were tested by the new generation sequencing (NGS) method. The following genes were analyzed: ATM, ATR, BARD1, BRCA1, BRCA2, BRIP1, CDH1, CDK12, CHEK1, CHEK2, EPCAM, FANCL, MLH1, MSH2, NBN, NF1, PALB2, PMS2, RAD51B, RAD51C, RAD51D, RAD54L, STK11, TP53, POLE, KRAS, NRAS, BRAF, EGFR, ERBB2, PIK3CA, MET ex14, BAT25, BAT26, NR21, NR24, MONO27, KIT, PDGFRA, Pi3Ca. Preparation of libraries for sequencing was carried out using NimblGen SepCapEZ Choice. Sequencing was performed on the Illumina MiSeq device. Results: In the study cohort of patients whose tumor blocks were sent for examination by the NGS method, there were more women – 19 (63.3%) than men – 11 (36.7%). When analyzing the age of patients, it should be noted that among all age groups, elderly patients predominated (60-74 years according to the WHO classification, 2016) – 12 (40%). In the majority of patients – 10 (33.3%) – the primary tumor focus was localized in the pancreas, in 6 (20%) patients it was primarily affected stomach, 7 (23.3%) – small intestine. Other parts of the gastrointestinal tract were affected much less frequently: the colon – in 1 (3.3%) patients. According to the division according to the degree of differentiation of gastrointestinal NET10 tumors had a degree of differentiation G1 (33.3%), 16 -G3 (54.3%), 4– G3 (13.3%). In the tumor sample of a patient with gastric NET G1 (Ki 67 = 2%), POLE mutations were found: c.2276G > A, p.R759H and CHEK2: c.470T > C, p.I157T. Also, mutations MLH1: c.199G > A, p.G67R BRCA1: c.1881 were found in the tumor sample of another patient with gastric NET G2 (Ki 67 = 7%). Conclusions: To improve the survival rates of patients, it is worth paying special attention to the molecular genetic study of the NET gastrointestinal tract. It is molecular genetic profiling that can become the basis for building more individualized algorithms for treating patients. The results of this study allow us to count on the fact that when conducting a study on a larger cohort of patients with gastrointestinal NET, it is possible to obtain results that will expand our knowledge of this nosology and allow us to supplement the already available information about prognosis factors and predictors of response to treatment.
Socioeconomic disparities causing delays in pancreatic cancer germline genetic testing.
Authors: Zou Xianghui , King Daniel , Sidiqi Baho , Patruni Sunita , Hollweg Christopher , Kauff Noah D. 
Published: January 2023

665 Background: Germline genetic testing is recommended for patients with pancreatic ductal adenocarcinoma (PDAC) and pre-diagnostic testing is offered to patients with a significant family history. However, only 36% of patients in our institution obtained genetic testing. We identified associations between patient social profiles (income, race, ethnicity, social work needs) and delays in obtaining germline genetic testing from New York’s largest healthcare system. Methods: Patients with PDAC were identified using billing records across our institution with an IRB-approved protocol. Median income was extrapolated using patient zip code. Date of diagnosis (DOD) was recorded as the date of biopsy or, if no biopsy was performed, the date of earliest lesion found on CT scan. Delays of testing was calculated as the difference between DOD and the date of germline sample collection. Results: Between Mar 2016 and Feb 2022, 305 patients with PDAC were identified, with 103 (36.3%) having reports found (F), and 202 (63.7%) not having reports found (NF). Availability of germline testing did not vary by median income (F: $95954, NF: $94368, t=0.414, p=0.68). There was no significant difference in the geographic distribution either (gender p=0.92, race p=0.92, ethnicity p=0.16). Pearson analysis between income (x) and delays of testing (y) showed a negative correlation (y=-0.0028x+316, r2=0.058, p=0.014). African American and Hispanic patients, grouped for this analysis as underserved (U), had a significant delay in obtaining germline genetic testing compared to the remainder of patients (not underserved, NU) (U: 92d, NU: 21d, u=305.5, p=0.0016). In addition, African American (AA) patients had a significant delay of testing compared to White (W) patients (AA: 92d, W: 13d, u=161.5, p=0.0002). Furthermore, all 11 patients (1 Asian, 10 White) who obtained pre-diagnostic testing were NU patients (χ2=5.005, p=0.025). Upon further analysis, patients who have social work (SW) needs have a significant delay in testing compared to patients without SW needs (SW: 109d, no SW: 23d, u=263, p=0.025). Of the 12 patients who have SW needs, the primary needs were home care, transportation, or financial assistance. In addition, there was a trend toward difference between English (E) and non-English (NE) speaking patients when comparing their delays in testing (E=26.5, NE=108.5, u=257, p=0.12). Conclusions: Analysis of germline and clinical data from our 305-patient cohort identified a striking and concerning negative correlation between patient income and delays in germline testing. In addition, underserved patients had significant delays in germline testing and did not obtain any pre-diagnostic testing. Furthermore, social needs and primary language may be barriers for germline testing. Interprofessional collaborations may be required to prompt germline testing at our institution or nationwide.