bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinicopathological features and clinical outcomes in individuals with Krukenberg tumors of colorectal origin.
Authors: Bergstrom Colin P , Wang Cindy , King Daniel , Lin Albert Y. , Fisher George A. 
Published: January 2024

191 Background: Krukenberg tumors (KT) are metastases to the ovary generally originating from a gastrointestinal primary such as colorectal carcinoma. The prognosis is poor with KT, and clinicopathological features associated with clinical outcomes have not been extensively studied. The study aimed to investigate the associations of clinicopathological features with outcomes in patients with KT of colorectal carcinoma (CRC) origin. Methods: This retrospective study utilized medical records and patient registries to identify 160 patients with a confirmed histopathological diagnosis of KT at Stanford University Medical Center between 2000 and 2020. Data collection included demographics, historical, clinicopathological, treatment and outcome variables. The primary tumor type was (N, %): CRC (101, 63.1%); gastric (24, 15%), breast (13, 8.1%); small bowel (10, 6.2%), other (12, 7.5%). Statistical analysis was performed using Chi-squared, Mann-Whitney U, and log-rank Kaplan-Meier analysis. Results: Analysis of the CRC cohort subdivided by location of the primary, N: 45 vs. 56, right colon (R) vs. left colon (L) revealed no significant difference in median age at diagnosis of KT, race/ethnicity, oligometastatic disease, histopathological differentiation or ovarian tumor volume. Patients with R vs L sided CRC primaries had a higher proportion of synchronous presentation at the time of KT diagnosis (75.6% vs 41.1%, R vs L, p<0.001). Time to progression was not different, but overall survival (OS) was shorter in R CRC (767 vs. 1246 days, R vs. L, p <0.01). By Kaplan-Meier analysis, patients with R CRC had a shorter OS (log-rank p=0.016). In the subgroup with unilateral KT, R sided CRC primaries involved the R ovary (85%) whereas L-sided CRC primaries involved the L ovary (70%) ( χ2, p<0.002). Patient with bilateral (B) versus unilateral (U) had a larger ovarian tumor volume (2,073cm3 vs. 307 cm3, p<0.01) but no difference in oligometastatic disease, chronicity, time to progression or overall survival. There was no statistical difference (p=0.93) between the association of bilateral KT inter-ovarian tumor size and CRC Laterality within individual patients. Conclusions: In this study, KT tumors predominantly originate from CRC. The clinical features of R versus L CRC, such as chronicity and OS are conveyed prognostically in patients with KT. Individuals with L CRC exhibited a better overall prognosis compared to those with R CRC. In patients with unilateral KT metastasis to ipsilateral ovary is significantly associated with location of CRC and is suggestive of a retrograde lymphatic or transcoelomic route of metastatic spread. Further studies are needed to confirm these findings and to elucidate ovarian organ tropism mediators that facilitate development and growth in metastatic ovarian cancer.
Early onset metastatic colorectal cancer: Clinical-prognostic characteristics and correlation to molecular profile.
Authors: Pretta Andrea , Ziranu Pina , Perissinotto Eleonora , Ciracì Paolo , Giuliani Lorenzo , Pusceddu Valeria , De Grandis Maria Caterina , Taravella Ada , Puzzoni Marco , Piva Vittoria Matilde , Boccaccio Chiara , Lai Eleonora , Prete Alessandra Anna Anna , Cerma Krisida , Marmorino Federica , Giampieri Riccardo , Lonardi Sara , Cremolini Chiara , Bergamo Francesca , Scartozzi Mario 
Published: January 2024

195 Background: Despite a reduction of both incidence and mortality of CRC in the elderly population, several studies published in the last decade have shown an increase in the incidence of early-onset CRC (EO-CRC). Clinical and prognostic data on this setting are limited and conflicting. The aim of our study was to evaluate the clinical, prognostic, and molecular differences in a large group of patients (pts) with early onset mCRC. Methods: We collected data from 589 metastatic EO-CRC from 4 different Italian Institutions. A historical control group of 316 pts > 50 year old was also included in the analysis. All pts had one or more metastatic sites, molecular profiling available (including RAS, BRAF, and MSI status), and underwent at least one line of treatment. The main objective of the study was to evaluate clinical outcome in terms of median overall survival for the global population of EO-CRC pts and in different molecular subgroups according to RAS and BRAF status. Results: In the EO-CRC group median age was 44 (±6) and 67 (±11) in the historical control group. M/F ratios were 2:1 and 1:1, respectively. In the overall population mOS was 34,1 in EO-CRC pts vs 42,0 months (mo) (p = 0,0006) in the control group. In the RAS/BRAF mutated subgroup mOS in EO-CRC pts was 28,6 vs 36,0 mo in the control group (p = 0,0065). In RAS/BRAF wild type subgroup mOS in EO-CRC pts was 44,1 vs 49 mo (p = 0,13). Finally, in the BRAF V600E mutated subgroup EO-CRC pts showed a 16 mo mOS vs 26 mo (p = 0,04). In the overall population mPFS was 12,0 in EO-CRC pts vs 10,0 mo (p = 0,02) in the control group. Furthermore, the overall response rate (ORR) was 53% in EO-CRC and 69% in LO-CRC. Conclusions: Our work including a large population of EO-CRC pts indicates a general worse prognosis for pts with early onset colorectal cancer compared to late onsets. Interestingly this seems to occur regardless of the molecular status. On the other hand findings in the RAS/BRAF wild type population might also suggest a less unfavourable impact of EO-CRC on prognosis possibly related to anti-EGFR therapy. Subsequent investigations will be needed to further understand the specific clinical and molecular characteristics of this growing group of pts to better define the more appropriate treatment strategy.
The TGF-beta pathway alterations in young-onset colorectal cancer.
Authors: Guven Deniz Can , Ferrell Morgan , Gonzalez Cyndi , Giza Richard , Cheng Svea , Syed Masood Pasha , Magge Tara , Singhi Aatur D. , Saeed Anwaar , Sahin Ibrahim Halil 
Published: January 2024

218 Background: Colorectal cancer (CRC) is the third most common cancer and the second most common cause of cancer-related deaths worldwide. The epidemiological evidence suggests an increased incidence of young-onset CRC, defined as the CRC in individuals 50 years old or younger. The TGF-beta alterations are among the pivotal events in the CRC carcinogenesis. However, the rate of mutations leading to TGF-beta alterations are yet to be defined in young-onset CRC. Therefore, we conducted a bioinformatics analysis of the mutations associated with TGF-pathway alterations according to age (≤50 years of age vs. >50 years) and primary tumor location (colon vs. rectum). Methods: We used published genomic data of 6286 patients with CRC from the 16 CRC datasets included in the cBioPortal database. The presence of mutations in the following genes was used to define TGF-beta alterations: TGFBR2, TGFB2, TGFBRAP1, TGFBR1, TGFBR3, TGFB1I1, TGFBI, TGFB1, TGFBR3L, TGFB3, TGFA, SMAD1-9, BMPR2, BMPER, BMP3, BMP2K, BMP1, BMP5, BMP10, BMPR1A, BMP15, BMP7, BMP23, BMP4, BMP6, BMPR1B, BMP8B, BMP8A. The presence of TGF-beta alterations according to the age (≤50 years of age vs. >50 years) were evaluated with Chi-square tests. The association between primary tumor distribution (colon vs. rectal) and age were evaluated across patients with and without TGF-beta pathway alterations. The effect of WNT pathway alterations on the overall survival and survival after the metastatic stage was evaluated with Kaplan-Meier survival curves. A type-I error level of 5% (p<0.05) was considered the threshold limit for statistical significance. Results: A total of 2280 patients with available age data was included in the analyses.The mutations associated with TGF-beta pathway alterations was more common >50 years of age compared to ≤50 years of age. (28% vs. 17.4%, p<0.001). Additionally, mutations associated with TGF-beta pathway alterations were more frequent in colon cancer compared to rectum (25.4% vs. 18.7, p<0.001). While progression-free survival was higher in patients with mutations associated with TGF-beta pathway alterations (12.5 vs. 10.7 months, p=0.012), the overall survival (59.6 vs. 58.9 months, p=0.896) and survival after metastatic stage (49.7 vs. 56.5 months, p=0.109) were similar across two groups. Conclusions: In this study, we observed a higher rate of mutations associated with TGF-beta pathway alterations in older CRC patients compared to patients with young-onset CRC. Furthermore, the mutations associated with TGF-beta pathway alterations were more frequent in colon primaries. The overall survival was independent of these mutations. Further research is required to delineate the association between TGF-beta pathway alterations and onset of CRC, as well as the CRC prognosis.
Application of GPT-4 foundation model for risk prediction and stratification in colorectal cancer.
Authors: Rueda-Lara Antonio , Viñal David , Alameda Maria , Martin-Montalvo Gema , Peña-Lopez Jesus , Jiménez-Bou Diego , Ruiz-Gutierrez Iciar , Rodriguez Salas Nuria , Feliu Jaime 
Published: January 2024

219 Background: Deep Learning Language Models (LLMs) show significant potential in analyzing complex data, particularly in oncology, where they can predict and stratify patient risks, detect non-linear interactions, and weigh multiple variables. This study applies LLMs to stage II/III localized colon cancer patients to assess their effectiveness in identifying risk subgroups. Methods: In this retrospective study, we examined a cohort of stage II and III localized colorectal cancer patients diagnosed from September 2016 to December 2022 at La Paz University Hospital. Utilizing the GPT-4 API beta version, patients were stratified into high and low-risk groups for relapse based on various risk parameters outlined in the table. Notably, adjuvant treatment data was excluded from the input. The model was prompted with the question, "Given the following risk parameters for localized colorectal cancer {param}, guess whether the patient is in low risk or high risk for relapse," and the model provided dichotomic responses categorized as either 1 (high risk) or 0 (low risk). Results: Patient characteristics are depicted in the table. During a median follow-up of 23.68 months, 63 recurrence events and 73 deaths were observed. The GPT-4 model stratified patients into low (37.9%) and high-risk (62.1%) groups, with the survival curves showing a significant difference in outcomes between the groups. Low-risk patients had a relapse-free rate of 93% at 36 months vs 63% in the high-risk group. In univariate analysis, the high-risk variable had a hazard ratio (HR) of 4.26 (95% CI: 2.03-8.95; p < 0.005). When stratified by adjuvant treatment, no significant difference in relapse probability was observed for those receiving therapy. However, without adjuvant therapy, high-risk patients had an HR of 12.41 (95% CI: 3.72-41.97; p < 0.005) for relapse. Conclusions: GPT-4 demonstrated its potential in predicting oncology outcomes by accurately understanding colorectal cancer risk factors. To fully harness the benefits of LLMs in the future of oncology, they must be fine-tuned on extensive oncological datasets to improve patient risk stratification and treatment selection, ultimately leading to better patient outcomes.[Table: see text]
Assessment of circulating tumor DNA (ctDNA) burden and association with outcomes in metastatic gastric cancer (mGC) patients using real-world data (RWD).
Authors: Peter Senaka A. , Cristescu Razvan , Pena Carol Elaine , Watkins Angela , Espenschied Carin R. , Liao Jiemin 
Published: January 2024

276 Background: CtDNA burden has been shown to have potential uses in early cancer detection, guiding treatment decisions, residual disease and drug resistance detection, and treatment response monitoring. While published literature suggested that ctDNA may be prognostic of clinical outcomes for various tumor types, there is limited RWD assessing its use in mGC. This study uses RWD to evaluate the association of pre-treatment ctDNA burden with clinical outcomes in mGC. Methods: Patients were identified from the Guardant INFORM real-world clinical-genomic database, which links ctDNA results via plasma-based next-generation sequencing Guardant360 assay (G360) to de-identified claims data. Adult mGC patients in the US, who received NCCN guideline treatments post-diagnosis and underwent testing with G360 from June 2014 to March 2022 were included. For those who received first line (1L) therapy within 60 days after a G360 test result, median of the maximum variant allele fraction (mVAF) was used to classify them into high or low ctDNA burden groups, with undetectable ctDNA burden considered low. Associations with time to next treatment (TTNT) and overall survival (OS) were assessed using log rank tests and multivariable Cox proportion hazards models adjusting for age, sex, Elixhauser comorbidity score, and anatomical location. Results: 2,200 mGC patients were identified, of which 824 (37%) initiated 1L therapy within 60 days after a G360 test. Among the 824 patients, mean age was 63 years, 70% were male and 47% had gastric adenocarcinoma and 53% gastroesophageal junction cancer. Median mVAF among these patients was 2.9%, with 91% having detectable ctDNA. Patients with high ctDNA burden treated with 1L chemotherapy (Chemo) showed significantly worse TTNT and OS than low ctDNA burden patients (Median TTNT= 4.7 months vs 7.5 months, p<0.001; Median OS=12.4 months vs 19.1 months, p<0.001). Multivariable Cox analyses showed similar results for 1L Chemo group. Treatment group outcomes based on adjusted Cox models were reported (Table). Conclusions: We used RWD to demonstrate that high pre-treatment ctDNA burden was associated with worse clinical outcomes in a mGC population treated with 1L Chemo. Our analysis adds to the body of evidence that suggest ctDNA burden could be used as a prognostic biomarker for mGC. The small sample size of the other 1L treatment groups warrants further investigation because the use of IO-based therapy is expected to increase with recent approvals. [Table: see text]
Helicobacter pylori infection and response of gastric cancer to immunotherapy.
Authors: Wang Yinghong , Shatila Malek , Sperling Gabriel , Pizuorno Machado Antonio , Vohra Muhammad , Baerman Elliot , De Toni Enrico N. , Török Helga-Paula , Zhao Dan , Zhou Yan , Shafi Mehnaz , Thomas Anusha , Alasadi Mazen 
Published: January 2024

277 Background: Helicobacter pylori is a known risk factor for gastric cancer, possibly via the PD-1/L1 pathway. Some suggest that H. pylori infection may counteract the action of immune checkpoint inhibitors in few studies with limited sample size. This study explores the effects of H. pylori infection status on survival outcomes in patients with gastric cancer. Methods: This single-center, retrospective chart review included patients with gastric adenocarcinoma between June 1985 and August 2022. Patients with different histological subtypes were excluded. Primary variables of interest included H. pylori infection status and treatment with ICIs. Other clinical information included demographics, cancer histology, the presence of other cancers, and vital status. Results: 2,930 patients were included in the initial analysis. 206 (7.0%) received ICIs, 196 (6.7%) had prior H. pylori infection, and 1,037 (35.4%) had a mucinous subtype. Mucinous cancer subtypes were associated with improved survival (p<0.05) at 3 and 5 years compared to non-mucinous adenocarcinomas. Mucinous cancers demonstrated better survival outcomes than non-mucinous at 10 years, but only among H. pylori-positive patients (p=0.013). H. pylori positivity was associated with worse survival at 3 years (OR: 2.0, p=0.041) among patients taking ICIs but not for patients not receiving ICIs (OR: 0.8; p=0.325). Conclusions: H. pylori infection may negatively impact the therapeutic effect of ICIs. These findings suggest H. pylori infection may be an obstacle to successful immunotherapy and may interact with cancer subtypes to differentially impact survival. Future studies are needed to validate the potential prognostic value of H. pylori positivity in gastric cancer.
Prospective study to assess taste related to eating disorders during chemotherapy using a dietary app: OISHY study.
Authors: Hirose Toshiharu , Abe HIroko , Tsuchiya Hayato , Funaki Honoka , Hamada Kazuki , Nojiri Tetsuya , Kato Ken 
Published: January 2024

302 Background: Adverse events (AE) such as nausea, vomiting, dysgeusia, oral mucositis, and anorexia during chemotherapy can lead to eating disorders. Nutritional specialists provide supportive care by intervening based on these symptoms. However, individual patients have diverse taste complaints, making assessment difficult. Recently, dietary apps have been developed that offer dietary recommendations and enable patients to record meals based on the patient's condition. In this study, we utilized a dietary app to record meals and quantify taste. The aim was to objectively assess the details of taste for AEs related to eating disorders. Methods: Patients diagnosed with gastrointestinal cancer between March 2021 and June 2022 at our hospital who received chemotherapy were included in the study. Patients searched for food recommendations using the dietary app according to their symptoms and recorded their meals. For each meal, the amount of intake and taste were recorded. Taste was recorded on a scale of 1-100 for sweet, salty, sour, bitter, umami, and spicy, with 1 indicating the weakest flavor and 100 the strongest. AEs that could cause eating disorders were assessed using CTCAE ver. 5.0 and taste was examined for each AE. Results: A total of 18 patients (9 with esophageal cancer, 8 with colorectal cancer, and 1 with gastric cancer) were enrolled in this study. Palliative chemotherapy was given to 9 patients and preoperative chemotherapy to 9. AEs (any grade) related to chemotherapy-induced eating disorders were anorexia in 13 patients, dysgeusia in 12, nausea in 10, and oral mucositis in 7. Median food intake and taste scores for all patients were 95.7%, sweet 50.1, salty 50.6, sour 49.6, bitter 48.4, umami 52.0, and spicy 49.5. When assessed by CTCAEs, the following were found: anorexia 94.0%, sweet 49.8, salty 50.7, sour 48.5, bitter 48.0, umami 52.0, spicy 47.0; dysgeusia 95.7%, sweet 48.3, salty 51.3, sour 48.0, bitter 46.2, umami 53.2, spicy 45.6; nausea 92.0%, sweet 50.1, salty 50.6, sour 49.4, bitter 45.8, umami 50.3, spicy 46.4; and oral mucositis 94.1%, sweet 47.6, salty 50.4, sour 47.0, bitter 48.9, umami 52.0, spicy 47.0. Compared with all patients, in anorexia there were no obvious sensitivities for any tastes, but the intake amount was decreased. In dysgeusia, patients less strongly perceived sweet and spicy, but more strongly perceived salty and umami. In nausea, the patients ate less and less strongly perceived bitter, umami, and spicy. In oral mucositis, sweet and sour tastes were perceived less strongly. Conclusions: By using a dietary app, detailed taste could be quantified for chemotherapy AEs related to eating disorders. Further large-scale studies may be needed. Clinical trial information: UMIN000046647 .
Pathologic complete response among patients with esophageal cancer receiving neoadjuvant chemotherapy or chemoradiation: A meta-analysis.
Authors: Gaber Charles , Sarker Jyotirmoy , Abdelaziz Abdullah , Okpara Ebere , Lee Todd , Klempner Samuel J. , Nipp Ryan David 
Published: January 2024

305 Background: Although neoadjuvant therapy improves overall survival in esophageal cancers, the benefit is largely confined to those with the greatest pathologic response. Current estimates of pathologic complete response (pCR) rates come from individual studies and lack precision. With this study, we sought to estimate summary pCR rates in patients with non-metastatic esophageal cancer who received either neoadjuvant chemotherapy or chemoradiation by conducting a systematic review and meta-analysis of clinical trials. Methods: Studies were identified from the Medline, EMBASE, and CENTRAL database searches. Eligible studies were published in English from 1992-2022 and consisted of clinical trials that focused on incident non-metastatic esophageal cancer or cancer of the gastroesophageal junction. Trials were required to contain at least one arm of patients receiving neoadjuvant chemotherapy (including perioperative) or neoadjuvant chemoradiation (including treatment with induction chemotherapy). Eligible studies had to report pCR in at least 20 patients who underwent neoadjuvant therapy and surgery. Pooled pCR prevalence was determined using the Freeman-Tukey double arcsine transformation and a random effects model. Results: Among 6,575 records first identified, we included 75 studies with 5,988 patients in the meta-analysis. Of the included studies, 38 (51%) were single arm trials, 35 (47%) were randomized trials, and 2 (3%) were non-randomized trials of multiple treatments. Geographically, 28 (37%), 24 (32%), 21 (28%), and 2 (3%) of the included trials were performed in Asia, Europe, North America, and Australia, respectively. Across 91 trial arms that delivered either neoadjuvant chemotherapy or chemoradiation, platinum and fluorouracil-based regimens were the most common (48.4%), followed by platinum and taxane-based regimens (26.4%), regimens that contained platinum-based agents, fluorouracil, and a taxane (13.2%), and other regimens (12.1%). The pooled prevalence of pCR after neoadjuvant chemotherapy in squamous cell carcinomas was 9% (95% CI: 6% – 14%) across 16 studies, ranging from 0%-32%. The pooled prevalence of pCR after neoadjuvant chemoradiation in squamous cell carcinomas was 32% (95% CI: 26% – 39%) across 21 studies, ranging from 8% to 66%. For adenocarcinomas, the pooled prevalence of pCR was 2% (95% CI: 0% – 7%) after neoadjuvant chemotherapy, across 3 studies, and 22% (17% - 27%) after neoadjuvant chemoradiation across 11 studies. Conclusions: In this meta-analysis, we found that under one-third of patients with non-metastatic esophageal cancer who receive neoadjuvant chemo(radiation) experience pCR. As pCR represents an increasingly utilized as an endpoint in neoadjuvant trials, these estimates of pooled pCR rates may serve as an important benchmark for future trial design.