bluuebunny/crossref_metadata_2025 huggingface dataset:
Rectal cancer disparities in a large, diverse health system in New York.
Authors: Naing Phyu Thin , Wu Vernon , King Daniel
Published: January 2024

16

Background: The disproportionate burden of colorectal cancer among African American (AA) patients is striking, with 40% increase relative risk of death compared to non-AA White population (Seer Cancer Statistics Review, 2022). NAPRC aims to ensure equitable delivery of evidence-based treatment to ensure optimal outcomes for all patients. Our study investigated whether care delivery outcomes differed for AA patients in our NAPRC cohort of patients, and explored the reasons associated with the disparities. Methods: Rectal cancer patients were identified by pooling 2019 to 2022 data from NAPRC coordinators from 4 regional sites under Northwell Health, spread across a large geographical area in NY: Westchester and Phelps (Northern), Lenox Hill (Western), NSUH/LIJ (Central), and Huntington (Eastern). The primary outcome was time from biopsy (Bx) to treatment (Tx) initiation, where Tx was rectal cancer resection, chemotherapy, or radiotherapy. The secondary outcome was time from tumor board (TB) to first Tx. Social deprivation index (SDI) is a composite measure of 7 demographic characteristics collected in the American Community Survey (ACS) matched with zip codes of patients. SDI and the deprivation severity have a positive and linear correlation. Results: We collected data on 381 patients; 337 had documented race data: 42 AA and 295 non-AA (includes White, Asians and others). AA, compared to non-AA, patients had significantly longer median time from Bx to Tx in Western (66 vs 42 days, p<0.01) and Central (56 vs 41 days, p= 0.03) regions. AA patients also had higher time from TB to Tx in the Western (29 vs 17 days, p=0.01) and Central (26 vs 19 days, p= 0.05) regions, respectively. Longer time to treatment was associated with: AA patients, Medicare patients, and patients requiring social work assistance. SDI is positively correlated with time from Bx to Tx (p<0.01) and time from TB to Tx (p<0.01). Conclusions: There are significant disparities between AA vs Non-AA in both primary and secondary outcomes. These findings highlight the need for further exploration such as interviewing social workers and developing patient surveys to explore why the care disparities in AA population is more significant in certain regions than others. We need to account for race and social barriers in treating cancer patients. Taking a proactive approach by sending social work referrals for all AA patients may be a potential solution for these marginalized patients.
Development of an improved risk stratification scheme for stage II and III colorectal cancers through incorporation of the digital pathology biomarker QuantCRC.
Authors: Pai Rish , Wu Christina , Kosiorek Heidi E. , Banerjee Imon , Hagen Catherine E. , Hartley Christopher P. , Graham Rondell P. , Sonbol Bassam Bassam , Bekaii-Saab Tanios S. , Xie Hao , Sinicrope Frank A. , Patel Bhavik , Westerling-Bui Thomas , Shivji Sameer , Conner James , Swallow Carol Jane , Savage Paul , Cyr David Patrick , Kirsch Richard , Pai Reetesh
Published: January 2024

162

Background: There is a need to improve current risk stratification of stage II and III colorectal cancer (CRC) to better inform risk of recurrence and guide adjuvant chemotherapy. The purpose of this study is to examine whether integration of QuantCRC, an AI-based digital pathology biomarker utilizing hematoxylin and eosin-stained slides, provides improved risk stratification over current American Society of Clinical Oncology (ASCO) guidelines. Methods: ASCO and QuantCRC-integrated risk schemes were applied to an observational cohort of 1,068 stage II and III CRCs. The stage II integrated scheme utilizes pT3 vs. pT4 and QuantCRC-derived risk groups. The stage III integrated scheme utilizes pT1-3 vs. pT4, pN1 vs. pN2, and QuantCRC-derived risk groups. Performance metrics included log-rank test, hazard ratios and Somers’ Dxy rank correlation. Results: Integration of QuantCRC provides improved risk stratification compared to the ASCO scheme for stage II and III CRC. The QuantCRC-integrated scheme placed more stage II tumors in the low-risk group compared to the ASCO scheme (69.3% vs. 60.4%) without decreased 3-year RFS. The QuantCRC-integrated scheme provided larger hazard ratios (HR) for both intermediate-risk (3.04, 95%CI 1.81-5.10, P=2.8x10-5) and high-risk (4.62, 95%CI 2.02-10.61, P=0.0003) groups compared to ASCO intermediate-risk (2.09, 95%CI 1.21-3.63, P=0.008) and high-risk (3.08, 95%CI 1.57-6.01, P=0.001) groups. The QuantCRC-integrated scheme for stage III tumors identified a small group of 80/518 (15.4%) CRCs at very high risk of recurrence with HR of 4.08 (95%CI 2.68-6.23, P=6.5x10-11) compared to a HR of 2.42 (95%CI 1.72-3.38, P=3.1x10-7) for 228/518 (44.0%) high-risk CRCs in the ASCO scheme. QuantCRC-integrated risk groups remained prognostic in stage III CRCs when stratified by presence or absence of any adjuvant chemotherapy. No difference in RFS were seen in QuantCRC-integrated low-risk and intermediate-risk stage III CRCs stratified by 3 vs. 6-months of oxaliplatin-based adjuvant chemotherapy suggesting that these two groups can be treated with 3-months of adjuvant therapy. Conclusions: Incorporation of QuantCRC into risk stratification provides a powerful predictor of RFS that has potential to guide subsequent treatment and surveillance.
Liver steatosis and fibrosis as independent prognostic factors affecting survival in colorectal cancer with liver metastases.
Authors: Gupta Nikhil , Somasundaram Eashwar , Dhawan Andrew , Scott Jacob
Published: January 2024

165

Background: Colorectal cancer is one of the leading causes of cancer-related death, and the liver represents the most common site of metastases. Greater depth of tissue invasion and lymph node metastases (more advanced T and N stage) are associated with increased risk of liver metastases, but how co-pathologies of the liver associate with disease progression and survival are not known. Further, prognostic factors associated with overall survival in patients with colorectal liver metastases (CRLM) remain poorly understood. Clinical factors affecting liver morphology and biomechanical properties, such as preexisting fibrosis or steatosis, may impact the pathogenesis of CRLM and thus the clinical prognosis. Current literature is mixed about whether prior steatosis and fibrosis contribute significantly to CRLM pathogenesis and prognosis. The purpose of this study is to evaluate whether liver steatosis and fibrosis impact outcomes in patients with CRLM. Methods: All CLRM cases (n = 197) that underwent resection between 2003 and 2007 from The Cancer Imaging Archive were included in our study cohort. For each clinical covariate, we generated a univariate model for overall survival and those meeting a modest predictive threshold (p < 0.15) were included in a multivariable model. These included: presence of major comorbidity, chemotherapy preceding resection of liver metastases, clinical risk score, presence of extrahepatic disease at time of diagnosis, presence of steatosis on CT imaging, percentage of residual tumor after treatment, and presence of fibrosis on CT. All statistics were performed in R (v.2022.12.0). Results: A multivariable Cox proportional hazards model identified four statistically significant clinical factors predictive of overall survival: clinical risk score (HR = 1.60, p = 0.026), presence of extrahepatic disease (HR = 2.33, p = 0.027), presence of steatosis (HR = 0.51, p = 0.0057), and fibrotic proportion of liver tissue less than 40% (HR = 2.63, p = 0.033). There were also four statistically significant clinical factors predictive of disease-free survival in the liver: chemotherapy preceding resection of liver metastases (HR = 2.28, p = 0.0011), presence of extrahepatic disease (HR = 2.18, p = 0.024), presence of steatosis (HR = 0.49, p = 0.0030), and fibrotic proportion of liver tissue less than 40% (HR = 2.74, p = 0.016). Conclusions: Our findings suggest that increased steatosis and fibrosis, as assessed by CT scans, are paradoxically protective in CRLM, showing longer disease-free survival and overall survival rates. We hypothesize that liver fibrosis and steatosis impact the microenvironment of the neoplastic cells in the liver, impairing tumor progression in this milieu. Further research is needed to assess how non-neoplastic co-pathologies resulting in biophysical changes affect tumor growth and overall survival.
The prognostic significance of extramural venous invasion detected via contrast-enhanced computed tomography colonography in colon cancer.
Authors: Kato Takeharu , Tsukamoto Shunsuke , Nagata Hiroshi , Takamizawa Yasuyuki , Moritani Konosuke , Kanemitsu Yukihide
Published: January 2024

167

Background: The precise effects of extramural venous invasion (EMVI) and Spiculation on colon cancer recurrence remain poorly understood. This study investigated the clinical significance of ctEMVI and ctSpiculation as diagnosed via preoperative contrast-enhanced CT colonography (CTC) using three-dimensional multiplanar reconstruction (3D MPR) images. Methods: Patients with stage I–Ⅲ colon cancer (T2 or deeper) diagnosed via CTC at the National Cancer Center Hospital in Japan between 2013 and 2018 were retrospectively evaluated for ctEMVI and ctSpiculation, diagnosed by two observers using 3D MPR images of slices 0.5 mm thick. The interobserver reliability was assessed with Cohen’s kappa statistic, and recurrence-free survival (RFS) was analyzed using Kaplan–Meier curves. Preoperative clinical factors were subjected to Cox regression analysis in relation to RFS. Results: Of 922 patients, 544 eligible cases were analyzed. There were 50 (9.2%) ctEMVI-positive cases and 494 (90.8%) ctEMVI-negative cases, along with 186 (34.2%) ctSpiculation-positive cases and 358 (65.8%) with negative findings. Kappa coefficients for ctEMVI and ctSpiculation were 0.830 and 0.718, respectively. Kaplan–Meier analysis and log-rank tests demonstrated lower RFS in ctEMVI- and ctSpiculation-positive cases (p<0.001). In multivariable analysis, ctT4 (HR 2.95, 95% CI 1.73–5.02) and ctEMVI (2.97, 1.81–4.87) were independent factors associated with RFS. When stratifying TNM stages based on ctEMVI status, in N(+) (i.e., Stage III), ctEMVI-positive group had worse prognoses than negative group (5-year RFS rates; 52.0% vs. 78.5%, p=0.003). Similarly, in N(–) (i.e., Stage I and II), T3N0EMVI(+) cases had significantly worse prognoses than T3N0EMVI(–) and Stage I cases (50.6% vs. 89.3% and 90.1%) and were comparable to the T4N0 group (50.6% vs. 46.7%, p=0.844). Conclusions: Both ctEMVI and ctSpiculation are associated with RFS. ctEMVI is an independent predictor of recurrence and may be valuable in combination with preoperative TNM staging to identify patients at high risk for recurrence. [Table: see text]
Molecular and clinical characteristics of POLE/POLD1 alterations among patients with colorectal cancer.
Authors: Syed Masood Pasha , Ferrell Morgan , Cheng Svea , Gonzalez Cyndi , Giza Richard , Magge Tara , Bao Riyue , Singhi Aatur D. , Saeed Anwaar , Sahin Ibrahim Halil
Published: January 2024

184

Background: POLE and POLD1 alterations (DNA polymerase ε and DNA polymerase δ) are key biomarkers of immune response for patients with MSS colorectal cancers (CRC). The clinical and molecular characteristics of POLE/POLD1 alterations are not yet well defined across CRCs. In this study, we investigated the clinical/molecular features of POLE and POLD1 alterations and its association with MSI-H CRC. Methods: All the patients and mutation data were selected from the cBioPortal database (https://www.cbioportal.org). All nonsynonymous mutations including missense, frameshift, nonsense, nonstop, splice site, and translation start site changes of POLE/POLD1 were considered. 21 studies were used in the analysis. 7179 data samples were obtained from 7179 patients. Tumors included were from all stages of CRCs. POLE/POLD1 mutations were from mutation tables, only protein-changing mutations were kept. MSI-H status was based on mutation data (presence of MLH1/PMS2/MSH2/MSH6 mutations). Results: Of 7179 patients with all stage CRCs, 6.1% (439) were found to harbor mutated POLE/POLD1 genes. Among those, 3446 patients had known MSI status and 14.9% (514/3446) had MSI-H disease. Notably, 3.3% patients with POLE/POLD1 mutations were found to have concurrent MSI-H disease (co-existence) and only 1.1% of patients with POLE/POLD1 mutations had MSS CRC. MSI status was unknown for 1.7% of patients with POLE/POLD mutant CRC. The mean age for patients with POLE/POLD1 + with or without MSI-H disease was 67. POLE/POLD mutations were exceedingly more common in colon than rectum regardless of MSI-H status (85% vs 15% overall and 88% vs 12% in MSI-H subgroup). No difference was seen among genders for the distribution of POLE/POLD1 mutations. Conclusions: POLE/POLD1 mutations frequently co-exist with MSI-H disease in CRC. Patients with MSS-CRC harboring POLE/POLD1 mutations represent a smaller subgroup of CRC (~1%). The incidence of POLE/POLD1 somatic mutations was more common among patients with colon cancer than those with rectal cancer.
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.
Atezolizumab and trastuzumab plus chemotherapy in patients with HER2+ locally advanced resectable gastric cancer or adenocarcinoma of the gastroesophageal junction: A multicenter, randomized, open-label phase II study.
Authors: Peng Zhi , Zhang Xiaotian , Liang Han , Zheng Zhichao , Wang Zhenning , Liu Hao , Hu Jiankun , Sun Yihong , Zhang Yanqiao , Yan Han , Tong Lin , Xu Jiahui , Xie Jessica , Ji Jiafu , Shen Lin
Published: January 2024

312

Background: Currently, there are no standard perioperative regimens for human epidermal growth factor receptor 2 positive (HER2+) gastric cancer (GC) or gastroesophageal junction (GEJ) cancer. Furthermore, despite advances in neoadjuvant or perioperative chemotherapy, the efficacy of treatment for locally resectable advanced GC or GEJ cancer remains unsatisfactory. To address this need, we evaluated the effectiveness of adding atezolizumab (programmed death ligand-1 inhibitor) to treatment with trastuzumab (a HER2 antibody) + capecitabine and oxaliplatin (XELOX) compared with trastuzumab + XELOX in patients eligible for surgery with HER2+ locally advanced GC or adenocarcinoma of the GEJ. Methods: Patients aged 18–75 years were randomized 1:1 to atezolizumab + trastuzumab + XELOX (Arm A) or trastuzumab + XELOX (Arm B) and received the regimen for three neoadjuvant cycles (3 weeks per cycle) and five adjuvant cycles. Treatment administration was atezolizumab 1200 mg, trastuzumab 6 mg/kg, oxaliplatin 130 mg/m2 intravenously on Day 1, and capecitabine 1000 mg/m2 orally twice daily on Days 1–14 of each 3-week cycle. The primary endpoint was the pathological complete regression (pCR) rate. Secondary endpoints were the objective response rate (ORR) during neoadjuvant systemic therapy (NAST) and the R0 resection rate. Time-to-event endpoints are not reported because of immaturity. Efficacy endpoints were analyzed in the intention-to-treat population. The clinical cutoff date for the primary analysis was 12 March 2023. Results: Forty-two Asian patients who provided informed consent were screened and randomized to Arm A (n = 21) or Arm B (n = 21); all patients completed NAST. Most patients were male (92.9%), and the median (range) age was 61 (33–72) years in Arm A and 65 (49–72) years in Arm B. The pCR rate was 38.1% (8/21) in Arm A and 14.3% (3/21) in Arm B (treatment difference: 23.8% [90% confidence interval (CI), 1.3%–44.7%]). The pCR rate was significantly better in Arm A than in Arm B (P = 0.079 <0.1; lower limit of the 90% CI >0). Subgroup analysis showed that age <65 years, male sex, and intestinal Lauren classification were associated with a better pCR rate for the atezolizumab inclusive treatment arm (Arm A); however, these results require further confirmation in future studies. No significant difference was detected between the two arms in ORR during NAST or the R0 resection rate. Conclusions: The addition of atezolizumab to trastuzumab + XELOX therapy was effective in patients with HER2+ locally advanced resectable GC or adenocarcinoma of the GEJ. Clinical trial information: NCT04661150 .
Infusional fluorouracil and weekly docetaxel as first-line therapy for gastric cancer with bone marrow metastasis and disseminated intravascular coagulation: A multi-center, phase II trial (Zhen Long).
Authors: Xiao Jian , Zhai Xiaohui , Li Shanshan , Zhang Haibo , Li Yong , Peng Jin , Huang Yisheng , Shi Lishuo , Liu Hailing , Zhang Rongqin , Hu Meiyu , Pang Xiaolin , Lin Xiaoru
Published: January 2024

337

Background: Gastric cancer (GC) with bone marrow metastasis (BMM) and disseminated intravascular coagulation (DIC) constitute a highly aggressive GC (HAGC) sub-type with distinctive features. The prognosis is poor and most HAGC patients die in weeks without effective treatment. Undue concerns about the myelosuppression mitigate against the application of cytotoxics in HAGC which is characterized by thrombocytopenia. Retrospective analysis showed low dose chemotherapy might relieve the DIC and bring with survival benefit but the standard of care (SOC) has not yet been established without a prospective study available. We completed a multi-center phase II trial evaluating the safety and efficacy of infusional fluorouracil and weekly docetaxel as first-line (1L) treatment for HAGC. Methods: This was a single-arm trial. A Simon's two-stage optimal design was applied. Eligible cases were: 18-75 years old, histologically confirmed GC, established BMM, overt DIC, platelet ≤ 50*109/L and Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 3. Fluorouracil 200mg/m2/d continuous infusion on days 1-21 and docetaxel 25mg/m2/d on days 1, 8, 15 were given every four weeks. Hematological response (HeR) was defined as the platelet restored to normal range. The primary end point was HeR rate. Secondary end points were time to HeR (TTHeR), one month mortality (OMM), overall survival (OS), adverse events (AEs) and quality of life (QoL). Results: From Jan 2021 to Sep 2022, 24 HAGC cases from three Chinese centers were enrolled (details shown in table below). 20 HeRs were achieved and the HeR rate was 83.3%. Median TTHeR was 13 days and OMM was 12.5%. Till the data cut-off date (Jul 31, 2023), 3 patients were still alive with a median follow-up of 403 days. The median OS was 242 days. Totally, twelve Grade 3 AEs were recorded in 7 (29.2%) patients, among which stomatitis (4, 16.7%) and aminotransferase elevation (3, 12.5%) were the most frequent. No drug-related grade 4 or 5 AEs were observed. QoL outcomes were significantly improved both during and after the treatment. Conclusions: Anti-cancer treatment is the key point to control DIC of HAGC. The Zhen Long regimen was well tolerated and showed promising efficacy in the 1L setting. It should be considered as the SOC in current practice, but further randomized trials are still needed. Clinical trial information: NCT04547153 . [Table: see text]
Real-world analysis of patient characteristics and outcomes among patients with metastatic colorectal cancer receiving trifluridine/tipiracil (FTD/TPI) plus bevacizumab versus FTD/TPI monotherapy.
Authors: Hubbard Joleen M. , Lee Lulu K. , Grisolano Jay L. , Perkowski Kacper , Salimi Tehseen , Kazerooni Reza , Epstein Robert S.
Published: January 2024

34

Background: Trifluridine/tipiracil (FTD/TPI) is a standard of care therapy for patients with refractory metastatic colorectal cancer (mCRC). Recently, FTD/TPI in combination with bevacizumab (BEV) was also approved in this setting based on outcomes from the phase 3 SUNLIGHT trial, including statistically significant improvements in overall survival (OS) compared with FTD/TPI. This study examined demographic/clinical characteristics, treatment duration, OS, and healthcare resource use (HCRU), including outpatient/emergency room (ER) visits and hospitalizations, among patients with mCRC receiving FTD/TPI+BEV versus FTD/TPI in a real-world setting. Methods: This was a retrospective study of adults with CRC, who initiated FTD/TPI as monotherapy or in combination with BEV, identified from the Cerner Enviza electronic health records (EHR) database (12/2020–06/2023). A manual chart review of patients’ medical records was conducted where last follow-up was defined as death or last encounter in the EHR. Descriptive statistics were reported for all study variables; Kaplan Meier curves were used to estimate OS. Results: Of 197 patients abstracted, 122 (62%) received FTD/TPI+BEV combination therapy and 75 (38%) FTD/TPI monotherapy. Mean age was similar between the FTD/TPI+BEV and FTD/TPI groups (60.2 y vs 61.8 y) and 66% vs 63%, respectively, were male. Mean Charlson Comorbidity Index was 8.9 for the FTD/TPI+BEV group vs 8.5 for the FTD/TPI group and body mass index was 26.9 kg/m2 vs 27.3 kg/m2, respectively. Most patients received treatment in the third or fourth line (65% FTD/TPI+BEV; 75% FTD/TPI). Median follow-up was 5.3 and 4.6 mo, respectively. Mean duration of treatment was 3.7 vs 2.7 mo for FTD/TPI+BEV vs FTD/TPI monotherapy (Table). Median OS (from FTD/TPI initiation to death) was 11.5 and 9.6 mo for FTD/TPI+BEV and FTD/TPI groups (number of deaths: 38 and 22), respectively. Patients receiving FTD/TPI+BEV had numerically more outpatient visits (20.5 vs 13.9), but similar ER visits (0.5 each) and slightly fewer hospitalizations (1.1 vs 1.2) compared with FTD/TPI, during follow-up. Overall HCRU costs were similar between groups (27,175 vs 27,891). Conclusions: This real-world study supports the value of FTD/TPI+BEV combination therapy vs FTD/TPI monotherapy as seen in the SUNLIGHT trial. Patients with FTDTPI+BEV were treated for longer duration with improved OS and no difference in trends for HCRU and associated costs. [Table: see text]
A retrospective analysis of the efficacy and safety of capecitabine plus oxaliplatin (CapeOX) and docetaxel plus S-1 (DS) as adjuvant chemotherapy for pathological stage III (p stage III) gastric cancer (GC).
Authors: Imai Toru , Hirano Hidekazu , Shoji Hirokazu , Hirose Toshiharu , Okita Natsuko Tsuda , Takashima Atsuo , Kato Ken
Published: January 2024

342

Background: Adjuvant chemotherapy following surgical resection is the standard treatment for patients with p stage III GC in Japan. Although CapeOX and DS are available for adjuvant chemotherapy for stage III GC, there is limited data on which treatment is more effective. We aim to compare the efficacy and safety of CapeOX and DS as adjuvant chemotherapy in patients with p stage III GC. Methods: We extracted data of patients with p stage III GC who received either CapeOX (capecitabine on days 1–14 plus oxaliplatin on day1 for 8 cycles [q 3week]) or DS (S-1 on days 1–14 at 1st cycle [q 3 week], docetaxel on day 1 plus S-1 on days 1–14 during 2–7 cycles [q 3 week], and S-1 on days 1–28 up to 1 year [q 6 week]) as adjuvant chemotherapy after surgical resection at our institution from February 2016 to May 2022. Three-year relapse-free survival (RFS) and adverse events (AEs) were assessed. Cox proportional hazard model was used in multivariable analysis to assess the effect of independent variables on RFS. Results: A total of 74 patients were included in this study (CapeOX 31/ DS 43). Patient characteristics (CapeOX/DS) were as follows: median age, 60/64 years; male, 77/65 %; ECOG-PS 0/1, 45%/44%, 55%/56 %; p stage IIIA/IIIB/IIIC, 10%/30%, 48%/51 %, 42%/19 %. The 3-year RFS was 37% in the (hazard ratio [HR] = 0.81, P=0.48). For p stage IIIA, IIIB, and IIIC, the 3-year RFS in the CapeOX group and the DS group was 67% vs. 75% (HR = 0.56, P =0.52), 43% vs. 42% (HR = 1.11, P =0.81), and 23% vs. 0% (HR = 1.59, P =0.39), respectively. Multivariable analysis adjusted for p stage showed no significant differences in RFS between the CapeOX group and the DS group (HR=1.06, P=0.85). Compared to DS, CapeOX was associated with lower incidences of febrile neutropenia (0% vs 7%) and alopecia (6% vs 74%), and a higher incidence of peripheral neuropathy (80% vs 23%). Conclusions: This analysis indicates that CapeOX and DS have comparable efficacy as adjuvant chemotherapy for p stage III GC in terms of RFS, albeit with different profiles of AEs.