bluuebunny/crossref_metadata_2025 huggingface dataset:
Trends in utilization of MSI testing and reporting among patients with gastrointestinal cancers: A review of NCDB Database.
Authors: Jafry Baqir , Buhaya Munir , Huang Emina , Verma Nilesh , Kazmi Syed Mohammad Ali
Published: January 2024

221

Background: MSI-H tumors have a different disease biology and clinical outcomes compared to MSS/MSI-low tumors. The frequency and pattern for MSI testing and reporting is unknown. The aim of this study was to characterize the trends of MSI testing and reporting among GI cancers. Methods: From the National Cancer Database, we identified all GI cancer patients from 2010 to 2016 to determine the number of patients where MSS/MSI low or MSI-H data were available. We describe the basic tumor and disease characteristics and treatment utilization for the two groups. Results: Between 2010-2016, MSI testing was done in 140,602 patients in colon, small intestine and rectal cancers among all GI cancers. MSI testing increased significantly during this study period (11,400 in 2010; 15,021 in 2011; 17,968 in 2012; 20,810 in 2013; 21,973 in 2014; 25,012 in 2015; 28,418 in 2016). We identified a total of 120,349 patients with MSI status reported, among these three tumor types, most commonly among colon followed by rectal and then small intestinal cancers. Overall 111,694 (92.8%) were MSS/MSI-low and 8,655 were MSI-H (7.2%). Among patients with reported MSI status, 52.1% were males and 47.9% were females. The mean age was 64.4 years. Most patients were whites (87.6%) and had insurance (96.8%), no existing comorbidities (70.4%), and grade 2 (70.8%) and AJCC Clinical Stage 4 (26.1%) GI cancer. A higher proportion of GI cancer patients with MSS/MSI-low utilized chemotherapy as first course compared to those with MSI high (48.2% vs 34.0%) whereas a lower proportion of GI cancer patients with MSS/MSI-low underwent a surgical procedure compared to those with MSI high (94.7% vs 97.1%). MSI status was reported most frequently in comprehensive community cancer program (40.3%) and academic center (34.8%), followed by integrated network cancer program (16.8%) and Community Cancer program (8.1%). Conclusions: The utilization of MSI testing has increased significantly between 2010 and 2016. Among all GI cancer patients, MSI status was most frequently reported in colon, rectum and small intestinal cancers. Comprehensive community cancer centers and academic centers reported MSI status more frequently than Integrated Network Cancer program and Community Cancer program.
Artificial intelligence-based model for recurrence prediction after local excision on whole slide images in T1 low rectal cancer.
Authors: Huang Chengzhi , Su Jiarui , Yao Xueqing
Published: January 2024

24

Background: According to current guidelines, patients with resected specimens showing high-risk features are recommended for additional surgery after local excision of T1 colorectal cancer, despite the low incidence (~7%) of recurrence. However, surgical resection in patients with low rectal cancer (RC) is challenging and may compromise anal function, leading to a low quality of life. To reduce unnecessary surgical resection for these patients, we utilized artificial intelligence to develop and validate a prediction model for the risk of recurrence in T1 low rectal cancer patients. Methods: H&E-stained whole slide images (WSIs) were scanned for local excision (endoscopically or transanally minimally) specimens of 507 consecutive patients with T1 low rectal cancers that were locally resected at 4 hospitals between 2005 and 2015. The area under the receiver operating characteristic curve (AUROC), specificity and sensitivity were used to evaluate the performance of the model for the risk of recurrence, and an external validation cohort was to verify the applicability of the model. Results: We constructed a prediction model using convolutional neural networks (CNN) without incorporating clinical features. The model yielded good discrimination and calibration, achieving a 5-year recurrence-free survival AUROC of 0.90 (95% confidence interval [CI]: 0.86–0.93), sensitivity of 0.91 (95% CI: 0.84–0.96), and specificity of 0.82 (95% CI: 0.78–0.88) through fivefold cross-validation. Additionally, the AI avoided 25.7% of unnecessary additional surgery compared to the current guidelines. Conclusions: We proposed a novel prediction model for the risk of recurrence in T1 low RC patients to assist physicians in determining whether additional surgery is required after local excision of T1 low RC.
Pembrolizumab plus FLOT vs FLOT as neoadjuvant and adjuvant therapy in locally advanced gastric and gastroesophageal junction cancer: Interim analysis of the phase 3 KEYNOTE-585 study.
Authors: Al-Batran Salah-Eddin , Shitara Kohei , Folprecht Gunnar , Moehler Markus H. , Goekkurt Eray , Ben-Aharon Irit , Lonardi Sara , Stein Stacey , Hubert Ayala , Chau Ian , Mishaeli Moshe , Villanueva Luis , Kavan Petr , Fang Xiao , Shih Chie-Schin , Bhagia Pooja , Wyrwicz Lucjan S.
Published: January 2024

247

Background: The phase 3 KEYNOTE-585 study (NCT03221426) evaluated neoadjuvant/adjuvant pembrolizumab (pembro) or placebo (pbo) + chemotherapy (chemo) followed by adjuvant pembro vs pbo in locally advanced, resectable gastric or gastroesophageal junction (G/GEJ) cancer. A separate cohort evaluated pembro + FLOT (FLOT cohort). We report results from safety and efficacy analyses of the FLOT cohort at third interim analysis. Methods: In the FLOT cohort, patients (pts) with untreated, locally advanced, resectable G/GEJ cancer were randomized 1:1 to neoadjuvant pembro 200 mg IV Q3W (pembro gp) or pbo (pbo gp) Q3W for 3 cycles + FLOT (docetaxel, oxaliplatin, leucovorin, and 5-FU) Q2W for 4 cycles. After surgery, pts received adjuvant pembro or pbo Q3W for 3 cycles + FLOT Q2W for 4 cycles, then adjuvant pembro or pbo Q3W for 11 cycles. Endpoints evaluated included safety, pathCR rate (BICR), EFS (RECIST 1.1, by investigator), and OS in the ITT. Data cut-off at third interim analysis was 09 Feb 2023. Results: A total of 203 pts were randomized (100 pembro + FLOT; 103 pbo + FLOT). Among these, 12 (6%) pts had cT1-T2, 161 (79%) had cT3, and 9 (4%) had cT4. 140 (69%) had N+ disease, and 79 (39%) had GEJ adenocarcinoma at baseline. Median follow-up was 31.6 months (mo) and 31.1 mo, respectively, at IA3. A total of 94 of 99 (95%) pts completed the neoadjuvant phase, 87 of 99 (87%) completed the surgery phase, and 45 of 77 (58%) completed adjuvant treatment. The R0-resection rate was 79% vs 80% in the pembro gp vs pbo gp, respectively. The pathCR rate was 17.0% (95% CI, 10.2-25.8) in the pembro gp and 6.8% (95% CI, 2.8-13.5) in the pbo gp, estimated difference (10.2% [95% CI, 1.3-19.7]). Median EFS was not reached (95% CI, 28.2-NR) in the pembro gp and 30.9 mo (22.8-NR) in the pbo gp (HR 0.79; 95% CI, 0.52-1.22). The 24-mo EFS rates were 66% and 57%, respectively. Median OS was not reached in either group (HR 1.04; 95% CI, 0.66-1.66). The 24-mo OS rates were 72% and 73%, respectively. Grade ≥ 3 drug-related AE rates in all phases combined were 76% and 63% in the pembro vs pbo gp, with serious drug-related AEs in 42% vs 20%, and surgery-related AEs in 20% vs 13%, respectively. A total of 3 (3%) vs 1 (1%) pt in the pembro vs pbo gp died due to a drug-related AE. Conclusions: Neoadjuvant/adjuvant pembro + FLOT was feasible with no new safety concerns. PathCR and EFS favored pembro + FLOT vs pbo + FLOT in pts with untreated, locally advanced resectable G/GEJ cancer. Clinical trial information: NCT03221426 .
Inpatient outcomes of metastatic epidural spinal cord compression in patients with gastric cancer compared to patients with other solid cancer.
Authors: Olafimihan Ayobami Gbenga , Turk Ekrem , Nieto Dominguez Alejandro , Pan Chun-Wei , Omaliko Chidiebele , Ibrahim Muhammad Bilal , Obomanu Elvis , Fawehinmi Praise , Batra Kunnal
Published: January 2024

255

Background: Metastatic epidural spinal cord compression (MESCC) is an oncologic emergency which can be associated with poor outcomes for cancer patients. Our aim was to study the differences in outcomes of MESCC in patients with gastric cancer (GC-MESCC) compared to those with other solid malignancies. Methods: Healthcare Cost and Utilization Project-Nationwide Inpatient Sample database (2016-2020) was queried to identify all solid (breast, prostate, lung, gastrointestinal, renal and thyroid) cancer patients admitted with spinal cord compression. Multivariate logistic regression was used to evaluate differences in socio-demographics, medical comorbidities and outcomes between MESCC in gastric cancer patients and those with other solid cancers. The primary outcome included inpatient mortality, length of stay (LOS), and total hospital charges (THC). Results: 78,385 patients with the above solid cancers were admitted for spinal cord compression. Among them, 710 had gastric cancer. Patients with gastric cancer were younger (Mean age: 59.1 vs 66.3 years, p < 0.001). They had higher prevalence of anemia (56 vs 41%), protein energy malnutrition (28.9 vs 18.9%, p < 0.001), and lower prevalence of COPD (8.45 vs 18.5%, p =0.003), smoking (22.5 vs 33.6%, p =0.007) and CKD (9.4 vs 12.3%, p =0.03). On multivariate regression, those with GC-MESCC had two-fold higher odds of all-cause mortality (adjusted odds ratio (aOR): 2.0; 95% CI: 1.05-3.96, p = 0.034). On subgroup analysis, mortality was about four times higher for females with GC-MESCC relative to the other group (aOR = 3.8, 95% CI: 1.69-8.52, p = 0.001). There was a trend towards increased LOS (8.9 vs 7.8 days) and THC ($115, 805 vs $96, 074) but it was not statistically significant. Compared with the other cohort, GC-MESCC patients had higher rates of blood transfusion (16.2 vs 9%, p = 0.003). Conclusions: Metastatic epidural spinal cord compression is associated with increased odds of inpatient mortality in gastric cancer patients compared to those with other solid malignancies. Hence, these patients ought to have urgent intervention and close monitoring to prevent adverse outcomes. [Table: see text]
Differential burdens: A study of gastric cancer hospitalization and outcomes across race and ethnicities.
Authors: Pan Chun-Wei , Nieto Dominguez Alejandro , Olafimihan Ayobami Gbenga , Ibrahim Muhammad Bilal
Published: January 2024

256

Background: Despite advances in H. pylori screening and eradication, gastric cancer remains a significant public health issue as the 4th most common cancer globally. Racial and ethnic disparities in disease presentation, surgical intervention, and healthcare burden in United States are not well understood. Methods: We retrospectively analyzed National Inpatient Sample data (2016-2020) for gastric cancer hospitalizations in patients ≥18 years. Primary outcome was in-hospital mortality. Secondary outcomes included disparities in gastrectomy, length of stay (LOS), and total hospital charges. Results: In our study, we analyzed 207,690 hospitalizations related to gastric cancer from 2016- 2019. Over this period, we observed a decrease in gastric cancer-related hospitalizations, from 42,865 to 39,855. However, among Hispanics, there was a significant increase in hospitalizations from 6,309 to 6,930 cases (annual percentage change [APC] of 1.89%, P<0.01). Notably, there was a significant higher in in-hospital mortality odds for African-American (AA) (aOR 1.15, 95CI: 1.03-1.29), Asian (aOR 1.23, 95CI: 1.06-1.42), and all other races (aOR 1.35, 95CI: 1.13-1.60). Surgical interventions differed among racial groups, with AA having lower odds of undergoing total gastrectomy (aOR 0.71, 95CI: 0.60-0.86), and Asians having higher odds of receiving partial gastrectomy (aOR 1.59, 95CI: 1.41-1.78). LOS also differs between ethnicities, AA had the highest LOS 7.9±0.1d days, followed by Native American/Other (NA) at 7.5±0.2 days. The financial impact of also differs, with Asians incurring the highest mean total charges at 101,436.8±3,253.5, followed by NA at 93,102.7±3,954.7. The total hospital charge burden of gastric cancer increased from 3,682.8 million to 3,880.0 million (APC 1.04%). The white population experienced the highest increase in this burden, from 1,879.2 million to 1,990.0 million (APC of 1.10%). Conclusions: Despite an overall decrease in gastric cancer hospitalizations, our study reveals notable disparities across racial and ethnic groups. Hospitalizations increased among Hispanics, and AA, Asians, and NA faced higher mortality odds. AA experienced the longest lengths of stay, while Asians bore the highest mean total charges. These findings highlight the need for targeted interventions to mitigate these disparities.[Table: see text]
Prognostic value of circulating tumor DNA following local therapy in colorectal cancer with liver metastases.
Authors: O'Donnell Conor , Storandt Michael H. , Mitchell Jessica L. , Jin Zhaohui
Published: January 2024

26

Background: Local therapies have the potential to cure a portion of patients with colorectal cancer with liver-only metastatic disease (CRLM). Peri-operative chemotherapy has not been shown to improve overall survival when added to local therapy in CRLM. Circulating-tumor DNA (ct-DNA) may have potential to help guide management decisions following local therapy. Methods: We conducted a retrospective analysis of health records of CRLM patients who had tumor-informed ct-DNA (Signatera) measurement following curative-intent local therapy prior to August 30th, 2023. Disease-free survival (DFS) was defined as the time from ct-DNA test until radiographic evidence of disease. Descriptive characteristics of the cohort, ct-DNA results and their impact on adjuvant therapy decisions were recorded. Survival analysis was carried out using R software v4.3.1 with survival and survminer packages. The Kaplan–Meier method was used to estimate the survival distribution. Log-rank test was used for comparison. A multivariable Cox proportional hazards model was used to assess prognostic factors associated with DFS ( coxph). Results: 27 patients with CRLM underwent local therapy followed by ct-DNA collection. The median age was 61 years, 67% were male, and 85% were White. Molecular characteristics: KRAS 31%, NRAS/BRAF 0%, microsatellite instability 4%. The median time from initial diagnosis to treatment of liver disease was 21.0 months. 63% of patients received less than 6 months of systemic therapy prior to local therapy. ct-DNA was checked prior to definitive therapy in 12 cases and was positive in 5 cases (detection rate of 42%). Liver-directed therapy involved: resection (n=15), ablation (6), radiation (2) or a combination (4). The median follow-up time from liver-directed therapy was 13.2 months. Post-local therapy chemotherapy was initiated prior to recurrence in 59% of cases. ct-DNA results contributed to immediate post-management decisions in 15% of cases. There were 14 radiographic recurrences (11 to liver only, 3 to other sites). Positive ct-DNA on initial testing following local therapy was associated with poorer DFS in univariate analysis and was the only prognostic factor identified on multivariable analysis. Conclusions: ct-DNA positivity following local therapy for CRLM is associated with earlier recurrence. Baseline testing before local therapy may be important for interpretation of testing results post-local therapy, given frequent missed disease detection. Additional clinical trial data is needed to explore ct-DNA-guided treatment decisions in CRLM. [Table: see text]
Natural history of gastric leiomyoma.
Authors: Park Kwangbeom , Ahn Ji Yong , Na Hee Kyong , Jung Kee Wook , Lee Jeong Hoon , Kim Do Hoon , Choi Kee Don , Song Ho June , Lee Gin Hyug , Jung Hwoon-Yong
Published: January 2024

262

Background: Most gastric leiomyomas are asymptomatic and benign subepithelial tumors (SETs); however, some may increase in size or become symptomatic. Understanding their natural history is therefore important to their management. We investigated the natural history of histologically proven gastric leiomyomas. Methods: We retrospectively reviewed histologically proven gastric leiomyoma cases at a tertiary center. The baseline characteristics of these cases were analyzed, and those with a follow-up period of at least 12 months without immediate resection were evaluated. The primary outcome was the frequency of size increase of more than 25% during the follow-up period, and the secondary outcome was the histopathologic results in cases that underwent resection. Results: Among the 231 patients with histologically proven gastric leiomyomas, the most frequent location was the cardia (77.1%), and the median size was 3 cm (IQR 2–4 cm). Eighty-four cases were followed up over a median period of 50.8 months (IQR 27.2–91.3 months). During the follow-up period, tumor size increased in two cases (2.4%). Surgical results showed that one case was leiomyoma, and the other was leiomyosarcoma. Among the remaining cases without change in size, 15 underwent surgical resection (n = 10) or endoscopic resection (n = 5), and all cases were confirmed as leiomyoma. Conclusions: Most gastric leiomyomas are benign SETs, and an increase in size is not frequent, even in large-sized cases. Close monitoring with routine follow-up without resection may be sufficient in cases of histologically proven gastric leiomyoma. However, in cases of ulceration or size increase, resection may be beneficial.
Prediction of lymph node status in stage T1 esophageal squamous cell carcinoma.
Authors: Chen Yongshun , Fan Xiangli , Chen Honglei
Published: January 2024

263

Background: With the development of endoscopic therapy and the introduction of immunotherapies, it is more important for preserving the esophagus and uninvaded lymph nodes to avoid the damages involving the long-term quality of life and normal immune function caused by esophagectomy with radical lymphadenectomy. Methods: We collected patients with T1 ESCC who underwent endoscopic resection or esophagectomy from 2014 to 2021 in three cancer centers. The primary end point was presence of lymph node metastasis (LNM) in surgical resection specimens or detection of metastases during follow-up. Univariate and multivariate logistic regression were used to screen the clinicopathological features related to LNM. Using the function 'lrm' constructed the prediction model. The area under the curve (AUC) of receiver operating characteristic and calibration graphs were used to assess the performance of the model. An external validation was conducted to evaluate the generalization of the model. We then prospectively collected 28 surgically resected tissue samples of T1 ESCC to further supplement the model from the cellular and molecular level, and used 6 markers (CK, CD34, D2-40, CD4, CD8, FOXP3) and DAPI dye to process multiple immunofluorescence (mIF) staining. Afterwards, we analyzed the density, spatial distribution of microvessels, lymphatic capillaries and tumor-associated immune cells and the interaction between them and malignant cells in the tumor microenvironment of T1 ESCC to explore the relationship between tumor microenvironment and risk of LNM. Results: 1109 patients with T1 ESCC were included. 653 patients from two centers constituted the training cohort, and 456 patients from the third center served as the validation cohort. Multivariate logistic regression based on the training cohort showed that tumor invasion into the submucosa, poor histological grade, and lymphovascular invasion were risk factors for LNM in T1 ESCC. Subsequently, we constructed a model based on three variables to predict the risk of LNM in T1 ESCC. The model demonstrated good discriminative ability (AUC 0.858, 95%CI 0.826-0.890). After mIF staining of 28 prospectively collected T1 ESCC tissue samples, we observed that microvessels and lymphatic capillaries were abundant in the mucosa in lymph node-positive samples but not in lymph node-negative samples. In addition, the average density of FOXP3+ T cells in samples with and without metastasis was 253/mm2 and 26/mm2 (P < 0.001), and the average density of CD8+ T cells was 112/mm2 and 432/mm2 (P < 0.001) in quantitative analysis, respectively. Conclusions: This study (RENMIN-237) developed a well-performing LNM risk stratification model of T1 ESCC to reduce both overtreatment and undertreatment, and we found that FOXP3+ T cells in the tumor microenvironment are a risk factor for LNM, while CD8+ T cells can serve as a protective factor against LNM.
Impact of time-of-day on nivolumab monotherapy infusion in patients with metastatic gastric cancer.
Authors: Ishizuka Yasunobu , Narita Yukiya , Sakakida Tomoki , Wakabayashi Munehiro , Kodama Hiroyuki , Honda Kazunori , Masuishi Toshiki , Taniguchi Hiroya , Kadowaki Shigenori , Ando Masashi , Tajika Masahiro , Muro Kei
Published: January 2024

268

Background: Nivolumab monotherapy, an immune checkpoint inhibitor, is a standard of care for patients with metastatic gastric cancer (mGC) as a later-line treatment. Several studies have suggested that the circadian rhythm is essential in immune system function, including anti-cancer immunity. This study evaluated whether the time-of-day patterns of nivolumab infusion alter the efficacy of mGC treatment. Methods: This study retrospectively analyzed 298 consecutive mGC patients who received nivolumab monotherapy at a single institution between December 2014 and December 2022. Patients were divided into early (EA)- and late (LA)-nivolumab infusion groups: EA group = ≥70% of their infusions before 14:00, and LA group = <70% of their infusions before 14:00. Treatment efficacy (overall response rate [ORR], disease control rate [DCR], progression-free survival [PFS], and overall survival [OS]) was evaluated. Multivariate analyses included variables with P values <0.1 in univariate analyses. Results: A total of 248 patients were eligible; 140 were classified as having EA, and 108 as having LA. Most baseline characteristics were similar between EA and LA. In contrast, the median infusion time was earlier in EA than in LA (11:50 vs. 14:22). The median follow-up time was 9.0 months (range, 1.2–64.7 months). ORR and DCR were significantly higher in the EA than in the LA among 149 patients with measurable lesions (ORR, 16.9% vs. 3.3%, P=0.01; DCR, 47.2% vs. 20.0%, P<0.01). Patients with EA had significantly better prognoses than those with LA in terms of PFS (median PFS, 2.3 vs. 1.6 months.; hazard ratios [HR], 0.65; P<0.01) and OS (median OS, 7.6 vs. 3.9 months.; HR, 0.64; P<0.01). EA patients received the subsequent chemotherapy more frequently than those in LA (54% vs. 32%; P<0.01). Multivariate analyses, including factors such as age, ECOG performance status, histological type, ascites, modified Glasgow Prognostic Score, and timing of nivolumab infusion, showed that EA was an independent prognostic factor for PFS (adjusted HR, 0.66; P<0.01) and OS (adjusted HR, 0.62; P<0.01). Conclusions: Our data suggest that efforts to schedule nivolumab infusions before mid-afternoon could be considered in daily practice.
Recurrence-free survival as a surrogate for overall survival in esophageal squamous cell carcinoma: Nationwide real-world data from Japan.
Authors: Okui Jun , Nagashima Kengo , Matsuda Satoru , Sato Yasunori , Okamura Akihiko , Kawakubo Hirofumi , Muto Manabu , Kakeji Yoshihiro , Kono Koji , TAKEUCHI HIROYA , Watanabe Masayuki , Doki Yuichiro , Bamba Takeo , Fukuda Takashi , Fujiwara Hitoshi , Sato Shinsuke , Noma Kazuhiro , Miyata Hiroshi , Fujita Takeo , Kitagawa Yuko
Published: January 2024

269

Background: One of the limitations of the established gold standard, overall survival (OS), is that it requires an extended follow-up period. Addressing this challenge involves investigating appropriate statistically and clinically relevant surrogate endpoints. However, there is a paucity of studies using real-world data (RWD) to explore surrogacy in patients with esophageal squamous cell carcinoma (ESCC). Our study aims to investigate whether recurrence-free survival (RFS) is a valid surrogate endpoint for OS in surgically resectable advanced ESCC patients, utilizing a comprehensive nationwide database in Japan. Methods: The ESCC patients who received neoadjuvant CF (cisplatin and 5-fluorouracil) or DCF (docetaxel, cisplatin and 5-fluorouracil) at 58 Japanese esophageal centers certified by the Japan Esophageal Society were retrospectively reviewed. Kendall's tau between RFS and OS was used at the individual level, and the coefficient of determination was used at the institutional level to assess surrogacy. Additionally, surrogacy between each short-term postoperative endpoint (pathological complete response [pCR] or pathological grade) and OS was investigated using novel statistical methods. Results: Our study encompassed 3154 ESCC patients who underwent subtotal esophagectomy from 2010 to 2015. The cStage I/II/III/IVA/IVB (due to supraclavicular lymph node metastasis) was 224 (7.1%), 1008 (32.0%), 1664 (52.8%), 117 (3.7%), and 140 (4.4%), respectively. The 5-year OS and RFS rate for the entire cohort was 56.6% and 47.7%, respectively. In the primary analysis, a strong correlation between RFS and OS was found (Kendall's tau = 0.797, 95% confidence interval [CI]: 0.782 to 0.812) at the individual level. Subgroup analysis revealed that the better the pathological response, the higher the tau value. An adjusted R2 of 100.0% (95% CI: 40.2 to 100.0) was obtained with the meta-regression model at the institutional level. The surrogate threshold effect was 0.703. Tau between pCR or pathological grade and OS were -0.025 (95% CI: -0.335 to 0.285) and 0.062 (95% CI: -0.086 to 0.209), respectively. Conclusions: The present study was the first nationwide RWD investigation to demonstrate a strong correlation between RFS and OS in surgically resectable ESCC patients who underwent neoadjuvant chemotherapy (NAC). Notably, this correlation was more pronounced in patients who had a more effective response to NAC. These findings hold promise for expediting the development of novel neoadjuvant treatment by shortening the duration of clinical trials.
Clinical presentation and delay to diagnosis and treatment in Mexican patients with gastric cancer.
Authors: Hernandez-Felix Jorge Humberto , Meneses-Medina Mónica I. Isabel , Jiménez Meza Marco Antonio , Conde Flores Emilio , Rosas Camargo Vanessa , Huitzil Melendez Fidel David David
Published: January 2024

291

Background: Gastric cancer is the fifth leading cause of cancer-related deaths in Mexico. Diagnosis is often made at advanced stages, resulting in a poor prognosis. The delay from the onset of the first symptom to diagnosis and treatment could influence the poor prognosis of gastric cancer patients (pts) in our country. In Mexico, information on this topic is limited. We aim to investigate the time delay between the onset of symptoms, histological diagnosis, and initiation of oncological treatment in pts with gastric adenocarcinoma. Methods: We conducted a retrospective review of the clinical records at our institution of all pts with confirmed histological diagnosis of gastric adenocarcinoma (GC) treated between Jan 2005 and Dec 2017. Overall Survival (OS) was estimated using the Kaplan-Meier method. Groups were compared using Log-Rank test. Results: We included 270 pts with confirmed histopathological diagnosis of GC, 53.3% (n=144) women, median age 58 years (IQR 25-75); 44% (n=121) reported family history of cancer, 39.6% (n=107) smoking, H. pylori infection was documented in 22% (n=61). Symptoms before diagnosis were present in 98.5% (n=266) of pts, most common were: weight loss 77.4% (n=209), fatigue 51.9% (n=140), early satiety 51.1% (n=138), nausea 48.9% (n=132), vomiting 48.1% (n=130), dysphagia 21.5% (n=58), and gastrointestinal bleeding 37.8% (n=102). The most common method for histological diagnosis was endoscopy with biopsy in 86.7% (n=234). The median time between the onset of symptoms and histopathological diagnosis was 4.21 (IQR 2.25–8.48) months (m), between the onset of symptoms and the initiation of oncological treatment 5.28 (IQR 2.86–9.52) m, and between histopathological diagnosis and oncological treatment 0.60 (IQR 0.13–1.21) m. 72.6% (n=196) of cases were stage IV, 14.1% (n=38) stage III, 8.1% (n=22) stage II, 4.8% (n=13) and stage 0 or I. The median OS for the entire cohort was 7.2 m, 3.7 m for stage IV, 17.3 m for stage III, and 84 m for stage I. Median OS for stage II was not reached, and it was 58% at 5 years. Symptoms associated with worse or better survival are shown in table. Conclusions: Reducing delays in histopathological diagnosis from symptom onset could lead to earlier detection and curative treatments. Identifying alarm signs and appropriate patient navigation would enable earlier diagnosis and early treatment. [Table: see text]
Real-world (RW) effectiveness of nivolumab plus chemotherapy (NIVO+chemo) in patients (pts) with advanced or metastatic gastric carcinoma, gastroesophageal junction carcinoma, or esophageal adenocarcinoma (GC/GEJC/EAC).
Authors: Chau Ian , Barzi Afsaneh , Zhang Ying , You Min , Bertwistle David , Davis Catherine , Chen Clara
Published: January 2024

295

Background: In the CheckMate 649 trial, NIVO+chemo demonstrated superior efficacy vs chemo alone in pts with previously untreated, advanced, non-human epidermal growth factor receptor 2 positive GC/GEJC/EAC. Our study was the first to evaluate the RW adoption patterns and effectiveness of NIVO+chemo as a first-line (1L) treatment of advanced GC/GEJC/EAC in the immediate period after NIVO approval in this setting. We report the 18-mo follow-up results. Methods: Pts in the United States ≥ 18 years of age with previously untreated advanced or metastatic GC/GEJC/EAC receiving NIVO+chemo or chemo alone (FOLFOX or CAPEOX) between 04/01/2021 and 12/31/2022 were identified in the Flatiron Health database. Pts were followed from the start of 1L therapy to death, loss of data availability, or the end of data abstraction, whichever occurred first. Results: 528 pts were eligible for the analysis (231 [44%] NIVO+chemo, 297 [56%] chemo). The prevalence of PD-L1 combined positive score (CPS) ≥ 5 before the 1L therapy was 55% for NIVO+chemo and 27% for chemo. Baseline demographic and clinical characteristics were comparable between treatment groups in the overall cohort and the CPS subgroups. Median follow-up (interquartile range) was 6.0 (2.4−9.8) mo for NIVO+chemo and 6.1 (2.5−9.7) mo for chemo. There were 87 (37.7%) deaths in the NIVO+chemo cohort and 138 (46.5%) in the chemo cohort. NIVO+chemo demonstrated superior overall survival (OS) in the overall cohort, with a 12-mo OS rate of 53.3% vs 38.1% for chemo and a 2.6-mo improvement in median OS (12.6 [95% confidence interval (CI), 10.2−17.9] mo vs 10.0 [8.9−11.5] mo, P = 0.047). Univariate Cox regression analysis of OS yielded a hazard ratio (HR) of 0.76 (95% CI, 0.58−1.00; P = 0.048) and multivariate Cox regression yielded an HR of 0.74 (95% CI, 0.56−0.98; P = 0.033) for NIVO+chemo vs chemo. There was also a consistent trend toward OS benefit with NIVO+chemo vs chemo in all CPS subgroups (Table). Multivariate analysis in the CPS ≥ 1 subgroup yielded a HR of 0.51 (95% CI, 0.30−0.89) for NIVO+chemo vs chemo but was not feasible in other subgroups due to sample size. Conclusions: NIVO+chemo showed superior OS vs chemo alone in previously untreated pts with advanced GC/GEJC/EAC in the RW setting. A trend toward OS benefit was also observed in all CPS subgroups, which will be further examined in future analyses with larger samples and longer follow-up. Clinical trial information: NCT02872116 . [Table: see text]
A multi-institutional prospective study to compare postoperative quality of life of patients who undergo proximal or total gastrectomy for early gastric cancer (CCOG1602).
Authors: Hojo Yumiko , Kanda Mitsuro , Mochizuki Yoshinari , Tanaka Chie , Ito Seiji , Watanabe Takuya , Sueoka Satoshi , Ishiyama Akiharu , Yamada Takanobu , Oshima Takashi , Hattori Masashi , Koike Shinya , Ishigure Kiyoshi , Teramoto Hitoshi , Murotani Kenta , Kodera Yasuhiro
Published: January 2024

296

Background: Proximal gastrectomy (PG) has become an increasingly preferred procedure for treating early cancer in the upper third of the stomach when oncological safety is ensured, with expectation for improvement of nutritional status and quality of life (QOL) attributable to the remnant stomach. Although few studies compare postoperative outcomes of patients who undergo total gastrectomy (TG) and PG based on questionnaires, their significant limitations include the retrospective design, use of a questionnaire not specific to a postgastrectomy setting, and observation at a fixed time or after a short postoperative period. Methods: A multi-institutional prospective study (CCOG1602) of patients who undergo PG or TG for cStage I gastric cancer was conducted. We used the Post-Gastrectomy Syndrome Assessment Scale (PGSAS)-37 and The European Organization for Research and Treatment of Cancer quality of life questionnaire (EORTC-QLQ-C30) to evaluate the changes in body weight and QOL over a 3-year postoperative period. The primary endpoint was the weight loss rate 3 years after surgery. Results: We enrolled 109 patients from 18 institutions and selected 65 and 19 patients for inclusion in the TG and PG groups, respectively. There were no differences in age, sex, or preoperative body mass index between the TG and PG groups. Mean postoperative weight loss rates were 16.0% and 11.7% for the TG and PG groups, respectively (Cohen's D 0.656) during postoperative year 1 and 15.0% and 10.8% for TG and PG (Cohen's D 0.543), respectively, during postoperative year 3, indicating that the PG group achieved a better trend with a moderate effect size. According to the PGSAS-37, the PG group experienced a better trend in the indigestion subscale (Cohen's D –1.085) and total symptom score (Cohen's D –0.59) during postoperative year 3 compared with the TG group. In contrast, the EORTC-QLQ-C30 identified no difference between the groups at any time point during the 3-year postoperative period. Conclusions: The CCOG1602 demonstrates that PG tended to be more favorable compared with TG with respect to postoperative weight loss and QOL, particularly regarding indigestion. Clinical trial information: UMIN000020070 .
Feasibility of functional evaluation in older adults with gastroesophageal cancer using fitness trackers.
Authors: Laderman Lauren , Meeker Caitlin R. , Handorf Elizabeth A. , Filchner Kelly A. , Tejani Mohamedtaki Abdulaziz , Williams Grant Richard , Winer Arthur , Arora Sukeshi Patel , Vijayvergia Namrata , Dotan Efrat
Published: January 2024

298

Background: With advances in treatment and an aging population, gastroesophageal cancer (GEC) in older adults (OA) is increasing. Geriatric assessment (GA) is recommended as part of treatment decision in patients ≥ 65. Unfortunately, due to the complex nature and multiorgan effects of GEC, it is often difficult for oncologists to discern whether GA abnormalities are secondary to aging or the GEC itself. Because of their objectivity, fitness trackers are becoming increasingly popular in the functional evaluation of cancer patients. While fitness trackers have shown feasibility and validity in some cancers, data for their use in OA is currently limited. Objective: Evaluate the feasibility of functional status assessment via Fitbit activity tracker (FB) in comparison to traditional geriatric assessments in OA with GEC. Methods: Patients age ≥65 with any stage of GEC completed a GA and were given a FB to wear for 3 days in line with the battery life of the device. GA included a comprehensive evaluation of all geriatric domains with functional status assessed by performance status (PS), falls, Timed Up and Go (TUG), Activities of Daily Living (ADLs), and Instrumental Activities of Daily Living (IADLs). FB collected total steps per day (SPD), and patients’ mean SPD was calculated. We compared patient characteristics and outcomes using Fisher’s exact and Wilcoxon tests grouped by below and above median SPD. Results: 82 patients completed GA, of which 69 (84%) wore FB for ≥8 hours. Mean SPD for all patients was 2827 (38 – 11032), median SPD was 2264. Patients with ≤ median SPD were older (75 vs 72 p=0.034), female (32% vs 14% p=0.093), Black (24% vs 9% p=0.068), and living alone (29% vs 14% p=0.153). Patients SPD below and above the median had similar distributions of education level (≤12 yrs 35% vs 31% p=0.802) and Stage (>2 82% vs 80% p=0.99). Patients with SPD below the median were more likely to have ≥ 2 abnormalities on GA (68% vs. 40%, p=0.03), self-reported PS >2 (24% vs 0% p=0.013), and impaired IADL (33% vs 9% p=0.064). Patients with lower SPD had higher rates ≥Gr 3 toxicity (47% vs 20% p=0.022) and hospitalization (32% vs 6% p=0.006). The rate of abnormal TUG was similar in both groups (21% vs 17%, p=0.285). Conclusions: FB use for short objective evaluation functional status is feasible among OA with GEC and provides data which correlates with other GA abnormalities and treatment tolerance. Additional research is warranted to further incorporate this assessment tool into clinical care.
Moving towards a personalised understanding of the nutritional impact of self-expanding metallic stents (SEMS) in gastro-oesophageal cancer: A retrospective case note review of a tertiary referral oncology centre.
Authors: Cunningham Aimee , Alattal Taibah , Foulkes Lindsey , Lewis Alexandra R , Backen Alison Catherine , Williamson Fiona , McQueenie Esther , Owen-Holt Vikki , Williams Kate , Hubner Richard , Waddell Tom , Valpione Sara , Laasch Hans-Ulrich , Mansoor Wasat , Weaver Jamie
Published: January 2024

301

Background: Dysphagia is a common life-impacting complication for patients with gastro-oesophageal (O-G) cancer. Options to alleviate dysphagia include insertion of SEMS or percutaneous endoscopic gastrostomy (PEG). SEMS improve quality of life by enabling a person to eat a varied diet, but are associated with complications including pain and need for reintervention. Although studies have shown SEMS improve dysphagia, consequent longitudinal impact on nutritional status has not been evaluated. There is a need to better characterise risks and benefits of SEMS to allow a personalised approach to both insertion and follow-up. Methods: We identified patients with a confirmed diagnosis of O-G cancer, who underwent SEMS insertion at The Christie NHS Foundation Trust in 2021 and 2022. Data was retrospectively collected about patient and stent characteristics, and patient outcomes to quantify benefits and risks of SEMS. Results: 112 patients had 127 SEMS inserted at The Christie. Patients’ International Dysphagia Diet Standardisation Initiative (IDDSI) score significantly improved after SEMS insertion (N=120); prior to SEMS 62% were only managing liquids and purees (IDDSI 3 and 4) and 24% were not able to eat enterally. Post SEMS, 76% tolerated textured foods (IDDSI 5 and above) and only 21.5% were limited to liquids/purees. We observed a significant reduction in the rate of weight loss (% body weight/10 days) following SEMS insertion (-0.010 ± 0.009 vs. -0.001 ± 0.010, P < 0.001). 12% of patients experienced grade 3 SEMS-related toxicity or stent failure within 30 days, and 20% developed significant pain within 24 hours of SEMS insertion. Conclusions: SEMS provide meaningful nutritional benefit in the majority of patients with O-G cancer, as weight loss is significantly slowed following insertion. However, we identified two groups of patients who did not benefit from SEMS; those who continued to lose weight and those who had stent failure. We did not find predictive factors for stent failure from multivariate analysis of baseline demographics or stent characteristics. Therefore, more detailed analysis of tumour factors, imaging findings and SEMS location from a larger cohort of patients may be required to identify patients who are unlikely to benefit from SEMS, and alternative interventions such as PEG feeding could be considered.
Efficacy and safety of nivolumab and CapeOX in patients with previously untreated FGFR2-positive, PD-L1-positive advanced gastric cancer: A single-arm, multicenter, phase 2 study NIVOFGFR2.
Authors: Tsimafeyeu Ilya , Musayeva Gunel , Samira Mahmudova , Otkhozoria Nana , Abbasov Bahadur , Kahharov Alisher
Published: January 2024

303

Background: Nivolumab in combination with chemotherapy has been approved in the first-line treatment of PD-L1-positive metastatic gastric cancer (GC). Fibroblast growth factor receptor 2 (FGFR2) is overexpressed in 30% of patients with GC and is a potential new target for targeted therapy with monoclonal antibodies1 or allosteric extracellular inhibitors.2 The aim of the NIVOFGFR2 study was to evaluate the preliminary efficacy of nivolumab in metastatic GC co-expressing PD-L1 and FGFR2. Methods: In this single-arm, multi-center, phase 2 study, eligible patients had metastatic untreated HER2-negative gastric adenocarcinoma with centrally confirmed expression of PD-L1 (CPS≥5; DAKO 28-8) and FGFR2 (moderate (2+) and strong (3+) membranous staining in more than 1% of tumor cells; Abсam EPR24075-418). Patients received nivolumab 360 mg with CapeOX (capecitabine and oxaliplatin) every 3 weeks. The primary endpoint was 1-year progression-free survival (PFS). Secondary endpoints included median PFS and overall survival (OS), objective response rate (ORR) and Grade ≥3 adverse events rate. Results: Seventy-four HER2-negative patients were screened and23 (31%) patients were enrolled (median age 61 years, men 74%, Caucasian 91%, ECOG PS 1-2 78%, organs with ≥2 metastases 78%; CPS (5-9) 22%, (≥10) 78%). 1-year PFS rate was 30,4%. The median PFS was 6.2 months (95% CI 4.4-7.6). The ORR was 21.7% with 1 complete response. With a median follow-up of 11.8 months at data cutoff, the median OS was not reached. Grade ≥3 treatment-related adverse events were reported in 9 (39.1%) patients. Conclusions: An interim analysis demonstrates modest efficacy and an acceptable safety profile of nivolumab in combination with chemotherapy in patients with FGFR2-positive, PD-L1-positive metastatic GC. Further follow-up is ongoing. 1. Wainberg, Lancet Oncol. 2022. 2. Tsimafeyeu, Invest New Drugs. 2023. Clinical trial information: NCT05859477 .
Nivolumab (NIVO) + chemotherapy (chemo) vs chemo as first-line (1L) treatment for advanced gastric cancer/gastroesophageal junction cancer/esophageal adenocarcinoma (GC/GEJC/EAC): 4 year (yr) follow-up of CheckMate 649.
Authors: Shitara Kohei , Moehler Markus H. , Ajani Jaffer A. , Shen Lin , Garrido Marcelo , Gallardo Carlos , Wyrwicz Lucjan S. , Yamaguchi Kensei , Cleary James M. , Elimova Elena , Bruges Maya Ricardo Elias , Karamouzis Michalis , Skoczylas Tomasz , Bragagnoli Arinilda , Liu Tianshu , Tehfe Mustapha , Feeney Kynan , Wang Rui , Nathani Raheel , Janjigian Yelena Y.
Published: January 2024

306

Background: NIVO + chemo demonstrated superior overall survival (OS) and clinically meaningful progression-free survival (PFS) benefit vs chemo and an acceptable safety profile in previously untreated, advanced non-HER2+ GC/GEJC/EAC, leading to approvals in many countries. NIVO + chemo continued to demonstrate clinically meaningful improvement in efficacy at 2 and 3-yr follow-ups. We present 4-yr follow-up results for NIVO + chemo vs chemo from CheckMate 649. Methods: Adults with previously untreated, unresectable advanced, or metastatic GC/GEJC/EAC were enrolled, regardless of programmed death ligand 1 (PD-L1) expression. HER2+ patients (pts) were excluded. Randomized pts received NIVO (360 mg Q3W or 240 mg Q2W) + chemo (XELOX Q3W or FOLFOX Q2W), NIVO + ipilimumab, or chemo. Dual primary endpoints for NIVO + chemo vs chemo were OS and PFS by blinded independent central review (BICR) in pts with PD-L1 combined positive score (CPS) ≥ 5. Results: 1581 pts were randomized to NIVO + chemo or chemo. At the 48-month (mo) minimum follow-up, NIVO + chemo continued to demonstrate OS and PFS benefit vs chemo in pts with PD-L1 CPS ≥ 5 and all randomized pts (Table) OS benefit with NIVO + chemo was observed in most prespecified subgroups. Objective response rates (ORR) were higher and responses were more durable with NIVO + chemo vs chemo in pts with PD-L1 CPS ≥ 5 and all randomized pts (Table). In the exploratory analysis of OS by response at the 18-week landmark timepoint, there were numerically more pts achieving response with NIVO + chemo vs chemo, and median OS (95% CI) with NIVO + chemo was numerically longer in responders vs non-responders both in pts with PD-L1 CPS ≥ 5 (20.5 [17.5–25.0] vs 14.0 [11.6–15.7]) and all randomized pts (19.4 [17.5–21.7] vs 13.1 [11.6–14.4]). No new safety signals were identified, consistent with the 3-yr follow-up. Conclusions: NIVO + chemo is the first PD-1 inhibitor/chemo combination to demonstrate long-term efficacy and acceptable safety after 4 yrs of follow up in previously untreated advanced GC/GEJC/EAC. These results are consistent with earlier follow-ups, further supporting NIVO + chemo as a standard 1L treatment in these pts. Clinical trial information: NCT02872116 .[Table: see text]
Abemaciclib in patients (pts) with esophageal cancer (EC) with CDKN2A loss or mutation (mut): Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) study.
Authors: Al Baghdadi Tareq , Rothe Michael , Mangat Pam K. , Garrett-Mayer Elizabeth , Yost Kathleen J , Chiu Vi Kien , Duvivier Herbert Leon , McKean Meredith , Rueter Jens , Taylor Mark A. , Grantham Gina N. , Gregory Abby , Hinshaw Dominique C. , Halabi Susan , Schilsky Richard L.
Published: January 2024

308

Background: TAPUR is a phase II basket study evaluating antitumor activity of commercially available targeted agents in pts with advanced cancers with specific genomic alterations. Results in a cohort of pts with EC with CDKN2A loss or mut treated with abemaciclib are reported. Methods: Eligible pts had measurable disease, ECOG performance status (PS) 0-2, adequate organ function, and no standard treatment (tx) options. Genomic testing was performed in CLIA-certified, CAP-accredited site selected labs. Pts received 200 mg (four 50 mg tablets) of abemaciclib twice daily for a total daily dose of 400 mg until disease progression. Primary endpoint was disease control (DC) per investigator defined as complete or partial (PR) response per RECIST v. 1.1, or stable disease of at least 16 weeks (wks) duration (SD16+). Simon 2-stage design tested the null DC rate of 15% vs. 35% (power = 0.85; α = 0.10). If ≥2 of 10 pts in stage 1 have DC, 18 more pts are enrolled; otherwise, the cohort is closed. If ≥7 of 28 pts have DC, the null DC rate is rejected. Secondary endpoints were objective response (OR), progression-free survival (PFS), overall survival (OS), duration of response (DOR) and safety. DOR is defined as time from pt’s first documented OR to progressive disease. Results: 10 pts with EC (8 adenocarcinoma, 2 squamous) and CDKN2A loss (n=5) or CDKN2A mut (n=5) were enrolled from Dec 2019 to June 2022. 6 pts had HER2 negative EC, 1 pt had HER2 low EC, 1 pt had HER2 positive EC, and 2 pts were not tested for HER2. All pts were evaluable for efficacy and toxicity. Table summarizes pt demographics and outcomes. 1 pt with CDKN2A loss had a 27-wk PR for a DC rate of 10% (1-sided 90% CI, 1% to 100%) and OR rate of 10% (95% CI, <1% to 45%). The null DC rate was not rejected (p=0.80). Median PFS was 8 wks (95% CI, 2 to 13) and median OS was 17 wks (95% CI, 9 to 35). The pt with PR had HER2 negative adenocarcinoma, ECOG PS of 1 and 2 prior lines of therapy. 4 pts had 12 serious adverse events at least possibly related to tx, including anemia, atrial fibrillation, increased creatinine, dehydration, dyspnea, generalized muscle weakness, heart failure, lung infection, pericardial effusion and thrombocytopenia. 4 pts had a drug-related grade 3 AEs including anemia, increased bilirubin and thrombocytopenia. Conclusions: Abemaciclib monotherapy did not demonstrate sufficient clinical activity in pts with advanced EC with CDKN2A loss or mut for continued evaluation in this pt population. Other tx should be considered for these pts, including tx offered in clinical trials. Clinical trial information: NCT02693535 . [Table: see text]