Borrmann type-4 (B-4) advanced gastric cancer is challenging to diagnose through routine endoscopy, leading to a poor prognosis. The objective of this study was to develop an artificial intelligence (AI)-based system capable of detecting B-4 gastric cancers using upper endoscopy.
Endoscopic images from 259 patients who were diagnosed with B-4 gastric cancer and 595 controls who had benign conditions were retrospectively collected from Seoul National University Hospital for training and testing. Internal validation involved prospectively collected endoscopic videos from eight patients with B-4 gastric cancer and 148 controls. For external validation, endoscopic images and videos from patients with B-4 gastric cancer and controls at the Seoul National University Bundang Hospital were used. To calculate patient-based accuracy, sensitivity, and specificity, a diagnosis of B-4 was made for patients in whom greater than 50% of the images were identified as B-4 gastric cancer.
The accuracy of the patient-based diagnosis was highest in the internal image test set, with accuracy, sensitivity, and specificity of 93.22%, 92.86%, and 93.39%, respectively. The accuracy of the model in the internal validation videos, the external validation images, and the external validation videos was 91.03%, 91.86%, and 86.71%, respectively. Notably, in both the internal and external video sets, the AI model demonstrated 100% sensitivity for diagnosing patients who had B-4 gastric cancer.
An innovative AI-based model was developed to identify B-4 gastric cancer using endoscopic images. This AI model is specialized for the highly sensitive detection of rare B-4 gastric cancer and is expected to assist clinicians in real-time endoscopy.
The GOSSAMER phase 2 study assessed the FMS-like tyrosine kinase 3 (FLT3) inhibitor gilteritinib as maintenance therapy in patients with FLT3–internal tandem duplication (FLT3-ITD) acute myeloid leukemia (AML) in first complete remission without previous hematopoietic stem cell transplantation (HSCT).
Patients had to be within 2 months of their last consolidation cycle and have completed the recommended number of cycles per local practice. FLT3 inhibitors were allowed only during induction and/or consolidation. The primary end point was relapse-free survival (RFS). Secondary end points included overall survival (OS), event-free survival, and measurable residual disease (MRD).
In total, 98 patients were randomized (gilteritinib, n = 63; placebo, n = 35). RFS was not significantly different between the arms (hazard ratio, 0.74; 95% confidence interval, 0.41–1.34; p = .16). RFS rates for the gilteritinib and placebo arms were 68.5% and 55.3% at 1 year, 51.8% and 44.9% at 2 years, and 41.2% and 40.8% at 3 years, respectively. OS was not significantly different between the arms but may have been affected by subsequent AML therapies after discontinuation. In patients who received subsequent therapy (gilteritinib, 46.8%; placebo, 60.0%), a higher percentage of placebo-treated (57.1%) versus gilteritinib-treated patients (27.6%) underwent HSCT. At the end of treatment, 96.4% of gilteritinib-treated and 85.7% of placebo-treated patients had undetectable MRD. Relapsed placebo-treated (86.7%) versus gilteritinib-treated patients (34.8%) had a greater FLT3 mutational burden. No new significant safety concerns were noted.
The primary end point was not achieved; however, an observed trend toward potential benefit was noted in patients with FLT3-ITD AML who had not undergone prior HSCT.
Older adults with advanced cancer are at higher risk of treatment-related toxicities, which can impair function. Relationships between clinician-rated and patient-reported toxicities with functional decline remain unclear.
This secondary analysis of the GAP70+ trial aimed to evaluate the associations between clinician-rated (Clinician-rated common Terminology Criteria for Adverse Events [CTCAE]) and patient-reported toxicities (PRO-CTCAE) with changes in physical performance and functional outcomes in older adults receiving systemic therapy. Physical performance was measured using the Short Physical Performance Battery (SPPB; impairment: score ≤9). Functional capacity was assessed using activities of daily living (ADL) and instrumental ADL (IADL); impairment: any task difficulty. Toxicities were captured by CTCAE and PRO-CTCAE, which assess symptom severity and activity interferences. Generalized estimating equations evaluated the association of toxicity grades (0–1, 2, ≥3) within 3 months of treatment initiation with new functional impairments within 6 months.
Patients were age 70 to 96 years. At baseline, 82.9% had impaired SPPB, 51.5% had impaired IADL, and 27.4% had impaired ADL. Among patients without baseline impairments, 57.7%, 47.4%, and 31.0% developed new SPPB, IADL, and ADL impairments, respectively. No association was found between CTCAE toxicity and new SPPB impairment (p = .70), but higher PRO-CTCAE toxicity severity (p = .02) and interference (p = .02) were associated with new SPPB impairments. New IADL impairments were more common with higher grades of CTCAE (p = .02) severe PRO-CTCAE toxicities (p = .02).
These findings emphasize the need to assess both clinician-rated and patient-reported toxicities to understand and mitigate functional decline in older adults with advanced cancer.
Previous estimates of the number of cancers attributable to physical inactivity in the United States have typically focused on only three malignancies (colon, endometrial, and postmenopausal breast cancer). Contemporary epidemiologic evidence suggests that physical inactivity could contribute to up to 15 types of cancer, and a dose–response effect has been demonstrated for 13 of these. This study estimated the number of cancers diagnosed in the United States in 2015 due to physical inactivity for these 13 sites.
Data from the 2005 National Health Interview Survey were used to estimate physical activity prevalence and, with the assumption of a 10-year latency period, 2015 cancer incidence data from the National Program of Cancer Registries and Surveillance, Epidemiology, and End Results Incidence US Cancer Statistics Public Use Database.
The potential impact fraction was estimated to be 4.1%, which meant that 30,951 of 761,625 incident cancers at the 13 sites could have been prevented in the United States in 2015 if adults had increased physical activity by one category in 2005 (approximately 7.5 additional metabolic equivalent task hours per week [MET-h/week]). Theoretically, 85,415 of 761,625 incident cancers at the 13 sites (population attributable fraction, 11.2%) could have been prevented if all adults had achieved the highest level of physical activity (>30 MET-h/week).
When estimates are based on updated epidemiologic evidence regarding physical inactivity and cancer risk, substantially more cancers are attributable to physical inactivity than previously reported. A greater focus on physical activity promotion is warranted for cancer control in the United States.
This study evaluated the safety, pharmacokinetics, and antitumor activity of LY3295668 erbumine as monotherapy and combination therapy in children with relapsed/refractory neuroblastoma.
Patients aged 2–21 years who had relapsed/refractory neuroblastoma were enrolled. LY3295668 erbumine was evaluated at two dose levels (12 and 15 mg/m2) and administered orally twice daily continuously as monotherapy and in combination with intravenous topotecan and cyclophosphamide in 28-day cycles.
Twenty-five patients were treated. No dose-limiting toxicity occurred in monotherapy; one patient had dose-limiting toxicities in the combination therapy cohort (grade 3 mucositis and grade 4 neutropenia). The recommended phase 2 dose for both monotherapy and combination therapy was 15 mg/m2. Twenty-two patients (88%) had one or more treatment-related adverse event(s) (TRAEs), and 18 (72%) experienced grade ≥3 TRAEs. Myelosuppression was the most common high-grade TRAE observed in the combination therapy cohort. At both dose levels, steady-state plasma concentrations exceeded xenograft 90% inhibitory concentration levels. In the monotherapy cohort, one patient had a minor response, and one patient had stable disease, both continuing for >12 months. In the combination therapy cohort, two patients had a partial response, two had a minor response, and six had stable disease. Overall, the response rate, according to New Approaches to Neuroblastoma Therapy version 2.0 criteria, was 8%, and the disease control rate was 52%.
LY3295668 erbumine had a manageable safety profile as monotherapy and in combination therapy. Although proof-of-concept clinical responses were observed, future studies with biomarker-selected populations and/or novel combinations may yield higher response rates with Aurora kinase A inhibition.
Alterations in mismatch repair (MMR) genes like MLH1, MSH2, MSH6, and PMS2 can lead to microsatellite instability–high (MSI-H) tumors. These mutations can be inherited, as in Lynch syndrome (LS), or occur de novo. Although immune checkpoint inhibitors (ICI) improves survival in MSI-H colorectal cancer (CRC) compared to chemotherapy, data comparing outcomes for patients with germline versus somatic MMR mutations are limited.
This retrospective study included patients from Mayo Clinic (Arizona, Minnesota, Florida) from 2008 to 2023. A total of 81 patient records were reviewed. Patients with MMR-deficient or MSI-H CRC (N = 18 LS, N = 63 non-LS) were included for analysis.
Pembrolizumab was used in 65% of patients with LS and 94% of patients without LS, with median treatment durations of 11.7 and 8.8 months, respectively. Median overall survival (OS) for all stages was 82 months. There were no differences observed in OS for LS vs non-LS when patients in Stages II, III, and IV were analyzed separately. In Stage IV patients, BRAF V600E mutations were associated with worse OS compared to BRAF wild-type (hazard ratio, 2.69; 95% CI, 1.03–7.01, p = .043), with median OS of 19 vs. 113 months and progression-free survival of 12 vs. 95 months.
Patients with MSI-H CRC treated with ICIs exhibited similar outcomes regardless of germline or somatic MMR mutations. However, the presence of a BRAF V600E mutation was associated with a worse prognosis.
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