Background: Early noninvasive screening of patients who would benefit from neoadjuvant chemotherapy (NCT) is essential for personalized treatment of locally advanced gastric cancer (LAGC). The aim of this study was to identify a radioclinical signatures from pretreatment oversampled CT images to predict the response to NCT and prognosis of LAGC patients. Methods: LAGC patients were retrospectively recruited from six hospitals from January 2008 to December 2021. An SE-ResNet50-based chemotherapy response prediction system was developed from pretreatment CT images preprocessed with an imaging oversampling method (i.e., DeepSMOTE). Then, the Deep learning (DL) signature and clinic-based features were fed into the deep learning radioclinical signature (DLCS). The predictive performance of the model was evaluated based on discrimination, calibration and clinical usefulness. An additional model was built to predict overall survival (OS) and explore the survival benefit of the proposed DL signature and clinicopathological characteristics. Result: A total of 1060 LAGC patients were recruited from six hospitals, the training cohort (TC) and internal validation cohort (IVC) patients were randomly selected from center I. An external validation cohort (EVC) of 265 patients from 5 other centers was also included. The DLCS exhibited excellent performance in predicting the response to NCT in the IVC (AUC, 0.86) and EVC (AUC, 0.82), with good calibration in all cohorts (P>0.05). Moreover, the DLCS model outperformed the clinical model (P<0.05). Additionally, we found that the DL signature could serve as an independent factor for prognosis (HR, 0.828, P=0.004). The C-index, iAUC, and IBS for the OS model were 0.64, 1.24 and 0.71 in the test set. Conclusion: We proposed a DLCS model that combined imaging features with clinical risk factors to accurately predict tumor response and identify the risk of OS in LAGC patients priors to NCT that can then be used to guide personalized treatment plans with the help of computerized tumor-level characterization.

The prognostic role of the V600E mutation of v-raf murine sarcoma viral oncogene homolog B1 (BRAF) in metastatic colorectal cancer (mCRC) is well established, but the therapeutic regimen targeting this disease is lacking. This study aimed to analyze the clinicopathologic features of and treatment efficacy of commonly used regimens on BRAF-mutated mCRCs. We collected and reviewed the medical records of mCRC patients treated at Peking University Cancer Hospital & Institute (Beijing, China) between July 2011 and July 2016. Kirsten rat sarcoma viral oncogene homolog (KRAS), neuroblastoma RAS viral oncogene homolog (NRAS), and BRAF mutational status was assayed using direct sequencing. The details of clinicopathologic characteristics of patients and their responses to FOLFOXIRI regimen or standard therapy were obtained by reviewing the medical records. The progression-free survival (PFS) and overall survival (OS) were assessed using Kaplan–Meier analysis and compared using the log-rank test. Of 1694 patients studied, 75 had BRAF exon 15 mutations. Of these 75 patients, 71 had V600E mutation, 1 had D594G mutation, 2 had K601E mutation, and 1 had a novel T599_V600insAGA alteration. No patients had KRAS or NRAS mutations. Of 63 patients with BRAF V600E-mutated mCRC and sufficient clinical data, 27 (42.9%) had right-sided colon tumors, 19 (30.2%) had left-sided colon tumors, and 17 (26.9%) had rectal tumors; 26 (41.3%) had peritoneal metastases, and 50 (79.4%) had distant lymph node metastases. The patients with BRAF K601E- and T599_V600insAGA-mutated tumors had similar clinicopathologic features to those with BRAF V600E-mutated tumors. Patients with the BRAF V600E mutation benefited more from FOLFOXIRI regimen compared with patients who underwent standard therapy (overall response rate 83.3% vs. 14.0%; median PFS 6.4 months vs. 2.8 months, P = 0.220; median OS 11.0 months vs. 6.9 months, P = 0.048). BRAF V600E mutations were commonly identified in right-sided tumors and showed a high incidence of peritoneal and distant lymph nodes metastases. This subtype of mCRC was characterized by short OS and unique patterns of metastasis. Compared with standard treatment regimens, the FOLFOXIRI regimen had acceptable and manageable toxicities and favorable efficacy on patients with BRAF-mutated mCRC.

Antibody–drug conjugates (ADCs) represent a novel class of targeted anti-tumor medications that utilize the covalent linkage between monoclonal antibodies and cytotoxic agents. This unique mechanism combines the cytotoxic potency of drugs with the targeting specificity conferred by antigen recognition. However, it is essential to recognize that many ADCs still face challenges related to off-target toxicity akin to cytotoxic payloads, as well as targeted toxicity and other potential life-threatening adverse effects, such as treatment-induced interstitial lung injury. Currently, of the four approved ADC drugs for breast cancer, several reports have documented post-treatment lung injury-related fatalities. As a result, treatment-induced interstitial lung injury due to ADC drugs has become a clinical concern. In this review article, we delve into the factors associated with ADC-induced interstitial lung injury in patients with advanced-stage breast cancer and highlight strategies expected to decrease the incidence of ADC-related interstitial lung injury in the years ahead. These efforts are directed at enhancing treatment outcomes in both advanced and early-stage cancer patients while also providing insights into the development and innovation of ADC drugs and bolstering clinicians’ understanding of the diagnosis and management of ADC-associated interstitial lung injury.

Original Article Trastuzumab in combination with chemotherapy for HER2-positive metastatic gastric cancer patients underwent conversion therapy Yanqiang Zhang, Xiaoqing Xu, Can Hu, Yian Du, Guangyu Ding, Jiahui Chen, Xiu Zhu, Zhiyuan Xu, Qing Wei

The reliability of the traditional HER2 immunohistochemistry (IHC) scoring system for classifying low-expression cases remains uncertain, creating a barrier to effectively deploying new antibody-drug conjugates. To assess inter-observer agreement, 15 pathologists independently scored HER2 IHC in 460 gastric cancer specimens. We found the highest overall percent agreement (OPA) for HER2 3+ scores (0.17). The OPA for HER2 IHC 2+ cases was 0.11. However, consensus could not be reached for specimens scored as 0 or 1+. These findings suggest that conventional HER2 IHC scoring is relatively reliable for identifying patients with high HER2 expression but reveals significant inconsistency in classifying HER2-low versus HER2-zero cases. This highlights a critical limitation of the current system for guiding modern therapies and underscores the necessity for revised, precise scoring methodologies.