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Ovarian Cancer Biomarkers: Current Options and Future Promise

Christine M. Coticchia, Jiang Yang, and Marsha A. Moses

As more effective, less toxic cancer drugs reach patients, the need for accurate and reliable cancer diagnostics and prognostics has become widely appreciated. Nowhere is this need more dire than in ovarian cancer; here most women are diagnosed late in disease progression. The ability to sensitively and specifically predict the presence of early disease and its status, stage, and associated therapeutic efficacy has the potential to revolutionize ovarian cancer detection and treatment. This article reviews current ovarian cancer diagnostics and prognostics and potential biomarkers that are being studied and validated. Some of the most recent molecular approaches being used to identify genes and proteins are presented, which may represent the next generation of ovarian cancer diagnostics and prognostics.

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HSR23-114: Clinical Characteristics and Outcomes of US Extensive Stage Small Cell Lung Cancer (ES-SCLC) Patients Not Receiving Guideline Preferred Regimens

Daniel Simmons, Yang Xiao, Corina Roca, Zhuoxin Jiang, and Marnie Boron

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A Routine Laboratory Data–Based Model for Predicting Recurrence After Curative Resection of Stage II Colorectal Cancer

Zhong Ye, Chun Wang, Limin Guo, Juan P. Palazzo, Zhixing Han, Yinzhi Lai, Jing Jiang, James A. Posey, Atrayee Basu Mallick, Bingshan Li, Li Jiang, and Hushan Yang

Background: Use of chemotherapy in stage II colorectal cancer (CRC) is controversial because it improves survival only in some patients. We aimed to develop a statistical model using routine and readily available blood tests to predict the prognosis of patients with stage II CRC and to identify which patients are likely to benefit from chemotherapy. Methods: We divided 422 patients with stage II CRC into a training and a testing set. The association of routine laboratory variables and disease-free survival (DFS) was analyzed. A prognostic model was developed incorporating clinically relevant laboratory variables with demographic and tumor characteristics. A prognostic score was derived by calculating the sum of each variable weighted by its regression coefficient in the model. Model performance was evaluated by constructing receiver operating characteristic curves and calculating the area under the curve (AUC). Results: Significant associations were seen between 5 laboratory variables and patient DFS in univariate analyses. After stepwise selection, 3 variables (carcinoembryonic antigen, hemoglobin, creatinine) were retained in the multivariate model with an AUC of 0.75. Compared with patients with a low prognostic score, those with a medium and high prognostic score had a 1.99- and 4.78-fold increased risk of recurrence, respectively. The results from the training set were validated in the testing set. Moreover, chemotherapy significantly improved DFS in high-risk patients, but not in low- and medium-risk patients. Conclusions: A routine laboratory variable–based model may help predict DFS of patients with stage II CRC and identify high-risk patients more likely to benefit from chemotherapy.

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Comparison of Mismatch Repair Status Between Primary and Matched Metastatic Sites in Patients With Colorectal Cancer

Wen-Zhuo He, Wan-Ming Hu, Fang Wang, Yu-Ming Rong, Lin Yang, Qian-Kun Xie, Yuan-Zhong Yang, Chang Jiang, Hui-Juan Qiu, Jia-Bin Lu, Bei Zhang, Pei-Rong Ding, Xiao-Jun Xia, Jian-Yong Shao, and Liang-Ping Xia

Background: Differences between the features of primary cancer and matched metastatic cancer have recently drawn attention in research. This study investigated the concordance in microsatellite instability (MSI) and mismatch repair (MMR) status between primary and corresponding metastatic colorectal cancer (CRC). Methods: Consecutive patients with metastatic CRC who had both primary and metastatic tumors diagnosed at our institution in January 2008 through December 2016 were identified. Immunohistochemistry was used to test the MMR status of both primary and matched metastatic tumors, and PCR analysis was performed to test MSI in patients with deficient MMR (dMMR) status. Results: A total of 369 patients were included. Of the 46 patients with MSI-high primary tumors, 37 (80.4%) also had MSI-high metastatic tumors, whereas 9 (19.6%) had microsatellite stable (MSS) metastatic tumors. A high concordance was found in patients with liver, lung, or distant lymph node metastases. Interestingly, the discrepancy was more likely to be limited to peritoneal (5/20) or ovarian (4/4) metastasis (chi-square test, P<.001). These organ-specific features were also found in the pooled analysis. Along with the change of MSI-high in primary cancer to MSS in metastatic cancer, lymphocyte infiltration decreased significantly (P=.008). However, the change did not influence survival; the median overall survival of MSI-high and MSS metastatic tumors was 21.3 and 21.6 months, respectively (P=.774). The discrepancy rate was 1.6% for patients with proficient MMR primary tumors. Conclusions: For patients with dMMR primary tumors, the concordance of MSI and MMR status in primary CRC and corresponding metastatic cancer is potentially organ-specific. High concordance is found in liver, lung, and distant lymph node metastases, whereas discrepancy is more likely to occur in peritoneal or ovarian metastasis. Rebiopsy to evaluate MSI-high/dMMR status might be needed during the course of anti–PD-1 therapy in cases of peritoneal or ovarian metastasis.

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Long-Term Outcomes of dMMR/MSI-H Rectal Cancer Treated With Anti–PD-1–Based Immunotherapy as Curative-Intent Treatment

Jie-Hai Yu, Le-En Liao, Bin-Yi Xiao, Xuan Zhang, Ai-Wen Wu, Yong Cheng, Jing-Hua Tang, Wu Jiang, Ling-Heng Kong, Kai Han, Wei-Jian Mei, Zhi-Gang Hong, Wan-Jun Yang, Dan-Dan Li, Zhi-Zhong Pan, Yun-Feng Li, Xiao-Shi Zhang, and Pei-Rong Ding

Background: Neoadjuvant anti–PD-1 therapy has shown encouraging efficacy in patients with deficient DNA mismatch repair (dMMR)/microsatellite instability-high (MSI-H) locally advanced rectal cancer (LARC), which suggests its potential as a curative-intent therapy and a promising treatment option for organ preservation. We aimed to investigate the long-term outcomes of patients with dMMR/MSI-H LARC who experienced clinical complete response (cCR) after anti–PD-1 therapy. Methods: We retrospectively analyzed patients with dMMR/MSI-H LARC who achieved cCR and received nonoperative management following neoadjuvant anti–PD-1–based treatment from 4 Chinese medical centers. Patients were followed up for at least 1 year after they achieved cCR, their clinical data were collected, and survival outcomes were analyzed using the Kaplan-Meier method. Results: A total of 24 patients who achieved cCR and received nonoperative management from March 2018 to May 2022 were included, with a median age of 51.0 years (range, 19.0–77.0 years). The median treatment course to reach cCR was 6.0 (range, 1.0–12.0). Fifteen patients (62.5%) continued their treatments after experiencing cCR, and the median treatment course was 17.0 (range, 3.0–36.0). No local regrowth or distant metastasis was observed in a median follow-up time of 29.1 months (range, 12.6–48.5 months) after cCR. The 3-year disease-free and overall survivals were both 100%. Conclusions: Patients with dMMR/MSI-H locally advanced or low-lying rectal cancer who achieved cCR following anti–PD-1–based therapy had promising long-term outcomes. A prospective clinical trial with a larger sample size is required to further validate these findings.