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Comparison of Pathologic Stage in Patients Receiving Esophagectomy With and Without Preoperative Chemoradiation Therapy for Esophageal SCC

Bing-Yen Wang, Ping-Yi Lin, Shiao-Chi Wu, Hui-Shan Chen, Po-Kuei Hsu, Chih-Shiun Shih, Chao-Yu Liu, Chia-Chuan Liu, and Yao-Li Chen

The prognostic value for the post-chemoradiation therapy (CRT) pathologic stage is uncertain. The purpose of this study was to compare the pathologic stage in patients undergoing esophagectomy with and without preoperative CRT for esophageal squamous cell carcinoma (ESCC). This study retrospectively reviewed the data from 2151 patients with ESCC who underwent esophagectomy with or without preoperative CRT between 2008 and 2011 in Taiwan. Patients were divided into 2 groups. Group A consisted of patients treated with primary surgery without prior treatments (n=1301), and group B consisted of patients receiving preoperative CRT followed by esophagectomy (n=850). In group A, 679 patients received surgery alone, 92 received postoperative chemotherapy, 416 received postoperative chemoradiation therapy, and 114 received postoperative radiation therapy. In group A, the 3-year survival rates by pathologic stage were 82.2% for stage 0, 67.6% for stage I, 50.7% for stage II, 21.5% for stage III, and 14.8% for stage IV (P<.001). In group B, the 3-year survival rates of post-CRT pathologic stages 0, I, II, III, and IV were 59.4%, 46.0%, 40.3%, 19.1%, and 8.2%, respectively (P<.001). In multivariate analysis, the pathologic T, N, and M were all independent prognostic factors in both group A (esophagectomy alone) and B (CRT plus esophagectomy). The current, 7th edition of the esophageal TNM staging system could adequately stratify prognostic groups in patients with squamous cell carcinoma who were treated with preoperative CRT and esophagectomy.

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Impact of Asian Race on Prognosis in De Novo Metastatic Prostate Cancer

Xudong Ni, Michael Luu, Weiwei Ma, Tingwei Zhang, Yu Wei, Stephen J. Freedland, Dingwei Ye, Timothy J. Daskivich, and Yao Zhu

Background: Little is known about the impact of Asian race on the long-term survival outcomes of males with de novo metastatic prostate cancer (PCa). Understanding racial disparities in survival is critical for accurate prognostic risk stratification and for informing the design of multiregional clinical trials. Methods: This multiple-cohort study included individual patient-level data for males with de novo metastatic PCa from the following 3 cohorts: LATITUDE clinical trial data (n=1,199), the SEER program (n=15,476), and the National Cancer Database (NCDB; n=10,366). Primary outcomes were overall survival (OS) in LATITUDE and NCDB and OS and cancer-specific survival in SEER. Results: Across all 3 cohorts, Asian patients diagnosed with de novo metastatic PCa had better survival than white patients. In LATITUDE, median OS was significantly longer in Asian versus white patients in the androgen deprivation therapy (ADT) + abiraterone + prednisone group (not reached vs 43.8 months; hazard ratio [HR], 0.45; 95% CI, 0.28–0.73; P=.001) as well as in the ADT + placebo group (57.6 vs 32.7 months; HR, 0.51; 95% CI, 0.33–0.78; P=.002). In SEER, among all patients diagnosed with de novo metastatic PCa, median OS was significantly longer in Asian versus white males (49 vs 39 months; HR, 0.76; 95% CI, 0.68–0.84; P<.001). Among those who received chemotherapy, Asian patients again had longer OS (52 vs 42 months; HR, 0.71; 95% CI, 0.52–0.96; P=.025). Using data on cancer-specific survival in SEER resulted in similar conclusions. In NCDB, Asian patients also had longer OS than white patients in aggregate and in subgroups of males treated with ADT or chemotherapy (aggregate: 38 vs 26 months; HR, 0.72; 95% CI, 0.62–0.83; P<.001; ADT subgroup: 41 vs 26 months; HR, 0.71; 95% CI, 0.60–0.84; P<.001; chemotherapy subgroup: 34 vs 25 months; HR, 0.67; 95% CI, 0.57–0.78; P<.001). Conclusions: Asian males have better OS and cancer-specific survival than white males with metastatic PCa across different treatment regimens. This should be considered when assessing prognosis and in designing multinational clinical trials.

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Real-World Use of Hypofractionated Radiotherapy for Primary CNS Tumors in the Elderly, and Implications on Medicare Spending

Kathryn R. Tringale, Andrew Lin, Alexandra M. Miller, Atif Khan, Linda Chen, Melissa Zinovoy, Yoshiya Yamada, Yao Yu, Luke R.G. Pike, and Brandon S. Imber

Background: For elderly patients with high-grade gliomas, 3-week hypofractionated radiotherapy (HFRT) is noninferior to standard long-course radiotherapy (LCRT). We analyzed real-world utilization of HFRT with and without systemic therapy in Medicare beneficiaries treated with RT for primary central nervous system (CNS) tumors using Centers for Medicare & Medicaid Services data. Methods: Radiation modality, year, age (65–74, 75–84, or ≥85 years), and site of care (freestanding vs hospital-affiliated) were evaluated. Utilization of HFRT (11–20 fractions) versus LCRT (21–30 or 31–40 fractions) and systemic therapy was evaluated by multivariable logistic regression. Medicare spending over the 90-day episode after RT planning initiation was analyzed using multivariable linear regression. Results: From 2015 to 2019, a total of 10,702 RT courses (ie, episodes) were included (28% HFRT; 65% of patients aged 65–74 years). A considerable minority died within 90 days of RT planning initiation (n=1,251; 12%), and 765 (61%) of those received HFRT. HFRT utilization increased (24% in 2015 to 31% in 2019; odds ratio [OR], 1.2 per year; 95% CI, 1.1–1.2) and was associated with older age (≥85 vs 65–74 years; OR, 6.8; 95% CI, 5.5–8.4), death within 90 days of RT planning initiation (OR, 5.0; 95% CI, 4.4–5.8), hospital-affiliated sites (OR, 1.4; 95% CI, 1.3–1.6), conventional external-beam RT (vs intensity-modulated RT; OR, 2.7; 95% CI, 2.3–3.1), and no systemic therapy (OR, 1.2; 95% CI, 1.1–1.3; P<.001 for all). Increasing use of HFRT was concentrated in hospital-affiliated sites (P=.002 for interaction). Most patients (69%) received systemic therapy with no differences by site of care (P=.12). Systemic therapy utilization increased (67% in 2015 to 71% in 2019; OR, 1.1 per year; 95% CI, 1.0–1.1) and was less likely for older patients, patients who died within 90 days of RT planning initiation, those who received conventional external-beam RT, and those who received HFRT. HFRT significantly reduced spending compared with LCRT (adjusted β for LCRT = +$8,649; 95% CI, $8,544–$8,755), whereas spending modestly increased with systemic therapy (adjusted β for systemic therapy = +$270; 95% CI, $176–$365). Conclusions: Although most Medicare beneficiaries received LCRT for primary brain tumors, HFRT utilization increased in hospital-affiliated centers. Despite high-level evidence for elderly patients, discrepancy in HFRT implementation by site of care persists. Further investigation is needed to understand why patients with short survival may still receive LCRT, because this has major quality-of-life and Medicare spending implications.

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Critical Evaluation of the Quality and Recommendations of Clinical Practice Guidelines for Nasopharyngeal Carcinoma

Yu-Pei Chen, Ya-Qin Wang, Wen-Fei Li, Lei Chen, Cheng Xu, Tai-Xiang Lu, Ai-Hua Lin, Ji-Jin Yao, Yang-Chan Li, Ying Sun, Yan-Ping Mao, and Jun Ma

Background: Given the distinct biological characteristics and regional distribution of nasopharyngeal carcinoma (NPC) compared with other head and neck cancers, and uncertainties regarding therapeutic strategies, physicians require high-quality clinical practice guidelines (CPGs) to provide transparent recommendations for NPC treatment. This study aimed to critically appraise the quality of NPC CPGs and assess the consistency of their recommendations. Methods: We identified CPGs that provided recommendations on the diagnosis and management of NPC published up to December 2015. Four investigators independently appraised CPG quality using the Appraisal of Guidelines for Research & Evaluation (AGREE) II instrument. Key recommendations by CPGs were also evaluated. Results: A total of 7 CPGs were eligible for this study: 5 produced by professional organizations or governmental agencies and 2 were developed based on expert consensus. Of the 6 AGREE II domains, the applicability domain scored consistently low across CPGs (range, 13.5%–30.2%); no CPG achieved a score of >50% in all 6 domains. The scope and purpose domain (≥73.6% for 4 CPGs) and editorial independence domain (≥75.0% for 6 CPGs) scored highest. Of the 23 AGREE II items, 9 scored less than half of the points available in all 7 CPGs. The recommendations by CPGs were consistent in general; heterogeneity mainly existed among recommended therapeutic strategies. Conclusions: Variation exists in NPC CPG development processes and recommendations. Increased efforts are required to make comprehensive resources available to guide healthcare providers and enhance delivery of high-quality, evidence-based care for NPC. International collaboration is necessary to enable the development of high-quality and regionally relevant CPGs for NPC.

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CLO20-041: Prognostic Factors in Major Salivary Gland Tumors Treated with Adjuvant Radiation Therapy

Jung Julie Kang, Hannah Verma, Kaveh Zakeri, Huili Wang, Dan Fan, Ming Fan, Anna Lee, Sarin Kitpanit, Linda Chen, Yao Yu, C. Jillian Tsai, Sean McBride, Nadeem Riaz, Daphna Gelblum, Alan S. Ho, Eric Sherman, Lara Dunn, Jay O. Boyle, Richard J. Wong, Ian Ganly, and Nancy Y. Lee

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Inherited Mutations in Chinese Men With Prostate Cancer

Yao Zhu, Yu Wei, Hao Zeng, Yonghong Li, Chi-Fai Ng, Fangjian Zhou, Caiyun He, Guangxi Sun, Yuchao Ni, Peter K.F. Chiu, Jeremy Y.C. Teoh, Beihe Wang, Jian Pan, Fangning Wan, Bo Dai, Xiaojian Qin, Guowen Lin, Hualei Gan, Junlong Wu, and Dingwei Ye

Background: Although China accounts for 7.8% of worldwide new prostate cancer (PCa) cases and 14.5% of new deaths according to GLOBOCAN 2020, the risk of PCa associated with germline mutations is poorly defined, hampered in part by lack of nationwide evidence. Here, we sequenced 19 PCa predisposition genes in 1,836 Chinese patients with PCa and estimated disease risk associated with inherited mutations. Patients and Methods: Patients were recruited from 4 tertiary cancer centers (n=1,160) and a commercial laboratory (n=676). Germline DNA was sequenced using a multigene panel, and pathogenic/likely pathogenic (P/LP) mutation frequencies in patients with PCa were compared with populations from the gnomAD (Genome Aggregation Database) and ChinaMAP (China Metabolic Analytics Project) databases. Clinical characteristics and progression-free survival were assessed by mutation status. Results: Of 1,160 patients from hospitals, 89.7% had Gleason scores ≥8, and 65.6% had metastases. P/LP mutations were identified in 8.49% of Chinese patients with PCa. Association with PCa risk was significant for mutations in ATM (odds ratio [OR], 5.9; 95% CI, 3.1–11.1), BRCA2 (OR, 15.3; 95% CI, 10.0–23.2), MSH2 (OR, 15.8; 95% CI, 4.2–59.6), and PALB2 (OR, 5.9; 95% CI, 2.7–13.2). Compared with those without mutations, patients with mutations in ATM, BRCA2, MSH2, or PALB2 showed a poor outcome with treatment using androgen deprivation therapy and abiraterone (hazard ratio, 2.19 [95% CI, 1.34–3.58] and 2.47 [95% CI, 1.23–4.96], respectively) but similar benefit from docetaxel. Conclusions: The present multicenter study confirmed that a significant proportion of Chinese patients with PCa had inherited mutations and identified predisposition genes in this underreported ethnicity. These data provide empirical evidence for precision prevention and prognostic estimation in Chinese patients with PCa.