Jama Oncology最新文献_第8页

Active Surveillance for Low-Risk Cancer-The Waiting Is the Hardest Part. 低风险癌症的主动监控--等待是最难的部分

IF 28.4 1区医学 Q1 Biochemistry, Genetics and Molecular Biology

Jama Oncology

Pub Date : 2024-11-01 DOI: 10.1001/jamaoncol.2024.2667

David A Haggstrom, Signe M Braafladt, Paul K J Han

引用次数: 0

Contributions to Colorectal Cancer Disparities. 对结直肠癌差异的贡献。

IF 28.4 1区医学 Q1 Biochemistry, Genetics and Molecular Biology

Jama Oncology

Pub Date : 2024-11-01 DOI: 10.1001/jamaoncol.2024.3516

John M Carethers

引用次数: 0

Lynch Syndrome and Somatic Mismatch Repair Variants in Pancreas Cancer. 胰腺癌中的林奇综合征和体细胞错配修复变异。

IF 28.4 1区医学 Q1 Biochemistry, Genetics and Molecular Biology

Jama Oncology

Pub Date : 2024-11-01 DOI: 10.1001/jamaoncol.2024.3651

Catherine A O'Connor, Emily Harrold, David Lin, Henry Walch, Andrea Gazzo, Megha Ranganathan, Sarah Kane, Fergus Keane, Joshua Schoenfeld, Drew Moss, Deborah M Thurtle-Schmidt, Sarah P Suehnholz, Debyani Chakravarty, Fiyinfolu Balogun, Anna Varghese, Kenneth Yu, David Kelsen, Alicia Latham, Britta Weigelt, Wungki Park, Zsofia Stadler, Eileen M O'Reilly

Importance: Microsatellite (MS) instability (MSI-H) occurs frequently in Lynch syndrome (LS)-associated tumors and is associated with response to immune checkpoint blockade (ICB) therapy. MSI-H is conferred by germline or somatic variants in mismatch repair genes. The contribution of somatic oncogenesis to MSI-H in pancreatic cancer (PC) is unknown.

Objective: To evaluate an LS-related PC cohort to define clinicogenomic features, describe somatic MSI-H cases (germline negative), characterize response to ICB, and guide preferred MS testing methods.

Design, setting, and participants: This single-institution, retrospective analysis was conducted from March 2012 to July 2023 at Memorial Sloan Kettering Cancer Center and included 55 patients with PC and either an LS germline pathogenic variant (gPV) or somatic mismatch repair (MMR) variant.

Main outcomes and measures: Composite MMR and MS status determined using orthogonal methods. An artificial intelligence classifier was used to account for low-cellularity specimens. Demographic and clinical data were abstracted from medical record. Zygosity status and somatic comutation landscape analyzed.

Results: Fifty-five patients (23 women [42%]) had PC and an MMR variant: 32 (58%) had LS (LS cohort) and 23 (42%) had a somatic MMR variant (no germline pathogenic variant, somatic MMR cohort). In the LS cohort, 10 (31%) had gMSH2, 9 (28%) gMSH6, 8 (25%) gPMS2, 4 (13%) gMLH1, 1 (3%) gEPCAM. The median age at diagnosis was 68 years (range, 45-88 years). For composite MS status, 17 (59%) were MSI-H, 12 (41%) MS stable, and 3 MS unknown. Five cases were reclassified as MSI-H by the artificial intelligence classifier. In the somatic MMR cohort, 11 (48%) had MSH6, 7 (30%) MLH1, 3 (13%) MSH2, and 2 (9%) PMS2. The median age at diagnosis was 72 years (range, 66-85 years). For composite MS status, 10 (43%) were MSI-H, 11 (48%) MS stable, and 2 (9%) MS indeterminate. Six cases were reclassified as MSI-H by the artificial intelligence classifier. For the LS and somatic MMR cohorts, 20 received ICB (n = 17 MSI-H). The median ICB duration was 27.7 months (95% CI, 11.5 to not reached); the disease control rate was 80%.

Conclusion: The results of this cross-sectional study suggest that MSI-H occurs due to LS or somatic oncogenesis in PC. Orthogonal MS testing is key in PC; the artificial intelligence classifier reclassified approximately 20% of cases, most of which were low cellularity. ICB for patients with LS or somatic MSI-H PC provided significant benefit.

重要性：微卫星（MS）不稳定性（MSI-H）经常发生在林奇综合征（LS）相关肿瘤中，并与对免疫检查点阻断（ICB）疗法的反应有关。MSI-H 由错配修复基因的种系或体细胞变异引起。体细胞致癌对胰腺癌（PC）MSI-H的影响尚不清楚：评估与LS相关的PC队列，以确定临床基因组学特征，描述体细胞MSI-H病例（种系阴性），描述对ICB的反应，并指导首选的MS检测方法：这项单一机构的回顾性分析于2012年3月至2023年7月在纪念斯隆-凯特琳癌症中心进行，共纳入55例PC患者和LS种系致病变异体（gPV）或体细胞错配修复（MMR）变异体：采用正交方法确定MMR和MS的复合状态。人工智能分类器用于考虑低细胞标本。人口统计学和临床数据摘自病历。对杂合子状态和体细胞变异情况进行分析：55名患者（23名女性[42%]）患有PC和MMR变异：32名（58%）患有LS（LS队列），23名（42%）患有体细胞MMR变异（无种系致病变异，体细胞MMR队列）。在LS队列中，10人（31%）有gMSH2，9人（28%）有gMSH6，8人（25%）有gPMS2，4人（13%）有gMLH1，1人（3%）有gEPCAM。诊断时的中位年龄为 68 岁（45-88 岁）。综合 MS 状态，17 例（59%）为 MSI-H，12 例（41%）为 MS 稳定型，3 例 MS 状态不明。5例被人工智能分类器重新分类为MSI-H。在体细胞MMR队列中，11例（48%）为MSH6，7例（30%）为MLH1，3例（13%）为MSH2，2例（9%）为PMS2。诊断时的中位年龄为 72 岁（66-85 岁）。综合 MS 状态，10 例（43%）为 MSI-H，11 例（48%）为 MS 稳定型，2 例（9%）为 MS 不确定型。人工智能分类器将 6 例重新分类为 MSI-H。在LS和体细胞MMR队列中，20例接受了ICB治疗（n = 17 MSI-H）。中位 ICB 持续时间为 27.7 个月（95% CI，11.5 到未达到）；疾病控制率为 80%：这项横断面研究的结果表明，MSI-H发生于PC的LS或体细胞致癌。人工智能分类器对约20%的病例进行了重新分类，其中大部分为低细胞性病例。对LS或体细胞MSI-H型PC患者进行ICB治疗有显著疗效。

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引用次数: 0

Ensuring Safety and Consistency in Artificial Intelligence Chatbot Responses-Reply. 确保人工智能聊天机器人回复的安全性和一致性--回复。

IF 28.4 1区医学 Q1 Biochemistry, Genetics and Molecular Biology

Jama Oncology

Pub Date : 2024-11-01 DOI: 10.1001/jamaoncol.2024.4327

David Chen, Srinivas Raman

引用次数: 0

metastatic. 转移。

IF 28.4 1区医学 Q1 Biochemistry, Genetics and Molecular Biology

Jama Oncology

Pub Date : 2024-10-31 DOI: 10.1001/jamaoncol.2024.4899

Tega Ebeye

引用次数: 0

Lazertinib in EGFR-Variant Non-Small Cell Lung Cancer With CNS Failure to Prior EGFR Tyrosine Kinase Inhibitors: A Nonrandomized Controlled Trial. 拉唑替尼治疗既往表皮生长因子受体酪氨酸激酶抑制剂治疗无效的表皮生长因子受体变异型非小细胞肺癌：非随机对照试验。

IF 28.4 1区医学 Q1 Biochemistry, Genetics and Molecular Biology

Jama Oncology

Pub Date : 2024-10-01 DOI: 10.1001/jamaoncol.2024.2640

Min Hee Hong, Yoon Ji Choi, Hee Kyung Ahn, Sun Min Lim, Bhumsuk Keam, Dong-Wan Kim, Tae Min Kim, Jeonghwan Youk, Yu Jung Kim, Shinwon Hwang, Sangwoo Kim, Ju Won Kim, Hye Ryun Kim, Jin Hyoung Kang

Importance: EGFR-variant non-small cell lung cancer (NSCLC) is associated with a high rate of central nervous system (CNS) metastases, even with treatment with first-generation or second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs).Objective: To investigate CNS activity with lazertinib, a third-generation EGFR TKI.Design, setting, and participants: This multicenter single-arm, phase 2 nonrandomized controlled trial was conducted in South Korea and included patients with EGFR-variant NSCLC who had asymptomatic or mildly symptomatic brain metastases after unsuccessful treatment with first-generation or second-generation EGFR TKIs. Data were collected from June 2021 to April 2022, with a data cutoff date of December 15, 2022.Exposure: Lazertinib, 240 mg, once daily.Main outcomes and measures: The primary end point was intracranial objective response rate (iORR) in the evaluable population according to the Response Evaluation Criteria in Solid Tumours version 1.1 assessed by the investigators. Secondary end points included intracranial progression-free survival (iPFS) and iORR in patients with T790M-negative disease and isolated CNS progression as well as overall ORR, duration of response, intracranial duration of response, disease control rate, overall survival, cerebrospinal fluid penetration of lazertinib, and safety.Results: Among 40 included patients, 25 (63%) were women, and the median (range) age was 63 (29-85) years. A total of 38 patients were evaluable for tumor response, including 12 patients with leptomeningeal metastases. At data cutoff, the median (range) follow-up was 13.6 (2.9-17.7) months. The iORR for the evaluable population was 55% (21 of 38; 95% CI, 38.3-71.4); for patients with T790M-positive disease, 80% (4 of 5; 95% CI, 28.4-99.5); for patients with T790M-negative disease, 43% (9 of 21; 95% CI, 21.8-66.0); and for patients with T790M-unknown disease, 67% (8 of 12; 95% CI, 34.9-90.1). The median iPFS was 15.8 months (95% CI, 15.2-not reached) for the evaluable population, 15.2 months (95% CI, 4.2-not reached) for the T790M-positive subgroup, 15.4 months (95% CI, 7.9-not reached) for the T790M-negative subgroup, and 18.0 months (95% CI, 3.9-not reached) for the T790M-unknown subgroup. The cerebrospinal fluid penetration rate of lazertinib was 46.2% (95% CI, 10.0-49.6), providing further support for its mechanism of intracranial response. Most adverse events were grade 1 or 2.Conclusions and relevance: In this study, lazertinib had substantial CNS activity, regardless of T790M status, against the progression of intracranial metastases with or without leptomeningeal metastases after unsuccessful treatment with first-generation or second-generation EGFR TKIs in patients with metastatic EGFR-variant NSCLC. These results suggest that

重要性：表皮生长因子受体（EGFR）变异型非小细胞肺癌（NSCLC）的中枢神经系统（CNS）转移率很高，即使使用第一代或第二代表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKIs）治疗也是如此：研究第三代表皮生长因子受体酪氨酸激酶抑制剂拉唑替尼的中枢神经系统活性：这项多中心单臂2期非随机对照试验在韩国进行，纳入了经第一代或第二代EGFR TKIs治疗失败后出现无症状或轻度症状脑转移的EGFR变异型NSCLC患者。数据收集时间为2021年6月至2022年4月，数据截止日期为2022年12月15日：拉唑替尼，240 毫克，每日一次：主要终点是研究者根据实体瘤反应评价标准1.1版评估的可评价人群的颅内客观反应率（iORR）。次要终点包括T790M阴性患者的颅内无进展生存期（iPFS）和iORR、孤立的中枢神经系统进展以及总ORR、应答持续时间、颅内应答持续时间、疾病控制率、总生存期、拉唑替尼的脑脊液渗透性和安全性：在纳入的40名患者中，25名（63%）为女性，年龄中位数（范围）为63（29-85）岁。共有38名患者的肿瘤反应可接受评估，其中包括12名出现脑膜转移的患者。数据截止时，随访时间的中位数（范围）为 13.6（2.9-17.7）个月。可评估人群的 iORR 为 55%（38 人中有 21 人；95% CI，38.3-71.4）；T790M 阳性患者的 iORR 为 80%（5 人中有 4 人；95% CI，28.4-99.5）；T790M 阴性患者的 iORR 为 43%（21 人中有 9 人；95% CI，21.8-66.0）；T790M 未知患者的 iORR 为 67%（12 人中有 8 人；95% CI，34.9-90.1）。可评估人群的 iPFS 中位数为 15.8 个月（95% CI，15.2-未达标），T790M 阳性亚组为 15.2 个月（95% CI，4.2-未达标），T790M 阴性亚组为 15.4 个月（95% CI，7.9-未达标），T790M 未知亚组为 18.0 个月（95% CI，3.9-未达标）。拉唑替尼的脑脊液渗透率为46.2%（95% CI，10.0-49.6），进一步证实了其颅内反应机制。大多数不良反应为1级或2级：在这项研究中，无论T790M状态如何，拉唑替尼对转移性表皮生长因子受体变异型NSCLC患者在接受第一代或第二代表皮生长因子受体TKIs治疗失败后出现的颅内转移（伴有或不伴有脑膜外转移）具有显著的中枢神经系统活性。这些结果表明，对于既往接受过EGFR TKI治疗后中枢神经系统转移进展的EGFR变异型NSCLC患者，使用拉唑替尼代替脑局部治疗可能是一种潜在的策略：试验注册：ClinicalTrials.gov Identifier：NCT05326425。

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引用次数: 0

Hidden Morbidity in Cancer Care-Mental Health in Spouses. 癌症护理中的隐性发病--配偶的心理健康。

IF 28.4 1区医学 Q1 Biochemistry, Genetics and Molecular Biology

Jama Oncology

Pub Date : 2024-10-01 DOI: 10.1001/jamaoncol.2024.2903

Casey Crump, Weiva Sieh

引用次数: 0

Neoadjuvant Immunotherapy-From Trials to Practice. 新辅助免疫疗法--从试验到实践。

IF 28.4 1区医学 Q1 Biochemistry, Genetics and Molecular Biology

Jama Oncology

Pub Date : 2024-10-01 DOI: 10.1001/jamaoncol.2024.2924

Elizabeth A Mittendorf, Sara M Tolaney

引用次数: 0

Breast Cancer Index in Premenopausal Women With Early-Stage Hormone Receptor-Positive Breast Cancer. 患有早期激素受体阳性乳腺癌的绝经前妇女的乳腺癌指数。

IF 28.4 1区医学 Q1 Biochemistry, Genetics and Molecular Biology

Jama Oncology

Pub Date : 2024-10-01 DOI: 10.1001/jamaoncol.2024.3044

Ruth M O'Regan, Yi Zhang, Gini F Fleming, Prudence A Francis, Roswitha Kammler, Giuseppe Viale, Patrizia Dell'Orto, Istvan Lang, Meritxell Bellet, Herve R Bonnefoi, Carlo Tondini, Federica Villa, Antonio Bernardo, Eva M Ciruelos, Patrick Neven, Per Karlsson, Bettina Müller, Wolfram Jochum, Khalil Zaman, Silvana Martino, Charles E Geyer, Katarzyna J Jerzak, Nancy E Davidson, Robert E Coleman, James N Ingle, Marion T van Mackelenbergh, Sherene Loi, Marco Colleoni, Catherine A Schnabel, Kai Treuner, Meredith M Regan

Importance: Adjuvant ovarian function suppression (OFS) with oral endocrine therapy improves outcomes for premenopausal patients with hormone receptor-positive (HR+) breast cancer but adds adverse effects. A genomic biomarker for selecting patients most likely to benefit from OFS-based treatment is lacking.Objective: To assess the predictive and prognostic performance of the Breast Cancer Index (BCI) for OFS benefit in premenopausal women with HR+ breast cancer.Design, setting, and participants: This prospective-retrospective translational study used all available tumor tissue samples from female patients from the Suppression of Ovarian Function Trial (SOFT). These individuals were randomized to receive 5 years of adjuvant tamoxifen alone, tamoxifen plus OFS, or exemestane plus OFS. BCI testing was performed blinded to clinical data and outcome. The a priori hypothesis was that BCI HOXB13/IL17BR ratio (BCI[H/I])-high tumors would benefit more from OFS and high BCI portended poorer prognosis in this population. Settings spanned multiple centers internationally. Participants included premenopausal female patients with HR+ early breast cancer with specimens in the International Breast Cancer Study Group tumor repository available for RNA extraction. Data were collected from December 2003 to April 2021 and were analyzed from May 2022 to October 2022.Main outcomes and measures: Primary end points were breast cancer-free interval (BCFI) for the predictive analysis and distant recurrence-free interval (DRFI) for the prognostic analyses.Results: Tumor specimens were available for 1718 of the 3047 female patients in the SOFT intention-to-treat population. The 1687 patients (98.2%) who had specimens that yielded sufficient RNA for BCI testing represented the parent trial population. The median (IQR) follow-up time was 12 (10.5-13.4) years, and 512 patients (30.3%) were younger than 40 years. Tumors were BCI(H/I)-low for 972 patients (57.6%) and BCI(H/I)-high for 715 patients (42.4%). Patients with tumors classified as BCI(H/I)-low exhibited a 12-year absolute benefit in BCFI of 11.6% from exemestane plus OFS (hazard ratio [HR], 0.48 [95% CI, 0.33-0.71]) and an absolute benefit of 7.3% from tamoxifen plus OFS (HR, 0.69 [95% CI, 0.48-0.97]) relative to tamoxifen alone. In contrast, patients with BCI(H/I)-high tumors did not benefit from either exemestane plus OFS (absolute benefit, -0.4%; HR, 1.03 [95% CI, 0.70-1.53]; P for interaction = .006) or tamoxifen plus OFS (absolute benefit, -1.2%; HR, 1.05 [95% CI, 0.72-1.54]; P for interaction = .11) compared with tamoxifen alone. BCI continuous index was significantly prognostic in the N0 subgroup for DRFI (n = 1110; P = .004), with 12-year DRFI of 95.9%, 90.8%, and 86.3% in BCI low-risk, intermediate-risk, and high-risk N0 cancers, respectively.Conclusions and relevance: In

重要性：口服内分泌治疗辅助卵巢功能抑制（OFS）可改善激素受体阳性（HR+）乳腺癌绝经前患者的预后，但会增加不良反应。目前还缺乏一种基因组生物标志物来选择最有可能从基于OFS的治疗中获益的患者：目的：评估乳腺癌指数（BCI）对HR+乳腺癌绝经前女性OFS获益的预测性和预后性：这项前瞻性-回顾性转化研究使用了来自卵巢功能抑制试验（SOFT）女性患者的所有可用肿瘤组织样本。这些患者被随机分配接受为期5年的单独他莫昔芬辅助治疗、他莫昔芬加OFS治疗或依西美坦加OFS治疗。BCI测试在临床数据和结果盲法下进行。先验假设是，BCI HOXB13/IL17BR比值（BCI[H/I]）高的肿瘤将从OFS中获益更多，而BCI高的肿瘤预示着预后较差。研究地点横跨国际多个中心。研究对象包括HR+早期乳腺癌绝经前女性患者，这些患者的标本在国际乳腺癌研究组肿瘤库中可用于提取RNA。数据收集时间为2003年12月至2021年4月，分析时间为2022年5月至2022年10月：主要终点是预测分析中的无乳腺癌间隔期（BCFI）和预后分析中的无远处复发间隔期（DRFI）：在SOFT意向治疗人群的3047名女性患者中，有1718名患者获得了肿瘤标本。1687名患者（98.2%）的标本可提供足够的RNA用于BCI检测，这些患者代表了母试验人群。中位（IQR）随访时间为12（10.5-13.4）年，512名患者（30.3%）的年龄小于40岁。972名患者（57.6%）的肿瘤为BCI（H/I）-低，715名患者（42.4%）的肿瘤为BCI（H/I）-高。与单用他莫昔芬相比，BCI(H/I)-低的肿瘤患者在依西美坦加用OFS的12年中，BCFI的绝对获益率为11.6%（危险比[HR]，0.48 [95% CI，0.33-0.71]），他莫昔芬加用OFS的绝对获益率为7.3%（HR，0.69 [95% CI，0.48-0.97]）。相反，与单用他莫昔芬相比，BCI（H/I）高的肿瘤患者从依西美坦加用OFS（绝对获益为-0.4%；HR，1.03 [95% CI，0.70-1.53]；交互作用P = .006）或他莫昔芬加用OFS（绝对获益为-1.2%；HR，1.05 [95% CI，0.72-1.54]；交互作用P = .11）中均未获益。在N0亚组中，BCI连续指数对DRFI（n = 1110；P = .004）有明显的预后作用，BCI低危、中危和高危N0癌症的12年DRFI分别为95.9%、90.8%和86.3%：在这项针对SOFT入组患者的前瞻性-回顾性转化研究中，BCI被证实对患有HR+乳腺癌的绝经前女性具有预后作用。BCI(H/I)-低肿瘤患者从含OFS的辅助内分泌治疗中获益大于BCI(H/I)-高肿瘤患者。BCI(H/I)-低状态可识别出可能从这种更密集的内分泌治疗中获益的绝经前患者。

{"title":"Breast Cancer Index in Premenopausal Women With Early-Stage Hormone Receptor-Positive Breast Cancer.","authors":"Ruth M O'Regan, Yi Zhang, Gini F Fleming, Prudence A Francis, Roswitha Kammler, Giuseppe Viale, Patrizia Dell'Orto, Istvan Lang, Meritxell Bellet, Herve R Bonnefoi, Carlo Tondini, Federica Villa, Antonio Bernardo, Eva M Ciruelos, Patrick Neven, Per Karlsson, Bettina Müller, Wolfram Jochum, Khalil Zaman, Silvana Martino, Charles E Geyer, Katarzyna J Jerzak, Nancy E Davidson, Robert E Coleman, James N Ingle, Marion T van Mackelenbergh, Sherene Loi, Marco Colleoni, Catherine A Schnabel, Kai Treuner, Meredith M Regan","doi":"10.1001/jamaoncol.2024.3044","DOIUrl":"10.1001/jamaoncol.2024.3044","url":null,"abstract":"Importance: Adjuvant ovarian function suppression (OFS) with oral endocrine therapy improves outcomes for premenopausal patients with hormone receptor-positive (HR+) breast cancer but adds adverse effects. A genomic biomarker for selecting patients most likely to benefit from OFS-based treatment is lacking.Objective: To assess the predictive and prognostic performance of the Breast Cancer Index (BCI) for OFS benefit in premenopausal women with HR+ breast cancer.Design, setting, and participants: This prospective-retrospective translational study used all available tumor tissue samples from female patients from the Suppression of Ovarian Function Trial (SOFT). These individuals were randomized to receive 5 years of adjuvant tamoxifen alone, tamoxifen plus OFS, or exemestane plus OFS. BCI testing was performed blinded to clinical data and outcome. The a priori hypothesis was that BCI HOXB13/IL17BR ratio (BCI[H/I])-high tumors would benefit more from OFS and high BCI portended poorer prognosis in this population. Settings spanned multiple centers internationally. Participants included premenopausal female patients with HR+ early breast cancer with specimens in the International Breast Cancer Study Group tumor repository available for RNA extraction. Data were collected from December 2003 to April 2021 and were analyzed from May 2022 to October 2022.Main outcomes and measures: Primary end points were breast cancer-free interval (BCFI) for the predictive analysis and distant recurrence-free interval (DRFI) for the prognostic analyses.Results: Tumor specimens were available for 1718 of the 3047 female patients in the SOFT intention-to-treat population. The 1687 patients (98.2%) who had specimens that yielded sufficient RNA for BCI testing represented the parent trial population. The median (IQR) follow-up time was 12 (10.5-13.4) years, and 512 patients (30.3%) were younger than 40 years. Tumors were BCI(H/I)-low for 972 patients (57.6%) and BCI(H/I)-high for 715 patients (42.4%). Patients with tumors classified as BCI(H/I)-low exhibited a 12-year absolute benefit in BCFI of 11.6% from exemestane plus OFS (hazard ratio [HR], 0.48 [95% CI, 0.33-0.71]) and an absolute benefit of 7.3% from tamoxifen plus OFS (HR, 0.69 [95% CI, 0.48-0.97]) relative to tamoxifen alone. In contrast, patients with BCI(H/I)-high tumors did not benefit from either exemestane plus OFS (absolute benefit, -0.4%; HR, 1.03 [95% CI, 0.70-1.53]; P for interaction = .006) or tamoxifen plus OFS (absolute benefit, -1.2%; HR, 1.05 [95% CI, 0.72-1.54]; P for interaction = .11) compared with tamoxifen alone. BCI continuous index was significantly prognostic in the N0 subgroup for DRFI (n = 1110; P = .004), with 12-year DRFI of 95.9%, 90.8%, and 86.3% in BCI low-risk, intermediate-risk, and high-risk N0 cancers, respectively.Conclusions and relevance: In ","PeriodicalId":48661,"journal":{"name":"Jama Oncology","volume":" ","pages":"1379-1389"},"PeriodicalIF":28.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11327904/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141983646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Hypofractionated vs Conventionally Fractionated Postmastectomy Radiation After Implant-Based Reconstruction: A Randomized Clinical Trial. 基于植入物的乳房再造术后的低分次放射治疗与常规分次放射治疗：随机临床试验。

IF 28.4 1区医学 Q1 Biochemistry, Genetics and Molecular Biology

Jama Oncology

Pub Date : 2024-10-01 DOI: 10.1001/jamaoncol.2024.2652

Julia S Wong, Hajime Uno, Angela C Tramontano, Lauren Fisher, Catherine V Pellegrini, Gregory A Abel, Harold J Burstein, Yoon S Chun, Tari A King, Deborah Schrag, Eric Winer, Jennifer R Bellon, Matthew D Cheney, Patricia Hardenbergh, Alice Ho, Kathleen C Horst, Janice N Kim, Kara-Lynne Leonard, Meena S Moran, Catherine C Park, Abram Recht, Daniel E Soto, Ron Y Shiloh, Susan F Stinson, Kurt M Snyder, Alphonse G Taghian, Laura E Warren, Jean L Wright, Rinaa S Punglia

Importance: Postmastectomy radiation therapy (PMRT) improves local-regional disease control and patient survival. Hypofractionation (HF) regimens have comparable efficacy and complication rates with improved quality of life compared with conventional fractionation (CF) schedules. However, the use of HF after mastectomy in patients undergoing breast reconstruction has not been prospectively examined.Objective: To compare HF and CF PMRT outcomes after implant-based reconstruction.Design, setting, and participants: This randomized clinical trial assessed patients 18 years or older undergoing mastectomy and immediate expander or implant reconstruction for breast cancer (Tis, TX, or T1-3) and unilateral PMRT from March 8, 2018, to November 3, 2021 (median [range] follow-up, 40.4 [15.4-63.0] months), at 16 US cancer centers or hospitals. Analyses were conducted between September and December 2023.Interventions: Patients were randomized 1:1 to HF or CF PMRT. Chest wall doses were 4256 cGy for 16 fractions for HF and 5000 cGy for 25 fractions for CF. Chest wall toxic effects were defined as a grade 3 or higher adverse event.Main outcomes and measures: The primary outcome was the change in physical well-being (PWB) domain of the Functional Assessment of Cancer Therapy-Breast (FACT-B) quality-of-life assessment tool at 6 months after starting PMRT, controlling for age. Secondary outcomes included toxic effects and cancer recurrence.Results: Of 400 women (201 in the CF arm and 199 in the HF arm; median [range] age, 47 [23-79] years), 330 patients had PWB scores at baseline and at 6 months. There was no difference in the change in PWB between the study arms (estimate, 0.13; 95% CI, -0.86 to 1.11; P = .80), but there was a significant interaction between age group and study arm (P = .03 for interaction). Patients younger than 45 years had higher 6-month absolute PWB scores if treated with HF rather than CF regimens (23.6 [95% CI, 22.7-24.6] vs 22.0 [95% CI, 20.7-23.3]; P = .047) and reported being less bothered by adverse effects (mean [SD], 3.0 [0.9] in the HF arm and 2.6 [1.2] in the CF arm; P = .02) or nausea (mean [SD], 3.8 [0.4] in the HF arm and 3.6 [0.8] in the CF arm; P = .04). In the as-treated cohort, there were 23 distant (11 in the HF arm and 12 in the CF arm) and 2 local-regional (1 in the HF arm and 1 in the CF arm) recurrences. Chest wall toxic effects occurred in 39 patients (20 in the HF arm and 19 in the CF arm) at a median (IQR) of 7.2 (1.8-12.9) months. Fractionation was not associated with chest wall toxic effects on multivariate analysis (HF arm: hazard ratio, 1.02; 95% CI, 0.52-2.00; P = .95). Fewer patients undergoing HF vs CF regimens had a treatment break (5 [2.7%] vs 15 [7.7%]; P = .03) or required unpaid time off from work (17 [8.5%] vs 34 [16.9%]; P = .02).Conclusions and releva

重要性：乳房切除术后放射治疗（PMRT）可提高局部区域疾病控制率和患者生存率。与传统分次放疗（CF）相比，低分次放疗（HF）方案的疗效和并发症发生率相当，生活质量也有所改善。然而，对乳房切除术后进行乳房重建的患者使用高频治疗的情况尚未进行前瞻性研究：目的：比较植入式乳房再造术后高频和CF PMRT的疗效：这项随机临床试验评估了 2018 年 3 月 8 日至 2021 年 11 月 3 日期间（中位数[范围]随访 40.4 [15.4-63.0] 个月）在 16 家美国癌症中心或医院接受乳腺癌（Tis、TX 或 T1-3）切除术和即刻扩张器或植入物重建术以及单侧 PMRT 的 18 岁或以上患者。分析在 2023 年 9 月至 12 月间进行：患者按 1:1 随机分配到 HF 或 CF PMRT。HF的胸壁剂量为4256 cGy，16次分割；CF的胸壁剂量为5000 cGy，25次分割。胸壁毒性反应定义为3级或以上不良事件：主要结果是开始PMRT治疗6个月后，乳腺癌治疗功能评估（FACT-B）生活质量评估工具中身体健康（PWB）领域的变化，并控制年龄。次要结果包括毒性反应和癌症复发：在400名女性患者中（CF组201人，HF组199人；年龄中位数[范围]为47[23-79]岁），330名患者在基线和6个月时均有PWB评分。研究臂之间的脉搏波速度变化没有差异（估计值，0.13；95% CI，-0.86 至 1.11；P = .80），但年龄组与研究臂之间存在显著的交互作用（交互作用的 P = .03）。如果采用高频治疗方案而非低频治疗方案，45 岁以下患者的 6 个月绝对脉搏波速度评分更高（23.6 [95% CI, 22.7-24.6] vs 22.0 [95% CI, 20.7-23.3]; P = .047），并称不良反应（高频治疗组平均[标度]为 3.0 [0.9]，低频治疗组为 2.6 [1.2]；P = .02）或恶心（高频治疗组平均[标度]为 3.8 [0.4]，低频治疗组为 3.6 [0.8]；P = .04）困扰较少。在治疗组群中，有 23 例远处复发（高频治疗组 11 例，低频治疗组 12 例）和 2 例局部区域复发（高频治疗组 1 例，低频治疗组 1 例）。39例患者（高频治疗组20例，低频治疗组19例）在中位数（IQR）为7.2（1.8-12.9）个月时出现胸壁毒性反应。多变量分析显示，分次治疗与胸壁毒性反应无关（高频治疗组：危险比为 1.02；95% CI 为 0.52-2.00；P = .95）。与 CF 方案相比，接受 HF 方案的患者中途中断治疗（5 [2.7%] vs 15 [7.7%]；P = .03）或需要无薪请假（17 [8.5%] vs 34 [16.9%]；P = .02）的人数较少：在这项随机临床试验中，与 CF 方案相比，HF 方案并未显著改善脉搏波速度的变化。这些数据丰富了植入式重建患者使用高频 PMRT 的经验：试验注册：ClinicalTrials.gov Identifier：试验注册：ClinicalTrials.gov Identifier：NCT03422003。

{"title":"Hypofractionated vs Conventionally Fractionated Postmastectomy Radiation After Implant-Based Reconstruction: A Randomized Clinical Trial.","authors":"Julia S Wong, Hajime Uno, Angela C Tramontano, Lauren Fisher, Catherine V Pellegrini, Gregory A Abel, Harold J Burstein, Yoon S Chun, Tari A King, Deborah Schrag, Eric Winer, Jennifer R Bellon, Matthew D Cheney, Patricia Hardenbergh, Alice Ho, Kathleen C Horst, Janice N Kim, Kara-Lynne Leonard, Meena S Moran, Catherine C Park, Abram Recht, Daniel E Soto, Ron Y Shiloh, Susan F Stinson, Kurt M Snyder, Alphonse G Taghian, Laura E Warren, Jean L Wright, Rinaa S Punglia","doi":"10.1001/jamaoncol.2024.2652","DOIUrl":"10.1001/jamaoncol.2024.2652","url":null,"abstract":"Importance: Postmastectomy radiation therapy (PMRT) improves local-regional disease control and patient survival. Hypofractionation (HF) regimens have comparable efficacy and complication rates with improved quality of life compared with conventional fractionation (CF) schedules. However, the use of HF after mastectomy in patients undergoing breast reconstruction has not been prospectively examined.Objective: To compare HF and CF PMRT outcomes after implant-based reconstruction.Design, setting, and participants: This randomized clinical trial assessed patients 18 years or older undergoing mastectomy and immediate expander or implant reconstruction for breast cancer (Tis, TX, or T1-3) and unilateral PMRT from March 8, 2018, to November 3, 2021 (median [range] follow-up, 40.4 [15.4-63.0] months), at 16 US cancer centers or hospitals. Analyses were conducted between September and December 2023.Interventions: Patients were randomized 1:1 to HF or CF PMRT. Chest wall doses were 4256 cGy for 16 fractions for HF and 5000 cGy for 25 fractions for CF. Chest wall toxic effects were defined as a grade 3 or higher adverse event.Main outcomes and measures: The primary outcome was the change in physical well-being (PWB) domain of the Functional Assessment of Cancer Therapy-Breast (FACT-B) quality-of-life assessment tool at 6 months after starting PMRT, controlling for age. Secondary outcomes included toxic effects and cancer recurrence.Results: Of 400 women (201 in the CF arm and 199 in the HF arm; median [range] age, 47 [23-79] years), 330 patients had PWB scores at baseline and at 6 months. There was no difference in the change in PWB between the study arms (estimate, 0.13; 95% CI, -0.86 to 1.11; P = .80), but there was a significant interaction between age group and study arm (P = .03 for interaction). Patients younger than 45 years had higher 6-month absolute PWB scores if treated with HF rather than CF regimens (23.6 [95% CI, 22.7-24.6] vs 22.0 [95% CI, 20.7-23.3]; P = .047) and reported being less bothered by adverse effects (mean [SD], 3.0 [0.9] in the HF arm and 2.6 [1.2] in the CF arm; P = .02) or nausea (mean [SD], 3.8 [0.4] in the HF arm and 3.6 [0.8] in the CF arm; P = .04). In the as-treated cohort, there were 23 distant (11 in the HF arm and 12 in the CF arm) and 2 local-regional (1 in the HF arm and 1 in the CF arm) recurrences. Chest wall toxic effects occurred in 39 patients (20 in the HF arm and 19 in the CF arm) at a median (IQR) of 7.2 (1.8-12.9) months. Fractionation was not associated with chest wall toxic effects on multivariate analysis (HF arm: hazard ratio, 1.02; 95% CI, 0.52-2.00; P = .95). Fewer patients undergoing HF vs CF regimens had a treatment break (5 [2.7%] vs 15 [7.7%]; P = .03) or required unpaid time off from work (17 [8.5%] vs 34 [16.9%]; P = .02).Conclusions and releva","PeriodicalId":48661,"journal":{"name":"Jama Oncology","volume":" ","pages":"1370-1378"},"PeriodicalIF":28.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11310844/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141908056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0