Jama OncologyPub Date : 2024-08-22DOI: 10.1001/jamaoncol.2024.3408
Hassal Lee, Neal A Palafox, Tobias Janowitz
{"title":"Inclusion of American Indian, Alaska Native, Native Hawaiian, and Pacific Islander Patients in Clinical Trial Travel Time-Reply.","authors":"Hassal Lee, Neal A Palafox, Tobias Janowitz","doi":"10.1001/jamaoncol.2024.3408","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.3408","url":null,"abstract":"","PeriodicalId":48661,"journal":{"name":"Jama Oncology","volume":null,"pages":null},"PeriodicalIF":28.4,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142019244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jama OncologyPub Date : 2024-08-22DOI: 10.1001/jamaoncol.2024.3074
Catherine H Marshall, Benjamin A Teply, Jiayun Lu, Lia Oliveira, Hao Wang, Shifeng S Mao, W Kevin Kelly, Channing J Paller, Mark C Markowski, Samuel R Denmeade, Serina King, Rana Sullivan, Elai Davicioni, James A Proudfoot, Mario A Eisenberger, Michael A Carducci, Tamara L Lotan, Emmanuel S Antonarakis
{"title":"Olaparib Without Androgen Deprivation for High-Risk Biochemically Recurrent Prostate Cancer Following Prostatectomy: A Nonrandomized Controlled Trial.","authors":"Catherine H Marshall, Benjamin A Teply, Jiayun Lu, Lia Oliveira, Hao Wang, Shifeng S Mao, W Kevin Kelly, Channing J Paller, Mark C Markowski, Samuel R Denmeade, Serina King, Rana Sullivan, Elai Davicioni, James A Proudfoot, Mario A Eisenberger, Michael A Carducci, Tamara L Lotan, Emmanuel S Antonarakis","doi":"10.1001/jamaoncol.2024.3074","DOIUrl":"10.1001/jamaoncol.2024.3074","url":null,"abstract":"<p><strong>Importance: </strong>Olaparib is a poly(adenosine diphosphate-ribose) polymerase inhibitor that provides benefit in combination with hormonal therapies in patients with metastatic prostate cancer who harbor homologous recombination repair (HRR) alterations. Its efficacy in the absence of androgen deprivation therapy has not been tested.</p><p><strong>Objective: </strong>To determine the activity of olaparib monotherapy among patients with high-risk biochemically recurrent (BCR) prostate cancer after radical prostatectomy.</p><p><strong>Design, setting, and participants: </strong>This phase 2, single-arm nonrandomized controlled trial enrolled genetically unselected patients across 4 sites in the US from May 2017 to November 2022. Eligible patients had BCR disease following radical prostatectomy, a prostate-specific antigen (PSA) doubling time of 6 months or shorter, an absolute PSA value of 1.0 ng/mL or higher, and a testosterone level of 150 ng/dL or higher.</p><p><strong>Intervention: </strong>Treatment was with olaparib, 300 mg, by mouth twice daily until doubling of the baseline PSA, clinical or radiographic progression, or unacceptable toxic effects.</p><p><strong>Main outcome and measure: </strong>The primary end point was a confirmed 50% or higher decline in PSA from baseline (PSA50). Key secondary end points were outcomes by HRR alteration status, as well as safety and tolerability.</p><p><strong>Results: </strong>Of the 51 male patients enrolled (mean [SD] age, 63.8 [6.8] years), 13 participants (26%) had a PSA50 response, all within the HRR-positive group (13 of 27 participants [48%]). All 11 participants with BRCA2 alterations experienced a PSA50 response. Common adverse events were fatigue in 32 participants (63%), nausea in 28 (55%), and leukopenia in 22 (43%), and were consistent with known adverse effects of olaparib.</p><p><strong>Conclusions and relevance: </strong>In this nonrandomized controlled trial, olaparib monotherapy led to high and durable PSA50 response rates in patients with BRCA2 alterations. Olaparib warrants further study as a treatment strategy for some patients with BCR prostate cancer but does not have sufficient activity in those without HRR alterations and should not be considered for those patients.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov Identifier: NCT03047135.</p>","PeriodicalId":48661,"journal":{"name":"Jama Oncology","volume":null,"pages":null},"PeriodicalIF":28.4,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11342218/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142019245","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}
Jama OncologyPub Date : 2024-08-15DOI: 10.1001/jamaoncol.2024.2903
Casey Crump, Weiva Sieh
{"title":"Hidden Morbidity in Cancer Care-Mental Health in Spouses.","authors":"Casey Crump, Weiva Sieh","doi":"10.1001/jamaoncol.2024.2903","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.2903","url":null,"abstract":"","PeriodicalId":48661,"journal":{"name":"Jama Oncology","volume":null,"pages":null},"PeriodicalIF":28.4,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141983647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jama OncologyPub Date : 2024-08-15DOI: 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
{"title":"Lazertinib in EGFR-Variant Non-Small Cell Lung Cancer With CNS Failure to Prior EGFR Tyrosine Kinase Inhibitors: A Nonrandomized Controlled Trial.","authors":"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","doi":"10.1001/jamaoncol.2024.2640","DOIUrl":"10.1001/jamaoncol.2024.2640","url":null,"abstract":"<p><strong>Importance: </strong>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).</p><p><strong>Objective: </strong>To investigate CNS activity with lazertinib, a third-generation EGFR TKI.</p><p><strong>Design, setting, and participants: </strong>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.</p><p><strong>Exposure: </strong>Lazertinib, 240 mg, once daily.</p><p><strong>Main outcomes and measures: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions and relevance: </strong>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","PeriodicalId":48661,"journal":{"name":"Jama Oncology","volume":null,"pages":null},"PeriodicalIF":28.4,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11327907/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141983648","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}
Jama OncologyPub Date : 2024-08-15DOI: 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
{"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":"<p><strong>Importance: </strong>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.</p><p><strong>Objective: </strong>To assess the predictive and prognostic performance of the Breast Cancer Index (BCI) for OFS benefit in premenopausal women with HR+ breast cancer.</p><p><strong>Design, setting, and participants: </strong>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.</p><p><strong>Main outcomes and measures: </strong>Primary end points were breast cancer-free interval (BCFI) for the predictive analysis and distant recurrence-free interval (DRFI) for the prognostic analyses.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions and relevance: </strong>In ","PeriodicalId":48661,"journal":{"name":"Jama Oncology","volume":null,"pages":null},"PeriodicalIF":28.4,"publicationDate":"2024-08-15","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}
Jama OncologyPub Date : 2024-08-15DOI: 10.1001/jamaoncol.2024.3036
Qianwei Liu, Fen Yang, Krisztina D László, Kejia Hu, Maria Feychting, Dang Wei, Katja Fall, Unnur Valdimarsdóttir, Jiong Li, Fang Fang
{"title":"Suicide Attempt and Suicide Death Among Spouses of Patients With Cancer.","authors":"Qianwei Liu, Fen Yang, Krisztina D László, Kejia Hu, Maria Feychting, Dang Wei, Katja Fall, Unnur Valdimarsdóttir, Jiong Li, Fang Fang","doi":"10.1001/jamaoncol.2024.3036","DOIUrl":"10.1001/jamaoncol.2024.3036","url":null,"abstract":"<p><strong>Importance: </strong>Little is known about the risk of suicidal behavior in relation to having a spouse with a cancer diagnosis.</p><p><strong>Objective: </strong>To estimate the risk of suicide attempt and suicide death among spouses of patients with cancer.</p><p><strong>Design, setting, and participants: </strong>This nationwide cohort study in Denmark collected registry-based data from 1986 through 2016. Analyses were performed from August 8, 2022, to October 30, 2023. Individuals who had a spouse with a cancer diagnosed during 1986 to 2015 were compared with individuals whose spouse did not have a cancer diagnosis during the same period, randomly selected from the general population and matched by birth year and sex.</p><p><strong>Exposure: </strong>Having a spouse with a cancer diagnosis.</p><p><strong>Main outcomes and measures: </strong>Suicide attempt was identified through the Danish National Patient Register and the Danish Psychiatric Central Research Register, whereas suicide death was identified through the Danish Causes of Death Register, through 2016. Flexible parametric and Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% CIs for suicide attempt and suicide death among spouses of patients with a cancer diagnosis.</p><p><strong>Results: </strong>The study included 409 338 exposed individuals and 2 046 682 unexposed individuals (median [IQR] age at cohort entry for both groups, 63 [54-70] years; 55.4% women). During the follow-up, 2714 incident cases of suicide attempt among exposed individuals (incidence rate [IR], 62.6 per 100 000 person-years) and 9994 among unexposed individuals (IR, 50.5 per 100 000 person-years) were identified, as well as 711 cases of suicide death among the exposed individuals (IR, 16.3 per 100 000 person-years) and 2270 among the unexposed individuals (IR, 11.4 per 100 000 person-years). An increased risk of suicide attempt (HR, 1.28; 95% CI, 1.23-1.34) and suicide death (HR, 1.47; 95% CI, 1.35-1.60) was observed among spouses of patients with cancer throughout the follow-up. The increased risk was particularly notable during the first year after the cancer diagnosis, with an HR of 1.45 (95% CI, 1.27-1.66) for suicide attempt and 2.56 (95% CI, 2.03-3.22) for suicide death. There was a greater risk increase for both suicide attempt and suicide death when the cancer was diagnosed at an advanced stage or when the spouse died after the cancer diagnosis.</p><p><strong>Conclusions and relevance: </strong>These findings suggest a need for clinical and societal awareness to prevent suicidal behaviors among spouses of patients with cancer, particularly during the first year following the cancer diagnosis.</p>","PeriodicalId":48661,"journal":{"name":"Jama Oncology","volume":null,"pages":null},"PeriodicalIF":28.4,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11327902/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141983649","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}
Jama OncologyPub Date : 2024-08-15DOI: 10.1001/jamaoncol.2024.2667
David A Haggstrom, Signe M Braafladt, Paul K J Han
{"title":"Active Surveillance for Low-Risk Cancer-The Waiting Is the Hardest Part.","authors":"David A Haggstrom, Signe M Braafladt, Paul K J Han","doi":"10.1001/jamaoncol.2024.2667","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.2667","url":null,"abstract":"","PeriodicalId":48661,"journal":{"name":"Jama Oncology","volume":null,"pages":null},"PeriodicalIF":28.4,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141983645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jama OncologyPub Date : 2024-08-15DOI: 10.1001/jamaoncol.2024.2607
Haiying Cheng
{"title":"The Role of Lazertinib in Patients With EGFR-Variant Non-Small Cell Lung Cancer.","authors":"Haiying Cheng","doi":"10.1001/jamaoncol.2024.2607","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.2607","url":null,"abstract":"","PeriodicalId":48661,"journal":{"name":"Jama Oncology","volume":null,"pages":null},"PeriodicalIF":28.4,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141983650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jama OncologyPub Date : 2024-08-08DOI: 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
{"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":"<p><strong>Importance: </strong>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.</p><p><strong>Objective: </strong>To compare HF and CF PMRT outcomes after implant-based reconstruction.</p><p><strong>Design, setting, and participants: </strong>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.</p><p><strong>Interventions: </strong>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.</p><p><strong>Main outcomes and measures: </strong>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.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusions and releva","PeriodicalId":48661,"journal":{"name":"Jama Oncology","volume":null,"pages":null},"PeriodicalIF":28.4,"publicationDate":"2024-08-08","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}