Pub Date : 2024-04-11DOI: 10.1001/jamaoncol.2024.0286
Kristen D. Brantley, Shoshana M. Rosenberg, Laura C. Collins, Kathryn J. Ruddy, Rulla M. Tamimi, Lidia Schapira, Virginia F. Borges, Ellen Warner, Steven E. Come, Yue Zheng, Gregory J. Kirkner, Craig Snow, Eric P. Winer, Ann H. Partridge
ImportanceAmong women diagnosed with primary breast cancer (BC) at or younger than age 40 years, prior data suggest that their risk of a second primary BC (SPBC) is higher than that of women who are older when they develop a first primary BC.ObjectiveTo estimate cumulative incidence and characterize risk factors of SPBC among young patients with BC.Design, Setting, and ParticipantsParticipants were enrolled in the Young Women’s Breast Cancer Study, a prospective study of 1297 women aged 40 years or younger who were diagnosed with stage 0 to III BC from August 2006 to June 2015. Demographic, genetic testing, treatment, and outcome data were collected by patient surveys and medical record review. A time-to-event analysis was used to account for competing risks when determining cumulative incidence of SPBC, and Fine-Gray subdistribution hazard models were used to evaluate associations between clinical factors and SPBC risk. Data were analyzed from January to May 2023.Main Outcomes and MeasuresThe 5- and 10- year cumulative incidence of SPBC.ResultsIn all, 685 women with stage 0 to III BC (mean [SD] age at primary BC diagnosis, 36 [4] years) who underwent unilateral mastectomy or lumpectomy as the primary surgery for BC were included in the analysis. Over a median (IQR) follow-up of 10.0 (7.4-12.1) years, 17 patients (2.5%) developed an SPBC; 2 of these patients had cancer in the ipsilateral breast after lumpectomy. The median (IQR) time from primary BC diagnosis to SPBC was 4.2 (3.3-5.6) years. Among 577 women who underwent genetic testing, the 10-year risk of SPBC was 2.2% for women who did not carry a pathogenic variant (12 of 544) and 8.9% for carriers of a pathogenic variant (3 of 33). In multivariate analyses, the risk of SPBC was higher among PV carriers vs noncarriers (subdistribution hazard ratio [sHR], 5.27; 95% CI, 1.43-19.43) and women with primary in situ BC vs invasive BC (sHR, 5.61; 95% CI, 1.52-20.70).ConclusionsFindings of this cohort study suggest that young BC survivors without a germline pathogenic variant have a low risk of developing a SPBC in the first 10 years after diagnosis. Findings from germline genetic testing may inform treatment decision-making and follow-up care considerations in this population.
{"title":"Second Primary Breast Cancer in Young Breast Cancer Survivors","authors":"Kristen D. Brantley, Shoshana M. Rosenberg, Laura C. Collins, Kathryn J. Ruddy, Rulla M. Tamimi, Lidia Schapira, Virginia F. Borges, Ellen Warner, Steven E. Come, Yue Zheng, Gregory J. Kirkner, Craig Snow, Eric P. Winer, Ann H. Partridge","doi":"10.1001/jamaoncol.2024.0286","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.0286","url":null,"abstract":"ImportanceAmong women diagnosed with primary breast cancer (BC) at or younger than age 40 years, prior data suggest that their risk of a second primary BC (SPBC) is higher than that of women who are older when they develop a first primary BC.ObjectiveTo estimate cumulative incidence and characterize risk factors of SPBC among young patients with BC.Design, Setting, and ParticipantsParticipants were enrolled in the Young Women’s Breast Cancer Study, a prospective study of 1297 women aged 40 years or younger who were diagnosed with stage 0 to III BC from August 2006 to June 2015. Demographic, genetic testing, treatment, and outcome data were collected by patient surveys and medical record review. A time-to-event analysis was used to account for competing risks when determining cumulative incidence of SPBC, and Fine-Gray subdistribution hazard models were used to evaluate associations between clinical factors and SPBC risk. Data were analyzed from January to May 2023.Main Outcomes and MeasuresThe 5- and 10- year cumulative incidence of SPBC.ResultsIn all, 685 women with stage 0 to III BC (mean [SD] age at primary BC diagnosis, 36 [4] years) who underwent unilateral mastectomy or lumpectomy as the primary surgery for BC were included in the analysis. Over a median (IQR) follow-up of 10.0 (7.4-12.1) years, 17 patients (2.5%) developed an SPBC; 2 of these patients had cancer in the ipsilateral breast after lumpectomy. The median (IQR) time from primary BC diagnosis to SPBC was 4.2 (3.3-5.6) years. Among 577 women who underwent genetic testing, the 10-year risk of SPBC was 2.2% for women who did not carry a pathogenic variant (12 of 544) and 8.9% for carriers of a pathogenic variant (3 of 33). In multivariate analyses, the risk of SPBC was higher among PV carriers vs noncarriers (subdistribution hazard ratio [sHR], 5.27; 95% CI, 1.43-19.43) and women with primary in situ BC vs invasive BC (sHR, 5.61; 95% CI, 1.52-20.70).ConclusionsFindings of this cohort study suggest that young BC survivors without a germline pathogenic variant have a low risk of developing a SPBC in the first 10 years after diagnosis. Findings from germline genetic testing may inform treatment decision-making and follow-up care considerations in this population.","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"108 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2024-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140547616","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}
Pub Date : 2024-04-11DOI: 10.1001/jamaoncol.2024.0294
George Rodrigues, Kristin A. Higgins, Andreas Rimner, Arya Amini, Joe Y. Chang, Stephen G. Chun, Jessica Donington, Martin J. Edelman, Matthew A. Gubens, Puneeth Iyengar, Benjamin Movsas, Matthew S. Ning, Henry S. Park, Andrea Wolf, Charles B. Simone
ImportanceThe treatment of locally advanced non–small cell lung cancer (LA-NSCLC) has been informed by more than 5 decades of clinical trials and other relevant literature. However, controversies remain regarding the application of various radiation and systemic therapies in commonly encountered clinical scenarios.ObjectiveTo develop case-referenced consensus and evidence-based guidelines to inform clinical practice in unresectable LA-NSCLC.Evidence ReviewThe American Radium Society (ARS) Appropriate Use Criteria (AUC) Thoracic Committee guideline is an evidence-based consensus document assessing various clinical scenarios associated with LA-NSCLC. A systematic review of the literature with evidence ratings was conducted to inform the appropriateness of treatment recommendations by the ARS AUC Thoracic Committee for the management of unresectable LA-NSCLC.FindingsTreatment appropriateness of a variety of LA-NSCLC scenarios was assessed by a consensus-based modified Delphi approach using a range of 3 points to 9 points to denote consensus agreement. Committee recommendations were vetted by the ARS AUC Executive Committee and a 2-week public comment period before official approval and adoption. Standard of care management of good prognosis LA-NSCLC consists of combined concurrent radical (60-70 Gy) platinum-based chemoradiation followed by consolidation durvalumab immunotherapy (for patients without progression). Planning and delivery of locally advanced lung cancer radiotherapy usually should be performed using intensity-modulated radiotherapy techniques. A variety of palliative and radical fractionation schedules are available to treat patients with poor performance and/or pulmonary status. The salvage therapy for a local recurrence after successful primary management is complex and likely requires both multidisciplinary input and shared decision-making with the patient.Conclusions and RelevanceEvidence-based guidance on the management of various unresectable LA-NSCLC scenarios is provided by the ARS AUC to optimize multidisciplinary patient care for this challenging patient population.
{"title":"American Radium Society Appropriate Use Criteria for Unresectable Locally Advanced Non–Small Cell Lung Cancer","authors":"George Rodrigues, Kristin A. Higgins, Andreas Rimner, Arya Amini, Joe Y. Chang, Stephen G. Chun, Jessica Donington, Martin J. Edelman, Matthew A. Gubens, Puneeth Iyengar, Benjamin Movsas, Matthew S. Ning, Henry S. Park, Andrea Wolf, Charles B. Simone","doi":"10.1001/jamaoncol.2024.0294","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.0294","url":null,"abstract":"ImportanceThe treatment of locally advanced non–small cell lung cancer (LA-NSCLC) has been informed by more than 5 decades of clinical trials and other relevant literature. However, controversies remain regarding the application of various radiation and systemic therapies in commonly encountered clinical scenarios.ObjectiveTo develop case-referenced consensus and evidence-based guidelines to inform clinical practice in unresectable LA-NSCLC.Evidence ReviewThe American Radium Society (ARS) Appropriate Use Criteria (AUC) Thoracic Committee guideline is an evidence-based consensus document assessing various clinical scenarios associated with LA-NSCLC. A systematic review of the literature with evidence ratings was conducted to inform the appropriateness of treatment recommendations by the ARS AUC Thoracic Committee for the management of unresectable LA-NSCLC.FindingsTreatment appropriateness of a variety of LA-NSCLC scenarios was assessed by a consensus-based modified Delphi approach using a range of 3 points to 9 points to denote consensus agreement. Committee recommendations were vetted by the ARS AUC Executive Committee and a 2-week public comment period before official approval and adoption. Standard of care management of good prognosis LA-NSCLC consists of combined concurrent radical (60-70 Gy) platinum-based chemoradiation followed by consolidation durvalumab immunotherapy (for patients without progression). Planning and delivery of locally advanced lung cancer radiotherapy usually should be performed using intensity-modulated radiotherapy techniques. A variety of palliative and radical fractionation schedules are available to treat patients with poor performance and/or pulmonary status. The salvage therapy for a local recurrence after successful primary management is complex and likely requires both multidisciplinary input and shared decision-making with the patient.Conclusions and RelevanceEvidence-based guidance on the management of various unresectable LA-NSCLC scenarios is provided by the ARS AUC to optimize multidisciplinary patient care for this challenging patient population.","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"72 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2024-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140547841","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}
Pub Date : 2024-04-05DOI: 10.1001/jamaoncol.2024.0734
Tamás Fazekas, Sung Ryul Shim, Giuseppe Basile, Michael Baboudjian, Tamás Kói, Mikolaj Przydacz, Mohammad Abufaraj, Guillaume Ploussard, Veeru Kasivisvanathan, Juan Gómez Rivas, Giorgio Gandaglia, Tibor Szarvas, Ivo G. Schoots, Roderick C. N. van den Bergh, Michael S. Leapman, Péter Nyirády, Shahrokh F. Shariat, Pawel Rajwa
ImportanceProstate magnetic resonance imaging (MRI) is increasingly integrated within the prostate cancer (PCa) early detection pathway.ObjectiveTo systematically evaluate the existing evidence regarding screening pathways incorporating MRI with targeted biopsy and assess their diagnostic value compared with prostate-specific antigen (PSA)–based screening with systematic biopsy strategies.Data SourcesPubMed/MEDLINE, Embase, Cochrane/Central, Scopus, and Web of Science (through May 2023).Study SelectionRandomized clinical trials and prospective cohort studies were eligible if they reported data on the diagnostic utility of prostate MRI in the setting of PCa screening.Data ExtractionNumber of screened individuals, biopsy indications, biopsies performed, clinically significant PCa (csPCa) defined as International Society of Urological Pathology (ISUP) grade 2 or higher, and insignificant (ISUP1) PCas detected were extracted.Main Outcomes and MeasuresThe primary outcome was csPCa detection rate. Secondary outcomes included clinical insignificant PCa detection rate, biopsy indication rates, and the positive predictive value for the detection of csPCa.Data SynthesisThe generalized mixed-effect approach with pooled odds ratios (ORs) and random-effect models was used to compare the MRI-based and PSA-only screening strategies. Separate analyses were performed based on the timing of MRI (primary/sequential after a PSA test) and cutoff (Prostate Imaging Reporting and Data System [PI-RADS] score ≥3 or ≥4) for biopsy indication.ResultsData were synthesized from 80 114 men from 12 studies. Compared with standard PSA-based screening, the MRI pathway (sequential screening, PI-RADS score ≥3 cutoff for biopsy) was associated with higher odds of csPCa when tests results were positive (OR, 4.15; 95% CI, 2.93-5.88; P ≤ .001), decreased odds of biopsies (OR, 0.28; 95% CI, 0.22-0.36; P ≤ .001), and insignificant cancers detected (OR, 0.34; 95% CI, 0.23-0.49; P = .002) without significant differences in the detection of csPCa (OR, 1.02; 95% CI, 0.75-1.37; P = .86). Implementing a PI-RADS score of 4 or greater threshold for biopsy selection was associated with a further reduction in the odds of detecting insignificant PCa (OR, 0.23; 95% CI, 0.05-0.97; P = .048) and biopsies performed (OR, 0.19; 95% CI, 0.09-0.38; P = .01) without differences in csPCa detection (OR, 0.85; 95% CI, 0.49-1.45; P = .22).Conclusion and relevanceThe results of this systematic review and meta-analysis suggest that integrating MRI in PCa screening pathways is associated with a reduced number of unnecessary biopsies and overdiagnosis of insignificant PCa while maintaining csPCa detection as compared with PSA-only screening.
{"title":"Magnetic Resonance Imaging in Prostate Cancer Screening","authors":"Tamás Fazekas, Sung Ryul Shim, Giuseppe Basile, Michael Baboudjian, Tamás Kói, Mikolaj Przydacz, Mohammad Abufaraj, Guillaume Ploussard, Veeru Kasivisvanathan, Juan Gómez Rivas, Giorgio Gandaglia, Tibor Szarvas, Ivo G. Schoots, Roderick C. N. van den Bergh, Michael S. Leapman, Péter Nyirády, Shahrokh F. Shariat, Pawel Rajwa","doi":"10.1001/jamaoncol.2024.0734","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.0734","url":null,"abstract":"ImportanceProstate magnetic resonance imaging (MRI) is increasingly integrated within the prostate cancer (PCa) early detection pathway.ObjectiveTo systematically evaluate the existing evidence regarding screening pathways incorporating MRI with targeted biopsy and assess their diagnostic value compared with prostate-specific antigen (PSA)–based screening with systematic biopsy strategies.Data SourcesPubMed/MEDLINE, Embase, Cochrane/Central, Scopus, and Web of Science (through May 2023).Study SelectionRandomized clinical trials and prospective cohort studies were eligible if they reported data on the diagnostic utility of prostate MRI in the setting of PCa screening.Data ExtractionNumber of screened individuals, biopsy indications, biopsies performed, clinically significant PCa (csPCa) defined as International Society of Urological Pathology (ISUP) grade 2 or higher, and insignificant (ISUP1) PCas detected were extracted.Main Outcomes and MeasuresThe primary outcome was csPCa detection rate. Secondary outcomes included clinical insignificant PCa detection rate, biopsy indication rates, and the positive predictive value for the detection of csPCa.Data SynthesisThe generalized mixed-effect approach with pooled odds ratios (ORs) and random-effect models was used to compare the MRI-based and PSA-only screening strategies. Separate analyses were performed based on the timing of MRI (primary/sequential after a PSA test) and cutoff (Prostate Imaging Reporting and Data System [PI-RADS] score ≥3 or ≥4) for biopsy indication.ResultsData were synthesized from 80 114 men from 12 studies. Compared with standard PSA-based screening, the MRI pathway (sequential screening, PI-RADS score ≥3 cutoff for biopsy) was associated with higher odds of csPCa when tests results were positive (OR, 4.15; 95% CI, 2.93-5.88; <jats:italic>P</jats:italic> ≤ .001), decreased odds of biopsies (OR, 0.28; 95% CI, 0.22-0.36; <jats:italic>P</jats:italic> ≤ .001), and insignificant cancers detected (OR, 0.34; 95% CI, 0.23-0.49; <jats:italic>P</jats:italic> = .002) without significant differences in the detection of csPCa (OR, 1.02; 95% CI, 0.75-1.37; <jats:italic>P</jats:italic> = .86). Implementing a PI-RADS score of 4 or greater threshold for biopsy selection was associated with a further reduction in the odds of detecting insignificant PCa (OR, 0.23; 95% CI, 0.05-0.97; <jats:italic>P</jats:italic> = .048) and biopsies performed (OR, 0.19; 95% CI, 0.09-0.38; <jats:italic>P</jats:italic> = .01) without differences in csPCa detection (OR, 0.85; 95% CI, 0.49-1.45; <jats:italic>P</jats:italic> = .22).Conclusion and relevanceThe results of this systematic review and meta-analysis suggest that integrating MRI in PCa screening pathways is associated with a reduced number of unnecessary biopsies and overdiagnosis of insignificant PCa while maintaining csPCa detection as compared with PSA-only screening.","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"127 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140352317","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}
Pub Date : 2024-04-04DOI: 10.1001/jamaoncol.2024.0191
Anna Jo Bodurtha Smith, Elizabeth A. Howell, Emily M. Ko
This Viewpoint highlights the need for recognition that ovarian cancer affects women from racial and ethnic minority groups worldwide and that the rates of ovarian cancer are increasing in those populations while decreasing among White women.
{"title":"Ovarian Cancer Isn’t Just a White Woman’s Disease","authors":"Anna Jo Bodurtha Smith, Elizabeth A. Howell, Emily M. Ko","doi":"10.1001/jamaoncol.2024.0191","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.0191","url":null,"abstract":"This Viewpoint highlights the need for recognition that ovarian cancer affects women from racial and ethnic minority groups worldwide and that the rates of ovarian cancer are increasing in those populations while decreasing among White women.","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"257 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140349207","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}
Pub Date : 2024-04-04DOI: 10.1001/jamaoncol.2024.0194
Ariadna Tibau, Thomas J. Hwang, Consolacion Molto, Jerry Avorn, Aaron S. Kesselheim
ImportanceThe number of new genome-targeted cancer drugs has increased, offering the possibility of personalized therapy, often at a very high cost.ObjectiveTo assess the validity of molecular targets and therapeutic benefits of US Food and Drug Administration–approved genome-targeted cancer drugs based on the outcomes of their corresponding pivotal clinical trials.Design and SettingsIn this cohort study, all genome-targeted cancer drugs that were FDA-approved between January 1, 2015, and December 31, 2022, were analyzed. From FDA drug labels and trial reports, key characteristics of pivotal trials were extracted, including the outcomes assessed.Main Outcomes and MeasuresThe strength of evidence supporting molecular targetability was assessed using the European Society for Medical Oncology (ESMO) Scale for Clinical Actionability of Molecular Targets (ESCAT). Clinical benefit for their approved indications was evaluated using the ESMO–Magnitude of Clinical Benefit Scale (ESMO-MCBS). Substantial clinical benefit was defined as a grade of A or B for curative intent and 4 or 5 for noncurative intent. Molecular targets qualifying for ESCAT category level I-A and I-B associated with substantial clinical benefit by ESMO-MCBS were rated as high-benefit genomic-based cancer treatments.ResultsA total of 50 molecular-targeted drugs covering 84 indications were analyzed. Forty-five indications (54%) were approved based on phase 1 or phase 2 pivotal trials, 45 (54%) were supported by single-arm pivotal trials, and 48 (57%) were approved on the basis of subgroup analyses. By each indication, 46 of 84 primary end points (55%) were overall response rate (median [IQR] overall response rate, 57% [40%-69%]; median [IQR] duration of response, 11.1 [9.2-19.8] months). Among the 84 pivotal trials supporting these 84 indications, 38 trials (45%) had I-A ESCAT targetability, and 32 (38%) had I-B targetability. Overall, 24 of 84 trials (29%) demonstrated substantial clinical benefit via ESMO-MCBS. Combining these ratings, 24 of 84 indications (29%) were associated with high-benefit genomic-based cancer treatments.Conclusions and RelevanceThe results of this cohort study demonstrate that among recently approved molecular-targeted cancer therapies, fewer than one-third demonstrated substantial patient benefits at approval. Benefit frameworks such as ESMO-MCBS and ESCAT can help physicians, patients, and payers identify therapies with the greatest clinical potential.
{"title":"Clinical Value of Molecular Targets and FDA-Approved Genome-Targeted Cancer Therapies","authors":"Ariadna Tibau, Thomas J. Hwang, Consolacion Molto, Jerry Avorn, Aaron S. Kesselheim","doi":"10.1001/jamaoncol.2024.0194","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.0194","url":null,"abstract":"ImportanceThe number of new genome-targeted cancer drugs has increased, offering the possibility of personalized therapy, often at a very high cost.ObjectiveTo assess the validity of molecular targets and therapeutic benefits of US Food and Drug Administration–approved genome-targeted cancer drugs based on the outcomes of their corresponding pivotal clinical trials.Design and SettingsIn this cohort study, all genome-targeted cancer drugs that were FDA-approved between January 1, 2015, and December 31, 2022, were analyzed. From FDA drug labels and trial reports, key characteristics of pivotal trials were extracted, including the outcomes assessed.Main Outcomes and MeasuresThe strength of evidence supporting molecular targetability was assessed using the European Society for Medical Oncology (ESMO) Scale for Clinical Actionability of Molecular Targets (ESCAT). Clinical benefit for their approved indications was evaluated using the ESMO–Magnitude of Clinical Benefit Scale (ESMO-MCBS). Substantial clinical benefit was defined as a grade of A or B for curative intent and 4 or 5 for noncurative intent. Molecular targets qualifying for ESCAT category level I-A and I-B associated with substantial clinical benefit by ESMO-MCBS were rated as high-benefit genomic-based cancer treatments.ResultsA total of 50 molecular-targeted drugs covering 84 indications were analyzed. Forty-five indications (54%) were approved based on phase 1 or phase 2 pivotal trials, 45 (54%) were supported by single-arm pivotal trials, and 48 (57%) were approved on the basis of subgroup analyses. By each indication, 46 of 84 primary end points (55%) were overall response rate (median [IQR] overall response rate, 57% [40%-69%]; median [IQR] duration of response, 11.1 [9.2-19.8] months). Among the 84 pivotal trials supporting these 84 indications, 38 trials (45%) had I-A ESCAT targetability, and 32 (38%) had I-B targetability. Overall, 24 of 84 trials (29%) demonstrated substantial clinical benefit via ESMO-MCBS. Combining these ratings, 24 of 84 indications (29%) were associated with high-benefit genomic-based cancer treatments.Conclusions and RelevanceThe results of this cohort study demonstrate that among recently approved molecular-targeted cancer therapies, fewer than one-third demonstrated substantial patient benefits at approval. Benefit frameworks such as ESMO-MCBS and ESCAT can help physicians, patients, and payers identify therapies with the greatest clinical potential.","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"28 15 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140349235","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}
Pub Date : 2022-10-13DOI: 10.1001/jamaoncol.2022.4445
Michael Webster-Clark, Alexander P Keil, Nicholas Robert, Jennifer R Frytak, Marley Boyd, Til Stürmer, Hanna Sanoff, Daniel Westreich, Jennifer L Lund
Importance: Delivery of adjuvant chemotherapy can differ substantially between trial and real-world populations. Adherence metrics like relative dose intensity (RDI) cannot capture the timing of modifications and mask differences in the total amount of chemotherapy received.
Objective: To compare oxaliplatin delivery between MOSAIC trial participants and patients treated in the US Oncology Network with stage III colon cancer using a longitudinal cumulative dose (LCD).
Design, setting, and participants: This cohort study used secondary data from the MOSAIC trial, an international randomized clinical trial (concluded in 2004), and electronic health records from US Oncology (2009-2018), a network of community oncology practices in the US. It included participants in MOSAIC with stage III colon cancer who were randomized to receive treatment with oxaliplatin and fluorouracil/leucovorin (n = 663) and US Oncology patients with stage III colon cancer who were treated with a modified FOLFOX-6 regimen (n = 2523).
Exposures: Oxaliplatin and fluorouracil/leucovorin.
Outcomes and measures: We evaluated RDI and LCD over time and at the end of treatment in the MOSAIC and US Oncology populations. We used bootstrapping to estimate 95% confidence bands for LCD differences between the populations.
Results: The 663 MOSAIC participants (296 women [44.7%]) and 2523 US Oncology patients (1245 women [49.4%]) were generally similar with respect to demographic characteristics. Median RDI was lower in US Oncology (80% in MOSAIC vs 70% in US Oncology). The LCD also suggested differences in the total amount of oxaliplatin received between populations; the final median LCD in US Oncology was 10.2% lower than in MOSAIC, equivalent to receiving 1.2 fewer treatment cycles less of oxaliplatin. This difference only began 133 days into treatment and persisted after accounting for covariates, likely in terms of more frequent oxaliplatin treatment discontinuation in US Oncology patients than their MOSAIC counterparts.
Conclusions and relevance: The study results suggest that real-world patients in community practice in the US treated with modified FOLFOX 6 received less oxaliplatin than their historical counterparts in the MOSAIC trial, with differences manifesting late in the treatment course. The LCD allowed us to identify the amount and extent of these differences, the timing of which was unclear when using RDI alone.
{"title":"Comparing Trial and Real-world Adjuvant Oxaliplatin Delivery in Patients With Stage III Colon Cancer Using a Longitudinal Cumulative Dose.","authors":"Michael Webster-Clark, Alexander P Keil, Nicholas Robert, Jennifer R Frytak, Marley Boyd, Til Stürmer, Hanna Sanoff, Daniel Westreich, Jennifer L Lund","doi":"10.1001/jamaoncol.2022.4445","DOIUrl":"10.1001/jamaoncol.2022.4445","url":null,"abstract":"<p><strong>Importance: </strong>Delivery of adjuvant chemotherapy can differ substantially between trial and real-world populations. Adherence metrics like relative dose intensity (RDI) cannot capture the timing of modifications and mask differences in the total amount of chemotherapy received.</p><p><strong>Objective: </strong>To compare oxaliplatin delivery between MOSAIC trial participants and patients treated in the US Oncology Network with stage III colon cancer using a longitudinal cumulative dose (LCD).</p><p><strong>Design, setting, and participants: </strong>This cohort study used secondary data from the MOSAIC trial, an international randomized clinical trial (concluded in 2004), and electronic health records from US Oncology (2009-2018), a network of community oncology practices in the US. It included participants in MOSAIC with stage III colon cancer who were randomized to receive treatment with oxaliplatin and fluorouracil/leucovorin (n = 663) and US Oncology patients with stage III colon cancer who were treated with a modified FOLFOX-6 regimen (n = 2523).</p><p><strong>Exposures: </strong>Oxaliplatin and fluorouracil/leucovorin.</p><p><strong>Outcomes and measures: </strong>We evaluated RDI and LCD over time and at the end of treatment in the MOSAIC and US Oncology populations. We used bootstrapping to estimate 95% confidence bands for LCD differences between the populations.</p><p><strong>Results: </strong>The 663 MOSAIC participants (296 women [44.7%]) and 2523 US Oncology patients (1245 women [49.4%]) were generally similar with respect to demographic characteristics. Median RDI was lower in US Oncology (80% in MOSAIC vs 70% in US Oncology). The LCD also suggested differences in the total amount of oxaliplatin received between populations; the final median LCD in US Oncology was 10.2% lower than in MOSAIC, equivalent to receiving 1.2 fewer treatment cycles less of oxaliplatin. This difference only began 133 days into treatment and persisted after accounting for covariates, likely in terms of more frequent oxaliplatin treatment discontinuation in US Oncology patients than their MOSAIC counterparts.</p><p><strong>Conclusions and relevance: </strong>The study results suggest that real-world patients in community practice in the US treated with modified FOLFOX 6 received less oxaliplatin than their historical counterparts in the MOSAIC trial, with differences manifesting late in the treatment course. The LCD allowed us to identify the amount and extent of these differences, the timing of which was unclear when using RDI alone.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov identifier: NCT00275210.</p>","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":" ","pages":""},"PeriodicalIF":28.4,"publicationDate":"2022-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9562097/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33504962","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}
Pub Date : 2022-10-13DOI: 10.1001/jamaoncol.2022.4792
Lars Björnebo, Martin Eklund, Anna Lantz
{"title":"Association of 5α-Reductase Inhibitor Use With Prostate Cancer-Specific Mortality-Reply.","authors":"Lars Björnebo, Martin Eklund, Anna Lantz","doi":"10.1001/jamaoncol.2022.4792","DOIUrl":"10.1001/jamaoncol.2022.4792","url":null,"abstract":"","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":" ","pages":""},"PeriodicalIF":28.4,"publicationDate":"2022-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33504845","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}
Pub Date : 2022-10-13DOI: 10.1001/jamaoncol.2022.4442
Stefania Canova, Stefano Arcangeli, Diego Luigi Cortinovis
{"title":"A Cast of Shadow on Postoperative Radiotherapy for pIIIA-N2 Non-Small Cell Lung Cancer?","authors":"Stefania Canova, Stefano Arcangeli, Diego Luigi Cortinovis","doi":"10.1001/jamaoncol.2022.4442","DOIUrl":"10.1001/jamaoncol.2022.4442","url":null,"abstract":"","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":" ","pages":""},"PeriodicalIF":28.4,"publicationDate":"2022-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33505407","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}
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