BACKGROUNDSurgery with both neoadjuvant and adjuvant chemotherapy represents the standard of care for extremity osteosarcoma despite a lack of high-quality evidence for its use, and trial evidence that suggests that up-front surgery may result in better outcomes. This study estimated the difference in overall survival for the standard of care ("Neoadjuvant First") vs upfront surgery first followed by adjuvant chemotherapy ("Surgery First").PATIENTS AND METHODSUsing Surveillance, Epidemiology, and End Results data, we identified patients age 5-29, diagnosed with a primary cancer of upper or lower extremity osteosarcoma between 2007 and 2019 who received surgery and chemotherapy. Our primary endpoint was the 5-year survival difference between the Surgery First and Neoadjuvant First groups.RESULTSAdjusted 5-year survival was 74% for Surgery First patients and 67% for Neoadjuvant First patients, with a survival difference of 6.9% (95% CI -4.2% - 16.1%). In sensitivity analyses of 5-year survival, the results were consistent, showing a 6.8% to 13.7% higher 5-year survival in Surgery First patients. Significant mortality risk factors included older age, larger tumor size, the type of resection (salvage vs amputation), and stage 3-4 disease (vs stage 1-2 disease).CONCLUSIONThe evidence supporting neoadjuvant therapy in osteosarcoma care is weak. However, there is evidence that pausing chemotherapy in the peri-surgical period might affect outcomes. Consequently, this study, and its consistency with the results from the only randomized trial, suggests that there is reason to revisit a prospective, randomized trial of osteosarcoma treatment regarding the timing of surgery and chemotherapy.
{"title":"Effect of Chemotherapy and Surgery Timing on Mortality in Upper and Lower Extremity Osteosarcoma.","authors":"Mark D Danese,John S Groundland","doi":"10.1093/jnci/djae229","DOIUrl":"https://doi.org/10.1093/jnci/djae229","url":null,"abstract":"BACKGROUNDSurgery with both neoadjuvant and adjuvant chemotherapy represents the standard of care for extremity osteosarcoma despite a lack of high-quality evidence for its use, and trial evidence that suggests that up-front surgery may result in better outcomes. This study estimated the difference in overall survival for the standard of care (\"Neoadjuvant First\") vs upfront surgery first followed by adjuvant chemotherapy (\"Surgery First\").PATIENTS AND METHODSUsing Surveillance, Epidemiology, and End Results data, we identified patients age 5-29, diagnosed with a primary cancer of upper or lower extremity osteosarcoma between 2007 and 2019 who received surgery and chemotherapy. Our primary endpoint was the 5-year survival difference between the Surgery First and Neoadjuvant First groups.RESULTSAdjusted 5-year survival was 74% for Surgery First patients and 67% for Neoadjuvant First patients, with a survival difference of 6.9% (95% CI -4.2% - 16.1%). In sensitivity analyses of 5-year survival, the results were consistent, showing a 6.8% to 13.7% higher 5-year survival in Surgery First patients. Significant mortality risk factors included older age, larger tumor size, the type of resection (salvage vs amputation), and stage 3-4 disease (vs stage 1-2 disease).CONCLUSIONThe evidence supporting neoadjuvant therapy in osteosarcoma care is weak. However, there is evidence that pausing chemotherapy in the peri-surgical period might affect outcomes. Consequently, this study, and its consistency with the results from the only randomized trial, suggests that there is reason to revisit a prospective, randomized trial of osteosarcoma treatment regarding the timing of surgery and chemotherapy.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"22 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142273389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background Although use of comprehensive genomic profiling (CGP) was approved by a novel CMS/FDA parallel review process, the quality of the supporting evidence is unclear. We evaluated the rigor of the peer-reviewed literature cited in the National Coverage Determination Memorandum for the FoundationOne CDx (F1CDx). Methods We identified studies cited in the memorandum. Two independent researchers evaluated each study and applied a modified version of the Fryback and Thornbury hierarchy[1], an established framework for evaluating the efficacy of diagnostic tests. Studies focused on clinical outcomes were then categorized by study design, guided by recommendations from the Center for Medical Technology Policy. Results The sample included 113 scientific studies. The majority (n = 60, 53.1%) used CGP outside the course of clinical care, and there was significant heterogeneity in the cancer types assessed and sequencing depth. We found 8 (7.1%) studies that assessed whether clinical care had changed due to CGP testing, and 38 (33.6%) assessed clinical outcomes. After excluding studies that tested for five or fewer genomic alterations, 25 remained in the clinical outcomes sample: Of these, only one included a comparator group that did not receive CGP testing. Only four studies used F1CDx as the primary genomic test, none of which compared the outcomes of patients who did vs did not receive the F1CDx test. Conclusions The findings indicate gaps in the supporting evidence for broad CGP use in patients with solid tumors. More rigorous studies that assess clinical utility would better inform the approval process for novel diagnostic tests.
{"title":"Strength of Evidence Underlying the CMS-FDA Parallel Review of Comprehensive Genomic Profiling Tests in the Cancer Setting","authors":"Sydnie Stackland, Dominic Schnabel, Michaela Dinan, Carolyn J Presley, Cary P Gross","doi":"10.1093/jnci/djae196","DOIUrl":"https://doi.org/10.1093/jnci/djae196","url":null,"abstract":"Background Although use of comprehensive genomic profiling (CGP) was approved by a novel CMS/FDA parallel review process, the quality of the supporting evidence is unclear. We evaluated the rigor of the peer-reviewed literature cited in the National Coverage Determination Memorandum for the FoundationOne CDx (F1CDx). Methods We identified studies cited in the memorandum. Two independent researchers evaluated each study and applied a modified version of the Fryback and Thornbury hierarchy[1], an established framework for evaluating the efficacy of diagnostic tests. Studies focused on clinical outcomes were then categorized by study design, guided by recommendations from the Center for Medical Technology Policy. Results The sample included 113 scientific studies. The majority (n = 60, 53.1%) used CGP outside the course of clinical care, and there was significant heterogeneity in the cancer types assessed and sequencing depth. We found 8 (7.1%) studies that assessed whether clinical care had changed due to CGP testing, and 38 (33.6%) assessed clinical outcomes. After excluding studies that tested for five or fewer genomic alterations, 25 remained in the clinical outcomes sample: Of these, only one included a comparator group that did not receive CGP testing. Only four studies used F1CDx as the primary genomic test, none of which compared the outcomes of patients who did vs did not receive the F1CDx test. Conclusions The findings indicate gaps in the supporting evidence for broad CGP use in patients with solid tumors. More rigorous studies that assess clinical utility would better inform the approval process for novel diagnostic tests.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"46 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142236872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Amit G Singal, Darine Daher, Manasa Narasimman, Sruthi Yekkaluri MHI, Yan Liu, Vanessa Cerda, Chaitra Banala, Aisha Khan, MinJae Lee, Karim Seif El Dahan, Caitlin C Murphy, Jennifer R Kramer, Ruben Hernaez
Background The value of hepatocellular carcinoma (HCC) screening is defined by the balance of benefits from early tumor detection vs harms due to false positive results. We evaluated the value of a mailed outreach strategy for HCC screening in patients with cirrhosis. Methods We conducted a multi-center pragmatic randomized clinical trial comparing mailed outreach for HCC screening (n = 1436) and usual care with visit-based screening (n = 1436) among patients with cirrhosis at three health systems from March 2018 to September 2021. Outcomes of interest were early-stage HCC detection (ie, screening benefit) and diagnostic evaluation for false positive or indeterminate results (ie, screening harm). Screening harm was categorized as mild, moderate, and severe based on number and type of diagnostic exams. All patients were included in intention-to-screen analyses. Results Of 125 patients diagnosed with HCC (67 outreach and 58 usual care), 71.2% were found at an early stage per the Milan Criteria. Early tumor detection did not significantly differ between the outreach and usual care arms (64.2% vs 79.3%, p = .06). The proportion of patients with physical harms also did not differ between the outreach and usual care arms (10.8% vs 10.7%, p = .95) with 5.9% in both arms having mild harms, 4.0% and 3.8% respectively with moderate harms, and 0.9% and 1.0% respectively with severe harms. Conclusion Most patients enrolled in HCC screening were detected at an early stage, and a minority experienced physical harms. A mailed outreach strategy did not significantly increase early HCC detection or physical harms compared to usual care. Clinical Trials number NCT02582918 and NCT03756051
{"title":"Benefits and Harms of Hepatocellular Carcinoma Screening Outreach in Patients with Cirrhosis: A Multi-Center Randomized Clinical Trial","authors":"Amit G Singal, Darine Daher, Manasa Narasimman, Sruthi Yekkaluri MHI, Yan Liu, Vanessa Cerda, Chaitra Banala, Aisha Khan, MinJae Lee, Karim Seif El Dahan, Caitlin C Murphy, Jennifer R Kramer, Ruben Hernaez","doi":"10.1093/jnci/djae228","DOIUrl":"https://doi.org/10.1093/jnci/djae228","url":null,"abstract":"Background The value of hepatocellular carcinoma (HCC) screening is defined by the balance of benefits from early tumor detection vs harms due to false positive results. We evaluated the value of a mailed outreach strategy for HCC screening in patients with cirrhosis. Methods We conducted a multi-center pragmatic randomized clinical trial comparing mailed outreach for HCC screening (n = 1436) and usual care with visit-based screening (n = 1436) among patients with cirrhosis at three health systems from March 2018 to September 2021. Outcomes of interest were early-stage HCC detection (ie, screening benefit) and diagnostic evaluation for false positive or indeterminate results (ie, screening harm). Screening harm was categorized as mild, moderate, and severe based on number and type of diagnostic exams. All patients were included in intention-to-screen analyses. Results Of 125 patients diagnosed with HCC (67 outreach and 58 usual care), 71.2% were found at an early stage per the Milan Criteria. Early tumor detection did not significantly differ between the outreach and usual care arms (64.2% vs 79.3%, p = .06). The proportion of patients with physical harms also did not differ between the outreach and usual care arms (10.8% vs 10.7%, p = .95) with 5.9% in both arms having mild harms, 4.0% and 3.8% respectively with moderate harms, and 0.9% and 1.0% respectively with severe harms. Conclusion Most patients enrolled in HCC screening were detected at an early stage, and a minority experienced physical harms. A mailed outreach strategy did not significantly increase early HCC detection or physical harms compared to usual care. Clinical Trials number NCT02582918 and NCT03756051","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142236859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jingxuan Zhao, Sandhya Kajeepeta, Christopher R Manz, Xuesong Han, Leticia M Nogueira, Zhiyuan Zheng, Qinjin Fan, Kewei Sylvia Shi, Fumiko Chino, K Robin Yabroff
This study examined the association of county-level jail and state-level prison incarceration rates and cancer mortality rates in the United States. Incarceration rates (1995-2018) were sourced from national data and categorized into quartiles. County- and state-level mortality rates (2000-2019) with invasive cancer as the underlying cause of death were obtained from the National Vital Statistics System. Compared with the first quartile (lowest incarceration rate), the second, third, and fourth quartiles (highest incarceration rate) of county-level jail incarceration rate were associated with 1.3%, 2.3%, and 3.9% higher county-level cancer mortality rates, respectively, in adjusted analyses. Compared with the first quartile, the second, third, and fourth quartiles of state-level prison incarceration rate were associated with 1.7%, 2.5%, and 3.9% higher state-level cancer mortality rates, respectively. Associations were more pronounced for liver and lung cancers. Addressing adverse effects of mass incarceration may potentially improve cancer outcomes in affected communities.
{"title":"County-level jail and state-level prison incarceration and cancer mortality in the United States","authors":"Jingxuan Zhao, Sandhya Kajeepeta, Christopher R Manz, Xuesong Han, Leticia M Nogueira, Zhiyuan Zheng, Qinjin Fan, Kewei Sylvia Shi, Fumiko Chino, K Robin Yabroff","doi":"10.1093/jnci/djae189","DOIUrl":"https://doi.org/10.1093/jnci/djae189","url":null,"abstract":"This study examined the association of county-level jail and state-level prison incarceration rates and cancer mortality rates in the United States. Incarceration rates (1995-2018) were sourced from national data and categorized into quartiles. County- and state-level mortality rates (2000-2019) with invasive cancer as the underlying cause of death were obtained from the National Vital Statistics System. Compared with the first quartile (lowest incarceration rate), the second, third, and fourth quartiles (highest incarceration rate) of county-level jail incarceration rate were associated with 1.3%, 2.3%, and 3.9% higher county-level cancer mortality rates, respectively, in adjusted analyses. Compared with the first quartile, the second, third, and fourth quartiles of state-level prison incarceration rate were associated with 1.7%, 2.5%, and 3.9% higher state-level cancer mortality rates, respectively. Associations were more pronounced for liver and lung cancers. Addressing adverse effects of mass incarceration may potentially improve cancer outcomes in affected communities.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"33 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142236836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Irene A Caspers, Astrid E Slagter, Pauline A J Vissers, Martha Lopez-Yurda, Laurens V Beerepoot, Jelle P Ruurda, Grard A P Nieuwenhuijzen, Suzanne S Gisbertz, Mark I Van Berge Henegouwen, Henk H Hartgrink, Danny Goudkade, Liudmila L Kodach, Johanna W Van Sandick, Marcel Verheij, Rob H A Verhoeven, Annemieke Cats, Nicole C T Van Grieken
Background Data on the clinicopathological characteristics of mucinous gastric cancer (muc-GC) are limited. This study compares the clinical outcome and response to chemotherapy between patients with resectable muc-GC, intestinal (int-GC) and diffuse (dif-GC) gastric cancer. Methods Patients from the D1/D2 study or the CRITICS trial were included in exploratory surgery-alone (SAtest) or chemotherapy test (CTtest) cohorts. Real-world data from the Netherlands Cancer Registry on patients treated between with surgery-alone (SAvalidation), and receiving preoperative chemotherapy with or without postoperative treatment (CTvalidation) were used for validation. Histopathological subtypes were extracted from pathology reports filed in the Dutch Pathology Registry and correlated with tumor regression grade (TRG) and relative survival (RS). Results In SAtest (n = 549) and SAvalidation (n = 8062) cohorts, muc-GC patients had a five-year RS of 39% and 31%, similar to or slightly better than dif-GC (43% and 29%, p = .52 and p = .011), but worse than int-GC (55% and 42%, p = .11 and p < .001). In CTtest (n = 651) and CTvalidation (n = 2889) cohorts, muc-GC showed favorable TRG (38% and 44% (near-)complete response) compared to int-GC (26% and 35%) and dif-GC (10% and 28%, p < .001 and p = .005). The 5-year RS in CTtest and CTvalidation cohorts for muc-GC (53% and 48%) and int-GC (58% and 59%) was significantly better compared to dif-GC (35% and 38%, p = .004 and p < .001). Conclusion Recognizing and incorporating muc-GC into treatment decision-making of resectable GC can lead to more personalized and effective approaches, given its favorable response to preoperative chemotherapy in relation to int-GC and dif-GC and its favorable prognostic outcomes in relation to dif-GC.
{"title":"Histopathological response to chemotherapy and survival of mucinous type gastric cancer","authors":"Irene A Caspers, Astrid E Slagter, Pauline A J Vissers, Martha Lopez-Yurda, Laurens V Beerepoot, Jelle P Ruurda, Grard A P Nieuwenhuijzen, Suzanne S Gisbertz, Mark I Van Berge Henegouwen, Henk H Hartgrink, Danny Goudkade, Liudmila L Kodach, Johanna W Van Sandick, Marcel Verheij, Rob H A Verhoeven, Annemieke Cats, Nicole C T Van Grieken","doi":"10.1093/jnci/djae227","DOIUrl":"https://doi.org/10.1093/jnci/djae227","url":null,"abstract":"Background Data on the clinicopathological characteristics of mucinous gastric cancer (muc-GC) are limited. This study compares the clinical outcome and response to chemotherapy between patients with resectable muc-GC, intestinal (int-GC) and diffuse (dif-GC) gastric cancer. Methods Patients from the D1/D2 study or the CRITICS trial were included in exploratory surgery-alone (SAtest) or chemotherapy test (CTtest) cohorts. Real-world data from the Netherlands Cancer Registry on patients treated between with surgery-alone (SAvalidation), and receiving preoperative chemotherapy with or without postoperative treatment (CTvalidation) were used for validation. Histopathological subtypes were extracted from pathology reports filed in the Dutch Pathology Registry and correlated with tumor regression grade (TRG) and relative survival (RS). Results In SAtest (n = 549) and SAvalidation (n = 8062) cohorts, muc-GC patients had a five-year RS of 39% and 31%, similar to or slightly better than dif-GC (43% and 29%, p = .52 and p = .011), but worse than int-GC (55% and 42%, p = .11 and p &lt; .001). In CTtest (n = 651) and CTvalidation (n = 2889) cohorts, muc-GC showed favorable TRG (38% and 44% (near-)complete response) compared to int-GC (26% and 35%) and dif-GC (10% and 28%, p &lt; .001 and p = .005). The 5-year RS in CTtest and CTvalidation cohorts for muc-GC (53% and 48%) and int-GC (58% and 59%) was significantly better compared to dif-GC (35% and 38%, p = .004 and p &lt; .001). Conclusion Recognizing and incorporating muc-GC into treatment decision-making of resectable GC can lead to more personalized and effective approaches, given its favorable response to preoperative chemotherapy in relation to int-GC and dif-GC and its favorable prognostic outcomes in relation to dif-GC.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142233454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background Allostatic load (AL) reflects the cumulative burden of chronic stress throughout life, potentially influencing the onset and prognosis of cancer. However, the associations between AL, colorectal cancer (CRC) risk and all-cause mortality in patients with CRC remain unclear. Methods We analyzed the association between AL and CRC risk in 304,959 adults and all-cause mortality in 1,794 patients with CRC from the UK Biobank, using Cox proportional hazards regression models. Results Compared to the AL level in the first quartile, individuals in the second to fourth quartiles had a respective 20%, 29%, and 43% increased risk of CRC; 15%, 24%, and 42% increased risk for colon cancer; and 30%, 38%, and 45% increased risk for rectal cancer. We identified a positive dose-gradient association of AL score with CRC risk, including colon and rectal cancer. Additionally, the association between AL and increased risk of CRC was observed across different strata of genetic susceptibility for CRC. Eliminating AL exposures could prevent nearly 39.24% (95% CI: 36.16-42.32) of CRC incident cases. Meanwhile, a significant association between the AL and all-cause mortality in patients with CRC was found, with a HR of 1.71 (95% CI: 1.16-2.50) for the fourth quartile compared to the AL score in the first quartile, demonstrating a positive dose-response relationship. Conclusion High AL was associated with increased CRC risk and all-cause mortality in CRC patients. Future research should prioritize the development of cognitive or behavioral intervention strategies to mitigate the adverse effects of AL on CRC incidence and prognosis.
背景 静态负荷（AL）反映了一生中慢性压力的累积负担，有可能影响癌症的发病和预后。然而，AL、结直肠癌（CRC）风险和 CRC 患者全因死亡率之间的关系仍不清楚。方法 我们使用 Cox 比例危险回归模型分析了英国生物库中 304,959 名成人的 AL 与 CRC 风险以及 1,794 名 CRC 患者的全因死亡率之间的关系。结果 与 AL 水平处于第一四分位数的人相比，处于第二至第四四分位数的人患 CRC 的风险分别增加了 20%、29% 和 43%；患结肠癌的风险分别增加了 15%、24% 和 42%；患直肠癌的风险分别增加了 30%、38% 和 45%。我们发现 AL 评分与包括结肠癌和直肠癌在内的癌症风险呈剂量梯度正相关。此外，在不同的 CRC 遗传易感人群中，都能观察到 AL 与 CRC 风险增加之间的关联。消除 AL 暴露可预防近 39.24%（95% CI：36.16-42.32）的 CRC 发病。同时，研究还发现 AL 与 CRC 患者的全因死亡率之间存在显著关联，与 AL 分值位于第一四分位数的患者相比，AL 分值位于第四四分位数的患者的 HR 为 1.71（95% CI：1.16-2.50），这表明两者之间存在正的剂量-反应关系。结论 AL值高与CRC患者的CRC风险和全因死亡率增加有关。未来的研究应优先发展认知或行为干预策略，以减轻 AL 对 CRC 发病率和预后的不利影响。
{"title":"Allostatic Load, Genetic Susceptibility, Incidence Risk, and All-cause Mortality of Colorectal Cancer","authors":"Jianhui Zhao, Erxu Xue, Siyun Zhou, Meng Zhang, Jing Sun, Yuqian Tan, Xue Li","doi":"10.1093/jnci/djae223","DOIUrl":"https://doi.org/10.1093/jnci/djae223","url":null,"abstract":"Background Allostatic load (AL) reflects the cumulative burden of chronic stress throughout life, potentially influencing the onset and prognosis of cancer. However, the associations between AL, colorectal cancer (CRC) risk and all-cause mortality in patients with CRC remain unclear. Methods We analyzed the association between AL and CRC risk in 304,959 adults and all-cause mortality in 1,794 patients with CRC from the UK Biobank, using Cox proportional hazards regression models. Results Compared to the AL level in the first quartile, individuals in the second to fourth quartiles had a respective 20%, 29%, and 43% increased risk of CRC; 15%, 24%, and 42% increased risk for colon cancer; and 30%, 38%, and 45% increased risk for rectal cancer. We identified a positive dose-gradient association of AL score with CRC risk, including colon and rectal cancer. Additionally, the association between AL and increased risk of CRC was observed across different strata of genetic susceptibility for CRC. Eliminating AL exposures could prevent nearly 39.24% (95% CI: 36.16-42.32) of CRC incident cases. Meanwhile, a significant association between the AL and all-cause mortality in patients with CRC was found, with a HR of 1.71 (95% CI: 1.16-2.50) for the fourth quartile compared to the AL score in the first quartile, demonstrating a positive dose-response relationship. Conclusion High AL was associated with increased CRC risk and all-cause mortality in CRC patients. Future research should prioritize the development of cognitive or behavioral intervention strategies to mitigate the adverse effects of AL on CRC incidence and prognosis.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142233453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hormuzd A Katki, Philip C Prorok, Philip E Castle, Lori M Minasian, Paul F Pinsky
Background Cancer screening trials have required large sample sizes and long time-horizons to demonstrate cancer mortality reductions, the primary goal of cancer screening. We examine assumptions and potential power gains from exploiting information from testing control-arm specimens, which we call the “intended effect” (IE) analysis that we explain in detail herein. The IE analysis is particularly suited to tests that can be conducted on stored specimens in the control arm, such as stored blood for multicancer detection (MCD) tests. Methods We simulated hypothetical MCD screening trials to compare power and sample size for the standard vs IE analysis. Under two assumptions that we detail herein, we projected the IE analysis for 3 existing screening trials (National Lung Screening Trial [NLST], Minnesota Colon Cancer Control Study [MINN-FOBT-A], and Prostate, Lung, Colorectal, Ovarian Cancer Screening Trial—colorectal component [PLCO-CRC]). Results Compared with the standard analysis for the 3 existing trials, the IE design could have reduced cancer-specific mortality P values 6-fold (NLST), 33-fold (MINN-FOBT-A), or 260 000-fold (PLCO-CRC) or, alternately, reduced sample size (90% power) by 25% (NLST), 47% (MINN-FOBT-A), or 63% (PLCO-CRC). For potential MCD trial designs requiring 100 000 subjects per arm to achieve 90% power for multicancer mortality for the standard analysis, the IE analysis achieves 90% power for only 37 500-50 000 per arm, depending on assumptions concerning control-arm test-positives. Conclusions Testing stored specimens in the control arm of screening trials to conduct the IE analysis could substantially increase power to reduce sample size or accelerate trials and could provide particularly strong power gains for MCD tests.
{"title":"Increasing power in screening trials by testing control-arm specimens: application to multicancer detection screening","authors":"Hormuzd A Katki, Philip C Prorok, Philip E Castle, Lori M Minasian, Paul F Pinsky","doi":"10.1093/jnci/djae218","DOIUrl":"https://doi.org/10.1093/jnci/djae218","url":null,"abstract":"Background Cancer screening trials have required large sample sizes and long time-horizons to demonstrate cancer mortality reductions, the primary goal of cancer screening. We examine assumptions and potential power gains from exploiting information from testing control-arm specimens, which we call the “intended effect” (IE) analysis that we explain in detail herein. The IE analysis is particularly suited to tests that can be conducted on stored specimens in the control arm, such as stored blood for multicancer detection (MCD) tests. Methods We simulated hypothetical MCD screening trials to compare power and sample size for the standard vs IE analysis. Under two assumptions that we detail herein, we projected the IE analysis for 3 existing screening trials (National Lung Screening Trial [NLST], Minnesota Colon Cancer Control Study [MINN-FOBT-A], and Prostate, Lung, Colorectal, Ovarian Cancer Screening Trial—colorectal component [PLCO-CRC]). Results Compared with the standard analysis for the 3 existing trials, the IE design could have reduced cancer-specific mortality P values 6-fold (NLST), 33-fold (MINN-FOBT-A), or 260 000-fold (PLCO-CRC) or, alternately, reduced sample size (90% power) by 25% (NLST), 47% (MINN-FOBT-A), or 63% (PLCO-CRC). For potential MCD trial designs requiring 100 000 subjects per arm to achieve 90% power for multicancer mortality for the standard analysis, the IE analysis achieves 90% power for only 37 500-50 000 per arm, depending on assumptions concerning control-arm test-positives. Conclusions Testing stored specimens in the control arm of screening trials to conduct the IE analysis could substantially increase power to reduce sample size or accelerate trials and could provide particularly strong power gains for MCD tests.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142231333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xu Ji, Xinyue (Elyse) Zhang, K Robin Yabroff, Wendy Stock, Patricia Cornwell, Shasha Bai, Ann C Mertens, Joseph Lipscomb, Sharon M Castellino
Background Many uninsured patients do not receive Medicaid coverage until a cancer diagnosis, potentially delaying access to care for early cancer detection and treatment. We examine the association of Medicaid enrollment timing and patterns with survival among children and adolescents/young adults (AYAs) diagnosed with blood cancers, where disease onset can be acute and early detection is critical. Methods We identified 28,750 children and AYAs (0-39 years) newly diagnosed with blood cancers from the 2006-2013 SEER-Medicaid data. Enrollment patterns included continuous Medicaid (preceding through diagnosis), newly gained Medicaid (at/shortly after diagnosis), other noncontinuous Medicaid enrollment, and private/other insurance. We assessed cumulative incidence of death from diagnosis, censoring at last follow-up, five years post-diagnosis, or December 2018, whichever occurred first. Multivariable survival models estimated the association of insurance enrollment patterns with risk of death. Results One-fourth (26.1%) of the cohort were insured by Medicaid; of these, 41.1% had continuous Medicaid, 34.9% had newly gained Medicaid, and 24.0% had other noncontinuous enrollment. The cumulative incidence of all-cause death five-year post-diagnosis was highest in patients with newly gained Medicaid (30.2%, 95%CI = 28.4-31.9%), followed by other noncontinuous enrollment (23.2%, 95%CI = 21.3-25.2%), continuous Medicaid (20.5%, 95%CI = 19.1-21.9%), and private/other insurance (11.2%; 95%CI = 10.7-11.7%). In multivariable models, newly gained Medicaid was associated with a higher risk of all-cause (hazard ratio = 1.39, 95%CI = 1.27-1.53) and cancer-specific death (hazard ratio = 1.50, 95%CI = 1.35-1.68), compared to continuous Medicaid. Conclusions Continuous Medicaid coverage is associated with survival benefits among pediatric and AYA patients diagnosed with blood cancers; however, less than half of Medicaid-insured patients have continuous coverage before diagnosis.
{"title":"Health Insurance Continuity and Mortality in Children and Adolescents/Young Adults with Blood Cancer","authors":"Xu Ji, Xinyue (Elyse) Zhang, K Robin Yabroff, Wendy Stock, Patricia Cornwell, Shasha Bai, Ann C Mertens, Joseph Lipscomb, Sharon M Castellino","doi":"10.1093/jnci/djae226","DOIUrl":"https://doi.org/10.1093/jnci/djae226","url":null,"abstract":"Background Many uninsured patients do not receive Medicaid coverage until a cancer diagnosis, potentially delaying access to care for early cancer detection and treatment. We examine the association of Medicaid enrollment timing and patterns with survival among children and adolescents/young adults (AYAs) diagnosed with blood cancers, where disease onset can be acute and early detection is critical. Methods We identified 28,750 children and AYAs (0-39 years) newly diagnosed with blood cancers from the 2006-2013 SEER-Medicaid data. Enrollment patterns included continuous Medicaid (preceding through diagnosis), newly gained Medicaid (at/shortly after diagnosis), other noncontinuous Medicaid enrollment, and private/other insurance. We assessed cumulative incidence of death from diagnosis, censoring at last follow-up, five years post-diagnosis, or December 2018, whichever occurred first. Multivariable survival models estimated the association of insurance enrollment patterns with risk of death. Results One-fourth (26.1%) of the cohort were insured by Medicaid; of these, 41.1% had continuous Medicaid, 34.9% had newly gained Medicaid, and 24.0% had other noncontinuous enrollment. The cumulative incidence of all-cause death five-year post-diagnosis was highest in patients with newly gained Medicaid (30.2%, 95%CI = 28.4-31.9%), followed by other noncontinuous enrollment (23.2%, 95%CI = 21.3-25.2%), continuous Medicaid (20.5%, 95%CI = 19.1-21.9%), and private/other insurance (11.2%; 95%CI = 10.7-11.7%). In multivariable models, newly gained Medicaid was associated with a higher risk of all-cause (hazard ratio = 1.39, 95%CI = 1.27-1.53) and cancer-specific death (hazard ratio = 1.50, 95%CI = 1.35-1.68), compared to continuous Medicaid. Conclusions Continuous Medicaid coverage is associated with survival benefits among pediatric and AYA patients diagnosed with blood cancers; however, less than half of Medicaid-insured patients have continuous coverage before diagnosis.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"22 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142233458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nikolaus Christian Simon Mezger,Tobias Paul Seraphin,Robert Ballé,Mirko Griesel,Yvonne Walburga Joko-Fru,Lucia Hämmerl,Jana Feuchtner,Biying Liu,Annelle Zietsman,Bakarou Kamaté,Freddy Houéhanou Rodrigue Gnangnon,Franck Gnahatin,Dimitry Moudiongui Mboungou,Mathewos Assefa,Phoebe Mary Amulen,Gladys Chesumbai,Tatenda Chingonzoh,Cesaltina Feirreira Lorenzoni,Anne Korir,Pablo S Carvalho Santos,Jörg Michael Mezger,Haifa Kathrin Al-Ali,Rafael Mikolajczyk,Donald Max Parkin,Ahmedin Jemal,Eva Johanna Kantelhardt
BACKGROUNDTo assess population-based quality of cancer care in Sub-Saharan Africa and to identify specific gaps and joint opportunities, we assessed concordance of diagnostic and treatment with NCCN harmonized guidelines for leading cancer types in 10 countries.METHODSAdult patients with female breast cancer (BC), cervical cancer (CC), colorectal cancer (CRC), Non-Hodgkin lymphoma (NHL) and prostate cancer (PC) were randomly drawn from 11 population-based cancer registries. Guideline concordance of diagnostics and treatment was assessed using clinical records. In a sub-cohort of 906 patients with potentially curable cancer (stage I-III BC, CC, CRC, PC, aggressive NHL (any stage)) and documentation for >1 month after diagnosis, we estimated factors associated with guideline-concordant treatment or minor deviations (GCT).FINDINGSDiagnostic information as per guidelines was complete for 1030 (31.7%)of 3246 patients included. In the sub-cohort with curable cancer, GCT was documented in 374 (41.3%, corresponding to 11.7% of 3246 included in the population-based cohort): aggressive NHL (59.8%/9.1% population-based), BC (54.5%/19.0%), PC (39.0%/6.1%), CRC (33.9%/9.5%), and CC (27.8%/11.6%). GCT was most frequent in Namibia (73.1% of curable cancer subset/32.8% population-based) and lowest in Kampala, Uganda (13.5%/3.1%). GCT was negatively associated with poor ECOG status, locally advanced stage, origin from low HDI countries, and a diagnosis of CRC or CC.INTERPRETATIONQuality of diagnostic workup and treatment showed major deficits, with considerable disparities among countries and cancer types. Improved diagnostic services are necessary to increase the share of curable cancer in SSA. Treatment components within NCCN guidelines synergetic for several cancers should be prioritized.
{"title":"NCCN guideline-concordant cancer care in Sub-Saharan Africa A population-based multi-country study of five cancers.","authors":"Nikolaus Christian Simon Mezger,Tobias Paul Seraphin,Robert Ballé,Mirko Griesel,Yvonne Walburga Joko-Fru,Lucia Hämmerl,Jana Feuchtner,Biying Liu,Annelle Zietsman,Bakarou Kamaté,Freddy Houéhanou Rodrigue Gnangnon,Franck Gnahatin,Dimitry Moudiongui Mboungou,Mathewos Assefa,Phoebe Mary Amulen,Gladys Chesumbai,Tatenda Chingonzoh,Cesaltina Feirreira Lorenzoni,Anne Korir,Pablo S Carvalho Santos,Jörg Michael Mezger,Haifa Kathrin Al-Ali,Rafael Mikolajczyk,Donald Max Parkin,Ahmedin Jemal,Eva Johanna Kantelhardt","doi":"10.1093/jnci/djae221","DOIUrl":"https://doi.org/10.1093/jnci/djae221","url":null,"abstract":"BACKGROUNDTo assess population-based quality of cancer care in Sub-Saharan Africa and to identify specific gaps and joint opportunities, we assessed concordance of diagnostic and treatment with NCCN harmonized guidelines for leading cancer types in 10 countries.METHODSAdult patients with female breast cancer (BC), cervical cancer (CC), colorectal cancer (CRC), Non-Hodgkin lymphoma (NHL) and prostate cancer (PC) were randomly drawn from 11 population-based cancer registries. Guideline concordance of diagnostics and treatment was assessed using clinical records. In a sub-cohort of 906 patients with potentially curable cancer (stage I-III BC, CC, CRC, PC, aggressive NHL (any stage)) and documentation for >1 month after diagnosis, we estimated factors associated with guideline-concordant treatment or minor deviations (GCT).FINDINGSDiagnostic information as per guidelines was complete for 1030 (31.7%)of 3246 patients included. In the sub-cohort with curable cancer, GCT was documented in 374 (41.3%, corresponding to 11.7% of 3246 included in the population-based cohort): aggressive NHL (59.8%/9.1% population-based), BC (54.5%/19.0%), PC (39.0%/6.1%), CRC (33.9%/9.5%), and CC (27.8%/11.6%). GCT was most frequent in Namibia (73.1% of curable cancer subset/32.8% population-based) and lowest in Kampala, Uganda (13.5%/3.1%). GCT was negatively associated with poor ECOG status, locally advanced stage, origin from low HDI countries, and a diagnosis of CRC or CC.INTERPRETATIONQuality of diagnostic workup and treatment showed major deficits, with considerable disparities among countries and cancer types. Improved diagnostic services are necessary to increase the share of curable cancer in SSA. Treatment components within NCCN guidelines synergetic for several cancers should be prioritized.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"291 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142233467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stephanie Tuminello,Wiley M Turner,Matthew Untalan,Tara Ivic-Pavlicic,Raja Flores,Emanuela Taioli
BACKGROUNDPrecision therapies, such as targeted and immunotherapies, have substantially changed the landscape of late-stage non-small cell lung cancer (NSCLC). Yet utilization of these therapies is disproportionate across strata defined by race and socioeconomic status (SES), possibly due to disparities in molecular diagnostic testing (or "biomarker testing"), which is a prerequisite to treatment.METHODSWe extracted a cohort of NSCLC patients from the Surveillance, Epidemiology and End Results (SEER)-Medicare linked data. The primary outcome was receipt of a molecular diagnostic test, based on claims data. The primary predictors were race and SES. Likelihood of receiving a molecular diagnostic test, and overall survival (OS), were investigated using logistic and Cox proportional hazards regression, adjusted for sex, age, residence, histology, marital status, and comorbidity.RESULTSOf the 28,511 NSCLC patients, 11,209 (39.3%) received molecular diagnostic testing. Compared to White patients, fewer Black patients received a molecular diagnostic test (40.4% vs 27.9%; p < .001). After adjustment, Black patients (ORadj [odds ratio]: 0.64; 95% CI [confidence interval]: 0.58-0.71) and those living in areas with greater poverty (ORadj: 0.85; 95% CI: 0.80-0.89) had statistically significant decreased likelihood of molecular diagnostic testing. Patients who did receive testing had a statistically significant decreased risk of death (HRadj [hazards ratio]: 0.74; 95% CI: 0.72-0.76). These results held in the stratified analysis of stage IV NSCLC patients.CONCLUSIONDisparities exist in comprehensive molecular diagnostics, which is critical for clinical decision making. Addressing barriers to molecular testing could help close gaps in cancer care and improve patient outcomes.
背景靶向疗法和免疫疗法等精准疗法大大改变了晚期非小细胞肺癌（NSCLC）的治疗现状。方法我们从监测、流行病学和最终结果（SEER）-医疗保险（Medicare）关联数据中提取了一组 NSCLC 患者。主要结果是根据理赔数据接受分子诊断检测。主要预测因素是种族和社会经济地位。结果 在 28,511 名 NSCLC 患者中，11,209 人（39.3%）接受了分子诊断检测。与白人患者相比，接受分子诊断检测的黑人患者较少（40.4% vs 27.9%; p < .001）。经调整后，黑人患者（ORadj[几率比]：0.64；95% CI[置信区间]：0.58-0.71）和生活在较贫困地区的患者（ORadj：0.85；95% CI：0.80-0.89）接受分子诊断检测的可能性在统计学上显著降低。接受检测的患者的死亡风险在统计学上显著降低（HRadj [危险比]：0.74；95% CI：0.72-0.76）。这些结果在对 IV 期 NSCLC 患者进行分层分析时也得到了证实。解决分子检测的障碍有助于缩小癌症治疗的差距并改善患者的预后。
{"title":"Racial and socioeconomic disparities in NSCLC molecular diagnostics uptake.","authors":"Stephanie Tuminello,Wiley M Turner,Matthew Untalan,Tara Ivic-Pavlicic,Raja Flores,Emanuela Taioli","doi":"10.1093/jnci/djae225","DOIUrl":"https://doi.org/10.1093/jnci/djae225","url":null,"abstract":"BACKGROUNDPrecision therapies, such as targeted and immunotherapies, have substantially changed the landscape of late-stage non-small cell lung cancer (NSCLC). Yet utilization of these therapies is disproportionate across strata defined by race and socioeconomic status (SES), possibly due to disparities in molecular diagnostic testing (or \"biomarker testing\"), which is a prerequisite to treatment.METHODSWe extracted a cohort of NSCLC patients from the Surveillance, Epidemiology and End Results (SEER)-Medicare linked data. The primary outcome was receipt of a molecular diagnostic test, based on claims data. The primary predictors were race and SES. Likelihood of receiving a molecular diagnostic test, and overall survival (OS), were investigated using logistic and Cox proportional hazards regression, adjusted for sex, age, residence, histology, marital status, and comorbidity.RESULTSOf the 28,511 NSCLC patients, 11,209 (39.3%) received molecular diagnostic testing. Compared to White patients, fewer Black patients received a molecular diagnostic test (40.4% vs 27.9%; p < .001). After adjustment, Black patients (ORadj [odds ratio]: 0.64; 95% CI [confidence interval]: 0.58-0.71) and those living in areas with greater poverty (ORadj: 0.85; 95% CI: 0.80-0.89) had statistically significant decreased likelihood of molecular diagnostic testing. Patients who did receive testing had a statistically significant decreased risk of death (HRadj [hazards ratio]: 0.74; 95% CI: 0.72-0.76). These results held in the stratified analysis of stage IV NSCLC patients.CONCLUSIONDisparities exist in comprehensive molecular diagnostics, which is critical for clinical decision making. Addressing barriers to molecular testing could help close gaps in cancer care and improve patient outcomes.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"57 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142165903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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