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Reduced long-term side effects with MRI-guided radiotherapy in prostate cancer MRI 引导下的前列腺癌放疗可降低长期副作用
IF 6.1 2区 医学 Q1 ONCOLOGY Pub Date : 2025-03-17 DOI: 10.1002/cncr.35762
Mary Beth Nierengarten

Magnetic resonance imaging (MRI)–guided stereotactic body radiotherapy (SBRT) for the treatment of prostate cancer reduces long-term gastrointestinal and genitourinary toxicity compared to computed tomography (CT)–guided SBRT after 2 years of treatment and is linked to less deterioration of bowel and sexual function according to a prespecified secondary analysis of the phase 3 MIRAGE trial published in European Urology.1

The results provide longer term data at 2 years after treatment on the incidence of physician-scored toxicity and patient-reported quality-of-life measures after MRI-guided radiotherapy versus CT-guided radiotherapy.

Previous results of the MIRAGE trial showed that MRI-guided radiotherapy, which included an aggressive reduction in the planning treatment margin from 4 mm (used with CT-guided radiotherapy) to 2 mm, significantly lowered rates of acute genitourinary and gastrointestinal toxicities scored by physicians as higher than grade 2 and lowered patient-reported deterioration of urinary and bowel quality of life in the first 3 months following treatment.2

At 2 years, MRI-guided SBRT significantly reduced the incidence of late grade 2 or higher genitourinary toxicity (27% vs. 51%, p = .004) and gastrointestinal toxicity (1.4% vs. 9.5%, p = .02) versus CT-guided SBRT.

Clinically relevant deterioration of urinary irritation with MRI-guided SBRT also was reported by patients (14 of 73 vs. 24 of 68, p = .03), as was deterioration of bowel function (19 of 72 vs. 30 of 71, p = .04).

“This work supports the use of MRI-guided stereotactic body radiation therapy with tight margins for men with clinically localized prostate cancer to reduce posttreatment adverse effects,” says Gianluca Giannarini, MD, associate editor of European Urology.

Commenting on the study, Walter M. Stadler, MD, Chief Clinical Officer for City of Hope, Chicago, says that although the results are promising, there are several issues that limit the applicability of MRI-guided SBRT. He says that SBRT versus current short-course radiotherapy for localized prostate cancer is not yet considered standard treatment for most patients with localized prostate cancer. Another issue is that the assessment of toxicity in the study was based on physician assessment—not patient derived—and this could be potentially biased.

“Finally, the increased cost and technology requirements for MRI-guidance means that the vast majority of centers do not have this capacity,” he says.

Given these issues, he thinks that “this is not yet appropriate for general practice.”

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引用次数: 0
A retrospective study of outcomes across time and treatment regimens in newly diagnosed, FMS-like tyrosine kinase 3 (FLT3)-mutated acute myeloid leukemia
IF 6.1 2区 医学 Q1 ONCOLOGY Pub Date : 2025-03-17 DOI: 10.1002/cncr.35813
Alexandre Bazinet MD, MSc, Alex Bataller MD, PhD, Tapan Kadia MD, Naval Daver MD, Nicholas J. Short MD, Musa Yilmaz MD, Koji Sasaki MD, PhD, Courtney D. DiNardo MD, MSCE, Gautam M. Borthakur MD, Ghayas Issa MD, Ian Bouligny MD, Sherry Pierce RN, Guillermo Garcia-Manero MD, Farhad Ravandi MD, Hagop M. Kantarjian MD

Background

FMS-like tyrosine kinase 3 (FLT3) mutations, either internal tandem duplications (FLT3-ITD) or tyrosine kinase domain (FLT3-TKD), are common in acute myeloid leukemia (AML). FLT3-ITD confers an adverse prognosis.

Methods

The authors performed a retrospective study including 619 patients to evaluate outcomes in newly diagnosed FLT3-mutated AML across treatment regimens.

Results

In patients with FLT3-ITD–mutated AML who received intensive chemotherapy (IC), the addition of a FLT3 inhibitor (FLT3i) was associated with trends toward improved relapse-free survival (median 32.3 vs. 14.3 months with vs. without a FLT3i; p = .055) and overall survival (OS; 35.5 vs. 18.9 months with vs. without a FLT3i; p = .098). In patients with FLT3-ITD mutations who received low-intensity (LIT) regimens, triplets (LIT plus a FLT3i plus venetoclax) were associated with significantly longer OS (19.1 months) compared with those who received other treatment combinations (11.2 months with LIT alone, 9.2 months with LIT plus FLT3i, and 10.3 months with LIT plus venetoclax). Patients with FLT3-ITD plus NPM1 co-mutations who received any therapy had a trend toward improved OS (2-year OS: 47% vs. 33%; p = .087). The FLT3-ITD allelic ratio; IDH1, IDH2, WT1, RUNX1, and myelodysplastic syndrome-related mutations; and adverse cytogenetics had no significant impact on OS. In landmark analyses, allogeneic stem cell transplantation was associated with a trend toward improved OS in patients with FLT3-ITD mutations who received IC (52.6 vs. 22.7 months with versus without allogeneic stem cell transplantation; p = .076) and a marked improvement in OS in those who received LIT (38.6 vs. 14.0 months with vs. without allogeneic stem cell transplantation; p < .0001).

Conclusions

A FLT3i and allogeneic stem cell transplantation are key treatment modalities for patients who have FLT3-mutated AML. LIT-based triplets are promising in IC-ineligible patients.

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引用次数: 0
First person profile: Jennifer S. Temel, MD
IF 6.1 2区 医学 Q1 ONCOLOGY Pub Date : 2025-03-17 DOI: 10.1002/cncr.35758
Mary Beth Nierengarten
<p>Pioneering work by Jennifer S. Temel, MD, has filled a large gap in cancer care. Although new treatments over the past decades have extended the lives of many patients with cancer and improved the quality of their lives, support for a myriad of physical and psychosocial needs accompanying a cancer diagnosis through treatment and end-of-life care for both patients and caregivers has lagged.</p><p>Dr Temel has changed that by developing a model that transformed palliative care from being an exclusive offering for very ill and hospitalized patients near death to an option for all patients with cancer at the time of diagnosis. Moving palliative care upstream in the outpatient setting and delivering it over the course of a patient’s illness have been demonstrated during more than 20 years of research to improve the patient experience as measured by patient-reported outcomes. It also improves a patient’s health care delivery, she says.</p><p>Findings from her research have been published in major medical journals. For example, a 2010 randomized study published in <i>The New England Journal of Medicine</i> showed that early palliative care significantly improved the quality of life and mood of patients with metastatic non–small cell lung cancer.<span><sup>1</sup></span></p><p>Two recent randomized studies published in 2024 in <i>JAMA</i> also demonstrated the efficacy and scalability of early palliative care. One showed the effectiveness and scalability of a stepped palliative care approach in which patients receive palliative care visits at key points in their cancer trajectories; when a decrement in quality of life is noted, more intensive palliative care is administered.<span><sup>2</sup></span> The other demonstrated the effectiveness and feasibility of delivering early palliative care via telehealth.<span><sup>3</sup></span></p><p>“A big piece of palliative care, especially when provided early in the disease in an outpatient setting, is about things like coping, living life to the fullest with a serious illness, and also things like accepting and understanding what the illness and prognosis mean,” says Dr Temel.</p><p>Because of her work, early palliative care is now recommended as the standard of care for patients with serious cancers by all national organizations, such as the American Society of Clinical Oncology and the National Comprehensive Cancer Network.</p><p>Dr Temel is a professor of medicine at the Harvard Medical School, a thoracic oncologist at the Massachusetts General Hospital (MGH) Cancer Center, and the Barbara McCue Endowed Chair in Oncology and Cancer Outcomes Research at MGH.</p><p>Although she wanted to be a physician from a young age, becoming an oncologist was not preordained. A thorny problem presented itself that made her think twice—a huge fear of blood. In college, she chose to work in a laboratory to see if laboratory science might be a better fit than being a physician. As chance would have it, her laboratory was in
{"title":"First person profile: Jennifer S. Temel, MD","authors":"Mary Beth Nierengarten","doi":"10.1002/cncr.35758","DOIUrl":"https://doi.org/10.1002/cncr.35758","url":null,"abstract":"&lt;p&gt;Pioneering work by Jennifer S. Temel, MD, has filled a large gap in cancer care. Although new treatments over the past decades have extended the lives of many patients with cancer and improved the quality of their lives, support for a myriad of physical and psychosocial needs accompanying a cancer diagnosis through treatment and end-of-life care for both patients and caregivers has lagged.&lt;/p&gt;&lt;p&gt;Dr Temel has changed that by developing a model that transformed palliative care from being an exclusive offering for very ill and hospitalized patients near death to an option for all patients with cancer at the time of diagnosis. Moving palliative care upstream in the outpatient setting and delivering it over the course of a patient’s illness have been demonstrated during more than 20 years of research to improve the patient experience as measured by patient-reported outcomes. It also improves a patient’s health care delivery, she says.&lt;/p&gt;&lt;p&gt;Findings from her research have been published in major medical journals. For example, a 2010 randomized study published in &lt;i&gt;The New England Journal of Medicine&lt;/i&gt; showed that early palliative care significantly improved the quality of life and mood of patients with metastatic non–small cell lung cancer.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;Two recent randomized studies published in 2024 in &lt;i&gt;JAMA&lt;/i&gt; also demonstrated the efficacy and scalability of early palliative care. One showed the effectiveness and scalability of a stepped palliative care approach in which patients receive palliative care visits at key points in their cancer trajectories; when a decrement in quality of life is noted, more intensive palliative care is administered.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; The other demonstrated the effectiveness and feasibility of delivering early palliative care via telehealth.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;“A big piece of palliative care, especially when provided early in the disease in an outpatient setting, is about things like coping, living life to the fullest with a serious illness, and also things like accepting and understanding what the illness and prognosis mean,” says Dr Temel.&lt;/p&gt;&lt;p&gt;Because of her work, early palliative care is now recommended as the standard of care for patients with serious cancers by all national organizations, such as the American Society of Clinical Oncology and the National Comprehensive Cancer Network.&lt;/p&gt;&lt;p&gt;Dr Temel is a professor of medicine at the Harvard Medical School, a thoracic oncologist at the Massachusetts General Hospital (MGH) Cancer Center, and the Barbara McCue Endowed Chair in Oncology and Cancer Outcomes Research at MGH.&lt;/p&gt;&lt;p&gt;Although she wanted to be a physician from a young age, becoming an oncologist was not preordained. A thorny problem presented itself that made her think twice—a huge fear of blood. In college, she chose to work in a laboratory to see if laboratory science might be a better fit than being a physician. As chance would have it, her laboratory was in ","PeriodicalId":138,"journal":{"name":"Cancer","volume":"131 6","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cncr.35758","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143638805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Higher rates of long-term complications after prostate cancer treatment
IF 6.1 2区 医学 Q1 ONCOLOGY Pub Date : 2025-03-17 DOI: 10.1002/cncr.35761
Mary Beth Nierengarten
<p>Men with prostate cancer treated with prostatectomy and radiotherapy have significantly higher rates of long-term complications after accounting for age-related symptoms and disease, according to a cohort study published in <i>JAMA Oncology</i>.<span><sup>1</sup></span></p><p>Compared to people who did not undergo prostate cancer treatment, patients who underwent prostatectomy and those who underwent radiotherapy had 7.23- and 2.76-times greater risks, respectively, of developing urinary or sexual complications at 12 years.</p><p>Radiotherapy also was linked to a 3-fold increased risk of bladder cancer and a 100-fold increased risk of radiation cystitis and radiation proctitis.</p><p>The results are based on a novel approach to assessing the long-term risk of complications following prostate cancer treatment by comparing the risk in patients with prostate cancer who underwent treatment to the risk in a control population (untreated group) that included people without prostate cancer or with untreated prostate cancer. Data for all participants were obtained from two large prostate cancer prevention trials that allowed for a comparison of rates of age-dependent functional changes that increase with age (e.g., erectile dysfunction).</p><p>Among the 29,196 participants in the two trials, 3946 had prostate cancer: 655 underwent prostatectomy, and 1056 underwent radiotherapy.</p><p>Other findings included a higher rate of artificial urinary sphincter placement 12 years after prostatectomy (4.76 cases per 1000 years of follow-up) in comparison with untreated patients (who underwent no sphincter operations) and an increased rate of penile prosthesis implantation in participants who underwent prostatectomy or radiotherapy (4.40 and 1.50 times for each 1000 years of follow-up, respectively) in comparison with untreated participants (0.43 times for each 1000 years of follow-up).</p><p>According to the study authors led by Joseph M. Unger, PhD, a biostatistician at the SWOG Statistics and Data Management Center of the Fred Hutchinson Cancer Center, the findings “should be explicitly reflected in national cancer screening and treatment guidelines and be integral to shared decision-making with patients before initiation of prostate-specific antigen screening, biopsy, or prostate cancer treatment.” They note that quantitative information such as these findings on treatment-related risks of prostate cancer are not currently included in the guidelines of any national organization, and they recommend their inclusion to help to foster informed decision-making.</p><p>Walter M. Stadler, MD, Chief Clinical Officer for City of Hope, Chicago, says that the study re-emphasizes the need to discuss long-term urinary, sexual, and bowel toxicities with patients with prostate cancer before embarking on definitive local therapy.</p><p>“More importantly, these toxicities need to be balanced with known benefits of definitive local therapy, especially in patients for whom the
{"title":"Higher rates of long-term complications after prostate cancer treatment","authors":"Mary Beth Nierengarten","doi":"10.1002/cncr.35761","DOIUrl":"https://doi.org/10.1002/cncr.35761","url":null,"abstract":"&lt;p&gt;Men with prostate cancer treated with prostatectomy and radiotherapy have significantly higher rates of long-term complications after accounting for age-related symptoms and disease, according to a cohort study published in &lt;i&gt;JAMA Oncology&lt;/i&gt;.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;Compared to people who did not undergo prostate cancer treatment, patients who underwent prostatectomy and those who underwent radiotherapy had 7.23- and 2.76-times greater risks, respectively, of developing urinary or sexual complications at 12 years.&lt;/p&gt;&lt;p&gt;Radiotherapy also was linked to a 3-fold increased risk of bladder cancer and a 100-fold increased risk of radiation cystitis and radiation proctitis.&lt;/p&gt;&lt;p&gt;The results are based on a novel approach to assessing the long-term risk of complications following prostate cancer treatment by comparing the risk in patients with prostate cancer who underwent treatment to the risk in a control population (untreated group) that included people without prostate cancer or with untreated prostate cancer. Data for all participants were obtained from two large prostate cancer prevention trials that allowed for a comparison of rates of age-dependent functional changes that increase with age (e.g., erectile dysfunction).&lt;/p&gt;&lt;p&gt;Among the 29,196 participants in the two trials, 3946 had prostate cancer: 655 underwent prostatectomy, and 1056 underwent radiotherapy.&lt;/p&gt;&lt;p&gt;Other findings included a higher rate of artificial urinary sphincter placement 12 years after prostatectomy (4.76 cases per 1000 years of follow-up) in comparison with untreated patients (who underwent no sphincter operations) and an increased rate of penile prosthesis implantation in participants who underwent prostatectomy or radiotherapy (4.40 and 1.50 times for each 1000 years of follow-up, respectively) in comparison with untreated participants (0.43 times for each 1000 years of follow-up).&lt;/p&gt;&lt;p&gt;According to the study authors led by Joseph M. Unger, PhD, a biostatistician at the SWOG Statistics and Data Management Center of the Fred Hutchinson Cancer Center, the findings “should be explicitly reflected in national cancer screening and treatment guidelines and be integral to shared decision-making with patients before initiation of prostate-specific antigen screening, biopsy, or prostate cancer treatment.” They note that quantitative information such as these findings on treatment-related risks of prostate cancer are not currently included in the guidelines of any national organization, and they recommend their inclusion to help to foster informed decision-making.&lt;/p&gt;&lt;p&gt;Walter M. Stadler, MD, Chief Clinical Officer for City of Hope, Chicago, says that the study re-emphasizes the need to discuss long-term urinary, sexual, and bowel toxicities with patients with prostate cancer before embarking on definitive local therapy.&lt;/p&gt;&lt;p&gt;“More importantly, these toxicities need to be balanced with known benefits of definitive local therapy, especially in patients for whom the ","PeriodicalId":138,"journal":{"name":"Cancer","volume":"131 6","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cncr.35761","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143638761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The relationship between cardiometabolic abnormalities and mortality in the Women’s Health Initiative: A comparison of associations among women with cancer to women without cancer
IF 6.1 2区 医学 Q1 ONCOLOGY Pub Date : 2025-03-12 DOI: 10.1002/cncr.35804
Sreejata Raychaudhuri MD, Eric McLaughlin MS, Michael L. Pennell PhD, Marcia Stefanick PhD, Kerryn Reding PhD, Alexi Vasbinder PhD, Richard K. Cheng MD, Ana Barac MD, Michael S. Simon MD, MPH

Background

Prior studies of participants with breast and other obesity-associated cancers in the Women’s Health Initiative (WHI) showed worse mortality and cardiovascular disease (CVD) outcomes for individuals with a higher number of cardiometabolic risk factors at study entry. The purpose of this analysis is to compare the relationship between cardiometabolic abnormalities and mortality among women with and without cancer in the WHI.

Methods

Women with one of five early-stage obesity-associated cancers (breast, colorectal, endometrial, ovarian, and non-Hodgkin lymphoma) and controls without any new or prior history of cancer were selected from the WHI-Life and Longevity after Cancer ancillary study. Cardiometabolic abnormalities included high waist circumference (≥88 cm), hypertension (>130/85 mm Hg), and self-reported history of diabetes and/or elevated cholesterol. Multivariable Cox proportional hazards models (all-cause mortality) and Fine-Gray models (CVD and non-CVD mortality) were used to evaluate the association between cardiometabolic risk factors and survival outcomes for the cancer and noncancer cohorts.

Results

A total of 7491 and 35,508 women were studied in the cancer and noncancer cohorts, respectively. Adjusted analyses showed that increased number of cardiometabolic abnormalities was associated with increased short-term risk of all-cause mortality, with the association being stronger among the noncancer “controls” compared to the cancer cohort (interaction p value = .02). Associations were similar between cancer cases and controls in competing risk models for CVD and non-CVD mortality.

Conclusion

Preexisting cardiovascular abnormalities are an important predictor of adverse health outcomes among women with and without cancer in the WHI.

{"title":"The relationship between cardiometabolic abnormalities and mortality in the Women’s Health Initiative: A comparison of associations among women with cancer to women without cancer","authors":"Sreejata Raychaudhuri MD,&nbsp;Eric McLaughlin MS,&nbsp;Michael L. Pennell PhD,&nbsp;Marcia Stefanick PhD,&nbsp;Kerryn Reding PhD,&nbsp;Alexi Vasbinder PhD,&nbsp;Richard K. Cheng MD,&nbsp;Ana Barac MD,&nbsp;Michael S. Simon MD, MPH","doi":"10.1002/cncr.35804","DOIUrl":"https://doi.org/10.1002/cncr.35804","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Prior studies of participants with breast and other obesity-associated cancers in the Women’s Health Initiative (WHI) showed worse mortality and cardiovascular disease (CVD) outcomes for individuals with a higher number of cardiometabolic risk factors at study entry. The purpose of this analysis is to compare the relationship between cardiometabolic abnormalities and mortality among women with and without cancer in the WHI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Women with one of five early-stage obesity-associated cancers (breast, colorectal, endometrial, ovarian, and non-Hodgkin lymphoma) and controls without any new or prior history of cancer were selected from the WHI-Life and Longevity after Cancer ancillary study. Cardiometabolic abnormalities included high waist circumference (≥88 cm), hypertension (&gt;130/85 mm Hg), and self-reported history of diabetes and/or elevated cholesterol. Multivariable Cox proportional hazards models (all-cause mortality) and Fine-Gray models (CVD and non-CVD mortality) were used to evaluate the association between cardiometabolic risk factors and survival outcomes for the cancer and noncancer cohorts.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 7491 and 35,508 women were studied in the cancer and noncancer cohorts, respectively. Adjusted analyses showed that increased number of cardiometabolic abnormalities was associated with increased short-term risk of all-cause mortality, with the association being stronger among the noncancer “controls” compared to the cancer cohort (interaction <i>p</i> value = .02). Associations were similar between cancer cases and controls in competing risk models for CVD and non-CVD mortality.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Preexisting cardiovascular abnormalities are an important predictor of adverse health outcomes among women with and without cancer in the WHI.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"131 6","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143602635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Caring for caregivers in early-phase clinical oncology trials
IF 6.1 2区 医学 Q1 ONCOLOGY Pub Date : 2025-03-12 DOI: 10.1002/cncr.35805
Leah L. Thompson MD, Caterina S. Florissi BA, Debra Lundquist PhD, RN, Rachel B. Jimenez MD
{"title":"Caring for caregivers in early-phase clinical oncology trials","authors":"Leah L. Thompson MD,&nbsp;Caterina S. Florissi BA,&nbsp;Debra Lundquist PhD, RN,&nbsp;Rachel B. Jimenez MD","doi":"10.1002/cncr.35805","DOIUrl":"https://doi.org/10.1002/cncr.35805","url":null,"abstract":"","PeriodicalId":138,"journal":{"name":"Cancer","volume":"131 6","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143602636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The human oral microbiome and risk of colorectal cancer within three prospective cohort studies in the United States
IF 6.1 2区 医学 Q1 ONCOLOGY Pub Date : 2025-03-11 DOI: 10.1002/cncr.35802
Emily Vogtmann PhD, MPH, Yukiko Yano PhD, MPH, Semi Zouiouich PhD, Xing Hua PhD, Yunhu Wan PhD, Vaishnavi Purandare MS, Shilan Li PhD, Casey L. Dagnall BS, Kristine Jones BS, Belynda D. Hicks MS, Amy Hutchinson MS, J. Gregory Caporaso PhD, William Wheeler PhD, Wen-Yi Huang PhD, Neal D. Freedman PhD, MPH, Dale P. Sandler PhD, MPH, Laura E. Beane Freeman PhD, Linda M. Liao PhD, Mitchell H. Gail MD, PhD, Jianxin Shi PhD, Christian C. Abnet PhD, MPH, Rashmi Sinha PhD

Background

Oral microbes detected in feces have been associated with colorectal cancer (CRC) in cross-sectional studies. This study investigated the prospective associations between the oral microbiome and incident CRC in the Agricultural Health Study (AHS), National Institutes of Health–AARP (NIH-AARP) Diet and Health Study, and Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial.

Methods

Individuals with oral samples collected before incident CRC diagnoses were identified in the AHS (N = 331), NIH-AARP (N = 249), and PLCO (N = 446) and compared with referent subcohorts (N = 3431). The V4 region of the 16S ribosomal RNA gene was sequenced from oral wash DNA, and the data were processed with QIIME2. Hazard ratios (HRs) and 95% confidence intervals (CIs) for overall CRC and by anatomic subsite (i.e., proximal colon, distal colon, and rectum) were estimated with Cox proportional hazards models with adjustment for potential confounders by cohort and then meta-analyzed.

Results

Overall, no associations were found between microbial characteristics and CRC risk. However, associations were observed with alpha and beta diversity indices and individual genera in analyses stratified by anatomic subsite. For instance, the presence of Olsenella was strongly positively associated with distal colon cancer risk (HR, 2.16; 95% CI, 1.59–2.95), whereas the presence of Prevotella 2 was positively associated with rectal cancer risk (HR, 1.68; 95% CI, 1.14–2.46).

Conclusions

This large study of the prospective association between the oral microbiome and CRC risk showed numerous site-specific associations, including multiple associations with distal colon and rectal cancer risk.

{"title":"The human oral microbiome and risk of colorectal cancer within three prospective cohort studies in the United States","authors":"Emily Vogtmann PhD, MPH,&nbsp;Yukiko Yano PhD, MPH,&nbsp;Semi Zouiouich PhD,&nbsp;Xing Hua PhD,&nbsp;Yunhu Wan PhD,&nbsp;Vaishnavi Purandare MS,&nbsp;Shilan Li PhD,&nbsp;Casey L. Dagnall BS,&nbsp;Kristine Jones BS,&nbsp;Belynda D. Hicks MS,&nbsp;Amy Hutchinson MS,&nbsp;J. Gregory Caporaso PhD,&nbsp;William Wheeler PhD,&nbsp;Wen-Yi Huang PhD,&nbsp;Neal D. Freedman PhD, MPH,&nbsp;Dale P. Sandler PhD, MPH,&nbsp;Laura E. Beane Freeman PhD,&nbsp;Linda M. Liao PhD,&nbsp;Mitchell H. Gail MD, PhD,&nbsp;Jianxin Shi PhD,&nbsp;Christian C. Abnet PhD, MPH,&nbsp;Rashmi Sinha PhD","doi":"10.1002/cncr.35802","DOIUrl":"https://doi.org/10.1002/cncr.35802","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Oral microbes detected in feces have been associated with colorectal cancer (CRC) in cross-sectional studies. This study investigated the prospective associations between the oral microbiome and incident CRC in the Agricultural Health Study (AHS), National Institutes of Health–AARP (NIH-AARP) Diet and Health Study, and Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Individuals with oral samples collected before incident CRC diagnoses were identified in the AHS (<i>N</i> = 331), NIH-AARP (<i>N</i> = 249), and PLCO (<i>N</i> = 446) and compared with referent subcohorts (<i>N</i> = 3431). The V4 region of the 16S ribosomal RNA gene was sequenced from oral wash DNA, and the data were processed with QIIME2. Hazard ratios (HRs) and 95% confidence intervals (CIs) for overall CRC and by anatomic subsite (i.e., proximal colon, distal colon, and rectum) were estimated with Cox proportional hazards models with adjustment for potential confounders by cohort and then meta-analyzed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Overall, no associations were found between microbial characteristics and CRC risk. However, associations were observed with alpha and beta diversity indices and individual genera in analyses stratified by anatomic subsite. For instance, the presence of <i>Olsenella</i> was strongly positively associated with distal colon cancer risk (HR, 2.16; 95% CI, 1.59–2.95), whereas the presence of <i>Prevotella 2</i> was positively associated with rectal cancer risk (HR, 1.68; 95% CI, 1.14–2.46).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This large study of the prospective association between the oral microbiome and CRC risk showed numerous site-specific associations, including multiple associations with distal colon and rectal cancer risk.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"131 6","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cncr.35802","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143595310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The missing data: A review of gender and sex disparities in research 缺失的数据:研究中的性别和性差异综述
IF 6.1 2区 医学 Q1 ONCOLOGY Pub Date : 2025-03-11 DOI: 10.1002/cncr.35769
Hannah C. Karpel MD, MS, Linda M. Zambrano Guevara MD, B. J. Rimel MD, Kari E. Hacker MD, PhD, Victoria Bae-Jump MD, PhD, Tara Castellano MD, John Curtin MD, MBA, Bhavana Pothuri MD, MS

This article highlights the gender data gaps in clinical trial inclusion and funding, with a particular focus on gynecologic oncology. Female patients have historically been excluded from clinical trials across all medical domains. Despite recent improvements, female patients remain underrepresented in key diseases, including several cancer types, despite experiencing increased burden of disease. Lack of representation is particularly stark for patients in racial, ethnic, and gender minoritized populations, including in gynecologic cancer trials. Furthermore, female health conditions receive disproportionately small amounts of funding relative to their disease burden. Despite their high lethality, gynecologic cancers, including ovarian, cervical, and uterine malignancies, rank among the lowest funded cancer sites from the National Cancer Institute. Likewise, there is significant bias against female investigators with regard to funding, publication, and academic advancement, which affects the prioritization of women’s health. In combination, gender disparities at multiple steps along the research pathway from investigator and disease funding to trial inclusion to publication and dissemination of research perpetuate a significant data gap in the diagnosis, treatment, and prevention of diseases affecting female patients, including gynecologic cancers. Strategies to improve this gender gap and prioritize women’s health funding include increasing female representation in clinical trials with a specific focus on inclusion of patients from historically marginalized backgrounds, considering disease burden–based funding policies, and prioritizing female academic leadership opportunities.

{"title":"The missing data: A review of gender and sex disparities in research","authors":"Hannah C. Karpel MD, MS,&nbsp;Linda M. Zambrano Guevara MD,&nbsp;B. J. Rimel MD,&nbsp;Kari E. Hacker MD, PhD,&nbsp;Victoria Bae-Jump MD, PhD,&nbsp;Tara Castellano MD,&nbsp;John Curtin MD, MBA,&nbsp;Bhavana Pothuri MD, MS","doi":"10.1002/cncr.35769","DOIUrl":"https://doi.org/10.1002/cncr.35769","url":null,"abstract":"<p>This article highlights the gender data gaps in clinical trial inclusion and funding, with a particular focus on gynecologic oncology. Female patients have historically been excluded from clinical trials across all medical domains. Despite recent improvements, female patients remain underrepresented in key diseases, including several cancer types, despite experiencing increased burden of disease. Lack of representation is particularly stark for patients in racial, ethnic, and gender minoritized populations, including in gynecologic cancer trials. Furthermore, female health conditions receive disproportionately small amounts of funding relative to their disease burden. Despite their high lethality, gynecologic cancers, including ovarian, cervical, and uterine malignancies, rank among the lowest funded cancer sites from the National Cancer Institute. Likewise, there is significant bias against female investigators with regard to funding, publication, and academic advancement, which affects the prioritization of women’s health. In combination, gender disparities at multiple steps along the research pathway from investigator and disease funding to trial inclusion to publication and dissemination of research perpetuate a significant data gap in the diagnosis, treatment, and prevention of diseases affecting female patients, including gynecologic cancers. Strategies to improve this gender gap and prioritize women’s health funding include increasing female representation in clinical trials with a specific focus on inclusion of patients from historically marginalized backgrounds, considering disease burden–based funding policies, and prioritizing female academic leadership opportunities.</p>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"131 6","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143595111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Improved survival with elevated BMI following immune checkpoint inhibition across various solid tumor cancer types
IF 6.1 2区 医学 Q1 ONCOLOGY Pub Date : 2025-03-11 DOI: 10.1002/cncr.35799
Eric V. Mastrolonardo MD, Pablo Llerena BS, Emma De Ravin MD, Kathryn Nunes BA, Praneet C. Kaki BS, Kelly M. Bridgham MD, Dev R. Amin MD, Daniel J. Campbell MD, Ramez Philips MD, Scott H. Koeneman PhD, David M. Cognetti MD, Adam J. Luginbuhl MD, Nicole L. Simone MD, Jennifer M. Johnson MD, Joseph M. Curry MD

Introduction/Background

Obesity is a well-known risk factor for various cancers, yet emerging research demonstrates its association with improved survival outcomes in cancer treatment, labeled as “the obesity paradox.” Studies investigating the clinical benefits of obesity across various cancer types after immune checkpoint inhibition (ICI) are limited.

Methods

Data were queried from the TriNetX database to identify patients with solid tumor malignancies of various organ systems (pulmonary/intrathoracic, cutaneous, head and neck, gastrointestinal, breast, genitourinary) who received ICI between 2012 and 2024. Propensity score matching was used to match cohorts for demographics, medical comorbidities, and oncologic staging. Primary outcome was overall survival (OS) up to 5 years and compared between obese body mass index (BMI; >30) and normal BMI (20–24.9) cohorts.

Results

After propensity score matching, there were a total of 18,434 patients, with 9217 patients in the obese BMI cohort and 9217 patients in the normal BMI cohort for all solid tumor malignancies. In the overall pan-cancer analysis, obese BMI was associated with significantly improved OS up to 5 years compared to the normal BMI cohort (hazard ratio [HR], 0.69 [0.66–0.72]). Subgroup analysis likewise demonstrated that obese BMI was associated with significantly improved OS up to 5 years for respiratory/intrathoracic (HR, 0.77 [0.72–0.83]), cutaneous (HR, 0.62 [0.63–0.78]), head and neck (HR, 0.67 [0.58–0.78]), gastrointestinal (HR, 0.67 [0.58–0.78]), breast (HR, 0.66 [0.55–0.79]), and genitourinary (HR, 0.57 [0.34–0.93]) malignancies (though not renal cell carcinoma specifically.)

Conclusions

Obesity was associated with improved 5-year OS after treatment with ICI across various solid tumor malignancies in this electronic health record–based big data study. Further investigation is warranted to understand the mechanism of this association.

{"title":"Improved survival with elevated BMI following immune checkpoint inhibition across various solid tumor cancer types","authors":"Eric V. Mastrolonardo MD,&nbsp;Pablo Llerena BS,&nbsp;Emma De Ravin MD,&nbsp;Kathryn Nunes BA,&nbsp;Praneet C. Kaki BS,&nbsp;Kelly M. Bridgham MD,&nbsp;Dev R. Amin MD,&nbsp;Daniel J. Campbell MD,&nbsp;Ramez Philips MD,&nbsp;Scott H. Koeneman PhD,&nbsp;David M. Cognetti MD,&nbsp;Adam J. Luginbuhl MD,&nbsp;Nicole L. Simone MD,&nbsp;Jennifer M. Johnson MD,&nbsp;Joseph M. Curry MD","doi":"10.1002/cncr.35799","DOIUrl":"https://doi.org/10.1002/cncr.35799","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction/Background</h3>\u0000 \u0000 <p>Obesity is a well-known risk factor for various cancers, yet emerging research demonstrates its association with improved survival outcomes in cancer treatment, labeled as “the obesity paradox.” Studies investigating the clinical benefits of obesity across various cancer types after immune checkpoint inhibition (ICI) are limited.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Data were queried from the TriNetX database to identify patients with solid tumor malignancies of various organ systems (pulmonary/intrathoracic, cutaneous, head and neck, gastrointestinal, breast, genitourinary) who received ICI between 2012 and 2024. Propensity score matching was used to match cohorts for demographics, medical comorbidities, and oncologic staging. Primary outcome was overall survival (OS) up to 5 years and compared between obese body mass index (BMI; &gt;30) and normal BMI (20–24.9) cohorts.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>After propensity score matching, there were a total of 18,434 patients, with 9217 patients in the obese BMI cohort and 9217 patients in the normal BMI cohort for all solid tumor malignancies. In the overall pan-cancer analysis, obese BMI was associated with significantly improved OS up to 5 years compared to the normal BMI cohort (hazard ratio [HR], 0.69 [0.66–0.72]). Subgroup analysis likewise demonstrated that obese BMI was associated with significantly improved OS up to 5 years for respiratory/intrathoracic (HR, 0.77 [0.72–0.83]), cutaneous (HR, 0.62 [0.63–0.78]), head and neck (HR, 0.67 [0.58–0.78]), gastrointestinal (HR, 0.67 [0.58–0.78]), breast (HR, 0.66 [0.55–0.79]), and genitourinary (HR, 0.57 [0.34–0.93]) malignancies (though not renal cell carcinoma specifically.)</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Obesity was associated with improved 5-year OS after treatment with ICI across various solid tumor malignancies in this electronic health record–based big data study. Further investigation is warranted to understand the mechanism of this association.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"131 6","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cncr.35799","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143595311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Glioma mutational signatures associated with haloalkane exposure are enriched in firefighters
IF 6.1 2区 医学 Q1 ONCOLOGY Pub Date : 2025-03-10 DOI: 10.1002/cncr.35732
Vincent L. Cannataro PhD, Paige M. Bracci PhD, MPH, Jennie W. Taylor MD, MPH, Lucie McCoy MPH, Terri Rice MPH, Helen M. Hansen BA, Anne E. Heffernan MPH, Joseph Wiemels PhD, John Wiencke PhD, Margaret Wrensch PhD, Elizabeth B. Claus MD, PhD

Background

Glioma is the most common malignant primary brain tumor and is associated with significant morbidity and mortality. Modifiable risk factors remain unidentified. New advances in exposure assessment, genomic analyses, and statistical techniques permit more accurate evaluation of glioma risk associated with exogenous occupational or environmental exposures.

Methods

By using whole-exome sequencing data from matched germline and glioma tumor samples, the authors compared tumor mutational signatures for 17 persons with glioma and a documented occupational history of firefighting with those of 18 persons with glioma without an occupational history of firefighting. All 35 individuals were participants in the University of California, San Francisco Adult Glioma Study.

Results

There was a positive correlation among firefighters between the median number of sample variants attributable to single-base substitution signature 42, a single-base substitution mutational signature associated with haloalkane exposure (from the Catalogue of Somatic Mutational Signatures in Cancer) and firefighting years (p = .04; R2 = 0.29). Among nonfirefighters, the individuals with the highest number of median variants attributable to single-base substitution signature 42 also had occupations that possibly exposed them to haloalkanes, such as painting and being a mechanic.

Conclusions

In summary, the authors identified gliomas that had mutational signatures associated with haloalkane exposure that were enriched in firefighters and other occupations.

{"title":"Glioma mutational signatures associated with haloalkane exposure are enriched in firefighters","authors":"Vincent L. Cannataro PhD,&nbsp;Paige M. Bracci PhD, MPH,&nbsp;Jennie W. Taylor MD, MPH,&nbsp;Lucie McCoy MPH,&nbsp;Terri Rice MPH,&nbsp;Helen M. Hansen BA,&nbsp;Anne E. Heffernan MPH,&nbsp;Joseph Wiemels PhD,&nbsp;John Wiencke PhD,&nbsp;Margaret Wrensch PhD,&nbsp;Elizabeth B. Claus MD, PhD","doi":"10.1002/cncr.35732","DOIUrl":"https://doi.org/10.1002/cncr.35732","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Glioma is the most common malignant primary brain tumor and is associated with significant morbidity and mortality. Modifiable risk factors remain unidentified. New advances in exposure assessment, genomic analyses, and statistical techniques permit more accurate evaluation of glioma risk associated with exogenous occupational or environmental exposures.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>By using whole-exome sequencing data from matched germline and glioma tumor samples, the authors compared tumor mutational signatures for 17 persons with glioma and a documented occupational history of firefighting with those of 18 persons with glioma without an occupational history of firefighting. All 35 individuals were participants in the University of California, San Francisco Adult Glioma Study.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>There was a positive correlation among firefighters between the median number of sample variants attributable to single-base substitution signature 42, a single-base substitution mutational signature associated with haloalkane exposure (from the Catalogue of Somatic Mutational Signatures in Cancer) and firefighting years (<i>p</i> = .04; R<sup>2</sup> = 0.29). Among nonfirefighters, the individuals with the highest number of median variants attributable to single-base substitution signature 42 also had occupations that possibly exposed them to haloalkanes, such as painting and being a mechanic.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In summary, the authors identified gliomas that had mutational signatures associated with haloalkane exposure that were enriched in firefighters and other occupations.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"131 6","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cncr.35732","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143581593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Cancer
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