Kristine A. Karvonen MD, MS, David R. Doody MS, Dwight Barry PhD, Kira Bona MD, MPH, Lena E. Winestone MD, MSHP, Abby R. Rosenberg MD, MS, MA, Jason A. Mendoza MD, MPH, Stephen M. Schwartz PhD, MPH, Eric J. Chow MD, MPH
Background
Historical redlining has been associated with inferior survival in adult-onset cancers. However, its relationship with pediatric, adolescent, and young–adult-onset cancer outcomes is unknown.
Methods
This study identified incident cancer among individuals <40 years of age living in Seattle and Tacoma between 2000–2019 via the population-based Cancer Surveillance System. The authors determined case redlining status using Home Owners’ Loans Corporation data overlaid with 2000 and 2010 census tracts. Kaplan–Meier methods and multivariable Cox proportional hazards models were used to determine 5- and 10-year overall survival and hazard ratio (HR) of death according to redlined status. Cox models adjusted for patient and tumor characteristics and area-level poverty; interaction between redlining and area-level poverty was also assessed.
Results
Among 4355 cases (median age at diagnosis 32 years), overall survival at 5 years was lower (85.1%; 95% confidence interval [CI], 83.5%–86.5%) among individuals residing in redlined neighborhoods compared with those in unexposed neighborhoods (90.3%; 95% CI, 89.0%–91.5%). Survival differences persisted at 10 years. The unadjusted hazard of death for redlined exposed individuals with cancer was higher than redlined unexposed (hazard ratio [HR], 1.62; 95% CI, 1.39–1.89). In the fully adjusted model, mortality remained higher for redlined cases (HR, 1.32; 95% CI, 1.12–1.56). There did not appear to be effect modification from area-level poverty in the relationship between redlining and death (p = .49).
Conclusions
Among young individuals with cancer, residence at diagnosis in previously redlined neighborhoods was associated with lower survival compared with those residing in nonredlined neighborhoods, supporting the hypothesis that structural racism exerts persistent effects on contemporary health outcomes.
{"title":"Historical redlining and survival among children, adolescents, and young adults with cancer diagnosed between 2000–2019 in Seattle and Tacoma, Washington","authors":"Kristine A. Karvonen MD, MS, David R. Doody MS, Dwight Barry PhD, Kira Bona MD, MPH, Lena E. Winestone MD, MSHP, Abby R. Rosenberg MD, MS, MA, Jason A. Mendoza MD, MPH, Stephen M. Schwartz PhD, MPH, Eric J. Chow MD, MPH","doi":"10.1002/cncr.35677","DOIUrl":"10.1002/cncr.35677","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Historical redlining has been associated with inferior survival in adult-onset cancers. However, its relationship with pediatric, adolescent, and young–adult-onset cancer outcomes is unknown.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study identified incident cancer among individuals <40 years of age living in Seattle and Tacoma between 2000–2019 via the population-based Cancer Surveillance System. The authors determined case redlining status using Home Owners’ Loans Corporation data overlaid with 2000 and 2010 census tracts. Kaplan–Meier methods and multivariable Cox proportional hazards models were used to determine 5- and 10-year overall survival and hazard ratio (HR) of death according to redlined status. Cox models adjusted for patient and tumor characteristics and area-level poverty; interaction between redlining and area-level poverty was also assessed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 4355 cases (median age at diagnosis 32 years), overall survival at 5 years was lower (85.1%; 95% confidence interval [CI], 83.5%–86.5%) among individuals residing in redlined neighborhoods compared with those in unexposed neighborhoods (90.3%; 95% CI, 89.0%–91.5%). Survival differences persisted at 10 years. The unadjusted hazard of death for redlined exposed individuals with cancer was higher than redlined unexposed (hazard ratio [HR], 1.62; 95% CI, 1.39–1.89). In the fully adjusted model, mortality remained higher for redlined cases (HR, 1.32; 95% CI, 1.12–1.56). There did not appear to be effect modification from area-level poverty in the relationship between redlining and death (<i>p</i> = .49).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Among young individuals with cancer, residence at diagnosis in previously redlined neighborhoods was associated with lower survival compared with those residing in nonredlined neighborhoods, supporting the hypothesis that structural racism exerts persistent effects on contemporary health outcomes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"131 3","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045119","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}
Joseph A. Arthur MD, Akhila Reddy MD, Uday Popat MD, Josiah Halm MD, Nicole Vaughan-Adams MSN, RN, Alan Myers PhD, Peiying Yang PhD, Aline Rozman De Moraes MD, Raul Laureano BS, Irma Lopez-Quinones BSN, MS, RN, Diana Urbauer MS, David Hui MD, Eduardo Bruera MD
Background
There is much concern that opioids administered as intravenous (iv) bolus for pain relief may inadvertently increase their risk for abuse. However, there is insufficient data to support this. The authors compared the abuse liability potential, analgesic efficacy, and adverse effect profile of fast (iv push) versus slow (iv piggyback) administration of iv hydromorphone among hospitalized patients requiring iv opioids for pain.
Methods
In this double-blind, double dummy, randomized, 2 × 2 crossover trial, patients with ≥4 cancer-related pain were randomly assigned to receive either iv hydromorphone 1 mg administered over 2 minutes (fast iv push) or 15 minutes (slow iv piggyback) during the first treatment period. Participants crossed over to receive the alternate treatments during the second period after a 6-hour washout period.
Results
Eighty-three eligible patients were allocated to slow–fast (42, 51%) or fast–slow (41, 49%). Both treatments produced low abuse potential scores with no difference between them (mean peak Drug Effect Questionnaire “drug liking” subscale of fast [24.00] vs. slow [24.34], p = .82). A total of 92% and 94% of slow and fast iv hydromorphone recipients, respectively, had similar improvements in pain scores over 120 minutes (odds ratio, 0.67; 95% confidence interval, 0.06–5.82, p = .65). Drowsiness was more frequent with the fast than the slow rate (50% vs. 29% at 15 minutes [p = .03] and 52% vs. 31% at 60 minutes [p = .03]).
Conclusions
Slow iv hydromorphone infusion resulted in similar abuse liability potential and pain improvement but less sedation than fast injection. These findings, taken together, suggest that the slow infusion may be considered as a first-line modality for iv opioid administration in hospitalized patients requiring intermittent opioids for pain.
{"title":"Abuse potential and analgesic efficacy of intravenous hydromorphone bolus administration among hospitalized patients with cancer pain: A double-blind, double dummy, randomized crossover trial","authors":"Joseph A. Arthur MD, Akhila Reddy MD, Uday Popat MD, Josiah Halm MD, Nicole Vaughan-Adams MSN, RN, Alan Myers PhD, Peiying Yang PhD, Aline Rozman De Moraes MD, Raul Laureano BS, Irma Lopez-Quinones BSN, MS, RN, Diana Urbauer MS, David Hui MD, Eduardo Bruera MD","doi":"10.1002/cncr.35723","DOIUrl":"10.1002/cncr.35723","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>There is much concern that opioids administered as intravenous (iv) bolus for pain relief may inadvertently increase their risk for abuse. However, there is insufficient data to support this. The authors compared the abuse liability potential, analgesic efficacy, and adverse effect profile of fast (iv push) versus slow (iv piggyback) administration of iv hydromorphone among hospitalized patients requiring iv opioids for pain.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this double-blind, double dummy, randomized, 2 × 2 crossover trial, patients with ≥4 cancer-related pain were randomly assigned to receive either iv hydromorphone 1 mg administered over 2 minutes (fast iv push) or 15 minutes (slow iv piggyback) during the first treatment period. Participants crossed over to receive the alternate treatments during the second period after a 6-hour washout period.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Eighty-three eligible patients were allocated to slow–fast (42, 51%) or fast–slow (41, 49%). Both treatments produced low abuse potential scores with no difference between them (mean peak Drug Effect Questionnaire “drug liking” subscale of fast [24.00] vs. slow [24.34], <i>p</i> = .82). A total of 92% and 94% of slow and fast iv hydromorphone recipients, respectively, had similar improvements in pain scores over 120 minutes (odds ratio, 0.67; 95% confidence interval, 0.06–5.82, <i>p</i> = .65). Drowsiness was more frequent with the fast than the slow rate (50% vs. 29% at 15 minutes [<i>p</i> = .03] and 52% vs. 31% at 60 minutes [<i>p</i> = .03]).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Slow iv hydromorphone infusion resulted in similar abuse liability potential and pain improvement but less sedation than fast injection. These findings, taken together, suggest that the slow infusion may be considered as a first-line modality for iv opioid administration in hospitalized patients requiring intermittent opioids for pain.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"131 3","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045113","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}
Leah M. Marcotte MD, MS, Sara Khor PhD, Ashok Reddy MD, MSc, Anna Morenz MD, MS, Karin Nelson MD, MSHS, Nkem Akinsoto MSc, E. Sally Lee PhD, Susan Onstad BA, Edwin S. Wong PhD
Background
Breast cancer screening (BCS) inequities are evident at national and local levels, and many health systems want to address these inequities, but may lack data about contributing factors. The objective of this study was to inform health system interventions through an exploratory analysis of potential multilevel contributors to BCS inequities using health system data.
Methods
The authors conducted a cross-sectional analysis within a large academic health system including 19,774 individuals who identified as Black (n = 1445) or White (n = 18,329) race and were eligible for BCS. They evaluated individual-level, provider-level, and clinic-level factors. They conducted logistic regression and Blinder-Oaxaca (BO) decomposition analyses to quantitatively estimate the contribution of factors to the mean difference in BCS outcomes between the two racialized groups. They calculated average marginal effects (AME) for the logistic regression models representing the estimated additive probability of receiving BCS in the Black versus White group.
Results
BCS was completed in 63.7% of Black and 71.7% of White individuals (AME, –0.08; 95% confidence interval (CI), –0.10 to –0.04; p < .001). In the BO decomposition, observed factors explained 13.3% difference in BCS. Lower patient portal use among Black versus White patients had the greatest estimated contribution to the BCS inequity (4.6 percentage points; 95% CI, 3.0–6.2).
Conclusion
Racialized group differences in patient portal use had the greatest estimated contribution to the explained difference in BCS between Black and White individuals. Patient portal use promotion could be considered as a part of multifaceted health system efforts to address BCS inequities.
{"title":"An analysis of multilevel factor contributions to breast cancer screening inequities in an academic health system","authors":"Leah M. Marcotte MD, MS, Sara Khor PhD, Ashok Reddy MD, MSc, Anna Morenz MD, MS, Karin Nelson MD, MSHS, Nkem Akinsoto MSc, E. Sally Lee PhD, Susan Onstad BA, Edwin S. Wong PhD","doi":"10.1002/cncr.35734","DOIUrl":"10.1002/cncr.35734","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Breast cancer screening (BCS) inequities are evident at national and local levels, and many health systems want to address these inequities, but may lack data about contributing factors. The objective of this study was to inform health system interventions through an exploratory analysis of potential multilevel contributors to BCS inequities using health system data.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The authors conducted a cross-sectional analysis within a large academic health system including 19,774 individuals who identified as Black (<i>n</i> = 1445) or White (<i>n</i> = 18,329) race and were eligible for BCS. They evaluated individual-level, provider-level, and clinic-level factors. They conducted logistic regression and Blinder-Oaxaca (BO) decomposition analyses to quantitatively estimate the contribution of factors to the mean difference in BCS outcomes between the two racialized groups. They calculated average marginal effects (AME) for the logistic regression models representing the estimated additive probability of receiving BCS in the Black versus White group.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>BCS was completed in 63.7% of Black and 71.7% of White individuals (AME, –0.08; 95% confidence interval (CI), –0.10 to –0.04; <i>p</i> < .001). In the BO decomposition, observed factors explained 13.3% difference in BCS. Lower patient portal use among Black versus White patients had the greatest estimated contribution to the BCS inequity (4.6 percentage points; 95% CI, 3.0–6.2).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Racialized group differences in patient portal use had the greatest estimated contribution to the explained difference in BCS between Black and White individuals. Patient portal use promotion could be considered as a part of multifaceted health system efforts to address BCS inequities.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"131 3","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045115","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}
Camilla Nero MD, PhD, Rita Trozzi MD, Federica Persiani MSc, Simone Rossi MSc, Luca Mastrantoni MD, Simona Duranti MD, Floriana Camarda MD, Ilenia Marino PharmD, Luciano Giacò PhD, Tina Pasciuto EngD, PhD, Maria De Bonis PhD, Martina Rinelli PhD, Emanuele Perrone MD, Flavia Giacomini PharmD, Domenica Lorusso MD, PhD, Alessia Piermattei MSc, Gianfranco Zannoni MD, PhD, Francesco Fanfani MD, PhD, Giovanni Scambia MD, Angelo Minucci PhD
Background
To date, 11 DNA polymerase epsilon (POLE) pathogenic variants have been declared “hotspot” mutations. Patients with endometrial cancer (EC) characterized by POLE hotspot mutations (POLEmut) have exceptional survival outcomes. Whereas international guidelines encourage deescalation of adjuvant treatment in early-stage POLEmut EC, data regarding safety in POLEmut patients with unfavorable characteristics are still under investigation. On the other hand, the spread of comprehensive genome profiling programs has underscored the need to interpret POLE variants not considered to be hotspots.
Methods
This study provides a comprehensive analysis of 596 sequenced patients with EC. The genomic landscape of POLEmut EC was compared with cases harboring nonhotspot POLE mutations within the exonuclease domain. Additionally, the genomic characteristics of multiple classifiers, as well as those exhibiting unfavorable histopathological and clinical features, were examined.
Results
No significant genomic differences were observed among patients with POLEmut EC when comparing multiple classifiers to not-multiple classifiers or those with unfavorable clinical features. However, the tumor mutational burden differed in both comparisons, whereas the percentage of C>G mutations only differed in the comparison based on clinical features. Specific POLE mutations, even if not considered to be hotspots, have genomic features comparable to POLEmut.
Conclusions
The present findings confirm the absence of significant genomic differences among POLEmut patients regardless of multiple-classifier status or association with high-risk clinical features. Prognostic data will be essential to elucidate the clinical significance of POLE mutations not classified as hotspots that exhibit genomic characteristics similar to those in POLEmut patients.
{"title":"POLE mutations in endometrial carcinoma: Clinical and genomic landscape from a large prospective single-center cohort","authors":"Camilla Nero MD, PhD, Rita Trozzi MD, Federica Persiani MSc, Simone Rossi MSc, Luca Mastrantoni MD, Simona Duranti MD, Floriana Camarda MD, Ilenia Marino PharmD, Luciano Giacò PhD, Tina Pasciuto EngD, PhD, Maria De Bonis PhD, Martina Rinelli PhD, Emanuele Perrone MD, Flavia Giacomini PharmD, Domenica Lorusso MD, PhD, Alessia Piermattei MSc, Gianfranco Zannoni MD, PhD, Francesco Fanfani MD, PhD, Giovanni Scambia MD, Angelo Minucci PhD","doi":"10.1002/cncr.35731","DOIUrl":"10.1002/cncr.35731","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>To date, 11 DNA polymerase epsilon (<i>POLE</i>) pathogenic variants have been declared “hotspot” mutations. Patients with endometrial cancer (EC) characterized by <i>POLE</i> hotspot mutations (<i>POLE</i>mut) have exceptional survival outcomes. Whereas international guidelines encourage deescalation of adjuvant treatment in early-stage <i>POLE</i>mut EC, data regarding safety in <i>POLE</i>mut patients with unfavorable characteristics are still under investigation. On the other hand, the spread of comprehensive genome profiling programs has underscored the need to interpret <i>POLE</i> variants not considered to be hotspots.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study provides a comprehensive analysis of 596 sequenced patients with EC. The genomic landscape of <i>POLE</i>mut EC was compared with cases harboring nonhotspot <i>POLE</i> mutations within the exonuclease domain. Additionally, the genomic characteristics of multiple classifiers, as well as those exhibiting unfavorable histopathological and clinical features, were examined.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>No significant genomic differences were observed among patients with <i>POLE</i>mut EC when comparing multiple classifiers to not-multiple classifiers or those with unfavorable clinical features. However, the tumor mutational burden differed in both comparisons, whereas the percentage of C>G mutations only differed in the comparison based on clinical features. Specific <i>POLE</i> mutations, even if not considered to be hotspots, have genomic features comparable to <i>POLE</i>mut.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The present findings confirm the absence of significant genomic differences among <i>POLE</i>mut patients regardless of multiple-classifier status or association with high-risk clinical features. Prognostic data will be essential to elucidate the clinical significance of <i>POLE</i> mutations not classified as hotspots that exhibit genomic characteristics similar to those in <i>POLE</i>mut patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"131 3","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11771542/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045121","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}
{"title":"Chronic conditions, cancer disparities, and the unique needs of Black women with ovarian cancer","authors":"Sarah M. Temkin MD","doi":"10.1002/cncr.35735","DOIUrl":"10.1002/cncr.35735","url":null,"abstract":"","PeriodicalId":138,"journal":{"name":"Cancer","volume":"131 3","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045117","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}
{"title":"Patient-reported outcomes in Chinese patients with chronic myeloid leukemia receiving olverembatinib: Quality of life matters!","authors":"Ahmet Emre Eşkazan MD","doi":"10.1002/cncr.35737","DOIUrl":"10.1002/cncr.35737","url":null,"abstract":"","PeriodicalId":138,"journal":{"name":"Cancer","volume":"131 3","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143031626","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}
Jibran Ahmed MD, Filip Janku MD, PhD, Daniel D. Karp MD, Sarina A. Piha-Paul MD, Apostolia M. Tsimberidou MD, PhD, Timothy Anthony Yap MD, PhD, Bettzy Stephen MBBS, Yali Yang PhD, Serdar Gurses PhD, Qian Liu PhD, Juhee Song PhD, Funda Meric-Bernstam MD, Aung Naing MD
Background
Talabostat, an oral small molecule inhibitor of dipeptidyl peptidases (DPP4 and DPP8/9), has shown synergistic activity with immune checkpoint inhibitors in preclinical studies. This open label, phase 2 basket trial assessed the antitumor activity of combining talabostat and pembrolizumab (anti–programmed death-1 antibody) in advanced solid tumor patients.
Methods
The primary objective was assessment of dose-limiting toxicity (DLT) rates in the first six patients (lead-in stage) and response rate (efficacy stage; included cohort A [checkpoint inhibitor (ICI) naive] and cohort B [ICI pretreated]) for the study treatment using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and immune RECIST (iRECIST). Efficacy was assessed using a Bayesian optimal phase 2 design.
Results
A total of 31 patients enrolled in this trial (14 in cohort A, 17 in cohort B). The median age was 61 years; 17 (55%) patients were male and 21 (68%) patients were White. Among 19 (61%) patients evaluable for response, the best response was stable disease in nine patients, unconfirmed progressive disease in seven patients, and clinical progressive disease in three patients based on iRECIST. Disease control rate was 47%. One patient with programmed death-ligand 1 negative, microsatellite stable endometrial cancer had unconfirmed partial response. Median progression-free survival was 2.7 months; median overall survival was 20.5 months. One patient (cohort A) experienced a grade 4 hypotension as a DLT and treatment discontinuation. The most common toxicities were hypotension (22.6%), fatigue (9.7%), diarrhea, rash, thrombocytopenia, vomiting, syncope, general disorders and administration site conditions-other, and skin and subcutaneous tissue disorders-other, each in 6.5% of patients.
Conclusions
This study of the combination of talabostat and pembrolizumab in patients with advanced solid tumors demonstrated predictable adverse events and limited activity. The combination was shown to be safe. Efficacy data shows immune stable disease in nine of 19 evaluable patients, and an unconfirmed immune partial response in a patient with endometrial cancer.
{"title":"A phase 2 basket study of talabostat, a small-molecule inhibitor of dipeptidyl peptidases, administered in combination with pembrolizumab in patients with advanced solid cancers","authors":"Jibran Ahmed MD, Filip Janku MD, PhD, Daniel D. Karp MD, Sarina A. Piha-Paul MD, Apostolia M. Tsimberidou MD, PhD, Timothy Anthony Yap MD, PhD, Bettzy Stephen MBBS, Yali Yang PhD, Serdar Gurses PhD, Qian Liu PhD, Juhee Song PhD, Funda Meric-Bernstam MD, Aung Naing MD","doi":"10.1002/cncr.35728","DOIUrl":"10.1002/cncr.35728","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Talabostat, an oral small molecule inhibitor of dipeptidyl peptidases (DPP4 and DPP8/9), has shown synergistic activity with immune checkpoint inhibitors in preclinical studies. This open label, phase 2 basket trial assessed the antitumor activity of combining talabostat and pembrolizumab (anti–programmed death-1 antibody) in advanced solid tumor patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The primary objective was assessment of dose-limiting toxicity (DLT) rates in the first six patients (lead-in stage) and response rate (efficacy stage; included cohort A [checkpoint inhibitor (ICI) naive] and cohort B [ICI pretreated]) for the study treatment using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and immune RECIST (iRECIST). Efficacy was assessed using a Bayesian optimal phase 2 design.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 31 patients enrolled in this trial (14 in cohort A, 17 in cohort B). The median age was 61 years; 17 (55%) patients were male and 21 (68%) patients were White. Among 19 (61%) patients evaluable for response, the best response was stable disease in nine patients, unconfirmed progressive disease in seven patients, and clinical progressive disease in three patients based on iRECIST. Disease control rate was 47%. One patient with programmed death-ligand 1 negative, microsatellite stable endometrial cancer had unconfirmed partial response. Median progression-free survival was 2.7 months; median overall survival was 20.5 months. One patient (cohort A) experienced a grade 4 hypotension as a DLT and treatment discontinuation. The most common toxicities were hypotension (22.6%), fatigue (9.7%), diarrhea, rash, thrombocytopenia, vomiting, syncope, general disorders and administration site conditions-other, and skin and subcutaneous tissue disorders-other, each in 6.5% of patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study of the combination of talabostat and pembrolizumab in patients with advanced solid tumors demonstrated predictable adverse events and limited activity. The combination was shown to be safe. Efficacy data shows immune stable disease in nine of 19 evaluable patients, and an unconfirmed immune partial response in a patient with endometrial cancer.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"131 3","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143031623","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}
Jordan Baeker Bispo PhD, MPH, Ahmedin Jemal DVM, PhD, Farhad Islami MD, PhD
Background
Low participation in cancer screening contributes to a disproportionate burden of cancer morbidity and mortality among adults with mental health (MH) disorders like depression and anxiety. It is unknown whether MH treatment affects screening participation in this population.
Methods
Using the 2019 and 2021 National Health Interview Survey, data from screening-eligible respondents with a history of depression or anxiety were analyzed. Dependent variables include up-to-date screening for breast (BC), cervical (CVC), and colorectal cancer (CRC). Exposures of interest included past year receipt of any MH treatment and delayed or nonreceipt of counseling because of cost. Multivariable logistic regression was used to model associations between MH treatment and screening, controlling for sociodemographic and health care access characteristics.
Results
The prevalence of up-to-date screening was lower for those who did not receive MH treatment than those who did among respondents reporting regular feelings of depression or anxiety (adjusted prevalence ratio [aPR] = 0.83; 95% CI, 0.76–0.91 for BC; aPR = 0.83; 95% CI, 0.77–0.88 for CVC; aPR = 0.78; 95% CI, 0.73–0.84 for CRC) or ever being diagnosed with depression or anxiety (aPR = 0.86; 95% CI, 0.81–0.91 for BC; aPR = 0.87; 95% CI, 0.83–0.91 for CVC; aPR = 0.84; 95% CI, 0.80–0.88 for CRC). BC screening was lower for those who reported delayed or nonreceipt of therapy because of cost than those who did not (aPR = 0.88; 95% CI, 0.78–0.99 among adults with regular feelings of depression or anxiety; aPR = 0.91; 95% CI, 0.83–0.99 among adults ever diagnosed).
Conclusions
MH treatment is associated with increased screening among adults with a history of depression or anxiety. Enhancing MH treatment receipt could reduce the cancer burden in this population.
{"title":"Association of mental health treatment receipt with cancer screening among US adults with a history of anxiety or depression","authors":"Jordan Baeker Bispo PhD, MPH, Ahmedin Jemal DVM, PhD, Farhad Islami MD, PhD","doi":"10.1002/cncr.35724","DOIUrl":"10.1002/cncr.35724","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Low participation in cancer screening contributes to a disproportionate burden of cancer morbidity and mortality among adults with mental health (MH) disorders like depression and anxiety. It is unknown whether MH treatment affects screening participation in this population.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using the 2019 and 2021 National Health Interview Survey, data from screening-eligible respondents with a history of depression or anxiety were analyzed. Dependent variables include up-to-date screening for breast (BC), cervical (CVC), and colorectal cancer (CRC). Exposures of interest included past year receipt of any MH treatment and delayed or nonreceipt of counseling because of cost. Multivariable logistic regression was used to model associations between MH treatment and screening, controlling for sociodemographic and health care access characteristics.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The prevalence of up-to-date screening was lower for those who did not receive MH treatment than those who did among respondents reporting regular feelings of depression or anxiety (adjusted prevalence ratio [aPR] = 0.83; 95% CI, 0.76–0.91 for BC; aPR = 0.83; 95% CI, 0.77–0.88 for CVC; aPR = 0.78; 95% CI, 0.73–0.84 for CRC) or ever being diagnosed with depression or anxiety (aPR = 0.86; 95% CI, 0.81–0.91 for BC; aPR = 0.87; 95% CI, 0.83–0.91 for CVC; aPR = 0.84; 95% CI, 0.80–0.88 for CRC). BC screening was lower for those who reported delayed or nonreceipt of therapy because of cost than those who did not (aPR = 0.88; 95% CI, 0.78–0.99 among adults with regular feelings of depression or anxiety; aPR = 0.91; 95% CI, 0.83–0.99 among adults ever diagnosed).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>MH treatment is associated with increased screening among adults with a history of depression or anxiety. Enhancing MH treatment receipt could reduce the cancer burden in this population.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"131 3","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996825","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}
{"title":"Addressing socioeconomic barriers in the implementation of American Society of Clinical Oncology palliative care guidelines","authors":"Raffaele Giusti MD, Giampiero Porzio MD","doi":"10.1002/cncr.35730","DOIUrl":"10.1002/cncr.35730","url":null,"abstract":"","PeriodicalId":138,"journal":{"name":"Cancer","volume":"131 3","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996824","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}
Neha Hippalgaonkar MD, Dezheng Huo PhD, Kent F. Hoskins MD
{"title":"The long road to unbiased estimates of pancreatic cancer incidence in the hereditary breast and ovarian cancer syndrome","authors":"Neha Hippalgaonkar MD, Dezheng Huo PhD, Kent F. Hoskins MD","doi":"10.1002/cncr.35722","DOIUrl":"10.1002/cncr.35722","url":null,"abstract":"","PeriodicalId":138,"journal":{"name":"Cancer","volume":"131 3","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996827","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}
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