Cancer最新文献

Background: Professional guidelines recommend molecular profiling for mismatch repair (MMR), p53, and polymerase epsilon (POLE) status in endometrial cancer (EC). However, adoption in the United States has not been documented, and barriers to the implementation of testing have not been described.

Methods: In this mixed-methods study, implementation science frameworks were used to develop a quantitative survey. Gynecologic oncologists, medical oncologists, radiation oncologists, and pathologists affiliated with NRG Oncology programs were contacted through snowball sampling and were surveyed during 2022-2023. A subset of respondents was interviewed. Statistical and thematic analyses were performed.

Results: At least 403 NRG Oncology-affiliated providers were contacted for the survey, and 107 (26.6%) responded. Greater than 90% of respondents perceived POLE, MMR, and p53 status as important for clinical care. MMR and p53 tests were perceived as easy to obtain, but only 24.2% of respondents reported that POLE testing was moderately or very easy to obtain. Respondents from academic sites reported better access to molecular classification and perceived greater importance of molecular classification compared with respondents from community sites. In thematic analysis of 13 qualitative interviews, cost concerns were reported as large barriers to testing. Interviewees reported a desire for prospective data to guide treatment selection based on classification results.

Conclusions: Although integrating molecular classification into standard pathologic reporting is recommended, and clinicians perceive molecular profiling in early stage EC as important, survey respondents noted significant implementation barriers. Implementation challenges that differ between community oncology and academic practice settings were identified. Strategies to improve equitable access to molecular classification of early stage EC are needed.

Background: The growth of patient and public involvement in clinical research highlights the paucity of literature on operational practices that ensure the success of large, patient-centered outcomes trials. The authors' objective was to identify tools launched by the Comparison of Intravesical Therapy and Surgery as Treatment Options for Bladder Cancer (CISTO) study team to determine their effectiveness in maximizing patient enrollment in this observational, pragmatic trial.

Methods: The primary outcomes for this study were patient screening and enrollment across 36 CISTO study sites. The operational strategies included CISTOquestion email correspondence and All Sites Meetings, specifically poll performance data from meetings, and a nonanonymized feedback survey about the CISTO study's management practices. Effectiveness was measured using correlation analysis with patient cohort data, including screenings, enrollments, post-hoc exclusions, and the post-hoc exclusion rate.

Results: Average screenings and enrollment rose after the implementation of CISTOquestion in April 2021, with the average number of screenings rising from 7.42 to 26.8 patients per month and enrollment rising from 3.76 to 16 patients per month. Use of CISTOquestion was correlated strongly with increased patient screenings and enrollment across all study sites. Eighty-three percent of sites with above-average post-hoc exclusion rates (≥0.092) sent below the average number of CISTOquestion inquiries. Poll performance and survey data revealed that all survey respondents who used CISTOquestion found that it was a valuable and accessible resource.

Conclusions: Of the several operational tools implemented within the CISTO study that aimed to improve patient enrollment, CISTOquestion, a centralized email for addressing eligibility questions, was most beneficial to overall patient accrual.

Background: Androgen-deprivation therapy (ADT) remains a cornerstone in treatment for patients with advanced prostate cancer. ADT is associated with several adverse effects, including osteoporosis, metabolic syndrome, and cardiovascular events, leading to guidelines recommending routine testing to monitor for these toxicities. There is a lack of data assessing adherence to these recommendations.

Methods: The authors conducted a retrospective cohort study using administrative data from Ontario, Canada between 2008 and 2021. They identified all older men (aged 65 years and older) who received ADT for prostate cancer using comprehensive provincial health databases. The primary outcomes were the use of testing for lipids, dysglycemia (glucose), bone health serum, and bone density between 6 weeks before and 1 year after the initiation of ADT.

Results: In total, 29,097 patients were examined, of whom 52.8% were prescribed ADT by urologists, 37.9% were prescribed ADT by radiation oncologists, 2.8% were prescribed ADT by medical oncologists, and 2.4% were prescribed ADT by other physicians. Adherence to guidelines was low: only 21.3% of patients received a bone density scan, 41.2% underwent bone health-related serum tests, 51.3% completed a lipid profile, and 65.9% underwent dysglycemia testing within 1 year of diagnosis. Overall, only 11.9% of patients received all of the recommended investigations. Adherence to testing did not appear to improve over time (2008-2021) or with guideline publication. Patient (age) and physician (specialty) factors had important associations with adherence to testing.

Conclusions: Most patients receiving ADT for prostate cancer do not receive recommended testing to monitor for treatment-related toxicity. Further study is required to address barriers to therapeutic monitoring of men on ADT and to reduce treatment-associated adverse events.

Introduction: Many childhood cancer survivors are at risk for cardiovascular disease and stroke. The North American Children's Oncology Group long-term follow-up guidelines recommend carotid ultrasound in cancer survivors 10 years after neck radiation therapy (RT) ≥40 Gy. The use of carotid ultrasound in this population has not been described.

Methods: Survivors of childhood cancer diagnosed 1970-1999 (N = 8693) and siblings (N = 1989) enrolled in the Childhood Cancer Survivor Study were asked if they had ever had a carotid ultrasound. Prevalence of carotid ultrasound was evaluated. Prevalence ratios (PR) and 95% confidence intervals (CIs) were evaluated in multivariate Poisson regression models.

Results: Among participants with no reported cardiovascular condition, prevalence of carotid ultrasound among survivors with RT ≥40 Gy to the neck (N = 172) was 29.7% (95% CI, 22.5-36.8), significantly higher than those with <40 Gy (prevalence 10.7%; 95% CI, 9.9%-11.4%). Siblings without a cardiovascular condition (N = 1621) had the lowest prevalence of carotid ultrasound (4.7%; 95% CI, 3.6%-5.7%). In a multivariable models among survivors with no reported cardiovascular condition and RT ≥40 Gy to the neck, those who were over age 50 (vs. 18-49) at follow-up (PR = 1.82; 95% CI, 1.09-3.05), with a history of seeing a cancer specialist in the last 2 years (PR = 2.58; 95% CI, 1.53-4.33), or having a colonoscopy (PR = 2.02; 95% CI, 1.17-3.48) or echocardiogram (PR = 6.42; 95% CI, 1.54-26.85) were more likely to have had a carotid ultrasound.

Conclusion: Many survivors do not undergo carotid ultrasound despite meeting existing guidelines. Health care delivery features such as having seen a cancer specialist or having other testing are relevant.

Background: Little is known about financial toxicity in early-phase clinical trial (EP-CT) participants. This study sought to describe financial toxicity in EP-CT participants and assess associations with patient characteristics and patient-reported outcomes (PROs).

Methods: Prospectively enrolled EP-CT participants from were followed from April 2021 through January 2023. Participants completed the Comprehensive Score for Financial Toxicity (<26 = financial toxicity) at time of treatment. Quality of life (QOL), symptoms, coping, and resource concerns were surveyed. Associations of financial toxicity with patient characteristics, PROs, and clinical outcomes were explored.

Results: Of 261 eligible patients, 197 completed baseline assessments (75.5%, median age = 63.4 years [31.8-88.6], 57.4% female). Most common cancers were gastrointestinal (33.0%) and breast (20.8%). More than one third (34.0%) of patients reported financial toxicity. Patients with financial toxicity were more likely to be <65 years (70.2% vs 48.5%, p = .004), unemployed (45.5% vs 16.9%, p < .001), not have attended college (53.1% vs 26.4%, p = .002), and have income <$60,000 (59.7% vs 25.4%, p < .001). In adjusted models, patients with financial toxicity reported lower QOL (B = -6.66, p = .004) and acceptance (B = -0.78, p = .002), and increased self-blame (B = 0.87, p < .001). They were more likely to have concerns regarding housing (10.6% vs 2.3%, p = .025), bills (31.8% vs 3.8%, p < .001), food (9.1% vs 0.8%, p = .006), and employment (21.2% vs 1.5%, p < .001). There was no difference in time on trial (hazard ratio, 1.03; p = .860) or survival (hazard ratio, 1.16; p = .496).

Conclusions: More than one third of EP-CT participants reported financial toxicity. Factors associated with financial toxicity and demonstrated novel associations among financial toxicity with QOL, coping, and resource concerns were identified, highlighting the need to address financial toxicity among this population.

A new model accurately predicts for which patients with chronic myeloid leukemia (CML) initial tyrosine kinase inhibitor (TKI) therapy will fail. This includes imatinib and second-generation TKIs. The model also offers physicians a new tool that may enable more personalized treatment approaches to CML according to a study published in Blood.¹

Developed by researchers in China, the model incorporates clinical covariates associated with TKI therapy failure to stratify patients into low-, intermediate-, and high-risk subgroups with significantly different cumulative incidences of treatment failure. The clinical covariates include sex, age, hemoglobin concentration, blood blast percentage, spleen size, and additional high-risk chromosomal abnormalities in Philadelphia chromosome–positive cells. The model was first developed using data from a single-center test cohort of 1955 patients with chronic-phase CML who were receiving as their initial treatment either a first-generation TKI (imatinib) or a second-generation TKI (nilotinib, dasatinib, or flumatinib), and it was then validated in 3454 patients from 76 other centers.

The model showed good predictive accuracy, as demonstrated by a high time-dependent area under the receiver operating characteristic curve (AUROC). Specifically, the model showed good prediction sensitivity and specificity with 1-, 3-, and 5-year AUROC scores of 0.83, 0.84, and 0.84, respectively (training set), and 0.77, 0.79, and 0.80, respectively (validation set). The AUROC scores range from 0 to 1, with 1 indicating a perfect performance and 0.5 indicating random guessing.

These AUROC values indicate better prediction discrimination than those offered by the Sokal and EUTOS long-term survival (ELTS) scores, the most widely used scores for guiding initial TKI therapy in patients with chronic-phase CML and predicting CML-related survival.

The authors say that they see their model as being used in conjunction with the Sokal and ELTS scores, not as a replacement, to further stratify patients to make risk assessment more precise.

“Using this model, physicians can better predict which patients are at high risk of therapy failure and make a more informed decision regarding the choice of the appropriate initial TKI,” says the senior author of the study, Qian Jiang, MD, professor and deputy chair of the Department of Hematology at Peking University People’s Hospital in Beijing, China.

Dr Jiang says that the model is ready for clinical use and that it can be readily applied in the clinical setting because the covariates on which the model is based are easily collected at the time of CML diagnosis.

Although the model is robust, he underscores that further validation is needed in Western populations to ensure its broad applicability and effectiveness across different demographic groups.

Background: Midlife baseline prostate-specific antigen (MB PSA), defined as a single PSA value measured between 40-59 years of age, has been proposed as a tool that can limit potential harms of PSA screening. This study aimed to examine the ability of MB PSA versus PSA doubling time (PSADT) and PSA velocity (PSAV) in assessing the likelihood of developing of lethal prostate cancer (PCa) in a diverse and contemporary North American population.

Methods: Men 40-59 years old, who received their first PSA between the years 1995 and 2019, were included. For MB PSA values, the first PSA test result was included. For PSADT, the first two PSA test results were included. For PSAV, the first three PSA test results within 30 months were included. Selection criteria resulted in a total of 77,594 patients with at least two PSA test results and 11,634 patients with at least three PSA test results. Multivariable Fine-Gray regression was used to examine the impact of the value of the PSA testing methods on the development of lethal PCa (defined as death from PCa or development of metastatic disease either at diagnosis or during follow-up). Time-dependent receiver operating characteristic/area under the curve (AUC) at 5, 10, and 15 years were plotted.

Results: In the main cohort, patients were most frequently in the 50-54 age category (32.8%), had a Charlson comorbidity index of 0 (70.5%), and were White (63.2%). Of these, 9.3% had the midlife baseline PSA in the top 10th percentile, and 0.4% had a PSADT 0-6 months. Lethal PCa was diagnosed in 593 (0.8%) patients. The median (interquartile range) time to lethal PCa was 8.6 (3.2-14.9) years. In the main cohort, MB PSA and PSADT showed significant associations with the occurrence of lethal PCa, with a hazard ratio (HR) of 6.10 (95% confidence interval [CI], 4.85-7.68) and HR of 2.20 (95% CI, 1.07-4.54) for patients in the top 10th percentile MB PSA group and in the PSADT between 0 to <6 months group, respectively. In patients with three PSA results available, MB PSA and PSAV showed significant associations with the occurrence of lethal PCa, with a HR of 3.95 (95% CI, 2.29-6.79) and 3.57 (95% CI, 2.17-5.86) for patients in the top 10th percentile MB PSA group and in the in the PSAV >0.4 ng/mL/year group, respectively. PSADT and PSAV did not exhibit higher AUCs than MB PSA in assessing the likelihood of lethal PCa. Specifically, they were 0.818 and 0.708 at 10 and 15 years, respectively, for the PSADT; 0.862 and 0.756 at 10 and 15 years, respectively, for the PSAV; and 0.868 and 0.762 at 10 and 15 years, respectively, for the MB PSA (all p > .05).

Conclusions: The study findings are that PSAV or PSADT were not superior to midlife baseline in assessing the likelihood of developing lethal PCa. This suggests that these variables may not have practical use in enhancing PSA screening strategies in a clinical setting.