JCO oncology practice最新文献

Purpose: Patients with myeloproliferative neoplasms (MPNs), including polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), have an increased incidence of second malignancies. This study describes the patterns, risk factors, and outcomes of second malignancies in MPN with the aim of refining our knowledge.

Methods: Using SEER database (2000-2021), we identified patients diagnosed with MPNs. The incidence, patterns, and risk factors of second malignancies including synchronous neoplasms (SYNs, within 6 months of MPN diagnosis), second primary malignancies (SPMs, after 6 months), and secondary AML (s-AML) were assessed separately. Standardized incidence ratios (SIRs) assessed the risk of SPM and s-AML in the MPN cohort compared with the general population.

Results: Among 43,930 patients with MPN, 1.6% developed SYN, 9.1% SPM, and 1.5% s-AML. Lung, prostate, breast, and colorectal cancers were most frequent solid SPMs, with lung cancer risk particularly higher in PV (SIR, 1.47) and ET (SIR, 1.23). Older age at MPN diagnosis (age 40-59 years, odds ratio [OR; 95% CI], 3.82 [3.09 to 4.78]; age 60-84 years, OR [95% CI], 6.19 [5.02 to 7.7]; ref: 18-39 years) and male sex (v female, OR [95% CI], 1.37 [1.28 to 1.46]) were associated with a higher risk of SPM. The overall SPM risk was higher than that of the general population (SIR [95% CI], 1.14 [1.11 to 1.18]; P < .05), with a particularly higher risk of hematologic SPMs (SIR [95% CI], 1.70 [1.55 to 1.85]; P < .05) and s-AML (SIR [95% CI], 19.36 [17.92 to 20.88]; P < .05). SPM development was associated with reduced median survival (125 v 184 months, P < .0001) after MPN diagnosis. s-AML progression reduced the median survival to 80, 82, and 43 months for patients with PV, ET, and PMF, respectively.

Conclusion: Patients with MPN have a higher risk of second malignancies, compared with the general population, which is associated with reduced survival. This necessitates age-appropriate cancer screening, dermatologic examinations, and long-term surveillance. Further studies are warranted to delineate the underlying factors contributing to this risk.

Purpose: For elderly patients with pancreatic ductal adenocarcinoma (PDAC), FOLFIRINOX (FFX) is often contraindicated due to frequent grade III adverse events (AEs) limiting available data on this population.

Materials and methods: This retrospective single-center study identified patients older than70 years treated with FFX for PDAC (2011-2022). Tumor, G8 score calculation (score <14/17 indicates geriatric examination), geriatric, and nutritional parameters were collected. The primary end point was toxicity, defined as grade ≥3 GI AEs or unplanned hospitalization. Overall survival (OS) and toxicity associated factors were analyzed using Cox regression with stepwise selection.

Results: We included 142 patients: 73 with metastatic PDAC (mPDAC) and 69 with non-mPDAC (nmPDAC). Median age was 74 years (71-84), with 43% age 75 years and older. 80% had Eastern Cooperative Oncology Group 0-1. G8 score ≤14 and severe malnutrition were more frequent in mPDAC (82% and 51%) than in nmPDAC (64% and 27%). Low muscle mass was present in >80% of cases. Median FFX exposure was four cycles in mPDAC and 4.5 in nmPDAC. Overall, 56% experienced toxicity, including two treatment-related deaths. Frequent grade ≥3 AEs included infections (26%), nausea/vomiting (22%), and diarrhea (18%). Early toxicity within 2 months was associated with worse OS. Factors linked to toxicity included metastatic status (hazard ratio [HR], 2.41) and psychiatric comorbidities (HR, 6.96), while cardiovascular disease (HR, 0.35) and history of cancer (HR, 0.22) were protective. In nmPDAC, multidimensional geriatric assessment (MGA) reduced toxicity in G8 ≤ 14 patients.

Conclusion: FFX is feasible in highly selected elderly patients with PDAC. Severe toxicity remains frequent and proactive supportive care-including MGA in cases of G8 ≤ 14-to avoid early severe toxicity that impact significantly survival.

Purpose: Clonal evolution is a mechanism of treatment resistance against epidermal growth factor receptor inhibitors (EGFRi) in metastatic colorectal cancer (mCRC). When EGFRi is discontinued, EGFRi-resistant tumor subclones decay with time, allowing for EGFRi rechallenge at later time. We conducted a meta-analysis to investigate the efficacy of EGFRi rechallenge in mCRC.

Methods: Clinical trials and observational studies investigating the efficacy of EGFRi rechallenge in mCRC were included from PubMed and Embase from inception to December 8, 2024. Hazard ratios (HRs) of overall survival (OS) and progression-free survival (PFS) were aggregated using Bayesian random-effects models. Objective response rates (ORRs) were aggregated using meta-random-effects models.

Results: Twenty-nine studies were included. The pooled median PFS, median OS, and ORR were 3.83 months (95% CI, 3.25 to 4.50), 10.43 months (95% CI, 8.14 to 13.36), and 14.61% (95% CI, 8.70 to 23.51), respectively. EGFRi rechallenge was associated with significantly longer pooled PFS (HR, 0.54 [95% CI, 0.31 to 0.93]) and numerically longer pooled OS (HR, 0.71 [95% CI, 0.46 to 1.09]) than non-EGFRi systemic therapy. Patients without detectable RAS/RAF mutations by circulating tumor DNA (ctDNA) at the time of EGFRi rechallenge had significantly longer OS (HR, 0.43 [95% CI, 0.24 to 0.75]) and PFS (HR, 0.40 [95% CI, 0.26 to 0.62]) than those with ctDNA RAS/RAF mutations. Studies with EGFRi-free intervals ≥4 months before rechallenge (18.77%) had a numerically greater pooled ORR than those with EGFRi-free intervals <4 months (6.60%). No unexpected adverse events were reported, and treatment discontinuation because of adverse events was 2.7%.

Conclusion: EGFRi rechallenge is associated with significantly longer PFS, numerically longer OS, and clinically meaningful ORR as compared with non-EGFRi systemic therapy in mCRC, particularly for ctDNA RAS/RAF wild-type mCRC.

Purpose: Employment is a core component of development in young adulthood and may be drastically affected by cancer. As part of a multi-institution financial navigation trial (ClinicalTrials.gov identifier: NCT05620979), we sought to explore employment-related experiences of long-term young adult (YA) survivors of cancer.

Methods: We conducted a secondary qualitative analysis of YA (age 18-39 years) survivors of hematologic malignancies. Participants completed baseline questionnaires pertaining to education and work. A subset of participants completed an optional semistructured interview after trial completion, focused on financial experiences. To contextualize the cohort and supplement qualitative findings, survey data were analyzed using descriptive statistics. We analyzed interview transcripts using directed content analysis and inductive reasoning to examine employment-related themes.

Results: One hundred thirty YA participants (median 31 years; Q1-Q3, 27-35) were enrolled with median time from cancer diagnosis of 10 years (Q1-Q3, 6-16). Most (82%) were currently employed, 77% of whom worked full time; 21% were students. Almost half (46%) reported that cancer continued to affect their education and/or employment; 29% had taken extended work leave in the previous year for cancer-related reasons. Challenges expressed in interviews with 45 participants included difficulties maintaining work because of treatment and side effects, interruptions affecting employment trajectory, and choosing work primarily for insurance/health-related reasons. Recommendations from YAs included building personal financial literacy, seeking financial resources, and suggesting clinicians incorporate screening and training for vocational and financial challenges.

Conclusion: Many long-term YA survivors of cancer reported substantial, ongoing impacts on their work-related achievement and trajectory. These findings underscore the need for universal screening and support throughout the cancer care continuum.

Purpose: To develop and evaluate real-world interventions to move guidelines on timely palliative care utilization into practice.

Methods: A knowledge-to-action cycle theory-informed, process improvement project facilitated implementation of a clinical practice guideline by (1) systematically screening clinic patients for unmet palliative care needs and alerting the oncologist, (2) using a dedicated community-based palliative care nurse for each referral, and (3) using Shared-care letters (structured communication between oncologist, family physician, and patient) to enhance information exchange and awareness of patients' needs. Implementation occurred for advanced colorectal cancer (CRC) within the GI clinics of the Tom Baker Cancer Center, Calgary, AB, Canada, and the neighboring city's Cross Cancer Institute, Edmonton, AB, Canada acted as control. The primary outcome was the proportion of adult decedents with CRC who received early specialist palliative care (SPC; defined as >90 days before death), evaluated using a pragmatic, controlled, before-and-after study. Eligible decedents in each city were identified using provincial cancer registry data and linked with administrative data identifying palliative care consultation, homecare, hospice, or inpatient unit usage.

Results: The cohort included 695 decedents: 341 baseline period (153 control, 188 intervention, April 2017-December 2018) and 354 implementation period (145 control, 209 intervention, April 2019-December 2020); the mean age was 66.5 years, 60% was male, and 95.2% was urban-dwelling. In the intervention arm, the proportion of decedents who received palliative care >90 days before death increased from 44.7% at baseline to 57.4% after implementation; in the control arm, the proportion decreased from 47.7% to 44.1% (17.7% difference in differences [95% CI, 3.1-32.4]; P = .018).

Conclusion: This intervention effectively increased early SPC utilization and provides a pragmatic approach to achieve and measure system-level change.

Circulating tumor DNA (ctDNA) is increasingly being used to monitor minimal residual disease (MRD) in various solid tumors, including urothelial carcinoma (UC). It has emerged as a promising biomarker for MRD and may serve as a valuable tool to guide treatment decisions, particularly in patients at high risk of recurrence after definitive therapy or those experiencing favorable responses to systemic therapy in the setting of locally advanced or metastatic disease. ctDNA technology is largely agnostic to the type of tumor, which can be either hematologic or solid organ malignancies. Its clinical utility requires validation across different tumor types as ctDNA release kinetics and threshold values for testing often vary. Moreover, it is essential to evaluate ctDNA testing across a range of clinical scenarios, including screening, diagnosis, prognosis, and therapeutic decision making. The optimal frequency and duration of testing also need to be defined, particularly in settings such as postdefinitive therapy and ongoing chemotherapy for metastatic disease. In this study, we will summarize the current literature on the role of ctDNA in urothelial cancer. We will discuss the data that inform us of current clinical practice. Furthermore, we will explore evolving developments in the field from other tumor types and potential future directions in UC. Finally, we will highlight selected clinical scenarios for applications of ctDNA testing and its interpretation.

Purpose: We examined clinician- and facility-level factors associated with selection of nonguideline chemotherapy at treatment initiation in women with stage I-IIIA breast cancer (BC).

Methods: The Optimal Breast Cancer Chemotherapy Dosing Study collected information on chemotherapy delivery in an integrated health care delivery system. This analysis included 9,758 women treated with chemotherapy for stage I-IIIA BC between 2006 and 2019 at Kaiser Permanente Northern California (KPNC). Prevalence ratios (PRs) and corresponding 95% CIs were estimated for the clinician and facility factors in relation to nonguideline regimen (NGR) use. Analyses were stratified by time (pre- and post-2015) to reflect the period before and after KPNC's transition to a subspecialized care model. Secondary outcomes focused on nonguideline drug combinations (NGDCs) and nonguideline administration schedules (NGASs).

Results: Women treated by clinicians with substantially greater time since medical school (30+ years v <10 years since medical school) were more likely to receive NGR (PR, 1.38; 95% CI, 1.01 to 1.88; P trend = .01) with significant associations observed for both NGDC and NGAS. While not associated in the primary analysis, larger practice size (10+ oncologists) was associated with a lower likelihood of NGDC use compared with smaller practices (<5 oncologists; PR, 0.43; 95% CI, 0.26 to 0.70; P trend = .01). Time stratification revealed that, in the study's early years, clinician sex and years since medical school were associated with NGR use, but neither association remained post-2015.

Conclusion: Clinician and facility characteristics significantly influenced the use of NGR in stage I-IIIA BC treatment. Notably, associations diminished over time, suggesting that health system changes in care delivery may enhance guideline adherence and reduce the impact of nonclinical factors on treatment decisions.