Journal of Clinical Oncology最新文献

Purpose: Many women carrying pathogenic variants (pvs) of BRCA1 and BRCA2 genes (pvBRCA1/2) elect to undergo bilateral risk-reducing mastectomy (BRRM) in the belief that it will improve their overall survival (OS). Although many are satisfied with their decision to undergo BRRM a significant minority exhibit regret. We compared long-term oncology outcomes in women with pvBRCA1/2 choosing BRRM with those choosing a program of imaging surveillance.

Methods: All participants were attendees at a regional family history/genetics service and had undergone genetic testing for pvBRCA1/2. Carriers of pvBRCA1/2 elected either to undergo BRRM or imaging surveillance as directed by UK national guidance. A prospective cohort design examined OS, breast cancer-specific death, and breast cancer incidence between the study groups.

Results: A total of 460 women elected to undergo BRRM, while 745 chose surveillance (median age, 37.2 years and 38.5 years, respectively; P = .06). Follow-up totaled 4,652 woman-years after BRRM. Overall annual incidence rate of breast cancer was 2.4%, falling to 0.15% after BRRM, a 94% reduction compared with surveillance alone (log-rank chi-square = 86.1; P < .001). There were nine occult cancers diagnosed at BRRM (2%). Breast cancer-specific deaths were similar in the BRRM and surveillance groups (two and four deaths, respectively; P = .36; 4,634 and 5,419 woman-years of follow-up, respectively). Proportionately, deaths from breast cancer were similar to deaths from ovarian cancer in both treatment groups.

Conclusion: For women electing imaging surveillance over risk-reducing surgery, our results may offer reassurance that their breast cancer-specific survival and OS are unlikely to be compromised. However, breast cancer incidence rates are significantly reduced after BRRM compared with imaging surveillance, which may be important information for women with pvBRCA1/2 considering BRRM.

Purpose: We conducted the PediQUEST Response to the Pediatric Oncology Symptom Experience (PQ Response) randomized controlled trial (RCT) to assess whether combining feedback from an electronic patient-reported outcome (ePRO) system with specialized pediatric palliative care (SPPC) consultation improved health-related quality of life (HRQOL) in children with advanced cancer.

Methods: This multicenter open-label RCT enrolled children 2 years and older with advanced cancer. The study was conducted between April 2018 and December 2021 at five US tertiary-level pediatric cancer centers. All parents and children 5 years and older answered weekly child HRQOL and symptom surveys over 18 weeks (2-week run-in). Child-parent dyads were assigned (1:1) to PQ Response (n = 74) or usual care (n = 80) for 16 weeks. Primary outcomes were the difference between average 16-week and baseline Pediatric Quality of Life Inventory (PedsQL-4.0) total scores reported by parents and children (range, 0-100; higher = better HRQOL; minimal clinically important difference [MCID], 4.5). Secondary outcomes were PedsQL subscales and symptom scores. Analyses followed an intention-to-treat approach.

Results: Of 154 participants randomly assigned, 50% were girls, 78% were White, 17% were Hispanic, and 45% had brain tumors. The mean age was 11 years (standard deviation, 6.1). Parents assigned to PQ Response reported greater improvements in child HRQOL (PedsQL total mean difference 3.45 points [{95% CI, 0.48 to 6.43}; P = .023]; PedsQL physical 4.61 [{95% CI, 0.40 to 8.82}; P = .032]). Children reported similar improvements. Effects did not exceed MCIDs. No improvements were observed in PedsQL-psychosocial or symptom scores. Sensitivity analyses showed consistent effects, with most physical HRQOL scores and several child-reported symptom scores exceeding MCIDs. We observed site-specific variability. At the site with the largest adherence, all effects exceeded MCIDs. No adverse events reported.

Conclusion: Findings suggest benefits of integrating electronic patient-reported outcome feedback and SPPC into pediatric advanced cancer care. Enhanced implementation strategies are needed to optimize clinical impact.

This poem reflects how cancer survivors endure profound loneliness caused by treatment and medical isolation, standing apart from collective celebration and social warmth, while sustaining a stoic, persistent hope through resilience and quiet ritual.

Purpose: To provide evidence-based recommendations for patients with stage IV non-small cell lung cancer (NSCLC) without driver alterations.

Methods: This ASCO living guideline offers continually updated recommendations based on an ongoing systematic review of randomized controlled trials (RCTs), with the latest time frame spanning March-October 2025. An Expert Panel of medical oncology, pulmonary, community oncology, research methodology, and advocacy experts was convened. The literature search included systematic reviews, meta-analyses, and RCTs. Outcomes of interest include efficacy and safety. Expert Panel members used available evidence and informal consensus to develop evidence-based guideline recommendations.

Results: This guideline consolidates all previous updates and reflects the body of evidence informing this guideline topic. Six new RCTs were identified in the latest search of the literature to date.

Recommendations: Evidence-based recommendations were updated to address first, second, and subsequent treatment options for patients without driver alterations.Additional information is available at www.asco.org/thoracic-cancer-guidelines.

Purpose: To provide evidence-based recommendations for patients with stage IV non-small cell lung cancer with driver alterations.

Methods: This ASCO living guideline offers continually updated recommendations based on an ongoing systematic review of randomized controlled trials (RCTs), with the latest time frame spanning March-October 2025. An Expert Panel of medical oncology, pulmonary, community oncology, research methodology, and advocacy experts was convened. The literature search included systematic reviews, meta-analyses, and RCTs. Outcomes of interest include efficacy and safety. Expert Panel members used available evidence and informal consensus to develop evidence-based guideline recommendations.

Results: This guideline consolidates all previous updates and reflects the body of evidence informing this guideline topic. Thirteen studies were identified in the latest search of literature to date.

Recommendations: Evidence-based recommendations were updated to address first, second, and subsequent treatment options for patients with driver alterations.Additional information is available at www.asco.org/thoracic-cancer-guidelines.

Purpose: Despite narrowing racial gaps, disparities persist across cancer types and socioeconomic levels. The diminishing returns hypothesis suggests that economic advantage yields fewer health benefits for Black individuals but is largely unexplored in the context of cancer. We examined the diminishing returns among Black and White individuals across cancer types using a nationally representative study population.

Methods: The study analyzed cancer-specific survival among 5.3 million non-Hispanic Black and White adults diagnosed with primary cancer (2006-2020) using SEER-22. We assessed how race and neighborhood socioeconomic status (SES) jointly affects survival across 21 cancer types. A 10-level race-SES variable was created, using White individuals in the highest-SES group as the reference. The main outcome was cancer-specific death. Diminishing returns were defined quantitively and qualitatively as worse survival for Black individuals even at higher SES. Cox models adjusted for demographics and clinical factors, with multiple imputation for missing data. Social gradients were also evaluated.

Results: Black women showed strong evidence of diminishing returns overall and for seven cancers, especially uterine and breast cancers. A social gradient was also evident in cancers with diminishing returns, except uterine cancer. For Black men, diminishing returns were not observed across all cancers combined but was present in eight cancers-including prostate and colorectal cancers. Most cancers among men exhibited a strong social gradient. Findings were consistent by time period and upon restricting to localized and regional disease in sensitivity analyses.

Conclusion: Higher SES improves cancer survival for White patients but not Black patients, worsening racial disparities for certain cancers.

Purpose: Detection of molecular residual disease using circulating tumor DNA (ctDNA) may enable postoperative risk stratification and guide adjuvant therapy. We evaluated the prognostic value of a tissue-free, epigenomic ctDNA assay in patients with stage III colon cancer (CC) enrolled in a phase III adjuvant chemotherapy trial.

Methods: Plasma samples were collected after surgery and before adjuvant infusional fluorouracil, leucovorin, and oxaliplatin alone or combined with cetuximab. ctDNA was analyzed using a tissue-free assay; in ctDNA-positive patients, tumor fraction (TF) was quantified and genotyping was performed with a 739-gene panel. Associations with disease-free survival (DFS), time to recurrence (TTR), and overall survival (OS) were assessed using multivariable Cox models adjusted for covariates.

Results: Among 2,260 evaluable patients, 461 (20.4%) were ctDNA-positive with significantly higher detection in advanced T-/N-stage, high-grade, obstruction/perforation, and BRAF^V600E tumors. At a median follow-up of 6.1 years, ctDNA positivity was independently associated with shorter TTR (hazard ratio [HR], 5.96 [95% CI, 5.11 to 6.96]), DFS (HR, 5.03 [95% CI, 4.36 to 5.81]), and OS (HR, 4.45 [95% CI, 3.76 to 5.27]; all P < .0001). The 5-year DFS was 27.7% (95% CI, 23.8 to 32.2) v 77.1% (95% CI, 75.1 to 79.1) in ctDNA-positive versus ctDNA-negative patients, and adverse prognostic impact was greater in lower T/N stage, low-risk, and dMMR subsets (interaction P = .0012-.041). Among ctDNA-positive patients, TF was nearly double in those who recurred or died (P = .0002) and stratified patients for TTR, DFS, and OS (all adjusted P < .002). Genotyping identified mutations in FLT1 (OR, 8.99) and PREX2 (OR, 7.73) genes that were most strongly associated with recurrence (P < .03).

Conclusion: Evaluation of ctDNA in resected stage III CC using a tissue-free assay provided robust and independent prognostic value. Higher ctDNA burden, dMMR, and specific mutations defined poor prognostic groups among ctDNA-positive patients.