JNCI Journal of the National Cancer Institute最新文献

Pediatric Hodgkin lymphoma (pHL) is a highly curable malignancy in children, adolescents, and young adults, and current treatment strategies aim to minimize adverse late effects. Many patients are enrolled in clinical trials with centralized review for both initial and interim staging. Although academic guidelines provide a structured framework for image interpretation, real-world clinical scenarios sometimes present imaging pitfalls that require nuanced judgment. Morphologic and metabolic imaging pitfalls refer to misinterpretation of findings that occur during staging, disease evaluation, or post-treatment surveillance. In pHL, such pitfalls may result from suboptimal imaging conditions, concurrent inflammatory, infectious, or other findings. These findings do not indicate neoplastic disease but rather are manifestations of other processes specific to each tissue or organ. This Staging, Evaluation and Response Criteria Harmonization for Childhood, Adolescent, and Young Adult Hodgkin Lymphoma (SEARCH for CAYAHL) initiative represents a transatlantic collaboration among multidisciplinary professionals, aiming to disseminate the insights gained from decades of centralized review experience in North American and European clinical trials. This paper aims to optimize patient care by integrating imaging and clinical expertise in disease staging and surveillance. Although not intended as a comprehensive staging guide, it highlights recurrent imaging pitfalls that may lead to incorrect staging or response assessment. By encouraging interdisciplinary exchange, this work seeks to complement existing literature and serve as a troubleshooting guide for situations where clinical realities diverge from academic paradigms.

Background: Obesity assessed at a single time point in adulthood has shown no consistent association with prostate cancer (PCa) incidence but has been positively associated with PCa death. We investigated the association of total and age-specific adult weight trajectories with PCa aggressiveness and death.

Methods: We analysed data from 258,494 men in Sweden with at least three weight observations between ages 17 and 60. Individual weight trajectories were estimated using linear mixed-effects models with natural cubic and linear splines for age, incorporating random intercepts and slopes. These estimates were included in multivariable-adjusted Cox proportional hazards models.

Results: Over a median follow-up of 25 years, 22,055 men were diagnosed with PCa and 4,547 died from the disease. Steep weight gain was inversely associated with PCa diagnosed during the PSA testing era (1997 onwards) and via asymptomatic PSA testing, but not with aggressive PCa. Among men with PCa, steep weight gain was associated with increased risk of PCa death (HR quintile 5 vs. 1 = 1.23, 95% CI = 1.08 to 1.40), primarily driven by weight gain between ages 45 and 60 (HR per 1 kg/year = 1.31, 95% CI = 1.10 to 1.57).

Conclusions: The associations observed for incident PCa appear to be influenced by PSA testing uptake; however, the extent to which detection bias contributes remains uncertain. Conversely, late midlife weight gain was associated with an elevated risk of PCa death, underscoring the importance of weight management during this period as a potentially modifiable factor for reducing PCa death.

Background: Most recurrences after curative surgery for esophageal cancer occur within 2 years. Conventional recurrence-free survival (RFS), calculated from the time of surgery, may underestimate prognosis for patients who remain recurrence-free during the early postoperative years. This study aimed to evaluate conditional RFS and recurrence timing to inform individualized follow-up strategies.

Methods: An individual patient data (IPD) analysis was conducted using randomized controlled trials (RCTs) comparing perioperative treatments for resectable esophageal or gastroesophageal junction cancer. Conditional RFS, defined as the probability of remaining recurrence-free for an additional y years given x years already survived without recurrence (RFSy|RFSx), was estimated.

Results: IPD from 10 phase III and 1 phase II RCTs were analyzed (n = 2268 patients with R0 resection). In squamous cell carcinoma (SCC), RFS5|RFS0 was 47.9%, which increased to 63.0%, 72.5%, 78.2%, and 81.2% at RFS5|RFS1-4. Among patients who recurred, 58.8% of pN-positive cases recurred within 1 year and 81.7% within 2 years, compared with 42.8% and 69.9% in pN0. At baseline (RFS5|RFS0), patients with pN-positive disease or pM1 disease had worse 5-year RFS than those with pN0 or pM0 disease. However, among patients who remained recurrence-free for 4 years after surgery (RFS5|RFS4), the pattern was reversed, with advanced groups showing better subsequent 5-year RFS. Similar trends were observed in adenocarcinoma.

Conclusions: Conditional RFS improves over time, particularly in advanced-stage esophageal cancer. Although advanced cases are typically monitored more intensively, findings suggest comparable follow-up intensity may be appropriate once patients remain recurrence-free for a certain postoperative period.

Childhood cancer survivors are at high risk for developing breast cancer (BC) as a treatment-related neoplasm. Their risk for, and survival after, BC recurrence has not been characterized. In this study, female survivors had a ten-year BC recurrence risk of 14% (95% CI: 10-20%), similar to controls with sporadic BC matched by age, race, ethnicity, and disease characteristics (N = 201 pairs; P = .62). Among survivors with recurrent BC (N = 68), first BCs were largely early stage (0/I/II: 77%). Nearly half (47%) underwent bilateral mastectomies, with 81% performed before recurrence, predominantly from distant metastases. Survivors' ten-year mortality risk after BC recurrence was 89% (95% CI: 61-97%), significantly exceeding controls (40%, 95% CI: 16-57%; P = .0013), for an adjusted 2.8-fold greater risk. BC was the leading cause of death in these survivors; the ten-year cause-specific mortality probability was 67% (95% CI: 53-83%). Comprehensive investigations of BC recurrence drivers and adverse outcomes in this population are needed.

Background: Reference sets are needed to evaluate performance of multi-cancer detection (MCD) assays. The National Cancer Institute (NCI) funded the Alliance reference set study to assess MCDs for use in future trials.

Methods: Individuals with cancer and controls were recruited; blood specimens were collected prior to cancer treatment. A performance evaluation study was designed utilizing reference set samples. Companies (n = 6) were selected to participate based on review of performance data and ability to utilize the blood collection tube. Companies received samples from cancer types their assay was designed to detect ("targeted"), plus additional "non-targeted" and control samples. Companies reported positive/negative calls, risk scores, and tissue-of-origin (TOO) predictions. Sensitivity was computed for early (I-II) and late (III-IV) stage cases, based on positive/negative calls (SEPN) and at fixed 98% specificity (SE98). Specificity and TOO accuracy were computed.

Results: 549 cases (encompassing 13 cancer types) and 413 controls from the reference set were included in the study. Companies assessed samples from median 6 (range 5-9) targeted cancer types and median 8 (range: 7-11) overall cancer types. Median (range) specificity was 92.3% (76.5%-98.5%). Median (range) SEPN was 32% (25%-42%) for early stage 73% (48%-89%) for late stage; while median (range) SE98 was 19% (8%-35%) for early stage and 66% (13%-79%) for late stage. Median sensitivity for non-targeted types was 40% (early stage) and 52% (late stage). Median (range) TOO accuracy (primary predicted site) was 75% (64%-78%).

Conclusions: Sensitivity and specificity varied widely across assays with early-stage sensitivity substantially lower than late-stage sensitivity.

Background: Self-reported smoking may not fully capture individualized risk of smoking-related cancer. Circulating proteins may reflect biological consequences of smoking. Thus, we developed a score from smoking-related proteins and evaluated its association with smoking-related cancer.

Methods: This prospective cohort study included 10,563 participants aged 47-70 years in the Atherosclerosis Risk in Communities study. Plasma proteins were measured by SomaScan. The score was constructed from proteins associated with current smoking, packyears, and/or recent quitting identified by linear regression and elastic net regression. Cox regression was used to estimate adjusted hazard ratios (aHR) and 95% confidence intervals (CI). We confirmed the association in a case-cohort study in the European Prospective Investigation into Cancer and Nutrition (EPIC).

Results: aHRs comparing score quartiles Q4 to Q1 for total incidence and mortality of 13 smoking-related cancers were 3.89 (95% CI 3.06-4.96) and 5.73 (95% CI 4.08-8.06) before, and 2.28 (95% CI 1.65-3.15) and 2.07 (95% CI 1.74-4.10) after adjusting for self-reported smoking. aHRs for lung cancer were 12.1 (95% CI 7.11-20.6) and 14.2 (95% CI 7.58-26.8) before, 3.04 (95% CI 1.59-5.81) and 4.12 (95% CI 1.99-8.53) after adjusting. In EPIC, aHRs for lung cancer were 9.47 (95% CI 6.82-13.15) before and 2.23 (95% CI 1.48-3.35) after adjusting.

Conclusion: The smoking-related protein score provided relative risk information for smoking-associated cancers beyond self-reported smoking, which was confirmed in an independent cohort. Such a score may be considered for use in risk stratification for prevention and cancer screening in settings in which detailed smoking history cannot be obtained.