Cancer Medicine最新文献

Introduction

Tumor histology at diagnosis is used in conjunction with other prognostic features to risk stratify patients with neuroblastoma and to assign therapy regimens. In patients with high-risk disease, adjustment of therapy is tailored to treatment response, largely based on disease imaging following induction chemotherapy and resection of the primary tumor. The goals of this study were to (i) quantify changes in histologic features in the primary tumor between diagnosis and resection, and (ii) assess the prognostic capability of such alterations.

Methods

Tumor histology from paired samples at diagnosis and resection was evaluated from 94 patients with high-risk neuroblastoma enrolled in Children's Oncology Group (COG) trials from 2001 to 2013. Presence of Schwannian stroma, neuropil, degree of differentiation, mitosis karyorrhexis index (MKI), necrosis, and percentage of neuroblastic cells were annotated. Changes in tumor histology between diagnosis and resection were analyzed for association with overall survival (OS) and progression-free survival (PFS).

Results

Significant changes between diagnosis and resection were observed in all histologic parameters (p < 0.01), suggesting a more phenotypically differentiated tumor following induction therapy. A higher percentage of intermediate-high MKI in tumor cells at diagnosis was associated with a lower PFS and OS (p < 0.05). No other histologic factor was associated with survival at diagnosis or resection. The tumor percentage of intermediate-high MKI decreased by a mean of 75% from diagnosis to resection (p < 0.0001). The shift from intermediate/high MKI at diagnosis to low MKI at resection had a PFS hazard ratio (HR) of 2.1 (95% CI: 0.9, 4.9; p = 0.0908) and OS HR = 2.3 (95% CI: 0.9, 5.9; p = 0.0773).

Conclusion

Our findings suggest that primary neuroblastoma tumors undergo a significant morphologic shift following induction chemotherapy to a differentiated, less mitotically active phenotype. However, the alterations are not prognostic of patient outcome either at resection alone, or when the change from diagnosis to resection is considered.

Background

Though tobacco use treatment (TUT) after a cancer diagnosis can improve cancer treatment outcomes and survival, delivery of evidence-based TUT remains underutilized in cancer care. The National Cancer Institute (NCI) Cancer Center Cessation Initiative (C3I) implemented TUT across 52 NCI-Designated Cancer Centers, but there is little information on its long-term sustainment. This study assesses TUT sustainment beyond initial implementation in C3I.

Methods

A web-based survey across 52 C3I centers was conducted during the sustainment phase (2023–2024) following NCI C3I funding. The surveys assessed program funding and the sustainment of the overall program, program components and practices, assessment of implementation and patient outcomes, partnerships, and program scale-out across settings. The survey data were analyzed using descriptive statistics.

Results

Among 47 responding sites (90% response rate), 83% reported continued TUT activity after NCI funding ended with annual operating budgets between $100,000 and $250,000. Most sites (78.7%) reported some institutional support, while few relied on fee-for-service reimbursement (27.7%), bundled payments (8.1%), or support from grants (27.7%) and philanthropic donations (21.3%). Key program components including electronic health record modifications, outcomes reporting, and staff training were largely maintained, with nearly all (46) sites continuing to screen for tobacco use and refer patients to TUT. Perceived program partnerships were strongest with clinicians and departmental leadership, and some programs were scaled out to primary care and other specialties.

Conclusions

Results confirm that most cancer centers sustained key TUT program functions and partnerships with some increasing TUT delivery across larger cancer treatment settings.

Background

Given COVID-19's emergence as a new entity and colorectal cancer's (CRC) rising incidence in certain populations, we conducted this retrospective cohort study to determine the link between COVID-19 and the mortality of those with CRC and how socioeconomic factors influence it.

Methods

Using the National Cancer Database (NCDB), we used logistic regression to get the odds ratio (OR) for delayed treatment and Cox proportional hazards modeling for each stage to get the adjusted hazard ratios (HR) of mortality.

Results

COVID-19 positivity was associated with higher mortality and delayed treatment. The association of race, ethnicity, insurance, urbanization, comorbidity burden, education levels, and income varied by when the patient tested positive relative to colorectal cancer diagnosis.

Conclusions

This implies that vaccinations may be a part of management and that CRC patients who develop COVID-19 infection may warrant closer follow-up during treatment.

Background

Giant cell tumors of bone (GCTB) are RANK/RANK-ligand positive, progressive osteolytic tumors. There was no medical treatment for GCTB based on efficacy and safety data from Chinese patients. A single-arm, phase II study demonstrated the promising efficacy of JMT103 in unresectable or surgically challenging GCTB. Patient-level outcomes from the single-arm trial were compared with real-world data from denosumab or non-denosumab treated patients to estimate comparative efficacy in unresectable or surgically challenging GCTB.

Methods

The real-world data were retrospectively collected from three hospitals between January 2013 and December 2023. The eligibility criteria of the two cohorts were based on the JMT103 single-arm study. Propensity score matching was used to balance the baseline characteristics of patients in the JMT103 and the real-world cohorts. The primary endpoint was histopathological or 12 week radiological objective tumor response rate (OTR). Secondary endpoints included tumor response rate throughout the study, objective response rate, disease control rate, and safety profiles.

Results

166 and 135 patients were finally included in the non-denosumab and denosumab cohorts, respectively. After 1:1 nearest neighbor matching, the OTR of the JMT103 cohort was significantly higher than that of the non-denosumab cohort (94.2% vs. 4.8%), and was comparable with that of the denosumab cohort (92.0% vs. 67.0%). The same results were observed in tumor response rate throughout the study (JMT103 vs. non-denosumab: 94.2% vs. 4.8%, JMT103 vs. denosumab: 94.3% vs. 86.4%), objective response rate (83.5% vs. 11.1%, 87.4% vs. 80.0%), and disease control rate (100% vs. 70.4%, 100.0% vs. 98.8%).

Conclusion

JMT103 has manageable safety profiles with better effectiveness than non-denosumab and a trend toward greater effectiveness than denosumab in patients with unresectable or surgically challenging GCTB.

Trial Registration

NCT05402865, NCT04255576

Objective

Pancreatic cancer (PC) is one of the common malignant tumors in gastrointestinal tract. The roles of CERKL in PC are unknown.

Methods

Here, online databases were used to analyze CERKL mRNA expression and mutation in PC, predict E3 ligase for CERKL. The roles of CERKL were investigated in cells, mice, and clinic samples. The regulations on CERKL by E3 and lipids fluctuations induced by CERKL were analyzed.

Results

It was found that the expression levels of CERKL mRNA and protein were significantly increased in PC. Meanwhile, CERKL promoted PC cells migration and invasion in vitro and in vivo. L296V mutation on CERKL in PC patient was found in cosmic database. Compared with CERKL, CERKL-L296V could further promote PC cells migration and invasion. Bioinformatics analysis revealed the negative correlation between E3 TRIM21 and CERKL. Furthermore, Trim21 was validated to negatively regulate and bind to CERKL protein. L296V mutation reduced the interaction between CERKL and Trim21, and the ubiquitination on CERKL. Lipidomic analysis showed CERKL down-regulation could increase phosphatidylinositol amount in PC cells. Phosphatidylinositol addition reversed the effects of CERKL in PC cells. Moreover, CERKL knocked down increased phosphatidylinositol 3-phosphate (PI3P) content and autophagy. When CERKL was overexpressed, PI3P and autophagy had opposite changes. Of note, CERKL-L296V had a stronger effect than CERKL on PI3P and autophagy. CERKL induced metastasis could be reduced by autophagy inducer. Thus, CERKL promoted the migration and invasion of pancreatic cancer. L296V mutation enhances the tumor-promoting effect of CERKL.

Conclusions

TRIM21/CERKL/autophagy pathway exists in PC.

Objective

This study examined all-cause and cause-specific cancer mortality among older migrants and non-migrants in Finland and the role of socioeconomic status in mortality differences.

Methods

We used the Finnish Causes of Death Register on all deaths (2002–2020) among individuals aged ≥ 70 (N = 718,717) and the corresponding population-at-risk data (N = 13,241,620 person years). Poisson regression was used with two sequential models adjusting for age at death, calendar year, and region of residence in Finland (M1), and personal annual disposable income (M2).

Results

We found an overall cancer mortality advantage for both migrant men (IRR in the full model 0.83, 95% CI: 0.78–0.89) and migrant women (IRR: 0.89, 95% CI: 0.83–0.95) and lung cancer mortality advantage for migrant men (IRR: 0.77, 95% CI: 0.67–0.89) and women (IRR: 0.67, 95% CI: 0.53–0.85). For migrant men, advantage was found in pancreatic cancer (IRR: 0.76, 95% CI: 0.58–0.99), prostate cancer (IRR: 0.78, 95% CI: 0.66–0.93), and leukaemia and lymphoma (IRR: 0.73, 95% CI: 0.58–0.93), and for women in genital cancers (IRR: 0.69, 95% CI: 0.55–0.86). Notable variations were observed by region of origin and in certain cases, migrants' lower income obscured the full extent of their cancer mortality advantage. A mortality disadvantage was observed in stomach cancer among men (IRR: 2.76, 95% CI: 2.08–3.65) and women (IRR: 2.32, 95% CI: 1.79–3.00) born in the former USSR. Liver cancer mortality disadvantage was found for men from the Global South and East (IRR: 2.00, 95% CI: 1.10–3.61), and this association was attenuated after adjustment for personal disposable income. In cancers of the urinary tract, men born in Sweden had elevated mortality (IRR: 2.09, 95% CI: 1.14–3.81).

Conclusion

Finings underscore the need for targeted cancer prevention and screening programmes that account for the diverse backgrounds, sex, socioeconomic status, and health risks of migrant populations, particularly those from higher-risk regions.

Introduction

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease, with often a high Ki-67 proliferation index. Prognosis is associated with lymphoma stage, lactate dehydrogenase level, and metabolic tumor volume. Thus, intuitively, time from symptom onset to diagnosis would be assumed to be essential for treatment outcome, but existing literature is conflicting.

Materials and Methods

This prospective study evaluated diagnostic pathways and their impact on treatment outcomes in 160 patients with DLBCL.

Results

The mean time from symptom onset to treatment initiation (TST) was 146 days. Mean patient-associated delay from the onset of symptoms to the first healthcare contact was 54 days; mean time from symptoms to biopsy was 130 days; and from biopsy to treatment initiation was 19 days. Prolonged time from symptom onset to treatment (TST) > 3 months was associated with a higher International Prognostic Index (IPI) score, whereas prolonged time from biopsy to treatment initiation (TBT) > 2 weeks was associated with better performance status and a lower IPI score. Prolonged time from symptom onset to treatment initiation was not associated with progression-free survival (PFS). Prolonged time from symptom onset to diagnostic biopsy > 7 weeks implied inferior progression free survival in the whole study cohort (2 year PFS 89% vs. 74%, p = 0.012), as well as among patients with highly proliferating tumors with Ki67 > 70% (2 year PFS 93% vs. 63%, p < 0.001). Longer time from biopsy to treatment initiation (TBT) > 2 weeks implied better progression-free survival (PFS) in patients with low proliferating tumors (2 year progression-free survival (PFS) 25% vs. 87%, p = 0.032), respectively.

Objective

To examine the association between adverse childhood events (ACEs) and cannabis use among adult cancer survivors in the United States.

Methods

We conducted a cross-sectional study of cancer survivors ≥ 18 years old using 2020 Behavioral Risk Factor Surveillance System data. ACEs were categorized as 0, 1, 2–3, and ≥ 4. Weighted multivariable logistic regression estimated the odds of cannabis use by ACE category.

Results

Among 7896 cancer survivors, cannabis use prevalence was 6.0%. ACE distribution was 44.1% (0), 22.7% (1), 20.2% (2–3), and 13.0% (≥ 4). Cannabis use was more common among younger adults, Hispanics, never-married individuals, smokers, and those reporting fair/poor health. Compared to those with 0 ACEs, cancer survivors with 2–3 ACEs (aOR: 2.56, 95% CI: 1.57–4.27) and ≥ 4 ACEs (aOR: 4.10, 95% CI: 2.54–6.64) had significantly higher odds of cannabis use.

Conclusions

Cancer survivors with a higher number of ACEs reported increased odds of cannabis use. These findings support further study of ACEs and substance use in cancer survivors and may inform trauma-informed survivorship care.

Background

Numerous induction therapies have been evaluated for high-risk neuroblastoma (HRNBL). It is not known how these regimens' response rates nor toxicities compare. We aimed to describe and compare key features of HRNBL induction regimens and their associations with study-level end-induction response (EIR).

Methods

We performed a systematic review (PubMed) of prospective trials of frontline HRNBL therapy published January 1, 1995–October 31, 2024 that reported EIR. EIR was measured as partial response or better (PR+) per protocol response criteria.

Results

1395 unique titles were screened, yielding 95 abstracts. Of these, 29 publications evaluating 36 induction regimens met inclusion criteria, with a median of 64.5 patients (range: 7–652) per regimen. Median cycle number was 6 (range: 2–9), cycle length was 21 days (10–28), and total duration of induction was 18 weeks (11.4–36). An alkylator and a platinum agent were used in all regimens. Only six regimens (16.7%) included a novel agent. The median study level EIR rate (PR+) was 84.4% (64.3–100), with a weighted average by the number of participants of 79.4%. Study level EIR did not vary over time. Anthracycline-containing regimens had higher EIRs. Dose cisplatin intensity was negatively associated with EIR. The median toxic death rate was 0% (0–4.1).

Conclusions

Over the past 30 years, induction regimens have relied heavily on conventional chemotherapy. Despite differences in agents, doses, and duration, study-level EIR rates have not improved over time. Future induction regimens incorporating novel agents will be crucial to improve EIR and reduce toxicities.

Background

Cancer-related cognitive impairment (CRCI), for example, impairments in reaction time, processing speed, memory and executive function, may be associated with breast cancer (BC) surgery which can disrupt biological and psychological stress markers. Evidence suggests that light therapy may ameliorate cognitive impairment and stress. In this double-blind, randomized controlled trial, we investigated the efficacy of light therapy on mitigating the impact of BC surgery on CRCI in a national Icelandic cohort of women with BC.

Methods

Participants were randomly allocated to receive circadian-effective blue light (BL, N = 60) or circadian-ineffective dim light (DL, N = 57) for 4 weeks after surgery. The primary outcome was overall cognitive performance (assessed via global composite score), and secondary outcomes were specific cognitive domains, cognitive complaints, psychological (depressive symptoms, overall cancer-related stress and its symptoms: hyperarousal, avoidance, and intrusive thoughts) and biological (cortisol and α-amylase) stress markers. Linear regression and path analyses within structural equation modeling frameworks were conducted, adjusted for baseline cognitive performance, age, education, subsequent cancer treatment, cancer stage, and treatment credibility.

Results

No group differences were found in overall cognitive performance or in specific cognitive domains, except for a non-significant trend for faster reaction times in the BL group (p < 0.11). Additionally, the BL group reported significantly fewer cognitive complaints compared with the DL group (p < 0.05), as well as a non-significant trend for less intrusive thoughts (p < 0.11). No group differences were observed in the biological stress markers.

Conclusion

Overall, these findings suggest that light therapy may help mitigate the adverse effects associated with BC surgery on CRCI and intrusive thoughts, although further research is warranted.

Trial Registration: NCT04418856