BJC reports最新文献

Background: There remains a critical need for prognostic biomarkers of treatment response in epithelial ovarian cancer (EOC). The KELIM score, derived from the rate of CA-125 elimination during the first 100 days of treatment, is a clinically available biomarker of treatment response to platinum-based chemotherapy, its utility is limited by the need for post-treatment data. Tumor-stroma proportion (TSP) has emerged as a prognostic biomarker across several malignancies. Studies from our group have shown that high TSP (≥50% stroma content assessed by pathologist evaluation, TSP_manual) is associated with platinum resistance and poor survival in EOC at diagnosis and before treatment.

Methods: We compared the prognostic value of TSP and KELIM by analyzing manual pathologist (TSP_manual) and artificial intelligence-derived assessments (TSP_auto) on digitized images from a cohort of EOC specimens.

Results: In this cohort, we showed the prognostic significance of TSP_manual, confirming prior findings. Furthermore, TSP_auto and TSP_manual assessments were highly concordant (94% agreement, Cohen's Kappa 0.89, p<0.001), providing a highly reproducible, automated approach. Unlike KELIM, which was only associated with platinum resistance, high TSP_auto was significantly associated with poor survival (HR 1.99, p = 0.02).

Conclusion: These findings support AI-derived TSP as a pre-treatment prognostic biomarker for EOC that complements KELIM.

The implementation of mainstream germline genetic testing in breast cancer patients has both benefits and challenges. Multiple aspects need to be considered for the outline of gene panels and the amount of pre-test genetic counselling. Mainstream genetic testing is mainly performed to stratify patients for targeted treatment. In addition, identification of germline pathogenic variants in cancer risk genes may have surgical implications, consequences for surveillance of other organs at risk of cancer, as well as family implications among relatives at risk. To ensure that patients are well informed, the introduction of mainstream genetic testing performed by non-genetic health care specialists requires an adapted pre-test counselling visit. Here, we review the literature and propose a web-based educational session and pocket guide to support implementation of mainstream testing in oncology practice.

Background: The aim is to determine the effects of obesity and metformin-use in predicting prostate cancer (PC) risk.

Methods: We used male participants from the Sax Institute's 45 and Up Study (Australia), recruited between 2005-2009. Participants completed a questionnaire at recruitment which included information on self-reported body mass index (BMI; kg/m²). Participants' baseline data were linked by the Centre for Health Record Linkage to the NSW Cancer Registry and to Services Australia to identify index prescription claims for diabetic medications between January 2012 and December 2019. Multivariable Joint Cox regression analyses were used to examine associations between BMI, diabetic medications, and PC risk by cancer spread.

Results: Of the 94,674 eligible participants, there were 5265 incident PC cases (localised n = 2638, regional n = 925, metastatic n = 1514 and unknown; n = 1514) diagnosed between January 2012 and December 2019. BMI ≥ 30 kg/m² was associated with increased risk of metastatic PC (versus <30 kg/m²; HR_adjusted = 1.67;95%CI:1.10-2.54); metformin-use was associated with reduced risk of localised PC (versus non-users; HR_{-metformin-only} = 0.65;95%CI:0.50-0.84; HR_{metformin-combination} = 0.51;95%CI:0.34-0.77). Reduced risk of localised PC diagnosis in metformin-users (versus non-users) was evident across all BMI categories.

Conclusion: Metformin-use in obese men is associated with reduced PC risk, if detected early. Further research could inform the repurposing of metformin for PC control.

Background: Neuroendocrine neoplasms (NENs) are rare and often present with non-specific symptoms. Diagnostic delays of 4 years or more have been reported in patient surveys, primarily attributed to low recognition of symptoms and multiple primary care consultations. However, population-based evidence is sparse. We characterised diagnostic pathways to guide improvement efforts.

Methods: We used National Cancer Diagnosis Audit (NCDA) 2018 data for all adults diagnosed with NEN of eleven cancer sites. Primary care-led investigations were grouped into blood, urinary, imaging, endoscopy, and other. The number of pre-referral consultations, the primary care interval (PCI), and the diagnostic interval (DI) were measured.

Results: Data were available on 919 adult patients. Case-mix by cancer site was comparable to national cancer registry data. 45% were referred as an Urgent Suspected Cancer; 18% as an emergency. The median PCI and DI were 7 and 54 days, respectively (2 and 36 among NCDA cases overall). Of 633 patients (69%) with at least one recorded GP consultation, 25% (161/633) had three or more pre-referral consultations. 30% of patients underwent diagnostic imaging.

Conclusions: Comparatively, median PCI and DI were longer (and use of diagnostic tests greater) for NEN than other cancers in the NCDA, but substantially shorter than previously reported.

Background: A previously conducted study reported that insomnia rates among oncology patients in Ireland are twice that of the general population, and that a breast cancer diagnosis was an independent predictor for clinical insomnia disorder. The aim of this study is to explore this interaction further in a larger cohort of breast cancer patients.

Methods: We evaluated sleep disturbance and sleep hygiene practices among adult breast cancer patients via questionnaires. Sociodemographic data, clinical characteristics, sleep history and attitudes towards sleep assessments were collected and analysed.

Results: The comprehensive 40-item questionnaire was completed by 315 patients. Of this cohort, 56% reported a change in their sleeping patterns since their cancer diagnosis, with over 55% of the study population having sub-threshold or clinical insomnia disorder. Although 64.2% of patients believed that questions regarding sleep should be part of breast cancer assessment, only 32% recalled being asked about sleep by a healthcare worker. Moreover, only 27.1% of respondents felt their sleeping difficulties were adequately dealt with since their diagnosis.

Conclusion: In summary, sleep disturbance is prevalent among breast cancer patients. Despite a majority of breast cancer patients recognising the importance of sleep assessment, a significant gap remains in healthcare providers addressing these concerns effectively.

Background: BRCA1 and BRCA2 carriers have increased risk of pancreatic cancer (PC). We have studied prospective incidence rate and cumulative risk of PC in a large cohort of confirmed carriers.

Methods: BRCA1/2 carriers without PC prior to genetic testing were identified from the clinical registry at Section for Hereditary Cancer, Oslo University Hospital. Cancer diagnoses were collected from Cancer Registry of Norway (CRN). Standardized incidence ratios (SIRs) were derived from national reference rates. The Kaplan-Meier method was used to calculate cumulative risk.

Results: Among 2681 BRCA1 carriers, we observed 13 cases versus 4.73 expected (SIR 2.75, 95% CI 1.46-4,70). In 1476 BRCA2 carriers, we observed 9 cases versus 1.89 expected (SIR 4.76, 95% CI 2.18-9.04). Suggestively, there were higher risks among female BRCA2 carriers (SIR 6.52, 95% CI 2.82-12.85, 8 cases) and male BRCA1 carriers (SIR 5.51, 95% CI 2.52-10.47, 9 cases), who had cumulative risks at 70 years of 1.2% and 2.5% respectively.

Conclusions: BRCA1/2 carriers had three times more cases of PC than expected, suggestively higher among female BRCA2 and male BRCA1 carriers. Cumulative risk of PC at 70 years in the latter two groups was less than 3% (0.5% and 0.7% in all Norwegian males and females observed until age 70 based on population data).

Objectives: Advanced non-small cell lung cancer (NSCLC) treatment paradigms include prolonged systemic anti-cancer therapy (SACT) courses. Treatment breaks during significant life events may align with patients' care goals but are poorly studied. We evaluated the temporal patterns of palliative SACT received by NSCLC patients during Christmas 2006-2023, a period during which treatment options increased.

Methods: A retrospective, longitudinal study using electronic records examined palliative SACT for NSCLC in the month of December 2006-2023. It was conducted in a hospital designated as a European Society of Medical Oncology Designated Centre of Integrated Oncology and Palliative Care Services.

Results: In December 2006-2023, 250 patients with NSCLC received palliative SACT with a mean age of 65.5 years (range: 36-94). Adenocarcinoma constituted 171 cases, and 188 patients were stage IV. During their last Christmas, 53% received palliative SACT (n = 133/250), 4% died within 30 days of treatment (n = 5/133) and 5% spent their last Christmas Eve/Day and/or Boxing Day admitted in hospital (n = 7/133). The proportion of those alive the following Christmas increased over the study period (p < 0.001).

Conclusions: Most advanced NSCLC patients received palliative SACT during their last Christmas, reflecting the need for greater cognisance of goal-concordant care and for studies to provide an evidence basis for treatment breaks.

Background: The 2018 World Cancer Research Fund (WCRF)/American Institute for Cancer Research (AICR) Cancer Prevention Recommendations aim to lower cancer incidence. Our study explored associations between adherence to these Recommendations and the risk of first cancer incidence in a US cohort.

Methods: Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial Study participants who were cancer-free at baseline and who had height, weight, physical activity, diet, and alcohol data to estimate the standardized 2018 WCRF/AICR Score (n = 69,061) were included. Associations between Score and cancer endpoints, including any cancers, any of the 17 WCRF/AICR-reviewed cancers, and individual cancer sites were investigated using multivariable Cox proportional hazard models, adjusting for covariates.

Results: Mean Score was 3.55 points (range 0-7). During a median follow-up of 10 years, 11,109 participants developed cancer. The 2018 WCRF/AICR Score was significantly inversely associated with risk of any cancers (HR per 1-point increment:0.97; 95% CI: 0.95-0.99), any of the 17 WCRF/AICR-reviewed cancers (HR: 0.97; 95% CI: 0.95-0.99), pancreatic (HR:0.86; 95% CI: 0.78-0.96), and breast (HR:0.91; 95% CI: 0.87-0.96) cancers.

Discussion: Our findings support adherence to the WCRF/AICR Cancer Prevention Recommendations for reducing risk of cancer incidence, particularly breast and pancreatic cancers, in the US.

Clinical registration numbers: The PLCO Cancer Screening Trial is registered with ClinicalTrials.gov: NCT00002540 (Prostate), NCT01696968 (Lung), NCT01696981 (Colorectal), NCT01696994 (Ovarian), and NCT00339495 (EEMS).

Background: Colorectal cancer (CRC) remains a significant clinical challenge. Immunotherapy against programmed cell death 1 protein (PD-1) in CRC has limited success. Intriguingly, CRC cells express PD-1 (ciPD-1) intrinsically, and we report here its function with respect to chemotherapy.

Methods: We evaluated the associations between ciPD-1 expression and disease progression, overall survival, and upregulation of survival pathways in human CRC tumors. Expression levels of ciPD-1 in CRC cells were modulated to evaluate its biological role in vitro.

Results: High expression levels of PD-1 in CRC tumors are associated with inferior outcomes; these tumors are also more aggressive and drug-resistant. Expression levels of ciPD-1 in CRC cells increase during 5-FU or CPT-11 treatment and are accompanied by upregulation of cell survival pathways. When ciPD-1 is inhibited, the cell-killing effects of 5-FU or CPT-11 were significantly increased. Our data show that ciPD-1 signaling occurs via MAPK signaling in CRC cells to support survival under stress conditions.

Conclusions: CRC tumors with high levels of ciPD-1 are more aggressive and associated with inferior outcomes. Reducing ciPD-1 levels in CRC cells make them more sensitive to chemotherapy. The aggregate results suggest that using a PD-1 inhibitor with first-line treatments in CRC could improve therapeutic efficacy. Proposed biological role of ciPD-1 in CRC cells. After exposure to chemotherapy, radiotherapy, or nutrient deprivation, ciPD-1 expression is elevated in CRC cells. Subsequently, ciPD-1 activates MAPK and AKT signaling pathways to increase proliferation and differentiation, resulting in drug resistance and tumor growth in CRC cells. The administration of anti-PD-1 immunotherapy with chemotherapy in CRC cells could abrogate ciPD-1 activity and enhance the efficacy of chemotherapy to overcome resistance.