International Journal of Cancer最新文献

The consensus molecular subtype (CMS) classification divides colon tumors into four subtypes holding promise as a predictive biomarker. However, the effect of adjuvant chemotherapy on recurrence free survival (RFS) per CMS in stage III patients remains inadequately explored. With this intention, we selected stage III colon cancer (CC) patients from the MATCH cohort (n = 575) and RadboudUMC (n = 276) diagnosed between 2005 and 2018. Patients treated with and without adjuvant chemotherapy were matched based on tumor location, T- and N-stage (n = 522). Tumor material was available for 464 patients, with successful RNA extraction and CMS subtyping achieved in 390 patients (surgery alone group: 192, adjuvant chemotherapy group: 198). In the overall cohort, CMS4 was associated with poorest prognosis (HR 1.55; p = .03). Multivariate analysis revealed favorable RFS for the adjuvant chemotherapy group in CMS1, CMS2, and CMS4 tumors (HR 0.19; p = .01, HR 0.27; p < .01, HR 0.19; p < .01, respectively), while no significant difference between treatment groups was observed within CMS3 (HR 0.68; p = .51). CMS subtyping in this non-randomized cohort identified patients with poor prognosis and patients who may not benefit significantly from adjuvant chemotherapy.

The therapeutic efficacy of the anticancer drug cisplatin is limited by acquired drug resistance. Cisplatin forms DNA crosslinks, that, if not removed, lead to replication stress. Due to this, the DNA damage response (DDR) gets activated regulating cell cycle arrest, DNA repair, cell death or survival. This makes DDR components promising targets for the development of new therapeutic approaches aiming to overcome acquired drug resistance. To this end, cisplatin-resistant bladder cancer cells were analyzed regarding their sensitivity to combination treatments with selected pharmacological DDR inhibitors. Synergistic cytolethal effects were achieved after combined treatment with low to moderate doses of the non-genotoxic RAD51-inhibitor (RAD51_i) B02 and CHK1-inhibitor (CHK1_i) PF477736. This effect was also found in cisplatin resistant tumor cells of other origin as well as with other RAD51_i and CHK1_i. Combined treatments promoted decelerated replication, S-phase blockage, accumulation of DNA strand breaks, DDR activation and stimulation of apoptotic cell death as compared to mono-treatment, which is independent of the expression of RAD51, CHK1, and PrimPol. Based on these data, we suggest combined inhibition of RAD51 and CHK1 to overcome acquired cisplatin resistance of malignant cells. We propose that the molecular mechanism of this synergistic toxicity relies on a simultaneous inactivation of two key DNA damage tolerance pathways regulating replication fork restart, thereby circumventing the activation of alternative compensatory mechanisms and, in consequence, eventually effectively triggering apoptotic cell death by replication fork collapse.

Esophageal cancer continues to pose a significant public health issue in areas with increased incidence rates such as China. Although involuntary smoking was defined as a group 1 carcinogen for lung cancer, few studies have explored the impact of environmental tobacco smoking (ETS) on esophageal cancer. In this paper, we examined the association between ETS and esophageal cancer in high-risk groups in Jiangsu Province, China. Epidemiologic data were collected for 2969 newly diagnosed cases and 8019 population controls including exposure to active/passive smoking and risk factors. The unconditional logistic regression model and the semi-Bayes (SB) method were applied to assess adjusted odds ratios (ORs) and confidence intervals (CIs). ETS exposure (ever vs. never) was positively associated with esophageal cancer with an SB-adjusted OR (95% CI) of 1.44 (1.31-1.58) among overall population, and 1.56 (1.35-1.82) among non-smokers (i.e., non-active smokers), with corresponding population attributable fractions of 15.0% (95% CI: 10.3%-18.9%) and 12.1% (95% CI: 8.8%-19.8%), respectively. The association was more prominent in men at work and in women at home, with SB-adjusted OR (95% CI) of 1.36 (1.17-1.58) and 1.61 (1.35-1.58), respectively. A dose-response relationship between ETS exposure and the disease was detected across the entire population as well as in non-smokers. This is the largest population-based case-control study of ETS and esophageal cancer and the first study to evaluate such association among non-smokers in a Chinese population. We recommend strengthening the ongoing anti-tobacco public health initiatives in China with a particular emphasis on creating a tobacco-free work/home environment.

The presence of human immunodeficiency virus (HIV) infection increases the risk of acquiring human papillomavirus (HPV) infection and developing HPV-related adversities. We aimed to estimate the cost-effectiveness of HPV vaccination for women living with HIV in a Chinese setting. A decision-analysis Markov model was developed to estimate the cost-effectiveness of 36 HPV vaccination strategies for women living with HIV aged 18-45 years, from the healthcare system perspective. With the status quo, not vaccinating women living with HIV would lead to 51.99% (51,985/100,000) HIV-related deaths; 35.10% (35,098/100,000) would develop genital warts, 0.36% (355/100,000) develop cervical cancer, and among which 63.66% (226/355) die from cervical cancer over their lifetime (1,601,457 person-years). With a willingness to pay (WTP) threshold of three times gross domestic product (GDP), Gardasil 4 vaccination for all women living with HIV aged 18-45 years was the most cost-effective strategy (ICER = US $32,766/QALY gained). This strategy would reduce genital warts by 35.52% (12,467/35,098), cervical cancers by 12.96% (46/355), and cervical cancer deaths by 12.39% (28/226) over the lifetime of the cohort. If the future domestic Cecolin 9 vaccine is priced at 60% of Gardasil 9, vaccinating all women living with HIV aged 18-45 years with Cecolin 9 would be the most cost-effective strategy (ICER = US $30,493/QALY gained). Improving adherence to antiretroviral therapy for HIV may substantially improve the cost-effectiveness of both Gardasil 4 and Cecolin 9 vaccination.

Virtual reality is on the rise and is currently postulated as one of the most innovative and promising techniques in the management of pain and anxiety in cancer patients, in the face of painful processes or the stress involved in chemotherapy treatment. The objective has been to find out the effectiveness of virtual reality in patients undergoing chemotherapy. Several literature reviews were conducted between November 2023 and January 2024 in the Pubmed, Web of Science and PEDro databases. The keywords "virtual reality," "cancer," "oncology," "exercise" and "chemotherapy" were combined using the Boolean operator AND. 641 manuscripts were selected as potential manuscripts and after elimination of duplicates and application of the inclusion and exclusion criteria, six articles comprised the final review sample. Virtual reality has proven to be an effective technique in reducing the anxiety, pain, asthenia and stress suffered by patients diagnosed with cancer and chemotherapy treatment. The distraction generated by this therapeutic modality, with a wide range of scenarios, helps to reduce the painful perception and worry of these procedures. However, there are no standard application guidelines or application protocols that demonstrate the superiority of one technique over another. Virtual reality could be a valid complementary tool in the treatment of patients undergoing chemotherapy, showing positive results in pain reduction, anxiety, stress or asthenia. More studies are needed, with larger sample sizes and long-term follow-ups to establish treatment protocols in relation to the frequency, intensity, duration and periodicity of interventions with virtual reality.

Whether fertility treatment increases the risk of ovarian cancer has been a concern for many decades, but previous research has yielded conflicting findings. We therefore investigated this association within a large population-based cohort study of infertile women aged 20-45 years and living in Denmark between 1995 and 2017, as identified in the Danish Infertility Cohort (n = 146,110). The study cohort was linked to nationwide registers to obtain information on fertility drug use, cancer diagnoses, covariates, emigration, and vital status was. Hazard ratios (HR) and 95% confidence intervals (CI) with adjustment for potential confounders for ovarian cancer overall and for serous ovarian cancer were estimated using Cox proportional hazard models. During a median 10.3 years of follow-up, 114 women were diagnosed with ovarian cancer of which 65 had serous ovarian cancer. Our results showed that the rate of serous ovarian cancer (HR 1.92; 95% CI 1.16-3.17) was increased after every use of progesterone but the association was not affected by increased follow-up time since first use or with increased cumulative dose. We performed a secondary analysis adding less extensive data from 1971 through 1994 from the Danish Infertility Cohort. In this study cohort, 332 women developed ovarian cancer of which 192 had serous ovarian cancer. The overall results were similar, including the association between every use of progesterone and serous ovarian cancer (HR 2.05: 95% CI: 1.31-3.21). In conclusion, the novel finding that use of progesterone is associated with an increased rate of serous ovarian cancer warrants further investigation.

Recent trials have highlighted the cardiotoxicity of ribociclib, a CDK4/6 inhibitor, particularly its association with QT prolongation. However, studies on the link between CDK4/6 inhibitors and cardiotoxic events show inconsistent results, and the factors influencing these events and related drug interactions remain underexplored. To address these uncertainties, our study utilizes the FDA adverse event reporting system database (Q1 2015 to Q1 2024) to examine the cardiotoxic events of CDK4/6 inhibitors in breast cancer patients. We employed a comprehensive analytical framework, applying disproportionality methods including Bayesian confidence propagation neural network, proportional reporting ratio, and reporting odds ratio. Our findings highlight significant variability in cardiotoxic events among different CDK4/6 inhibitors, with ribociclib (IC: 0.26, 95%CI: 0.18-0.34) exhibiting pronounced cardiotoxicity. Notably, ribociclib was associated with serious cardiotoxic events such as torsade de pointes/QT prolongation (IC: 2.11, 95% CI: 1.90-2.29) and conduction defects (IC: 2.07, 95% CI: 1.87-2.23). For the first time, palbociclib has been identified with positive signals for cardiotoxic events at the preferred terms level, including pulmonary oedema, increased blood pressure, myocardial infarction, and cardiac flutter. Moreover, multivariable logistic regression and Bayesian network analyses reveal that age, geographic location, and the number of concomitant medications significantly influence cardiotoxic events. Our study also highlights significant drug interactions that increase the probability of specific cardiotoxic outcomes, notably with drugs like sertraline, lansoprazole, capecitabine, and torasemide. These findings highlight the need for personalized treatment plans to mitigate cardiotoxic events and improve patient safety.

Hematologic adverse events (AEs) are common and serious toxicities in patients with hematologic malignancies undergoing blinatumomab therapy. However, restrictive selection criteria in pivotal clinical trials can lead to an underestimation of rare but fatal toxicities. In this study, we systematically analyzed hematologic AEs associated with blinatumomab using the Food and Drug Administration Adverse Event Reporting System (FAERS) from October 2014 to December 2023. Disproportionate analysis was performed to identify overreported AEs, with a reporting odds ratio (ROR), and a lower bound of the 95% confidence interval (ROR₀₂₅) exceeding one considered significant. Additionally, adjusted mortality rates and risk ratios (RR) of the top 10 reported hematologic AEs were calculated using a logistic regression model. Among 4745 blinatumomab-related cases, 418 (8.81%) involved hematologic AEs. We identified 22 significantly overreporting hematologic AEs compared to the full database, with myelosuppression (n = 39 [9.33%], ROR₀₂₅ = 8.04), disseminated intravascular coagulation (DIC, n = 31 [7.42%], ROR₀₂₅ = 15.14), and bone marrow failure (n = 14 [3.35%], ROR₀₂₅ = 3.41) notably underestimated in clinical trials. DIC resulted in a substantial mortality rate of 45.16%. Finally, DIC was found to be independently associated with death in a multivariable logistic regression analysis (RR = 2.47 [95% CI: 1.11-3.83]). These findings could aid clinicians in the early detection of these rarely reported but fatal hematologic AEs, thereby reducing the risk of severe toxicities in blinatumomab recipients.

Radiotherapy for breast cancer has been associated with an increased risk of secondary malignancies, including primary lung cancer. Whether this association varies by histological subtype of lung cancer remains unknown. Based on the data from 12 Surveillance, Epidemiology, and End Results registries, we examined the association between radiotherapy receipt and the risk of subtype-specific subsequent primary lung cancer (SPLC) among female first primary breast cancer cases diagnosed between ages 20 and 84 from 1992 to 2020. More than half (53%) of the 550,007 breast cancer survivors identified had undergone radiotherapy as part of their initial breast cancer treatment. Over an average follow-up of 9.7 years, 8014 survivors developed SPLCs. For small-cell carcinoma, the standardized incidence ratio (SIR) compared with the general population was higher for survivors who received radiotherapy (SIR = 1.15, 95% confidence interval [CI] = 1.06-1.25) but similar for those who did not receive radiotherapy (SIR = 1.00, 95% CI = 0.91-1.09), with the difference in SIRs being statistically significant (p = .003). Similar associations were found for squamous cell carcinoma (SIR_yes = 1.16, 95% CI = 1.08-1.24 vs. SIR_no/unknown = 1.06, 95% CI = 0.98-1.15; p = .07). The increased risks were confined to ipsilateral SPLC, with the greatest SIRs for small-cell carcinoma occurring 5-10 years since breast cancer diagnosis (SIR = 1.83, 95% CI = 1.53-2.19) and for squamous cell carcinoma with a latency of 10 years or more (SIR = 1.64, 95% CI = 1.42-1.88). In contrast, the risk of developing adenocarcinoma did not vary by radiotherapy receipt (SIR_yes = 1.23, 95% CI = 1.18-1.28 vs. SIR_no/unknown = 1.17, 95% CI = 1.12-1.22; p = .18), indicating additional risk factors in play. The findings suggest a distinct carcinogenic pathway of radiation-induced lung cancer across histological subtypes and may inform risk-stratified surveillance guidelines for SPLC.

Often relying on mother's recollections of past events, the possible relationship between maternal illness in pregnancy and risk of malignancy in their offspring has long been a focus of research. Free from recall bias, this study of childhood cancer (0-14 years) examined these associations using data abstracted from mothers' primary-care (1623 cases, 2521 controls) and obstetric (2721 cases, 5169 controls) records. Maternal infections and other illnesses in pregnancy were examined for any possible associations with childhood leukaemia, lymphoma, CNS or embryonal tumours using pooled information from the two medical record sources (2885 cases and 5499 controls), accounting for potential confounders. Maternal anaemia was associated with childhood acute myeloid leukaemia (AML) (odds ratio, OR = 2.07, 95%CI [1.40-3.08]). Anaemia during pregnancy was also recorded more frequently in the notes of mothers of children with medulloblastoma, retinoblastoma and embryonal rhabdomyosarcoma: ORs 2.36 [1.36-4.11], 1.83 [1.01-3.33] and 2.91 [1.64-5.16] respectively. Other associations included urinary tract infections (UTIs) and non-Hodgkin lymphoma (NHL); preeclampsia and NHL; and polyhydramnios with both AML and NHL. No evidence was found to suggest that influenza during pregnancy impacted on childhood leukaemia risk. In conclusion, our findings are supportive of an association between maternal anaemia in pregnancy and childhood AML, and maternal anaemia and embryonal tumours; underscoring the need for further research exploring the potential causes and roles of iron and vitamin deficiencies. Due to small numbers and lack of corroborative evidence, the associations observed for UTIs, preeclampsia, and polyhydramnios must be treated cautiously.