BMC Cancer最新文献

Prostate cancer (PCa) ranks among the most prevalent malignancies in men, with notable associations to Hereditary Breast and Ovarian Cancer Syndrome (HBOC) and Lynch Syndrome, both linked to germline likely pathogenetic variant/pathogenetic variant (LPV/PV) in genes involved in DNA repair. Among these genes, BRCA2 in PCa patients is the most frequently altered. Despite progresses, challenges in BRCA carriers detection persist, with a quarter of PCa cases lacking family history.To address these challenges, a multidisciplinary expert panel from six Italian Scientific Societies, formulated a care pathway to integrate BRCA testing into routine clinical practice in different Italian geographical areas.The development process, promoted by the Italian Society of Uro-Oncology (SIUrO), involved three key stages. A preliminary meeting convened teams from different Italian regions to establish minimal requirements for a mini-counseling program (defined as a pre-test consultation carried out by clinicians responsible of patients' management) and propose care pathway models. At the same time, a comprehensive survey was launched to highlight regional variations in BRCA testing and identify eventual obstacles to testing activities. A subsequent meeting synthesized care pathway proposals and formulated a unified framework, acknowledging regional legislative variations as enriching factors. Lastly, implementation of the unified framework was promoted by the project faculty and identified regional team leaders.Survey results revealed significant regional disparities in BRCA testing, reimbursement policies, and access to genetic counseling. The proposed mini-counseling program outlined essential steps for patient identification, information provision, and multidisciplinary review, aiming to streamline BRCA testing processes.Expert recommendations emphasized offering tumor genetic testing to metastatic PCa patients eligible for PARP-i treatment and outlined criteria for genetic counseling and germline testing. Key considerations included family history and tumor characteristics.In conclusion, the proposed care pathway represents a critical step towards integrating BRCA testing into routine PCa care, aiming to optimize patient management and familial risk assessment within the constraints of the Italian healthcare system.

Background: Prostate cancer (PCa) is definitively diagnosed by systematic prostate biopsy (SBx) with 13 cores. This method, however, can increase the risk of urinary retention, infection and bleeding due to the excessive number of biopsy cores.

Methods: We retrospectively analyzed 622 patients who underwent SBx with prostate multiparametric MRI (mpMRI) from two centers between January 2014 to June 2022. The MRI data were collected to manually segment Regions of Interest (ROI) of the tumor layer by layer. ROI reconstructions were fused to form outline of the volume of interest (VOI), which were exported and applied to subsequent extraction of radiomics features. The t-tests, Mann-Whitney U-tests and chi-squared tests were performed to evaluate the significance of features. The logistic regression was used for calculating the PCa risk score (PCS). The PCS model was trained to optimize the SBx core number, utilizing both mpMRI radiomics and clinical features.

Results: The predicted number of SBx cores was determined by PCS model. Optimal core numbers of SBx for PCS subgroups 1-5 were calculated as 13, 10, 8, 6, and 6, respectively. Accuracies of predicted core numbers were high: 100%, 95.8%, 91.7%, 90.6%, and 92.7% for PCS subgroups 1-5. Optimized SBx reduced core rate by 41.9%. Leakage rates for PCa and clinically significant PCa were 8.2% and 3.4%, respectively. The optimized SBx also demonstrated high accuracy on the validation set.

Conclusion: The optimization PCS model described in this study could therefore effectively reduce the number of systematic biopsy cores obtained from patients with high PCS, especially for biopsy cores far away from suspicious lesions. This method can enhance patient experience without reducing tumor detection rate.

Background: As the roles of chemotherapy (Chemo) and radiation therapy (Radio) in the definitive treatment of breast cancer have expanded, a broader understanding of the factors associated with breast cancer-related lymphedema (BCRL) has become increasingly essential. Therefore, we investigated the association between multimodality treatment and the risk of BCRL.

Methods: In this retrospective study conducted using National Health Insurance data and the Korea National Cancer Incidence Database (2006-2017), 114,638 participants who underwent Surgery (Surg) or Chemo within 6 months after breast cancer diagnosis were enrolled, and the effect of multimodality treatment on the risk of BCRL was analyzed using the Cox proportional-hazards model. Multimodality treatment administered through six months of treatment was grouped as only Surg; Surg/Chemo; Surg/ Chemo/Radio; Surg/Radio; only Chemo; and Chemo/Radio.

Results: The risk of BCRL was higher in the Surg/Chemo group (hazard ratio [HR]: 1.54, 95% confidence interval [CI]: 1.43-1.65), Surg/Chemo/Radio group (HR: 1.51, 95% CI: 1.43-1.65), only Chemo group (HR: 1.58, 95% CI: 1.45-1.71), and Chemo/Radio group (HR: 1.13, 95% CI: 1.00-1.29) in comparison with the only Surg group.

Conclusion: BCRL occurrence is an after-effect of complex breast cancer treatments, and the risk may vary depending on the treatment method, including Surg, chemo, and radio. Our findings suggest that multidisciplinary strategies are required to minimize the risk of BCRL development in patients with breast cancer.

Background: Most breast cancers are detected at an early stage in which case conservative surgery is indicated. An accurate preoperative localization technique is essential for conservative surgery of non-palpable breast lesions. Currently, the gold standard technique is wire localization (WL). However, this technique has well-known drawbacks. Several wire-free techniques have been developed to overcome these drawbacks; one technique is localisation by Radiofrequency Identification (RFID). The purpose of this clinical trial was to assess the superiority of RFID tags (HOLOGIC) in terms of patient satisfaction, over wire localization of non-palpable breast lesions.

Methods: This was a single-centre, prospective, controlled and non-interventional trial. Patients were followed from their inclusion at the time of the preoperative consultation to the postoperative consultation, one month after surgery. Data on anxiety and satisfaction was collected from patients and clinicians using questionnaires, and clinical data was collected from the medical files. The primary outcome was the patients' satisfaction scores, assessed using a visual analogue scale.

Results: Eighty patients were sequentially enrolled in two groups: the wire group (n = 40) and the RFID group (n = 40). One patient from the RFID group was excluded from the analysis because of a substantial migration during deployment. On a 10-point Visual Analogue Scale, the patients' median satisfaction score was 9.8 (IQR = 1.32) for the wire group and 10 (IQR = 0.07) for the RFID group (p < 0.001). A reduction in pain between device insertion and surgery was observed in the RFID group (p = 0.009). The median placement time was shorter in the RFID group (15 min, IQR = 6) than in the wire group (20 min, IQR = 30) (p = 0.01).

Conclusion: Our results show a statistically significant difference in median patient satisfaction score with the localization of non-palpable breast cancer lesions using RFID tags compared to the use of the WL. Although our results did not show clinically significant outcomes in terms of satisfaction, RFID tags are a reliable alternative to WL and simplify the organization of patients' healthcare trajectories.

Trial registration: ClinicalTrials.gov ID; NCT04750889 registered on February 11, 2021. https://clinicaltrials.gov/ct2/show/NCT04750889?term=rfid&draw=2&rank=1.

Background: Immune-combinations have recently become the standard first-line treatment for patients with metastatic renal cell carcinoma (mRCC). This study evaluated the applicability of the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk model in predicting outcomes for patients treated with either immune-oncologic drug doublet (IO-IO) or immune-oncologic drug tyrosine kinase inhibitor combinations (IO-TKI). A secondary objective to compare the effectiveness of IO-IO versus IO-TKI within the IMDC risk groups over a short follow-up period.

Methods: A retrospective analysis was conducted on 172 patients with mRCC treated with first-line immunotherapy combinations. Progression free survival (PFS), time to treatment failure 2 (TTF2), and overall survival (OS) were compared between IMDC risk categories. Model fit was assessed using the c-index. The inverse probability of treatment weighting (IPTW) method was used to adjust and compare outcomes between IO-IO and IO-TKI, except for IMDC favorable risk patients due to the small number of IO-IO cases.

Results: The IMDC risk model demonstrated a c-index of 0.684 (OS) for entire cohort, 0.600 (PFS), 0.596 (TTF2), and 0.624 (OS) for IO-IO, and 0.667 (PFS), 0.702 (TTF2), and 0.751 (OS) for IO-TKI. In the IMDC intermediate and poor risk groups after IPTW adjustment, PFS (HR 0.72), TTF2 (HR 0.67), and OS (HR 0.74) did not significantly differ between IO-IO and IO-TKI. Specifically, in the IMDC intermediate risk group, PFS (HR 0.79), TTF2 (HR 0.69), and OS (HR 0.65) were longer in IO-TKI, though the differences were not statistically significant. In the IMDC poor risk group, PFS (HR 0.76), TTF2 (HR 0.77), and OS (HR 1.03) were comparable.

Conclusions: The impact of IMDC risk model on survival was modest in IO-IO, while remained statistically substantial in IO-TKI. Survival outcomes did not significantly differ between IO-IO and IO-TKI during the short follow-up period.

Background: Identifying high risk factors and predicting lung cancer incidence risk are essential to prevention and intervention of lung cancer for the elderly. We aim to develop lung cancer incidence risk prediction model in the elderly to facilitate early intervention and prevention of lung cancer.

Methods: We stratified the population into six subgroups according to age and gender. For each subgroup, random forest, extreme gradient boosting, deep neural networks, support vector machine, multiple logistic regression and deep Q network (DQN) models were developed and validated. Models were trained and tested using samples from 2000 to 2015 and independent external validated through those from 2016 to 2019. The suitable model for lung cancer risk prediction and high risk factors identification was chosen based on internal validation and independent external validation.

Results: The DQN model achieved the optimal prediction performance in stratified subgroups, with AUROC ranging from 0.937 to 0.953, recall ranging from 0.932 to 0.943, F₂-score ranging from 0.929 to 0.946, precision ranging from 0.926 to 0.952, F₁-score ranging from 0.933 to 0.963 and RMSE ranging from 0.21 to 0.27. SHAP values were supplied for model interpretability. High risk factors of lung cancer incidence were identified in the elderly. Men ≥ 65 carrying C > A/G > T mutation had the highest lung cancer incidence decrease of 39.5% after five years quitting in stratified elderly groups, which were 1.83 times more than women ≥ 65 not carrying C > A/G > T mutation.

Conclusions: The DQN model may be suitable for identifying high risk factors and predicting lung cancer risk with high performance. The proposed intervention and diagnosis pathways could be used for early screening and intervention before the occurrence of lung cancer, which could help oncologists develop targeted intervention strategies for the stratified elderly to reduce lung cancer incidence and improve therapeutic effect. Proposed method could also be used in predicting the risk of other chronic diseases to help conduct intervention and reduce incidence.

Purpose: To evaluate the safety and efficacy of Helical Tomotherapy stereotactic body radiotherapy (HT-SBRT) in treating multiple primary lung cancers (MPLCs) and second primary lung cancer (SPLC).

Methods: From January 2010 to September 2023, 106 MPLCs and SPLC (T1-3N0M0) underwent HT-SBRT. The cumulative incidence for local recurrence (LR) was calculated using the competing risk approach and compared using Gray's test. Cancer-specific survival (CSS) and progression-free survival (PFS) were assessed using Kaplan-Meier analysis and log-rank tests.

Results: After adjusting for competing risks, the LR rates for all lesions (n = 150) was 15.3%, with 2- and 4-year rates of 7.5% and 11.4%. For second primary lung nodules post-surgery, the cumulative incidence of LR was 16.1%, with 2- and 4-year rates of 6.9% and 8.7%. In MPLCs treated with HT-SBRT, the cumulative incidence of LR was 14.3%, with 2- and 4-year rates of 8.2% and 14.3%. In patients with MPLCs treated with HT-SBRT (n = 27), the CSS rates at 2, 4, and 10 years were 90.5%, 78.6%, and 53.6%, respectively, and the PFS rates were 59.5%, 32.8%, and 24.6%. In patients with SPLC who received HT-SBRT after surgery (n = 79), the CSS rates at 2, 4, and 10 years were 90.9%, 81.7%, and 61.0%, respectively, while the PFS rates were 75.4%, 64.4%, and 58.5%. Additionally, 0.9% of patients experienced grade 3 acute radiation pneumonitis, and no severe (grade 4-5) toxicities were reported.

Conclusions: HT-SBRT may be a safe and effective treatment for MPLCs and SPLC, though prospective studies are needed to confirm its efficacy.

Background: No study has directly compared the outcomes of surgery and concurrent chemoradiotherapy (cCRT) in patients with stage III non-small cell lung cancer (NSCLC) to date. This study aimed to compare the treatment efficacy of complete resection and definitive cCRT.

Methods: Patients were recruited in this retrospective study from Yokohama Municipal Citizens' Hospital between January 2013 and December 2022. We analyzed patients with pathological stage III NSCLC who underwent complete surgical resection and those with clinical stage III NSCLC who underwent definitive cCRT. Propensity score matching was performed to balance baseline clinicopathological factors, and the prognoses of patients in each treatment group were examined using Cox proportional hazards regression.

Results: Of the 923 patients with NSCLC who underwent surgery, 97 with pathologic stage III NSCLC underwent complete resection (surgery group) and 125 with clinical stage III NSCLC underwent cCRT (cCRT group), of whom 54 (43.2%) received consolidation therapy with durvalumab. Overall survival (OS) was significantly higher in the surgery group than in the cCRT group (5-year OS: 60.5% versus 43.0%), hazard ratio [HR] = 0.585, 95% confidence interval [CI]: 0.390-0.877, p = 0.010). However, no significant difference in OS was found between the two groups after propensity score matching (5-year OS: 59.8% versus 48.1%, HR = 0.728, 95% CI: 0.416-1.277, p = 0.268).

Conclusions: The outcomes of the surgery and cCRT groups did not significantly differ in the treatment of stage III NSCLC. Appropriate evaluation of the treatment required should be reviewed on a case-by-case basis.

Background: Effective diagnostic tools for prompt identification of high-risk locally advanced cervical cancer (LACC) patients are needed to facilitate early, individualized treatment. The aim of this work was to assess temporal changes in tumor radiomics (delta radiomics) from T2-weighted imaging (T2WI) during concurrent chemoradiotherapy (CCRT) in LACC patients, and their association with progression-free survival (PFS). Furthermore, to develop, validate, and compare delta- and pretreatment radiomic signatures for prognostic modeling.

Methods: A total of 110 LACC patients undergoing CCRT with MRI at baseline and mid-treatment were divided into training (cohort_T: n = 73) and validation (cohort_V: n = 37) cohorts. Radiomic features were extracted from tumors segmented on pre-CCRT and mid-CCRT T2WI and radiomic deltas (delta features) were computed. Two radiomic signatures for predicting PFS were constructed by least absolute shrinkage and selection operator (LASSO) Cox regression: Delta_rad (from delta features) and Pre-CCRT_rad (from pre-CCRT features). Prognostic performance of the radiomic signatures, 2018 International Federation of Gynecology and Obstetrics (FIGO) stage (I-IV), and baseline MRI-derived maximum tumor diameter (Tumor_max: ≤2 cm; >2 and ≤ 4 cm; >4 cm) was evaluated by area under time-dependent receiver operating characteristics (tdROC) curves (AUC) in cohort_T and cohort_V (AUC_T/AUC_V). Mann-Whitney U tests assessed differences in radiomic delta features. PFS was evaluated using the Kaplan-Meier method with log-rank tests.

Results: Delta_rad (AUC_T/AUC_V: 0.74/0.79) marginally outperformed Pre-CCRT_rad (0.72/0.75) for predicting 5-year PFS, and both signatures clearly surpassed that of FIGO (0.61/0.61) and Tumor_max (0.58/0.65). In total, four features within Delta_rad and Pre-CCRT_rad significantly differed in delta feature values between progressors and non-progressors, being consistently lower in progressors (p ≤ 0.03 for all). High Delta_rad and Pre-CCRT_rad radiomic scores were associated with poor PFS (p ≤ 0.04 for Delta_rad in cohort_T/Pre-CCRT_rad in both cohorts; p = 0.11 for Delta_rad in cohort_V).

Conclusions: Delta- and pretreatment radiomic signatures equally allow early prognostication in LACC, outperforming FIGO stage and MRI-assessed maximum tumor diameter.

Background: Not all breast cancer (BC) patients can benefit from neoadjuvant therapy (NAT). A poor response may result in patients missing the best opportunity for treatment, ultimately leading to a poor prognosis. Thus, to identify an effective predictor that can assess and predict patient response at early time points, we focused on circulating tumor DNA (ctDNA), which is a vital noninvasive liquid biopsy biomarker. We performed a meta-analysis to explore the predictive value of response by monitoring ctDNA at four time points of NAT using pathologic complete response (pCR) and residual cancer burden (RCB).

Methods: By searching Embase, PubMed, the Cochrane Library, and the Web of Science until December 24, 2023, we selected studies concerning the relationship between ctDNA and response or prognosis. We analysed the results at the following various time points: baseline (T0), first cycle of NAT (T1), mid-treatment (MT), and end of NAT (EOT). pCR and RCB were used to evaluate the response as the primary endpoint. The secondary endpoint was to investigate the relationship between ctDNA and prognosis. Odds ratios (ORs) and hazard ratios (HRs) were used as effect indicators.

Results: Thirteen reports from twelve studies were eligible for inclusion in this meta-analysis. The results demonstrated that ctDNA negativity was associated with pCR at T1 (OR = 0.34; 95% CI: 0.21-0.57), MT (OR = 0.35; 95% CI: 0.20-0.60), and EOT (OR = 0.38; 95% CI: 0.22-0.66). When RCB was used to evaluate responses, ctDNA negativity was associated with RCB-0/I at the MT (OR = 0.34; 95% CI: 0.21-0.55) and EOT (OR = 0.26; 95% CI: 0.15-0.46). Furthermore, ctDNA positivity at T1 predicted a worse prognosis for patients (HR = 2.73; 95% CI: 1.29-5.75). We also performed a subgroup analysis to more accurately assess the predictive value of ctDNA for triple-negative breast cancer.

Conclusions: Our meta-analysis suggested that the ctDNA status at the early stage of NAT can predict patient response, which provides evidence for adjusting personalized treatment strategies and improving patient survival.

Prospero registration number: CRD42024496465.