Significant Difference In Overall Survival Research Articles

The efficacy and safety of CDK4/6 inhibitors combined with endocrine therapy versus endocrine therapy alone in the adjuvant treatment of patients with high-risk invasive HR+/HER2-early breast cancer: A comprehensive updated meta-analysis of randomized clinical trials

BackgroundThis paper aimed to evaluate the effectiveness of incorporating CDK 4/6 inhibitors (CDK4/6i) into ET for the adjuvant treatment of HR + HER2-resected early-stage breast cancer (ESBC) patients, employing meta-analysis. MethodsIn this paper, we compiled randomized clinical trials focusing on CDK4/6i used in the adjuvant treatment of high-risk invasive HR-positive and HER2-ESBC patients. A meta-analysis was performed in line with the PRISMA guidelines. ResultsWe identified four clinical trials that met our inclusion criteria and were published between 2020 and 2024. These trials involved a combined sample size of 17,749 patients diagnosed with breast cancer. The data obtained from the pooled analysis revealed a remarkable beneficial trend in terms of invasive disease-free survival (iDFS) for the use of ET in combination with CDK4/6i compared to the group receiving ET alone (HR = 0.81, 95 % CI: 0.67–0.98, p = 0.03). Of note, CDK4/6 inhibitors demonstrated a notably beneficial effect in both grade 2 (HR = 0.69, 95 % CI: 0.59–0.81, p < 0.001) and grade 3 (HR = 0.76, 95 % CI: 0.65–0.89, p < 0.001). Significant improvements were noted in terms of distant relapse-free survival (dRFS) in the groups treated with abemaciclib and ribociclib (HR = 0.65, 95 % CI: 0.56–0.76, p < 0.001; HR = 0.72, 95 % CI: 0.58–0.89, p = 0.003, respectively). CDK4/6i didn't yield a statistically significant difference in overall survival (OS) (HR = 0.96, 95 % CI: 0.77–1.19, p = 0.69). The use of CDK4/6i with ET was associated with an increased risk of adverse events, particularly anemia and neutropenia, compared with ET alone (OR = 9.12, 95 % CI = 5.04–16.48, p < 0.001). ConclusionThe findings of this paper demonstrate a significant improvement in iDFS when ET is combined with CDK4/6i, compared to ET alone. Specifically, treatments with abemaciclib and ribociclib showed notable enhancements in dRFS.

Choosing the optimal therapy for metastatic renal cell carcinoma: Insights from a real-world comparative study.

The evolution of combination therapies integrating immune checkpoint inhibitors has revolutionized the first-line treatment of metastatic renal cell carcinoma (mRCC). Although these therapies are clinically approved, direct comparisons between dual immune checkpoint inhibitors (IOIO) and immune checkpoint inhibitors combined with tyrosine kinase inhibitors (IOTKI) in clinical trials are lacking. This gap creates uncertainties in selecting the most appropriate treatment based on patient-specific factors. This study employed the inverse probability of treatment weighting (IPTW) method to analyze progression-free survival (PFS) and overall survival (OS) for patients with mRCC receiving IOIO or IOTKI treatment regimens. A total of 171 patients were analyzed after applying inclusion criteria and propensity scoring. The study found no significant differences in PFS and OS between the two treatment modalities in the IPTW cohort. However, subgroup analyses revealed that IOTKI therapy was associated with better PFS and OS for patients without bone metastases and better OS for patients with a body mass index (BMI) over 25. IOIO therapy showed better OS for patients with a BMI below 18.5. Both IOIO and IOTKI therapies were effective. Therapy selection could be better tailored to patient characteristics by including factors such as the presence of bone metastases and BMI. This study enhances understanding of how patient-specific factors interact with different treatment modalities, potentially guiding more personalized treatment decisions in clinical practice for mRCC.

Involved-field high-dose chemoradiotherapy with respiratory motion management for esophageal squamous cell carcinoma.

We investigated the clinical outcomes of involved-field high-dose (≥66 Gy) chemoradiotherapy (CRT) combined with respiratory motion management for esophageal squamous cell carcinoma (ESCC). Patients who underwent definitive CRT for histologically confirmed ESCC in our department between 2012 and 2018 were retrospectively analyzed. Respiratory motion management strategies included breath-holding (63%) and mask immobilization (29%) based on individual measurements of respiratory tumor motion using radiographic fluoroscopy with endoscopically placed clip markers as landmarks. We evaluated patient characteristics, treatment efficacy, failure patterns, and toxicities. We enrolled 35 patients with a prescribed dose of 66-70 Gy in 33-35 fractions. The overall response rate within 6 months post-CRT was 94.3%; the median follow-up period for survivors was 43 months. The 2-year overall survival (OS), progression-free survival, and locoregional failure-free survival rates were 51.4%, 42.9%, and 42.9%, respectively. A significant difference in OS was observed between patients with and without esophageal fistulas after CRT (p = 0.002, log-rank test). Disease failure occurred in 16 patients (45.7%), including one (2.9%) with out-of-field regional nodal failure. Major grade 3 or higher toxicities included decreased white blood cell count (48.6%), neutrophil count (34.3%), and esophageal stenosis (31.4%). No grade 3 or higher cardiopulmonary toxicities were observed. Bronchial/tracheal tumor compression and a higher radiotherapy dose (70 Gy) were significantly correlated with esophageal fistulas. Involved-field high-dose CRT with respiratory motion management may be a feasible treatment option for ESCC. However, a comprehensive assessment of esophageal fistula risk is required to identify suitable candidates.

Survival and prognostic factors for relapsed childhood acute lymphoblastic leukemia after treatment with the Chinese children's cancer group ALL-2015 protocol: a single center results.

This retrospective study was conducted to assess the survival rates and prognostic factors in children with relapsed acute lymphoblastic leukemia (ALL) who were treated according to the Chinese Children's Cancer Group ALL-2015 protocol at the Children's Hospital of Chongqing Medical University. The study cohort involving 852 evaluable children with ALL reported a total of 146 relapses during a median follow-up period of 53 months. The primary outcomes measured were the second complete remission (CR2) rates, and 5-year event-free survival (EFS) and overall survival (OS) for patients who received re-treatment post-relapse. Patient data were stratified by ALL subtype (B-ALL vs. T-ALL), age at relapse, site of relapse, and timing of relapse. Univariate and multivariate analyses were performed to identify factors significantly associated with EFS and OS. As of March 31, 2023, 146 relapses were observed, including 128 B-ALL and 18 T-ALL cases. The 8-year CIR was (19.8 ± 1.6)%, with no significant difference between B-ALL and T-ALL (P=0.271). Among the 105 patients who underwent re-treatment, 70 achieved CR2, resulting in a CR2 rate of 67.6%. The 5-year EFS and OS rates for re-treated patients were (45.0 ± 5.4)% and (56.9 ± 5.2)%, respectively. Significant differences in 5-year OS and EFS were found between B-ALL and T-ALL relapses (P < 0.001). The 5-year EFS and OS varied significantly with relapse timing and site of relapse. Factors significantly affecting EFS after relapse included the site of relapse, immunophenotyping, CR2 achievement, and hematopoietic stem cell transplantation (HSCT). Immunophenotyping, CR2 achievement, and HSCT were also identified as significant factors affecting OS after relapse. Despite treatment with the CCCG-ALL-2015 protocol, a significant relapse rate was observed, with 72% of children opting for re-treatment post-relapse. The study highlights the importance of considering specific prognostic factors to inform tailored treatment strategies for relapsed childhood ALL. The findings emphasize the need for further research into improving therapeutic approaches for this patient population. This retrospective study was conducted to assess the survival rates and prognostic factors in children with relapsed acute lymphoblastic leukemia (ALL) who were treated according to the Chinese Children's Cancer Group ALL-2015 protocol at the Children's Hospital of Chongqing Medical University.

Comparing Open, Laparoscopic and Robotic Liver Resection for Metastatic Colorectal Cancer-A Systematic Review and Network Meta-Analysis.

Colorectal liver metastases (CRLM) can be surgically managed through open resections (OLR), laparoscopic resections (LLR), or robotic liver resections (RLR). However, there is ongoing uncertainty regarding the safety and effectiveness of minimally invasive approaches like LLR and RLR. This study aims to clarify these issues by conducting a network meta-analysis (NMA) to compare outcomes across OLR, LLR and RLR for patients with CRLM. Following the PRISMA-NMA guidelines, the meta-analysis included 13 studies with a combined total of 6582 patients. Of these, 50.6% underwent LLR, 45.3% underwent OLR, and 4.1% underwent RLR. The analysis found no significant differences in R0 resection rates between LLR (odds ratio [OR] 1.03, 95% confidence interval [CI]: 0.84-1.26) and RLR (OR 1.57, 95% CI: 0.98-2.51) when compared to OLR. Additionally, there were no significant differences in disease-free survival (DFS) and overall survival (OS) at 1, 3, and 5 years. Despite these findings, both LLR and RLR were associated with reduced postoperative complication rates (RLR: OR 0.52, 95% CI: 0.32-0.86; LLR: OR 0.50, 95% CI: 0.37-0.68). However, patients undergoing LLR were more likely to require conversion to open surgery compared to those undergoing RLR (OR: 12.46, 95% CI: 2.64-58.67). Furthermore, RLR was associated with a reduced need for blood transfusions (OR: 0.13, 95% CI: 0.05-0.32), and LLR resulted in shorter hospital stays (mean difference: -6.66 days, 95% CI: -11.6 to -1.88 days). This study demonstrates the oncological safety of LLR and RLR approaches for CRLM relative to OLR, with enhanced perioperative outcomes anticipated following minimally invasive resections of CRLM.

T cell exhaustion methylation signature drives differential immune responses in glioblastoma.

Methylation-related signatures play crucial roles in tumorigenesis and progression. However, their roles in the immune response in primary glioblastoma (GBM) remains unclear. We analyzed the differential expression of specific members of T cell exhaustion-related pathways in GBM from the perspective of T cell exhaustion. We further screened for significantly negatively correlated methylation sites as candidate methylation markers for T cell exhaustion. Using consensus clustering, we divided the samples into two categories with significant differences in overall survival (OS). We then performed univariate and multivariate Cox regression analyses to construct the T Cell Exhaustion Methylation (TEXM) signature. Finally, we confirmed that this signature served as an independent prognostic factor, and further characterized it in terms of drug resistance and immunotherapy. We identified 95 significantly differentially expressed T cell exhaustion-related genes and 51 methylation markers associated with T cell exhaustion. The cancer samples were classified according to methylation site markers, thus indicating two subtypes with significant differences in OS: subtype A and subtype B. Tumor scores, stromal scores, tumor purity, and ESTIMATE scores all showed significant differences between subtypes (P < 0.05). Univariate Cox regression analysis identified five methylation sites significantly associated with OS, and multivariate Cox regression analysis was used to construct the TEXM signature model by using these five methylation sites. Significant differences in OS were found between the groups with high and low TEXM signature scores, on the basis of calculation of the TEXM signature scores of tumor samples and using the median score to divide them into high and low score groups. Survival analysis revealed that the high score group had poorer OS and DFS than the low score group in the validation set. Notably, we observed a significant difference in drug sensitivity between the high and low TEXM signature score groups, with the high score group showing higher drug resistance and poorer prognosis. The tumor immune state, as predicted with Tracking Tumor Immunophenotype (TIP), revealed significant differences in antitumor immune scores between the high and low TEXM signature score groups. Finally, we identified 43 significantly differentially regulated metabolism-associated biological processes. The epigenetic methylation-related TEXM signature plays a key role in driving differential immune responses in GBM.

Comparison of survival between lobectomy and trisegmentectomy for clinical stage T1c-2aN0M0 non-small cell lung cancer in the left upper segment of the lung.

Left upper trisegmentectomy is expected to be as curative as lobectomy for lung cancer because the left upper lobe is anatomically the same as the combined upper and middle lobes of the right lung and the procedure can provide a sufficient surgical margin. In the present multicenter study, we compared the results of trisegmentectomy and lobectomy in patients with clinical stage T1c-2aN0M0 left upper lung cancer. We retrospectively analyzed the outcomes of patients with clinical stage T1c-2aN0M0 lung cancer in the left upper segment who underwent lobectomy or trisegmentectomy between January 2006 and June 2022. The trisegmentectomy group (S group) and lobectomy group (L group) comprised 33 and 132 patients, respectively. Comparisons of postoperative survival revealed no significant differences in overall survival (p = 0.761) or disease-free survival (p = 0.508) between the two groups. There were also no significant differences in survival after adjustment for clinical factors by Cox proportional hazards models and propensity score matching. Local recurrence was significantly more predominant in the S group than in the L group (p = 0.006). The S group had a worse postoperative survival than the L group when the tumor was located in anterior segment. Trisegmentectomy can provide an equivalent postoperative survive to lobectomy in patients with clinical stage T1c-2aN0M0 left upper segment lung cancer except in patients with tumor in anterior segment.

A Machine Learning-Based Clustering Using Radiomics of F-18 Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography for the Prediction of Prognosis in Patients with Intrahepatic Cholangiocarcinoma

Background: Intrahepatic cholangiocarcinoma (IHCC) is highly aggressive primary hepatic malignancy with an increasing incidence. Objective: This study aimed to develop machine learning-based radiomic clustering using F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for predicting recurrence-free survival (RFS) and overall survival (OS) in IHCC. Methods: We retrospectively reviewed pretreatment F-18 FDG PET/CT scans of 60 IHCC patients who underwent surgery without neoadjuvant treatment between January 2008 and July 2020. Radiomic features such as first order, shape, and gray level were extracted from the scans of 52 patients and analyzed using unsupervised hierarchical clustering. Results: Of the 60 patients, 36 experienced recurrence and 31 died during follow-up. Eight patients with a negative FDG uptake were classified as Group 0. The unsupervised hierarchical clustering analysis divided the total cohort into three clusters (Group 1: n = 27; Group 2: n = 23; Group 3: n = 2). The Kaplan–Meier curves showed significant differences in RFS and OS among the clusters (p &lt; 0.0001). Multivariate analyses showed that the PET radiomics grouping was an independent prognostic factor for RFS (hazard ratio (HR) = 3.03, p = 0.001) and OS (HR = 2.39, p = 0.030). Oxidative phosphorylation was significantly activated in Group 1, and the KRAS, P53, and WNT β-catenin pathways were enriched in Group 2. Conclusions: This study demonstrated that machine learning-based PET radiomics clustering can preoperatively predict prognosis and provide valuable information complementing the genomic profiling of IHCC.

Impact of systemic steroids on the efficacy of first line imatinib treatment of patients with advanced gastrointestinal stromal tumors (GISTs).

Effective management of adverse events is required to maintain sufficient imatinib dosing when treating patients with gastrointestinal stromal tumors (GISTs). Skin rash is a common adverse event of imatinib, which can be effectively controlled by systemic steroid treatment without imatinib dose modification or interruption. However, the impact of the use of systemic steroids on the efficacy of imatinib treatment remains unclear. Between October 2014 and February 2022, 277 consecutive patients from a prospective registry of GIST patients were included as the study population. Patients who started systemic steroids due to grade ≥ 3 skin rash or grade 2 skin rash with grade 2 pruritis were classified as the steroid group, whereas patients who did not develop a skin rash or those who did not require steroids for a mild skin rash were classified as the control group. Efficacy outcomes were compared between the two groups. Among the 277 patients, 30 (10.8%) were treated with systemic steroids for skin rash. There was no significant difference in progression free survival (PFS) or overall survival (OS) between the steroid and control groups (3-year PFS, 67.7% vs. 65.1%, p = 0.53; 3-year OS, 91% vs. 89.9%, p = 0.67, respectively). The use of systemic steroids was not an independent factor associated with PFS (hazard ratio 0.73, 95% confidence interval 0.36-1.49, p = 0.39) and OS (hazard ratio 0.37, 95% confidence interval 0.12-1.18, p = 0.09). In the steroid group, patients who successfully maintained the imatinib dosage showed a trend toward more favorable survival outcomes than those who did not (3-year PFS, 73.3% vs. 44.4%, p = 0.34; 3-year OS, 95.8% vs. 75.0%, p = 0.15, respectively). The use of systemic steroids for the control of imatinib induced severe skin rash did not adversely affect the efficacy outcomes of imatinib in patients with advanced GIST.

Impact of Etiology on Efficacy Outcomes with Atezolizumab Plus Bevacizumab in Patients with Advanced Hepatocellular Carcinoma: A Multinational Retrospective Analysis in Asia-Pacific.

Atezolizumab-bevacizumab is a standard first-line treatment for unresectable hepatocellular carcinoma (uHCC). Given the diversity in HCC etiology and its potential impact on the tumor microenvironment, understanding how different liver disease etiologies affect treatment efficacy is important. We assessed the influence of liver disease etiology on the efficacy of atezolizumab-bevacizumab and evaluated changes in liver function during treatment with atezolizumab-bevacizumab. This study included 390 patients with uHCC treated with first-line atezolizumab-bevacizumab from Asan Medical Center, South Korea, and National Cancer Centre Singapore, Singapore from July 2016 to March 2023. Patients were classified to viral, metabolic dysfunction-associated liver disease (MASLD) and nonviral/non-MASLD groups. Albumin-bilirubin (ALBI) scores were recorded at baseline and every two cycles up to cycle six and at the time of disease progression. The majority of patients presented with viral etiologies (74.1%), and 17.2% had MASLD. Across etiological groups (viral versus MASLD versus nonviral/non-MASLD) no significant differences in objective response rate (23.2% versus 29.9% versus 23.5%, respectively; p = 0.515), progression-free survival (median 5.4 versus 7.7 versus 6.0 months; p = 0.320), and overall survival (18.1 versus 18.9 versus 14.4 months; p = 0.400) were observed. Among the patients with disease progression, ALBI scores at the time of progression were significantly higher than at baseline. Subsequent therapy was administered significantly less often to patients with ALBI grade 3 at disease progression compared with those with ALBI grades 1 or 2 (48.4% versus 78.8%, p = 0.002) CONCLUSIONS: Atezolizumab-bevacizumab demonstrates consistent efficacy regardless of HCC etiology, supporting its use as a first-line treatment across diverse patient populations. Liver function assessments remain crucial for managing therapy and predicting outcomes.

Maternal and obstetric outcomes in women with pregnancy-associated haematological malignancies: an observational nationwide cohort study.

Pregnancy-associated haematological malignancy is a rare event; therefore, data available to guide the treatment are scarce. We aimed to evaluate the incidence, overall survival, and maternal morbidity and mortality of women with pregnancy-associated haematological malignancies. We conducted a nationwide observational cohort study using the French National Healthcare Data System (SNDS), a health-care administrative database covering up to 99% of the French population. We included all pregnancies in France ending between Jan 1, 2012, and Dec 31, 2022. Pregnancies with terminations or miscarriages managed on an outpatient basis, and women with a history of haematological malignancies before pregnancy were excluded. A Cox proportional hazards model was used to assess overall survival, defined as the date of haematological malignancy diagnosis to either death or the end of the study follow-up, in the haematological malignancy during pregnancy group (pregnancies with a diagnosis of haematological malignancy during pregnancy) compared with the haematological malignancy post-pregnancy group (pregnancies with a diagnosis of haematological malignancy in the year following pregnancy). Severe maternal morbidity was compared in the haematological malignancy during pregnancy group versus the reference group (pregnancies without a history of haematological malignancy or a diagnosis of pregnancy-associated haematological malignancy). Births were classified as very preterm (<32 weeks of pregnancy), preterm (32-36 weeks), and term (≥37 weeks) and compared in the haematological malignancy during pregnancy group versus the reference group. Inverse probability weighting (IPW) was used for confounder adjustment, using maternal age (categorised), comorbidities, socioeconomic status, and year of delivery (as a category). Of 9 996 523 pregnancies in 5 995 235 women, 1366 pregnancy-associated haematological malignancies were identified: 413 during pregnancy (4·13 per 100 000 pregnancies) and 953 (9·53 per 100 000 pregnancies) within 12 months of the end of pregnancy (post-pregnancy). No significant differences in overall survival were observed between the haematological malignancy during and post-pregnancy groups across all types of haematological malignancy (IPW-adjusted hazard ratio 0·91 [95% CI 0·62-1·34], p=0·63), specifically for Hodgkin lymphoma (0·56 [0·07-4·53], p=0·59), aggressive B-cell non-Hodgkin lymphoma (0·52 [0·12-2·38], p=0·40), and acute leukaemia alone (0·84 [0·50-1·41], p=0·51). Severe maternal morbidity was more frequent in the haematological malignancy during pregnancy group than in the reference group (86 [26·2%] of 328 completed pregnancies vs 120 335 [1·5%] of 7 945 909 completed pregnancies; IPW-adjusted odds ratio 22·71 [95% CI 17·72-29·10], p<0·0001). We observed an increase in very preterm birth (32 [9·8%] vs 92 712 [1·2%]; IPW-adjusted odds ratio 11·90 [95% CI 7·91-17·91], p<0·0001) and preterm birth (116 [35·4%] vs 430 472 [5·4%]; 11·76 [9·34-14·81], p<0·0001) in the haematological malignancy during pregnancy group compared with the reference group. This nationwide observational study examines pregnancy-associated haematological malignancies in France, revealing no significant difference in overall survival between women diagnosed during pregnancy and post-pregnancy. Our data highlight an increased frequency of severe maternal morbidity and obstetric complications among women diagnosed during pregnancy. Notably, the study underscores the necessity for specialised care to manage these complex cases effectively. None. For the French translation of the abstract see Supplementary Materials section.

Prior Local Therapy and First-Line Apalutamide in Patients With Nonmetastatic Castration-Resistant Prostate Cancer

Preclinical studies suggest that exposure to prostate-directed local therapy (LT) may influence the efficacy of subsequent systemic therapy including androgen receptor pathway inhibitors. However, there is insufficient clinical evidence to support this premise in patients with nonmetastatic castrate-resistant prostate cancer (nmCRPC). To determine whether exposure to prior prostate-directed LT (radical prostatectomy [RP], radiation therapy [RT], or both) played any effect-modifying role in the treatment effect of apalutamide on metastasis-free survival (MFS) and overall survival (OS) in patients with nmCRPC. This post hoc secondary analysis used individual patient data from SPARTAN (Study of Apalutamide [ARN-509] in Men With Non-Metastatic Castration-Resistant Prostate Cancer), a phase 3, double-blinded, placebo-controlled randomized clinical trial conducted at 332 sites in 26 countries. Between October 14, 2013, and December 15, 2016, patients with nmCRPC and a prostate-specific antigen doubling time of 10 months or less were randomly assigned to apalutamide vs placebo; all patients received androgen deprivation therapy. The final data analysis was performed on December 31, 2023. Prior prostate-directed LT. Separate Cox proportional hazards regression models were constructed for OS and MFS, which included prior LT, treatment group, and an interaction term, in addition to a minimally sufficient set of confounders. Adjusted hazard ratios (HRs) with 95% CIs for MFS and OS were determined for the apalutamide groups with or without prior LT. Among the 1179 evaluable patients included in this analysis, 795 received prior LT and 384 did not. The median age of patients with and without prior LT was 70 (IQR, 45-90) years and 75 (IQR, 50-95) years, respectively. The median follow-up was 52.0 (IQR, 51.5-52.8) months. A differential treatment effect of apalutamide on MFS was observed between patients with and without prior LT (P for interaction = .009), with greater benefits for those with prior LT (adjusted HR, 0.22 [95% CI, 0.17-0.27]) compared with those without prior LT (adjusted HR, 0.35 [95% CI, 0.25-0.51]). However, there was insufficient evidence of a differential treatment effect on OS among subgroups stratified by exposure to prior LT (P for interaction = .23), with improved OS in the subgroup with prior LT (adjusted HR, 0.72 [95% CI, 0.57-0.92]) but no significant difference in OS in the subgroup without prior LT (adjusted HR, 0.92 [95% CI, 0.64-1.31]). This post hoc analysis of the SPARTAN trial provides evidence of an interaction between prior LT and apalutamide in patients with nmCRPC, with a clinically significant and more favorable treatment effect from apalutamide on MFS among patients with prior LT. Further studies are needed to validate these findings. ClinicalTrials.gov Identifier: NCT01946204.

Long-Term Outcomes in Patients With Locally Advanced Rectal Cancer Following R1 Resection After Either Induction Chemotherapy and Chemoradiotherapy or Chemoradiotherapy Alone

IntroductionTotal neoadjuvant treatment (TNT) with induction chemotherapy (ICT) followed by chemoradiotherapy (CRT) has improved long-term outcomes for patients with locally advanced rectal cancer (LARC). However, long-term outcomes have not been investigated for patients with incomplete (R1) resection separately. This study investigates overall survival (OS), disease-free survival (DFS) and local and distant recurrence rates in patients with R1 resection after preoperative treatment with ICT and CRT or CRT. Patients and methodsFrom the NORD database 689 patients with LARC who received treatment between 2006 and 2017 were screened for inclusion. All patients with R1 resection were included. ICT consisted of at least 1 cycle of capecitabine and oxaliplatin (CAPOX) and was followed by radiotherapy concomitant with capecitabine. ResultsAmong 46 patients with R1 resection, 27 (59%) received both ICT and CRT, and 19 (41%) patients received CRT. The 5-year OS was 44% (95% CI, 26%-63%) (ICT + CRT) versus 37% (95% CI, 15%-59%) (CRT) (P = .25) and 5-year DFS was 44% (95% CI, 26%-63%) (ICT + CRT) versus 32% (95% CI, 11%-53%) (CRT) (P = .22). The local recurrence rates showed a small nonstatistical significant difference in local control in the ICT group: 15% compared to 26% in the CRT group (P = .22). Distant recurrence rates were similar: 41% (ICT + CRT) versus 47% (CRT) (P = .48). ConclusionThere was no significant difference in OS, DFS or local and distant recurrence rates between patients who received ICT + CRT versus patients who received CRT only.

A subset of image-defined risk factors predict completeness of resection in children with high-risk neuroblastoma: An international multicenter study.

Image-defined risk factors (IDRFs) were promulgated for predicting the feasibility and safety of complete primary tumor resection in children with neuroblastoma (NB). There is limited understanding of the impact of individual IDRFs on resectability of the primary tumor or patient outcomes. A multicenter database of patients with high-risk NB was interrogated to answer this question. Patients with high-risk NB (age <20years) were eligible if cross-sectional imaging was performed at least twice prior to resection. IDRFs and primary tumor measurements were recorded for each imaging study. Extent of resection was determined from operative reports. There were 211 of 229 patients with IDRFs at diagnosis, and 171 patients with IDRFs present pre-surgery. A ≥90% resection was significantly more likely in the absence of tumor invading or encasing the porta hepatis, hepatoduodenal ligament, superior mesenteric artery (SMA), renal pedicles, abdominal aorta/inferior vena cava (IVC), iliac vessels, and/or diaphragm at diagnosis or an overlapping subset of IDRFs (except diaphragm) at pre-surgery. There were no significant differences in event-free survival (EFS) and overall survival (OS) when patients were stratified by the presence versus absence of any IDRF either at diagnosis or pre-surgery. Two distinct but overlapping subsets of IDRFs present either at diagnosis or after induction chemotherapy significantly influence the probability of a complete resection in children with high-risk NB. The presence of IDRFs was not associated with significant differences in OS or EFS in this cohort.

Lavage cytology diagnosed by immunostaining may be a poor prognostic factor in pathological stage III colorectal cancer

AbstractAimTo clarify the prognostic impact of positive lavage cytology diagnosed by immunostaining on long‐term outcomes following curative resection for pathological stage III colorectal cancer (CRC).MethodWe retrospectively investigated patients who underwent radical resection and intraoperative lavage cytology (LCY) simultaneously for pathological stage III primary CRC between 2005 and 2017. All LCY specimens were evaluated by Papanicolaou staining and immunostaining for carcinoembryonic antigen and Ber‐EP4. Only Class V diagnosed by either staining method was defined as positive LCY, and patients were classified into two groups: a positive lavage cytology (LCY+) group; and a negative lavage cytology (LCY−) group. Overall survival (OS) and relapse‐free survival (RFS) were compared between groups. Multivariate analysis was performed to identify clinicopathological factors affecting OS and RFS.ResultsAmong 708 patients with pathological stage III CRC, 30 patients (4.2%) showed positive LCY. OS and RFS were significantly lower in the LCY(+) group than in the LCY(−) group. Five‐y OS rates in the LCY(+) and LCY(−) groups were 58.7% and 91.0%, respectively, and 5‐y RFS rates were 28.8% and 76.6%, respectively. Multivariate analysis revealed that positive LCY was independently associated with lower OS and RFS. In the LCY(+) group, the proportion of patients with negative Papanicolaou staining but positive immunostaining was 20.0% (6 of 30). No significant differences in OS and RFS were evident between those patients and patients with positive results for both Papanicolaou staining and immunostaining.ConclusionPositive LCY as diagnosed by immunostaining may represent a poor prognostic factor for pathological stage III CRC.

Role of Surgery in Potentially Resectable Small-Cell Lung Cancer Based on the Eighth Edition of the TNM Classification: A Population Study of the US SEER Database.

This study aimed to identify a specific SCLC population that would benefit from surgery. This study utilized patient data retrieved from the Surveillance, Epidemiology, and End Results (SEER) database spanning 2010 to 2017. To mitigate clinical biases, the propensity score matching (PSM) technique was employed. Separate cohorts were aligned using PSM according to the AJCC 8th edition TNM classification. The Kaplan-Meier method and a competing risk model were applied to evaluate overall survival (OS) and lung cancer-specific survival (LCSS), respectively. Among the 3394 patients with potentially resectable SCLC included in the study, 3062 underwent chemoradiotherapy and 332 underwent surgical treatment with adjuvant chemotherapy. Surgery was associated with better OS (median OS: 49 months; 95% CI: 35-63 months vs. 27 months; 95% CI: 21-33 months, p < 0.001) and LCSS (SHR, 0.578; 95% CI: 0.411-0.815, p < 0.001) in stage I patients after PSM. However, there was no significant difference in OS and LCSS between the surgery and nonsurgery groups in stage II and III patients after PSM. In the entire cohort, lobectomy was associated with improved OS (median OS: 48.6 vs. 28.7 months, p < 0.0001), but not LCSS (SHR, 0.696; 95% CI: 0.466-1.040, p = 0.078) compared with sublobar resection after PSM. Surgery with adjuvant chemotherapy significantly improved the survival prognosis of patients with early-stage SCLC. However, surgical treatment should be carefully considered in patients with stage II/III disease. Lobectomy is oncologically equal to sublobar resection.

Effect of Breast Cancer Receptor Subtypes and CSF Cytology Status on Survival of Patients With Leptomeningeal Disease

BackgroundIt is unclear whether breast cancer (BC) subtypes or CSF cytology results are associated with overall survival (OS) among patients with BC leptomeningeal disease (LMD). This single-institution retrospective study compares OS among BC patients with LMD across various breast cancer subtypes and CSF cytology results. MethodologyThe study enrolled BC patients diagnosed with LMD between 2010 and 2023. Breast cancer subtypes were classified as A. ER+/HER2-, HER2+, or triple-negative BC (TNBC); B. HER2+, HER2-Low, HER2-Zero. CSF cytology subtypes included CSF+, CSF-, or CSF not tested (NT). OS was summarized via Kaplan-Meier analysis and compared using log-rank test. Cox models were used for multivariate analyses. ResultsOut of 69 patients registered, median OS (95% CI) for ER+/HER2- (n = 33), HER2+ (n = 12) and TNBC (n = 24) subtypes were 8.0 (3.02, 24.8), 5.71 (1.61, not estimated) and 3.2 (1.11, 4.95) months (P = .17). In multivariate analysis, TNBC was associated with worse OS versus ER+/HER2- [Hazard Ratio (HR), 95% CI: 2.64, 1.23-5.80, P = .04]. HER2 subtypes (HER2-Zero, n = 21; HER2-Low, n = 32; HER2+, n = 12) showed no significant differences in OS. Median OS (95% CI) for CSF+ (n = 16), CSF- (n = 18), and CSF NT (n = 35) groups were 3.54 (1.61, 12.72), 13.41 (4.95, 61.93) and 3.28 (1.44, 6.92) months (P = .04). Multivariate analysis showed both CSF+ and CSF NT were associated with shorter OS compared to CSF- group [HR (95% CI) 4.50 (1.75, 12.11) for CSF+ vs. CSF-; 2.91 (1.45, 6.26) for CSF NT vs. CSF-; P = .002]. ConclusionTNBC LMD group was associated with worse OS than ER+/HER2- BC LMD when adjusting for other prognostic factors. CSF- LMD patients had better OS than CSF+ or CSF NT LMD.

Transarterial chemoembolization combined with lenvatinib plus tislelizumab for unresectable hepatocellular carcinoma: a multicenter cohort study.

Comparing the efficacy of transarterial chemoembolization (TACE) combined with lenvatinib plus tislelizumab (TLT) with TACE combined with lenvatinib (TL) for unresectable hepatocellular carcinoma, particularly in determining which patients can benefit more from the TLT treatment. From March 2021 to September 2023, a total of 169 patients from three centers were included in this study, with 103 patients receiving TLT and 66 patients receiving TL. The Kaplan-Meier method was utilized to evaluate the cumulative overall survival (OS) and progression-free survival (PFS) between the two groups and were assessed using the log-rank test. Subgroup analysis on tumor number, maximum tumor diameter, presence of portal vein thrombosis, AFP level, and Child-Pugh class were conducted. The median OS was 26 months in the TLT group, and 20 months in the TL group. The median PFS was 14 months in the TLT group and 9 months in the TL group. The Kaplan-Meier curve demonstrated a significantly superior OS and PFS in the TLT group compared to the TL group. Subgroup analysis showed that for patients with a maximum tumor diameter greater than 7 cm, AFP > 400 ng/ml and accompanied by portal vein tumor thrombus, and Child-Pugh class A, there was a statistically significant difference in OS between TLT and TL groups. OS and PFS were significantly improved in patients who received TLT compared to those who received TL, patients with a largest tumor diameter greater than 7 cm, AFP > 400 ng/ml, Child-Pugh class A and PVTT appeared to derive more benefit.

Stroke Prevention With Prophylactic Left Atrial Appendage Occlusion in Cardiac Surgery Patients Without Atrial Fibrillation: A Meta-Analysis of Randomized and Propensity-Score Studies.

The role of left atrial appendage occlusion (LAAO) in patients without previous atrial fibrillation (AF) is not established. This meta-analysis was conducted on patients with normal sinus rhythm who underwent cardiac surgery, with and without concomitant LAAO, to evaluate its effect on the incidence of cerebrovascular accidents (CVAs). A systematic review was conducted from inception until December 2023 for randomized and propensity-score studies comparing CVA in patients without AF undergoing cardiac surgery with or without LAAO. Six studies met our inclusion criteria with a total of 4130 patients: 2146 in the LAAO group and 1984 in the no-LAAO group. The risk ratio of postoperative AF was 1.05 (95% CI, 0.86-1.28); P=0.628. The CVA rates at 5 years were 6.8±1.0% in the no-LAAO group and 4.3±0.8% in the LAAO group (log-rank P=0.021). The Cox regression analysis for CVA in patients undergoing LAAO reported a hazard ratio of 0.65 (95% CI, 0.45-0.94); P=0.022. Landmark analysis at 4 years highlighted a significant difference in overall survival between no-LAAO and LAAO groups, 86±12.2% versus 89.6±11.0%; P=0.041. In this meta-analysis of patients without previous AF undergoing cardiac surgery, LAAO was associated with a decreased risk of CVA, no difference in the incidence of postoperative atrial fibrillation, and a significant overall survival benefit at a 4-year landmark analysis. Although these findings support LAAO, the randomized LeAAPS trial (Left Atrial Appendage Exclusion for Prophylactic Stroke Reduction Trial), LAA-CLOSURE trial (A Randomized Prospective Multicenter Trial for Stroke Prevention by Prophylactic Surgical Closure of the Left Atrial Appendage in Patients Undergoing Bioprosthetic Aortic Valve Surgery), and LAACS-2 trial (Left Atrial Appendage Closure by Surgery-2) will help define the effectiveness of LAAO in patients undergoing cardiac surgery who have risk factors for AF and CVA. URL: https://www.crd.york.ac.uk/prospero/; Unique identifier: CRD42024496366.

Multicenter evaluation of CT deep radiomics model in predicting Leibovich score risk groups for non-metastatic clear cell renal cell carcinoma

BackgroundNon-metastatic clear cell renal cell carcinoma (nccRCC) poses a significant risk of postoperative recurrence and metastasis, underscoring the importance of accurate preoperative risk assessment. While the Leibovich score is effective, it relies on postoperative histopathological data. This study aims to evaluate the efficacy of CT radiomics and deep learning models in predicting Leibovich score risk groups in nccRCC, and to explore the interrelationship between CT and pathological features. Patients and MethodsThis research analyzed 600 nccRCC patients from four datasets, dividing them into low (Leibovich scores of 0–2) and intermediate to high risk (Leibovichscores exceeding 3) groups. Radiological models were developed from CT subjective features, and radiomics and deep learning models were constructed from CT images. Additionally, a deep radiomics model and a fusion model integrating radiological, radiomics, and deep learning features were introduced. Model performance was assessed by AUC values, while survival differences across predicted groups were analyzed using survival curves and the DeLong test. Moreover, the research investigated the connection between CT and pathological features derived from whole-slide pathological images in the second validation dataset. ResultsWithin the training dataset, four radiological, three radiomics, and thirteen deep learning features were selected to develop models predicting nccRCC Leibovich score risk groups. The deep radiomics model demonstrated superior predictive accuracy, evidenced by AUC values of 0.881, 0.829, and 0.819 in external validation datasets. Notably, significant differences in overall survival were observed among patients classified by this model (DeLong test p < 0.05 across all datasets). Furthermore, a correlation and complementarity were observed between deep radiomics features and pathological deep learning features. ConclusionsThe CT deep radiomics model precisely predicts nccRCC Leibovich score risk groups preoperatively and highlights the synergistic effect between CT and pathological data.