Difference In Overall Survival Research Articles

Efficacy of androgen receptor signaling inhibitors in combination with androgen deprivation therapy for castration-sensitive metastatic prostate cancer: a retrospective analysis in a Japanese cohort.

This study aimed to evaluate the efficacy of androgen receptor signaling inhibitors (ARSIs) combined with androgen deprivation therapy (ADT) for treating castration-sensitive metastatic prostate cancer in Japanese patients, focusing on the effects on time to the development of castration-resistant prostate cancer (CRPC) and overall survival (OS). This retrospective muti-institutional analysis included 332 patients diagnosed with metastatic prostate cancer in Japan between 2018 and 2023. The patients were categorized into two groups: patients receiving ADT combined with ARSI (ARSI group) and those receiving ADT alone or with bicalutamide (ADT group). Data on demographics, treatments, and outcomes were compared using the Kaplan-Meier method with propensity score matching. We found an increasing trend in ARSI use over time. The median time to CRPC was significantly longer in the ARSI group than in the ADT group (47.1 vs. 15.2months, p < 0.001); however, no significant differences in OS were observed before or after propensity score matching. The 1-year-survival rate of patients in the ARSI group tended to be higher than that of patients in the ADT group in subgroups with high tumor volume (96.1% vs. 85.0%) and high Gleason grade (98.1% vs. 85.9%). Adding ARSI to ADT extended the time to CRPC but did not significantly affect OS. However, it potentially suppressed the short-term risk of death in high-risk subgroups. This study highlights the need for further research to explore the characteristics of Japanese patients with metastatic prostate cancer in whom upfront ARSIs are effective.

Characterization of PSA dynamics and oncological outcomes in patients with metastatic hormone-sensitive prostate cancer treated with androgen receptor signaling inhibitors.

This study investigated the characteristics of prostate-specific antigen (PSA) dynamics when androgen receptor signaling inhibitor (ARSI), or vintage agent (bicalutamide) was used for patients with metastatic hormone-sensitive prostate cancer (mHSPC). A total of 213 mHSPC patients from each of the ARSI and bicalutamide groups treated between 2015 and 2022 were selected from multiple institutions using propensity score-matched analysis to align backgrounds. PSA progression-free survival (PFS) and overall survival (OS) were assessed. PSA level at 3months, PSA nadir level, and time to PSA nadir were examined to analyze of PSA kinetics. ARSI treatment significantly improved PSA PFS compared to bicalutamide (P = 0.0063), although no significant difference in OS was seen (P = 0.3134). No significant differences were observed between treatment groups in median PSA levels at 3months (1.47 vs 0.52ng/ml, P = 0.3042) or PSA nadir levels (0.263 vs 0.1345ng/ml, P = 0.1228). Bicalutamide treatment demonstrated longer time to nadir than ARSI in progression-free cases (median: 243 vs 213.5days, P = 0.0003). Survival tree analysis found that PSA nadir ≤ 1.5ng/ml and time to nadir ≥ 145days were the optimal cut-offs for best stratifying OS with bicalutamide, while PSA nadir ≤ 0.45ng/ml and time to nadir ≥ 70days were optimal with ARSI. No significant differences in PSA response was seen between groups; however, distinct optimal cut-offs were demonstrated for PSA nadir and time to nadir. The present findings will be useful for optimal PSA monitoring for mHSPC patients and for early identification of poor-prognosis populations.

Efficacy and safety of hypomethylating agents in the treatment of AML/MDS patients relapsed post allogenetic hematopoietic stem cell transplantation

IntroductionAcute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) constitute myeloid malignancies, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) is considered as a potentially optimal approach for achieving a long term cure. However, post-allo-HSCT relapse remains a leading cause of mortality and therapeutic failure.MethodsTo evaluate the efficacy and safety of combining hypomethylating agents (HMAs) with Bcl-2 inhibitors in the treatment of AML/MDS relapse following allo-HSCT, we retrospectively collected data from 42 patients who experienced relapse between April 2012 and March 2022 at Peking University First Hospital. Among these patients, 21 underwent intensive chemotherapy (IC) alone, while the other 21 received treatment with HMAs after IC treatment, either alone or in combination with the Bcl-2 inhibitor venetoclax (VEN).ResultsThe median overall survival (OS) was 9 ± 2.153 months, and the one-year OS rate was 41.5%. The overall response rate (ORR) in the chemotherapy group and the IC+HMAs ± VEN group was 52.38% (11/21) and 76.19% (16/21), respectively, with no significant difference found (P=0.107). Kaplan-Meier analysis revealed a significant difference in OS between the chemotherapy group and the IC+HMAs ± VEN group in our retrospective cohort study (P=0.041, χ2= 4.016). Additionally, a significant difference in overall survival (OS) rates was observed between the two groups for patients categorized as intermediate/high risk (P=0.008). The secondary relapse rate was 45.45% (5/11) in the IC cohort and 25% (4/16) in the IC+HMAs ± VEN group, respectively, with no significant difference identified between the two cohorts (P=0.268). Furthermore, upon assessing the risk of graft-versus-host disease (GvHD), infection, and agranulocytosis, no notable differences were observed with the use of HMAs, suggesting that HMAs did not increase the risk. In the IC+HMAs ± VEN group, 7 patients received VEN in addition to HMAs, and no significant statistical difference was found in OS when comparing patients who received HMAs alone and those who received HMA+VEN (P=0.183), also, a statistically significant difference in OS was noted between the two groups whenaccounting for competing risks (P=0.028).ConclusionsThis retrospective study highlights the efficacy of IC+HMAs ± VEN in treating AML/MDS patients experiencing relapse post allo-HSCT, improving survival rates, especially for those classified as intermediate/high risk, with favorable tolerability.

Mid-term follow-up results of neoadjuvant sintilimab combined with chemotherapy for locally advanced resectable esophageal squamous cell carcinoma.

The study was conducted in order to investigate whether neoadjuvant immunotherapy combined with chemotherapy can bring survival benefits to patients with locally advanced resectable esophageal squamous cell carcinoma (ESCC) in the real world. We retrospectively analysed patients with locally advanced resectable ESCC who underwent surgery at the Jining First People's Hospital from April 2020 to April 2022. Based on their medical history, the enrolled patients were divided into a neoadjuvant immunochemotherapy plus surgery group (nICT group) and a surgery-only group (S group). Primary endpoints were the two-year overall survival (OS) and disease-free survival (DFS) rates. Secondary endpoints were the safety and efficacy of neoadjuvant immunochemotherapy for patients with locally advanced esophageal cancer, and compared the surgery and postoperative outcomes between the two groups. A total of 47 patients in the nICT group and 73 patients in the S group were included for further analysis, the stage of the nICT group was more advanced than that of the S group. In the group nICT, 8 patients (17%) achieved the complete pathological response (pCR), 29 patients (61.7%) achieved major pathological response (MPR), including 6 patients (12.8%) with a primary tumor achieving pCR but had residual tumor cells in the lymph nodes (pT0N+), and the treatment-related AES was manageable. The surgery and postoperative outcomes were comparable in both groups. The two-year OS and DFS rates for the nICT group were 91.5% and 85.5% respectively, while those for the S group were 71.2% and 68.5%, and Kaplan-Meier survival analysis and log-rank test revealed significant differences in DFS and OS between the two groups. Patients who achieved MPR in the nICT group showed better DFS and OS, while the Three-cycle subgroup did not exhibit any survival benefit compared to the Two-cycle subgroup. Neoadjuvant sintilimab combined with chemotherapy has promising efficacy and safety in the treatment of locally advanced resectable ESCC. The treatment modality has the potential to become a standard therapy for locally advanced resectable ESCC.

Adjuvant immunotherapy in high-risk muscle-invasive urothelial cancer: an updated meta-analysis of randomized controlled trials

Introduction: Neoadjuvant cisplatin-based chemotherapy followed by radical surgery is the standard treatment for muscle-invasive urothelial carcinoma (MIUC). The Checkmate-274 and AMBASSADOR trials have demonstrated improvements in disease-free survival (DFS) with adjuvant immunotherapy. Consequently, this meta-analysis aimed to assess the effectiveness of strategies involving checkpoint inhibitors in managing high-risk MIUC. Patients and Methods: We searched PubMed, Embase, Cochrane, ClinicalTrials.gov, EAU24, and ASCO GU abstracts for randomized controlled trials (RCTs) comparing adjuvant PD-1 and PD-L1 inhibitors against control (placebo or observation) for MIUC. Outcomes included DFS, grade ≥ 3 adverse events (AEs), and overall survival (OS). Heterogeneity was assessed using I2 statistics, employing a random-effects model for analysis. Results: In a cohort of 2,220 patients from three RCTs, 1,113 (50.14%) underwent adjuvant immunotherapy. This treatment significantly increased DFS (HR 0.76; 95% CI 0.65-0.90; p < 0.01), particularly in lower tract tumors (HR 0.71; 95% CI 0.56-0.91; p < 0.01). No substantial DFS improvement surfaced in the upper tract subgroup (p = 0.28) (p-interaction = 0.01). PD-L1 status (p-interaction = 0.83) and previous neoadjuvant chemotherapy (p-interaction = 0.11) did not significantly affect outcomes. However, immunotherapy correlated with higher grade ≥ 3 AEs (RR 1.47; p<0.01), with no notable difference in OS (p=0.07). Conclusions: Adjuvant PD-1/PD-L1 inhibitors notably enhance MIUC DFS, particularly in lower tract tumors, regardless of PD-L1 status. These findings support immunotherapy, especially anti-PD1, as a valuable adjuvant treatment strategy for high-risk MIUC patients. Micro abstractThis meta-analysis investigates the use of adjuvant anti-PD1/PDL1 therapy for high-risk muscle-invasive urothelial cancer (MIUC). By analyzing data from three randomized controlled trials involving 2,220 patients, the study demonstrates that immune checkpoint inhibitors, particularly PD1 inhibitors, significantly improve disease-free survival, regardless of PD-L1 status. These findings support considering ICIs as a viable adjuvant treatment option for patients with MIUC.

Clinical characteristics and prognostic analysis of metachronous bilateral breast carcinoma: a retrospective study based on propensity score matching.

To investigate clinical characteristics, treatment, outcomes, and prognostic risk factors of metachronous bilateral breast carcinoma (MBBC) and provide a theoretical basis for clinical management of MBBC. This was a retrospective study. From January 1, 2010 to March 31, 2022, a total of 23,010 patients with breast cancer underwent surgical treatment at the Breast Center of the Fourth Hospital of Hebei Medical University, including 386 patients with MBBC. Propensity score matching (PSM) was performed on MBBC patients and unilateral breast cancer (UBC) patients in a 1:1 ratio, and 210 UBC patients and 210 MBBC patients were finally matched. Clinical medical records of all patients were collected, including age of onset, family history of breast cancer, tumor size, lymph node status, TNM stage, mode of surgery, menstruation, pathological type, immunohistochemical (IHC) typing, treatment, disease-free survival (DFS), and overall survival (OS). The result showed that age of onset of the second primary cancer (SPC) was significantly older than that of the first primary cancer (FPC) (P = 0.024). Baseline data from MPPC patients showed that the tumor size of FPC was significantly larger than that of SPC (P = 0.043), and the proportion of PR ( +) in FPC is significantly higher than that in SPC (P = 0.045). Among MBBC patients with FPC for estrogen receptor (ER) or progesterone receptor (PR) ( +) and Her-2 (-), clinical characteristics and treatment results showed that the proportion of PR ( +) in the drug-resistant group was significantly lower than that in the non-drug-resistant group. The 2-year OS rate of SPC in the drug-resistant group was significantly shorter than those of the non-drug-resistant group (78.9% vs 100%, P < 0.05). The result of PSM-based comparison between MBBC patients and UBC patients showed significantly lower proportion of MBBC patients with SPC received chemotherapy compared to UBC patients (P = 0.026), and there was no significant difference in OS and DFS between SPC course of MBBC patients and UBC patients (P > 0.05). The univariate analysis showed that high TNM stage was a risk factor for death and disease progression in MBBC patients, with the risk of death in stage III MBBC patients being about 5 times higher than that in stage I MBBC patients (HR = 4.97, 95%CI = 1.42-17.31, P = 0.012), and the risk of disease recurrence being about 3.5 times higher than that in stage I MBBC patients (HR = 3.55, 95%CI = 1.07-11.81, P = 0.039). In summary, this study presented clinical characteristics, treatment options, and outcomes of MBBC patients and patients with MBBC who were resistant to endocrine therapy have a worse SPC survival prognosis. The course of SPC in MBBC patients was similar to that of UBC in terms of prognosis and survival, which suggested that SPC can be treated according to UBC treatment regimen. High TNM stage was a prognostic risk factor for SPC patients.

Efficacy and safety of preoperative intravenous iron versus standard care in colorectal cancer patients with iron deficiency anemia: a systematic review and meta-analysis.

Anemia, particularly iron deficiency (ID) anemia, is common in colorectal cancer (CRC) patients, affecting up to 58% of individuals. This study aimed to compare the effectiveness and safety of preoperative intravenous iron (IVI) with standard care (no iron or oral iron) in CRC patients with ID anemia. A systematic search across multiple databases identified studies comparing IVI versus no iron or oral iron in CRC patients with ID anemia. Pooled data were analyzed for changes in hemoglobin (Hb) levels, need for red blood cell transfusions (RBCT), overall mean number of transfused RBC units, overall survival (OS), disease-free survival (DFS), and complications. The authors analyzed data from 11 studies with 2024 patients and found that IVI significantly increased Hb levels at crucial time points: preoperative (MD=1.17, 95% CI [0.95-1.40], P<0.01), postoperative day one (MD=1.32, 95% CI [0.89-1.76], P<0.01), hospital discharge (MD=0.76, 95% CI [0.28-1.24], P=0.002), and 30 days postoperative (MD=1.57, 95% CI [1.27-1.87], P<0.01). IVI significantly decreased the overall need for RBCT, particularly in the postoperative period (RR=0.69, 95% CI [0.52-0.92], P=0.01). It also reduced the mean number of transfused RBC units, total complications, and wound dehiscence. However, there were no significant differences in total death, hospital stay, infections, paralytic ileus, OS, or DFS. Preoperative IVI significantly increased Hb levels at critical time points and markedly reduced the overall need for RBCT, complications, and wound dehiscence. To further validate these findings and ensure robust conclusions, more well-designed randomized controlled trials are warranted.

In-field prostate cancer recurrence following radical prostatectomy and salvage radiation.

To define the natural history, patterns of recurrence and treatment modalities for local prostate cancer (PCa) recurrence following radical prostatectomy (RP) and radiation therapy (RT), and to investigate factors that could predict metastasis-free survival (MFS) in this unique patient population. We queried a prospectively maintained PCa registry to identify men developing in-field recurrence (IFR) following RP and RT from 2008 to 2021 at a single institution. IFR was defined as biopsy-proven recurrent PCa or the presence of persistent positron emission tomography-avid lesions in the prior radiation field without evidence of metastasis. Cox regression was conducted to determine predictors of MFS. Kaplan-Meier methods were used to calculate MFS, cancer-specific survival (CSS) and overall survival (OS) for patients in three primary therapy categories: cryoablation, androgen deprivation therapy (ADT) alone, and surveillance. Of 4575 patients from our registry, 108 (2.3%) with IFR were identified. The median (interquartile range [IQR]) time to IFR from salvage treatment was 78 (50-126) months. A total of 29 patients (26%) were managed with cryoablation, 23 (21%) with ADT, and 28 (25%) with surveillance. The median (IQR) follow-up was 76 (48-100) months. There were no statistically significant differences in MFS (P = 0.67) or OS (P = 0.07) among the three primary treatment cohorts. Patients treated with ADT or cryoablation had longer CSS compared to patients managed with surveillance (P = 0.047). We found that IFR may present years after completion of primary treatment for PCa. While curative management strategies may be attempted, local and distant metastatic recurrence is common and often requires systemic therapy.

Management of cutaneous head and neck squamous cell carcinoma with trigeminal nerve involvement: a systematic review

Cutaneous head and neck squamous cell carcinoma (cHNSCC) is the second most common cancer worldwide, carrying a favorable prognosis. Perineural invasion/spread dramatically reduces survival outcomes. The trigeminal nerve (CNV) is most commonly affected, providing abundant opportunities for skull base and intracranial cavity invasion. Standard treatment includes surgery and radiotherapy (SRT). We intended to systematically review the literature on cHNSCC with CNV involvement and evaluate the effects of treatment modalities and pattern of CNV invasion/spread on outcomes. We performed a systematic review according to the preferred reporting items for systematic reviews and meta-analysis (PRISMA). Kaplan-Meier curves were utilized to determine the impact of treatment and pattern of invasion/spread on disease-free survival (DFS) and overall survival (OS). Fifty-one studies were identified, generating a sample size of 172 patients with cHNSCC and CNV involvement. The most common treatment modality was SRT (n=90, 52.9%), and all three major CNV branches were affected with similar frequency (V1 33.7%, V2 33.7%, V3 32.6%). Cox proportional hazards regression models revealed significant differences in OS for V1 vs V2 involvement (HR 2.84 95% CI 1.02-7.89), skull base invasion (HR 3.90 95%CI 1.30-11.65), SRT vs RT alone (HR 5.77 95% CI 2.13-15.6), SRT vs other treatment (HR 6.21 95 CI 2.24-17.20). Only SRT and RT had a significant difference in DFS (HR of 3.90, 95%CI 1.30-11.65). In cHNSCC with CNV involvement, treatment modality and the pattern of CNV are crucial for locoregional control and mortality. V1 involvement and definitive RT are associated with significantly lower survival curves.

Long-term prognosis of surgical treatment for peri-gastric cardial gastrointestinal stromal tumors

Objective: To explore the long-term prognosis of surgical treatment for peri-gastric cardial gastrointestinal stromal tumors (GISTs). Methods: In this retrospective cohort study, we analyzed selected data of patients with peri-gastric cardial GISTs who had undergone radical surgery in Renji Hospital, Shanghai Jiao Tong University School of Medicine, from May 1998 to December 2020. Inclusion criteria comprised radical surgery, pathologically confirmed primary gastric GIST; tumor involving the cardia or within 5 cm of the cardia dentate line; and relatively complete clinical data, including adjuvant therapy and follow-up information. Exclusion criteria comprised presence of multiple GISTs or a history of other malignancies and evidence of distant metastasis or local invasion either preoperatively or intraoperatively. The study cohort comprised 170 patients, including 98 men (57.6%), with a median age of 62 years (range: 30-85 years). Tumors were located less than 2 cm from the dentate line in 97 patients and 2 to 5 cm from it in 73. Tumor growth patterns were intraluminal in 85 patients, extraluminal in 61, and both intraluminal and extraluminal in 24. Tumor diameters were ≤2.0 cm in 11 patients, 2.1-5.0 cm in 90, 5.1-10.0 cm in 60, and >10.0 cm in nine. Mitosis counts (per 50 high-power fields) were ≤5 in 129 patients, 5-10 in 21, and >10 in 20. Risk stratification categorized patients as at extremely low risk in 10 patients, at low risk in 79, at intermediate risk in 43, and at high risk in 38. The guidelines for treatment were adhered to in 128 patients; 21 of 38 high-risk patients had received imatinib for ≥3 years. Primary outcomes included surgical procedure, overall survival (OS), and disease-free survival (DFS). Data were analyzed using SPSS 28.0 and R studio. Results: Ninety of the patients had undergone open surgery, including five total gastrectomies, 49 proximal gastrectomies, and 36 local resections. In addition, 80 patients had undergone laparoscopic local resections. The median follow-up time was 82.5 months (range 13-278 months). The OS rates at 1, 3, 5, and 10 years were 100.0%, 98.2%, 96.9%, and 89.6%, respectively. The DFS rates at 1, 3, 5, and 10 years were 99.4%, 95.9%, 92.0%, and 88.0%, respectively. After adjusting for tumor diameter, mitotic count, adjuvant therapy, distance from the cardia, and growth pattern using propensity score matching, we found no statistically significant differences in DFS and OS between proximal gastrectomy and partial resection, or between open local resection and laparoscopic local resection (all P>0.05). Conclusions: Surgical treatment of peri-gastric cardial GISTs has a favorable long-term prognosis. The oncological efficacy of proximal gastrectomy and partial resection, whether performed via laparoscopic or open approaches, appears comparable for treatment of peri-gastric cardial GISTs.

Light-chain amyloidosis with concomitant symptomatic myeloma (CRAB-SLiM features): clinical characteristics, cytogenetic abnormalities, and outcomes

BackgroundPatients with light-chain (AL) amyloidosis and concomitant multiple myeloma (MM) are known to have a worse prognosis, while the prognostic implication of cytogenetic abnormalities (CA) and optimal treatment schemes are not well-established. By comparing patients with MM or AL amyloidosis (AL) alone, this study aimed to evaluate the clinical characteristics, CA, and outcomes of patients with AL amyloidosis and concomitant symptomatic MM (MM-AL) and sought to provide evidence for their management.MethodsIn total, 915 consecutive patients with newly diagnosed AL amyloidosis or MM were retrospectively analyzed. Patients were classified as MM-alone, MM-AL or AL-alone. The presence of symptomatic MM was based on the International Myeloma Working Group criteria, and the diagnosis of AL amyloidosis was confirmed by Congo-red-positive biopsy and immunoelectron microscopy.ResultsOf 915 patients, 658, 106, and 151 were in the MM-alone group, MM-AL group, and AL-alone group, respectively. The three groups shared a similar incidence rate of CA, while the prevalence of t(11;14) was significantly higher in the AL-alone group than in the MM-AL and MM-alone group (40.7% vs. 25.7% vs. 16.6%, p < 0.001), and the prevalence of del13q, gain1q21 and high-risk CA (HRCA) decrease in turn in MM-alone, MM-AL and AL-alone group (del13q, 46.5% vs. 39.4% vs. 28.5%, p < 0.001; gain1q21, 52.6% vs. 45.2% vs. 27.3%, p < 0.001; HRCA, 27.5% vs. 16.0 vs. 7.3%, p < 0.001). The progression-free survival (PFS) and overall survival (OS) of MM-AL patients (median, 12.8, and 25.2 months) were significantly inferior to patients with MM-alone and AL-alone. No significant difference in PFS and OS was found between MM-AL patients with and without HRCA. When stratified by the type of plasma cell disease and status of t(11;14), patients with MM-AL and t(11;14) presented the worst OS (median, 8.2 months, p < 0.001). Regarding the management of MM-AL, extended cycles of induction therapy and the use of maintenance therapy contributed to a better prognosis.ConclusionsThere was an apparent discrepancy in the distribution and prognostic implication of CA among different plasma cell diseases. Patients with MM-AL had the worst clinical outcomes, requiring extended duration of induction therapy and maintenance therapy.

The Therapeutic Implications of Biomarkers Testing in Non-small Cell Lung Cancer in Middle- and Low-income Country: The Example of Morocco

Introduction: The Identification of PD-L1, EGFR and ALK status is essential to guide personalized treatment of NSCLC. The objective of our study is to evaluate the implication of changing the therapeutic protocol on the prognosis of Moroccan patients with NSCLC. Methods: Between January 2019 and February 2023, 96 patients with NSCLC were recruited. Results: In our population, the patients were treated with different first-line protocols: 83.34% (N=80) with neo-adjuvant chemotherapy, 14.58% (N=14) with immunotherapy and 2.08% (N=2) with targeted therapy. Of the 82 patients who received neo-adjuvant chemotherapy (N=80), 24 were able to switch to immunotherapy. While, the 2 patients who received targeted therapy beforehand also switched to immunotherapy. The influence of the number of chemotherapy (Chemo) cycles on vital status and overall survival (OS) of the 24 patients who switched from their initial protocol to immunotherapy (IO) showed that patients who received IO after completing the 4 or 5 cycles of chemo had a good OS, with a mean of 29.07 months. In comparison, patients who received less than 4 cycles of chemo had a mean OS of 14.70 months, while those who received more than 5 cycles of chemo had a mean OS of 21.38 months. Furthermore, the association between change in treatment protocol and patient vital status was significant (p=0.013). However, there was a significant difference in OS between patients who maintained the treatment protocol (mean OS=12.43 months) and those who changed the protocol (mean OS=24.01 months) (p=0.000). Multivariate analysis indicated that maintaining the initial therapeutic protocol was independently associated with a reduced OS (p=0.003). Conclusion: Our results highlight the impact of changing the protocol on the OS of NSCLC patients taking into account the importance of choosing the right timing to switch to IO based on the number of prior chemo cures.

Predicting survival, neurotoxicity and response in B-cell lymphoma patients treated with CAR-T therapy using an imaging features-based model

BackgroundThis multicentre retrospective observational study aims to develop imaging-based prognostic and predictive models for relapsed/refractory (R/R) B-cell lymphoma patients undergoing CAR-T therapy by integrating clinical data and imaging features. Specifically, our aim was to predict 3- and 6-month treatment response, overall survival (OS), progression-free survival (PFS), and the occurrence of the immune effector cell-associated neurotoxicity syndrome (ICANS).ResultsSixty-five patients of R/R B-cell lymphoma treated with CAR-T cells in two centres were included. Pre-infusion [18F]FDG PET/CT scans and clinical data were systematically collected, and imaging features, including kurtosis, entropy, maximum diameter, standardized uptake value (SUV) related features (SUVmax, SUVmean, SUVstd, SUVmedian, SUVp25, SUVp75), total metabolic tumour volume (MTVtotal), and total lesion glycolysis (TLGtotal), were extracted using the Quibim platform. The median age was 62 (range 21–76) years and the median follow-up for survivors was 10.47 (range 0.20–45.80) months. A logistic regression model accurately predicted neurotoxicity (AUC: 0.830), and Cox proportional-hazards models for CAR-T response at 3 and 6 months demonstrated high accuracy (AUC: 0.754 and 0.818, respectively). Median predicted OS after CAR-T therapy was 4.73 months for high MTVtotal and 37.55 months for low MTVtotal. Median predicted PFS was 2.73 months for high MTVtotal and 11.83 months for low MTVtotal. For all outcomes, predictive models, combining imaging features and clinical variables, showed improved accuracy compared to models using only clinical variables or imaging features alone.ConclusionThis study successfully integrates imaging features and clinical variables to predict outcomes in R/R B-cell lymphoma patients undergoing CAR-T. Notably, the identified MTVtotal cut-off effectively stratifies patients, as evidenced by significant differences in OS and PFS. Additionally, the predictive models for neurotoxicity and CAR-T response show promising accuracy. This comprehensive approach holds promise for risk stratification and personalized treatment strategies which may become a helpful tool for optimizing CAR-T outcomes in R/R lymphoma patients.

Prognostic Value of Baseline Skeletal Muscle Index in Colorectal Cancer Patients Treated with Fruquintinib: A multi-center real world analysis

BackgroundThe Skeletal Muscle Index (SMI) serves as an objective metric for assessing nutritional status in patients with malignant tumors. Research has found baseline nutritional status can influence both the efficacy and prognosis of targeted anti-tumor therapies, with growth factor tyrosine kinase inhibitors frequently inducing drug-related sarcopenia. Fruquintinib has received approval for the treatment of metastatic colorectal cancer. This study examines the prognostic significance of baseline SMI in patients with metastatic colorectal cancer undergoing treatment with fruquintinib. Additionally, the study investigates the incidence of SMI reduction following fruquintinib therapy to assess its impact on patient prognosis.MethodsA retrospective multicenter study was conducted to analyze patients with metastatic colorectal cancer who received fruquintinib treatment across eight medical centers in Eastern China. The muscle area at the third lumbar vertebra was assessed, and both baseline and post-treatment SMI values were calculated independently. The relationship between SMI and patient survival was subsequently examined.ResultsThe median progression-free survival (PFS) for the cohort of 105 patients was 4.2 months (95% CI, 3.7 to 4.9 months), while the median overall survival (OS) was 10.2 months (95% CI, 9.0 to 12.7 months). Notably, the baseline SMI prior to the initiation of fruquintinib therapy exhibited a significant correlation with OS (P = 0.0077). Multivariate analysis indicated that baseline SMI serves as an independent prognostic factor for OS (P = 0.005). Furthermore, after Propensity Score Matching (PSM) analysis, there was still a significant correlation between baseline SMI and OS. Among the patients, 28.87% developed sarcopenia following oral administration of fruquintinib. However, no statistically significant difference in OS was observed between the group with reduced SMI and the group without SMI reduction after treatment with fruquintinib.ConclusionThe baseline SMI was identified as an independent prognostic factor for OS and may influence the survival outcomes of patients with metastatic colorectal cancer undergoing treatment with fruquintinib. Despite the potential of fruquintinib to induce sarcopenia, no significant correlation was observed between changes in SMI following treatment and patient survival.

Association Between Antibiotic and Outcomes of Chemoimmunotherapy for Extensive-Stage Small Cell Lung Cancer: A Multicenter Retrospective Study of 132 Patients.

To evaluate the impact of antibiotic (ATB) exposure on the outcome of chemoimmunotherapy in patients with extensive-stage small cell lung cancer (ES-SCLC). In this multicenter retrospective study, 132 patients with ES-SCLC who received chemoimmunotherapy were included from three hospitals in China. Patients receiving ATB within 30 days prior to initiating ICI therapy (p-ATB) and those receiving concurrent ICI therapy until cessation (c-ATB)were compared to those who did not (n-ATB). Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and immune-related adverse events (irAEs) were assessed. To avoid immortal time bias, c-ATB was analyzed as a time-dependent covariate in the Cox proportional hazards model. Among the 132 patients, 25 were included in the p-ATB group and 26 in the c-ATB group, while 81 patients were categorized in the n-ATB group. Multivariate analysis revealed no significant differences in PFS (aHR = 1.028, 95% CI: 0.666-1.589, p = 0.900) and OS (aHR = 0.957, 95% CI: 0.549-1.668, p = 0.877) between the p-ATB and n-ATB groups. Similarly, p-ATB had no significant impact on ORR (p = 0.510) or irAEs (p = 0.516). The use of c-ATB had no significant effect on either PFS (aHR: 1.165, 95% CI: 0.907-1.497; p = 0.232) or OS (aHR: 1.221, 95% CI: 0.918-1.624; p = 0.171) by multivariate analysis. p-ATB has no significant impact on PFS, OS, ORR, or the incidence of irAEs in ES-SCLC patients receiving chemoimmunotherapy. Similarly, c-ATB does not seem to affect PFS or OS.

First Cycle Toxicity and Survival in Patients with Rare Cancers Treated with Checkpoint Inhibitors.

Associations between immune-related adverse events (irAEs) from checkpoint inhibitor therapy and outcomes have been previously evaluated, with most prior research finding a positive association between toxicity and survival. This prior research has generally reported on more common tumor types. We use a unique data resource of a federally-funded basket trial ((NCT02834013) for patients with rare cancers (N = 684) to evaluate associations between irAEs and overall survival and progression-free survival. Patients were treated with nivolumab and ipilimumab; the trial was opened at > 1000 sites. Landmark Cox regression models were used to assess first cycle irAE associations with progression-free and overall survival. We found that grade 1-2 treatment-related irAEs in the first cycle of therapy were associated with longer overall survival (OS) (multivariable hazard ratio, 95% confidence interval, p-value: 0.61, 0.49-0.75, p < .001) compared to no treatment-related irAE, while grade 3-4 irAEs were associated with shorter OS (HR = 1.41, 95% CI = 1.04-1.90, p = .025). Similar, but weaker, associations were observed with progression-free survival (PFS) and grade 1-2 treatment-related irAEs: HR = 0.83, 95% CI = 0.67-1.01, p = .067 and grade 3-4: HR = 1.35, 95% CI = 1.02-1.78, p = .037 compared to no treatment-related irAEs. Grade 1-2 dermatologic toxicity was associated with improved OS compared to other grade 1-2 toxicities (HR = 0.67, 95% CI = 0.52-0.85, p = .002). There was no significant OS difference between patients with Grade 1-2 fatigue, gastrointestinal, metabolic, hepatic, endocrine, and thyroid toxicities vs other Grade 1-2 toxicities. In this large cohort of patients with rare tumors receiving checkpoint inhibitor therapy, grade of irAE in the first cycle was predictive for survival.

The molecular subtypes of small cell lung cancer defined by key transcription factors and their clinical significance

BackgroundLung cancer, a prevalent and deadly malignancy, is classified into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). SCLC is further subdivided into four molecular subtypes—SCLC-A, SCLC-N, SCLC-P, and SCLC-I—based on key transcription factor expression. MethodsImmunohistochemistry (IHC) was used to assess ASCL1, NEUROD1, and POU2F3 expression in tumor tissues. The H-Score quantified these results. Clinical characteristics, overall survival (OS), progression-free survival (PFS), and treatment responses were analyzed by subtype, and sensitivity to different treatments was assessed. Risk factors were identified through univariate and multivariate analyses. ResultsIHC and H-Score analysis showed that POU2F3 expression was mutually exclusive with ASCL1 or NEUROD1. Subtype distribution was as follows: SCLC-A (40 %), SCLC-N (33 %), SCLC-P (7 %), and SCLC-I (20 %). There were no significant differences in baseline characteristics, OS (p = 0.829), or PFS (p = 0.924) among subtypes. However, the SCLC-I subtype showed a trend toward improved outcomes with platinum-based doublet chemotherapy plus immune checkpoint inhibitors. Multivariate COX regression identified M stage (HR: 1.72, 95 % CI: 1.13–2.63, p = 0.012) and bone metastasis at diagnosis (HR: 1.58, 95 % CI: 1.02–2.43, p = 0.040) as independent risk factors. ConclusionThis study confirmed the SCLC subtyping based on key transcription factors. While no significant differences in OS and PFS among subtypes were found, the SCLC-I subtype showed potential benefit from platinum-based chemotherapy combined with immune checkpoint inhibitors. M stage and bone metastasis at diagnosis were identified as independent risk factors for SCLC.

Impact of Antibiotic on Efficacy and Adverse Reactions of Chemoimmunotherapy in Non‐small Cell Lung Cancer Patients: A Retrospective Cohort Study

ABSTRACTBackgroundThis study aimed to evaluate the impact of antibiotic exposure on efficacy and adverse reactions in non‐small cell lung cancer (NSCLC) patients receiving chemoimmunotherapy, and to explore any specific associations on the basis of antibiotic class.MethodsA retrospective study was conducted on NSCLC patients who received chemoimmunotherapy in two Shandong hospitals between January 2018 and October 2023. The association between antibiotic exposure and progression‐free survival (PFS), overall survival (OS), objective response rate (ORR) and incidence of immune related adverse reactions (irAE) of patients were evaluated.ResultsOf the 316 patients, 134 (42.41%) received antibiotics (ATB group), and 182 (57.59%) did not (N‐ATB group). There was no significant difference in PFS (aHR = 1.009, 95% CI: 0.770–1.323; p = 0.946) or OS (aHR = 1.420, 95% CI: 0.986–2.047; p = 0.060) between ATB and N‐ATB groups. The impact on efficacy was related to the type of antibiotic. β‐Lactams (aHR = 1.737, 95% CI: 1.148–2.629; p = 0.009), in particular β‐lactam/β‐lactamase inhibitor combinations (BLBLIs) (aHR = 1.885, 95% CI: 1.207–2.944, p = 0.005) were associated with poorer OS. However, quinolones (aHR = 1.192, 95% CI: 0.861–1.650; p = 0.291) were not associated with OS. The incidence of irAEs was not significantly different between ATB and N‐ATB groups (p = 0.073), but was higher with BLBLIs (p = 0.013).ConclusionsIn NSCLC patients receiving chemoimmunotherapy, no significant difference was observed in efficacy and incidence of irAEs between the ATB and the n‐ATB groups. In antibiotic class analysis, β‐lactams and specifically BLBLIs were observed to be associated with worse OS.

Delineation of features, responses, outcomes, and prognostic factors in pediatric PDGFRB-positive acute lymphoblastic leukemia patients: A retrospective multicenter study.

PDGFRB fusions in acute lymphoblastic leukemia (ALL) is rare. The authors identified 28 pediatric PDGFRB-positive ALL. They analyzed the features, outcomes, and prognostic factors of this disease. This multicenter, retrospective study included 6457 pediatric patients with newly diagnosed PDGFRB fusion ALL according to the CCCG-ALL-2015 and CCCG-ALL-2020 protocols from April 2015 to April 2022 in 20 hospitals in China. Of these patients, 3451 were screened for PDGFRB fusions. Pediatric PDGFRB-positive ALL accounted for only 0.8% of the 3451 cases tested for PDGFRB. These patients included 21 males and seven females and 24 B-ALL and 4 T-ALL; the median age was 10 years; and the median leukocyte count was 29.8 × 109/L at baseline. Only one patient had eosinophilia. Three patients had an IKZF1 deletion, three had chromosome 5q31-33 abnormalities, and one suffered from a complex karyotype. The 3-year event-free survival (EFS), overall survival (OS), and cumulative incidence of relapse (CIR) were 33.1%, 65.5%, and 32.1%, respectively, with a median follow-up of 25.5 months. Twenty patients were treated with chemotherapy plus tyrosine-kinase inhibitors (TKIs) and eight were treated without TKI. Complete remission (CR) rates of them were 90.0% and 63.6%, respectively, but no differences in EFS, OS, or CIR. Univariate analyses showed patients with IKZF1 deletion or measurable residual disease (MRD) ≥0.01% after induction had inferior outcomes (p<.05). Pediatric PDGFRB-positive ALL has a poor outcome associated with high-risk features. Chemotherapy plus TKIs can improve the CR rate, providing an opportunity for lower MRD levels and transplantation. MRD ≥0.01% was a powerful adverse prognostic factor, and stratified treatment based on MRD may improve survival for these patients. Pediatric acute lymphoblastic leukemia patients with PDGFRB fusions are associated with high-risk clinical features such as older age, high white blood cell count at diagnosis, high measurable residual disease after induction therapy, and increased risk of leukemia relapse. Chemotherapy plus tyrosine-kinase inhibitors can improve the complete remission rate and provide an opportunity for lower measurable residual disease (MRD) levels and transplantation for pediatric PDGFRB-positive acute lymphoblastic leukemia (ALL) patients. The MRD level was also a powerful prognostic factor for pediatric PDGFRB-positive ALL patients.

The risk of venous thromboembolism in adult patients with diffuse glioma: a nationwide population-based study.

Venous thromboembolism (VTE) is a cause of increased morbidity and risk of death. Studies report VTE in up to 30% of glioma patients but the results vary. The VTE risk is relevant when evaluating prophylaxis to avoid unnecessary bleeding or overdiagnosis. This study examines the VTE incidence in patients with glioma WHO grade 2-4, and when VTE occurred, risk factors, and overall survival (OS) for patients with WHO grade 4. In total 3,630 patients with WHO grade 2 (n = 230), grade 3 (n = 317), and grade 4 (n = 3,083) gliomas from 2010 to 2018 were identified using the Danish Neuro-Oncology Registry. VTE diagnoses and time of death were obtained from Statistics Denmark. The VTE incidence was 5.2, 6.3, and 6.8% in patients with WHO grade 2, 3, and 4 gliomas, respectively. The VTE incidence rate was highest during the first 3 months after the diagnosis with 53 events. Increasing age (HR 1.03, 95%CI 1.01-1.04), male sex (HR 1.47, 95%CI 1.09-1.99), poor performance status (HR 1.57, 95%CI 1.10-2.25), and post-operative long-course radiochemotherapy (HR 2.10, 95%CI 1.19-3.72) were predictors of VTE in patients with glioma WHO grade 4. There was no difference in OS comparing patients having VTE to those without (p = 0.068). In conclusion, patients with glioma WHO grade 2-4 were at high risk of VTE, especially the first 3 months after diagnosis. Increasing age, male sex, poor performance status, and long-course radiochemotherapy were associated with increased risk of VTE in patients with glioma WHO grade 4.