Improvement In Overall Survival Research Articles

Disparities in utilization of novel cancer therapies in advanced stage III and IV melanoma and variance in outcomes.

Significant gains in advanced melanoma have been made through immunotherapy trials. Factors influencing equitable access and survival impact of these novel therapies are not well-defined. Retrospective analysis using National Cancer Database of patients with advanced stage III and IV melanoma from 2004 to 2021. Multivariable logistic regression was used to study the use of immunotherapy and Cox proportional hazard regression to evaluate overall survival (OS). 47,427 patients with increasing utilization of immunotherapy from 13.78% in 2004 to 65.88% by 2021. Inequitable adoption were impacted by age, sex, socioeconomic status/affordability, insurance types and residential educational/income level. Receiving immunotherapy was associated with a 44% improvement in OS (HR 0.56, 95% CI 0.54-0.57) and receiving a clinical trial-based therapy was associated with a 37% improvement (HR 0.63, 95% CI 0.53-0.75). Among patients who received immunotherapy or clinical trial-base therapy, there was 40% worse survival in non-Hispanic Black patients (HR 1.40, 95% CI 1.16-1.69) compared to non-Hispanic Whites. There are disparities in utilization of immunotherapy that is influenced by socioeconomic status. Race and ethnicity had a significant influence in differential impact on survival outcomes of immunotherapies highlighting the importance of increasing underrepresented population participation in trials that lead to novel therapies.

Efficacy and safety of PD-1 inhibitor plus chemotherapy in advanced nasopharyngeal carcinoma: A meta-analysis.

The combination of programmed cell death protein 1 (PD-1) inhibitors and chemotherapy has shown promising results in the treatment of various malignancies. This meta-analysis aims to evaluate the effectiveness and safety of combing PD-1 inhibitor with chemotherapy in patients with advanced NPC. A thorough search of the literature was carried out using comprehensive methods. The assessed outcomes included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). This meta-analysis included seven studies with a total of 1204 patients. The use of a combination therapy involving PD-1 inhibitor and chemotherapy demonstrated significant improvements in OS (HR=0.60, 95%CI: 0.45, 0.80; P<0.001), PFS (HR=0.51, 95%CI: 0.42, 0.61; P<0.001), ORR (RR=1.23, 95%CI: 1.07, 1.40; P=0.003) and DCR (RR=1.13, 95%CI: 1.03, 1.23; P=0.003) compared to other treatments in patients with advanced NPC. Subgroup analyses based on PD-1 inhibitor type, chemotherapy regimen and study design indicated that these factors influenced OS but not PFS. Prognostic factor analysis consistently demonstrated a PFS benefit associated with the combination treatment across various patient subgroups. The incidences of AEs, grade 3 or higher AEs were comparable between the two groups. However, the combination group was significantly more likely to discontinue treatment because of AEs. This meta-analysis provides evidence supporting the effectiveness and safety of PD-1 inhibitor plus chemotherapy in advanced NPC. The combination therapy showed superior outcomes in terms of OS, PFS, ORR, and DCR.

Belzutifan for renal cell carcinoma: Balancing regulatory approval with societal and patient impact.

LITESPARK-005 evaluated belzutifan against everolimus in advanced renal cell carcinoma (RCC),1 demonstrating significant progression-free survival improvement but failing to meet the overall survival (OS) co-primary endpoint. Despite FDA approval, the trial highlights key obstacles in drug development in RCC, given the absence of OS improvement, lack of biomarker studies, high financial toxicity, and limited accessibility outside the United States.

Efficacy and safety of neoadjuvant therapy for hepatocellular carcinoma with portal vein thrombosis: A meta‑analysis.

Hepatocellular carcinoma (HCC) with coexisting portal vein tumor thrombus (PVTT) is associated with poor patient outcomes. The efficacy and safety of neoadjuvant therapy in patients with HCC with PVTT remain a subject of debate. In the present study, a comprehensive search of electronic databases, including PubMed, Web of Science, Embase and the Cochrane Library, was conducted to identify studies evaluating the outcomes of neoadjuvant therapy in patients with HCC and PVTT. The primary outcomes assessed were overall survival (OS) and relapse-free survival (RFS), with complication rates as a secondary outcome. A total of six studies comprising 750 patients were included in the present meta-analysis. The neoadjuvant therapy group exhibited significantly superior OS [hazard ratio (HR), 0.39; P<0.001] and RFS (HR, 0.31; P<0.001) compared with the primary hepatectomy control group. Compared with the control group, neoadjuvant radiotherapy improved OS (HR, 0.34; P<0.001) and RFS (HR, 0.24; P=0.004). While the neoadjuvant intervention subgroup exhibited an improved OS compared with controls (HR, 0.37; P=0.001), no significant difference in RFS was observed (HR, 0.11; P=0.095). Geographical analysis revealed that the Chinese subgroup demonstrated a significantly improved OS and RFS (HR, 0.41 for both; P<0.001), compared with the control group. However, the Japanese and Korean subgroups showed no improvement in OS (HR, 0.25; P=0.057) compared with the control group, and the results did not reach statistical significance. There were no significant differences between the groups in terms of blood transfusion, blood loss, operation time, bile leakage, ascites, peritoneal infection, postoperative bleeding, complications or mortality (all P>0.05). Overall, neoadjuvant therapy significantly improved survival outcomes in patients with HCC and PVTT without increasing complication rates, supporting its efficacy and manageable safety profile.

Dynamic assessment of long-term survival in survivors with stage III non-small cell lung cancer: a novel conditional survival model with a web-based calculator

BackgroundConditional survival (CS) analysis can estimate further survival probabilities based on the time already survived, providing dynamic updates for prognostic information. This study aimed to develop a CS-nomogram to promote individualized disease management for stage III non-small cell lung cancer (NSCLC).MethodsThis study included patients diagnosed with stage III NSCLC in the Surveillance, Epidemiology, and End Results database from 2010 to 2017 (N = 3,512). The CS was calculated as CS(y|x) = OS(y + x)/OS(x), where OS(y + x) and OS(x) were the overall survival (OS) in the year (y + x) and year x, respectively, calculated by the Kaplan–Meier method. We used the least absolute shrinkage and selection operator (LASSO) regression to identify predictors and developed the CS-nomogram based on these predictors and the CS formula.ResultsThe CS analysis provided real-time updates on survival, with 5-year OS improving dynamically from 14.4 to 29.9%, 47.9, 66.0, and 80.8% (after 1–4 years of survival). Six independent predictors (age, tumor size, N status, surgery, radiotherapy and chemotherapy) were identified for the development of the CS-nomogram and its web version (https://dynapp.shinyapps.io/NSCLC/). The model performed with an excellent concordance index (C-index) of 0.71 (95% CI: 0.70–0.72), and a median time-dependent AUC of 0.71–0.73 from 200 iterations 5-fold cross-validation.ConclusionThe study demonstrated the improvement in real-time OS over time in stage III NSCLC survivors and developed the novel CS-nomogram to provide patients with updated survival data. It provided novel insights into clinical decisions in follow-up and treatment for survivors, offering a convenient tool for optimize resource allocation.

Thermal ablation included in multimodality treatment predicts enhanced survival in advanced non-small cell lung cancer: a propensity score-matched outcome study

Background Advanced non-small cell lung cancer (NSCLC) presents significant treatment challenges, with limited effective therapies for late-stage patients. This study aimed to evaluate the impact of adding thermal ablation (TA) in treatment regimens for advanced NSCLC to improve survival outcomes. Methods A retrospective cohort study was conducted at a medical center in Taiwan, analyzing data from 1,083 patients diagnosed with stage IIIB or IV NSCLC between 2008 and 2020. Survival outcomes were compared between patients treated with TA and those who received conventional therapies. Statistical analyses, including propensity score matching and Cox regression models, were used to account for potential confounders. Results The TA group demonstrated a significantly longer median overall survival (OS) of 37 months compared to 15 months in the non-TA group (p < 0.001), with five-year OS rates of 32.4% and 9.8%, respectively. Median progression-free survival (PFS) was 36 months in the TA group versus 14 months in the non-TA group, with five-year PFS rates of 24.1% versus 6.3% (p < 0.001). Subgroup analyses showed enhanced survival in patients undergoing targeted therapy and chemotherapy when TA was included. Survival outcomes with TA were comparable to lobectomy, offering a less invasive option for selected patients. Conclusions Thermal ablation is associated with significant improvements in OS and PFS in patients with advanced NSCLC, providing a viable treatment option for those not eligible for surgery. The results support the integration of TA into standard care protocols, with further prospective studies needed to confirm these findings and optimize treatment strategies.

Observational Study of Best Supportive Care With or Without Oral Capecitabine in Patients With Metastatic Gallbladder Carcinoma at a Tertiary Center in India.

To compare overall survival (OS), toxicity, and quality of life (QOL) in patients with metastatic gallbladder cancer receiving oral capecitabine (X) with best supportive care (BSC) and BSC alone. Patients with metastatic gallbladder cancer and Karnofsky Performance Status (KPS) ≥70 were accrued and assigned to either arm A or B. Assignment to these two arms was based on physician/patient discretion. Arm A received oral capecitabine 825 mg/m2 twice a day d1-14, repeated every 3 weeks for six cycles with BSC, and arm B received BSC alone. The Kaplan-Meier method computed OS and comparison was using a log-rank test. QOL was measured using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 administered at baseline, 3 months, and 6 months. The linear mixed-effects model was used for the longitudinal analysis of QOL. Between December 2020 and April 2022, 64 patients diagnosed with metastatic gallbladder carcinoma and KPS ≥70 were accrued in the study, and 32 patients were assigned to each arm. In arm A versus B, the median age was 52 versus 55 (P = .21); the median KPS was 80 versus 70 (P = .008). The median OS in arm A versus B was 3.4 versus 2 months (P = .001). Grade 1-2 vomiting and diarrhea were seen in 50% versus 78% (P = .041) and 59% versus 9.3% (P = .01) patients in arm A versus B, respectively. Grade 1-2 hand-foot syndrome was seen in 12 (37.5%) patients in arm A. Dynamic changes showed an improvement in pain in the linear mixed model with a significant difference between the arms (P = .011); arm A experienced a significant improvement in pain over time (arm × time P = .020). Global QOL improved over time (P = .038) with parallel improvement between arms (arm × time P = .490). Compared with BSC alone, patients who receive X + BSC experience an OS improvement of 1.4 months and better pain control without grade 3 toxicities or negative impact on QOL.

Identifying subgroups of ypN1 breast cancer patients who may exempt from axillary lymph node dissection after neoadjuvant chemotherapy: insights from a large cohort study.

In patients with breast cancer staged ypN1 after neoadjuvant chemotherapy (NAC), there is limited evidence-based guidance regarding exemption from axillary lymph node dissection (ALND). This study analyzed ypN1 breast cancer patients post-NAC from the Surveillance, Epidemiology, and End Results databases. Patients were categorized into the breast-conserving surgery (BCS) group and the total mastectomy (TM) group, and further divided by the number of positive lymph nodes (LNs). The effects of three axillary management strategies, ALND, sentinel lymph node biopsy combined with radiotherapy (SLNB + RT), and ALND + RT were compared. The overall survival (OS) and breast cancer-specific survival (BCSS) of all subgroups and their independent risk factors were analyzed. Independent prognostic factors selected from multivariate Cox analysis were utilized to create nomograms for predicting OS and BCSS. A total of 3641 patients were involved, with 1331 in the BCS group and 2310 in the TM group. In the TM group, patients with 3 residual positive LNs exhibited significant improvements in OS and BCSS when treated with ALND + RT. For patients with 1 or 2 residual positive LNs in the TM group and all BCS patients, no significant survival differences in survival outcomes were observed among the three axillary management methods. The accuracy of the nomograms was validated via calibration curves, receiver operating characteristic curves, and decision curve analysis curves. For TM group patients with 3 residual positive LNs after NAC, ALND + RT is recommended. For other subgroups of ypN1 patients, SLNB + RT can be considered an alternative to ALND. The nomogram developed to predict OS and BCSS in ypN1 breast cancer patients demonstrated excellent predictive ability.

Toripalimab plus chemotherapy for first line treatment of advanced non-small cell lung cancer (CHOICE-01): final OS and biomarker exploration of a randomized, double-blind, phase 3 trial.

A randomized double-blind phase 3 trial (CHOICE-01, NCT03856411) demonstrated that combining toripalimab with chemotherapy substantially improves progression-free survival (PFS) in advanced non-small cell lung cancer (NSCLC) patients without pretreatment. This study presents the prespecified final analysis of overall survival (OS) and biomarkers utilizing circulating tumor DNA (ctDNA) and tissue-based sequencing. Additionally, the analysis revealed a higher median overall survival (OS, 23.8 months) in the toripalimab group than that in the control group (17.0 months). (HR = 0.69, 95%CI: 0.57-0.93, nominal P = 0.01). This survival benefit was particularly notable in the non-squamous subgroup. As the first phase 3 study to perform both baseline tissue whole-exome sequencing (WES) and peripheral blood ctDNA testing, we investigated efficacy predictive biomarkers based on both tissue and ctDNA, Genomic sequencing of ctDNA showed high concordance with tumor tissue independently confirmed that individuals exhibiting a high tumor mutational burden, as well as mutations in the FA-PI3K-Akt and IL-7 signaling pathways benefited more from the toripalimab treatment. Furthermore, a ctDNA response observed on cycle 3 day 1, was associated with improved clinical outcomes for patients treated with the combination therapy. In conclusion, Toripalimab plus chemotherapy yields significant improvements in OS as a first-line treatment. The study highlights the utility of ctDNA as a proxy for tumor tissue, providing novel prospects for predicting efficacy of immuno-chemotherapy through continuous ctDNA monitoring.

The efficacy of adjuvant chemotherapy for curative resected biliary tract cancers: a systematic review and network meta-analysis of randomized clinical trials.

Despite complete resection, recurrence rate of biliary duct cancer (BTC) remains high, leading to poor prognosis. Postoperative adjuvant chemotherapy (ACT) following radical resection may substantially reduce the recurrence risk by eradicating micrometastatic lesions. However, the benefits of postoperative ACT and the optimal ACT strategy are still unclear for BTC. The objectives of this study are to evaluate the prognostic value of ACT and compare the effectiveness of different ACTs among BTC patients after curative resection. A comprehensive literature search was conducted across PubMed, Cochrane Library, Web of Science and EMBASE database to identify randomized controlled trials (RCTs) comparing the benefits of ACT versus no intervention or other ACTs in BTC patients after curative resection. A random-effects network meta-analysis was performed to compare overall survival (OS) and relapse-free survival (RFS). The quality of evidence was rated using the GRADE-framework. Eight RCTs comprising 1803 patients were included in the meta-analysis. ACT was associated with significant improvements in 5-year all-cause mortality (4 RCTs, HR 0.93; 95%CI 0.87-1.00, marginally significant; low-certainty evidence), RFS (5 RCTs, HR 0.87; 95%CI 0.78-0.98; moderate-certainty evidence) and OS (7 studies, HR 0.85; 95%CI 0.75-0.96; low-certainty evidence) compared with observation. ACT had significantly better survival benefits on patients with negative margin(R0), lymph node positive (N+) and TNM-stage I/II (P<0.05). Further network meta-analysis demonstrated fluorouracil-based ACT was significantly inferior to gemcitabine-based ACT (HR 1.20, 95%CI 1.10-1.25) in improving RFS. However, both were superior to observation (P<0.05). No statistical difference in OS was observed between gemcitabine-based and fluorouracil-based chemotherapy (HR 1.00, 95%CI 0.86-1.20). In subgroup analysis, fluorouracil-based ACT but not gemcitabine-based ACT achieved significantly better OS benefits on patients with N+ (HR 0.67; 95%CI 0.52-0.86) and R0 (HR 0.69; 95%CI 0.54-0.88). Compared with observation, ACT should be routinely recommended to improve survival outcomes in BTC patients after curative resection, especially for those with R0, N+and TNM stage I/II. Gemcitabine-based ACT performed better than other chemotherapies on improving RFS. This network meta-analysis provides precise information for determining the best adjuvant treatment for resected BTC. Further thorough and high quality RCTs are needed.

Improved prognosis of de novo metastatic prostate cancer after an introduction of life-prolonging agents for castration-resistant prostate cancer.

In Japan, since 2014, new treatments such as androgen receptor signaling inhibitors and cabazitaxel have become applicable for metastatic castration-resistant prostate cancer (mCRPC), leading to dramatic changes in treatment options. This study aims to evaluate the impact of recent advancements in treatment options on the overall survival (OS) of patients diagnosed with de novo metastatic castration-sensitive prostate cancer (mCSPC) in Japan. A retrospective analysis was conducted on 2450 Japanese men diagnosed with de novo mCSPC between 2008 and 2018. Patients were stratified into two groups based on the period of diagnosis: an earlier period (2008-2013) and a later period (2014-2018). OS was compared between earlier and later periods using Kaplan-Meier analysis in total and propensity score matched subpopulation as well as risk-stratified subgroups. Patients diagnosed in the later period exhibited significantly improved OS compared to those diagnosed in the earlier period. The risk score, calculated based on ISUP grade group, LDH levels, and ALP levels, was a poor prognostic factor. In the later period, compared to the earlier period, there was no improvement in OS in the favorable-risk group, but a significant improvement was observed in the poor-risk group. It was suggested that the introduction of novel androgen receptor signaling inhibitors and chemotherapy treatment regimens since 2014 has led to improved survival outcomes for patients with de novo mCSPC, particularly those with poor-risk profiles. The findings highlight the impact of recent advancements in treatment on the prognosis of patients with metastatic prostate cancer in Japan.

An Indirect Treatment Comparison of Lenvatinib for the First-Line Treatment of Patients with Unresectable Hepatocellular Carcinoma.

This study compared the relative efficacy of first-line lenvatinib, a standard-of-care treatment for unresectable hepatocellular carcinoma (uHCC), vs licensed/license in-progress comparators. Using inverse probability of treatment weighting (IPTW) and network meta-analysis (NMA), updated evidence for lenvatinib monotherapy from LEAP-002, in addition to evidence from REFLECT, was included in the analyses. Randomized controlled trials (RCTs) were identified via systematic review. REFLECT and LEAP-002 investigated lenvatinib in uHCC, with patient-level data available for each; however, only REFLECT included a comparator arm of interest (sorafenib). The lenvatinib arm from LEAP-002 was adjusted to match aggregate data for confounding factors from REFLECT using IPTW. Weighted Cox regressions, including matching variables as covariates, were used to derive hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS). These HR estimates were included in Bayesian NMAs to compare lenvatinib with comparators; survival was significantly improved if the 95% credible interval for the HR did not include 1.0. Scenario analyses explored alternative choices for IPTW estimators. Eight RCTs (including REFLECT) and the single-arm adjusted lenvatinib data from LEAP-002 were included in the NMA base case. Lenvatinib demonstrated significant improvement in OS compared with sorafenib 400 mg twice daily (BID) and significant improvement in PFS compared with sorafenib 400 mg BID, tremelimumab 300 mg plus durvalumab 1500 mg every 4 weeks (Q4W), and durvalumab 1500 mg Q4W. These results suggest that patients with uHCC treated with lenvatinib have similar or significantly improved OS and PFS compared with licensed/license in-progress therapies.

Surgical Resection Enhances Survival in Patients With Liver Metastases From Gastric Cancer: A Population-Based, Case-Control Study.

Gastric cancer with liver metastases (GCLM) is a challenging condition that significantly reduces long-term survival rates, but recent advancements in surgical techniques have shown promise. This study aims to comprehensively evaluate the impact of surgical resection on survival rates in GCLM patients. We conducted a population-based analysis utilizing the SEER database for patients diagnosed with GCLM between 2010 and 2015. Overall survival (OS) was compared between patients who underwent cancer-directed surgery (CDS) and those who did not. The overlap weighting method based on lasso regression with penalty factors was employed to minimize selection bias. Survival outcomes were compared using Kaplan-Meier curves and Cox proportional hazards models, with subgroup analyses to further explore the effects of surgery among patients. A total of 3694 patients with GCLM were identified. Of those, 354 (9.58%) patients underwent CDS. After propensity score adjustment, The median OS was significantly higher in the surgical resection group (12 months, 95% confidence interval (CI) 11-16) compared to the nonresection group (6 months, 95% CI: 5-6). Cox regression analysis revealed a substantial improvement in OS for the surgical resection group, with a hazard ratio (HR) of 0.562 (95% CI: 0.482-0.656), including patients with adverse conditions. The analysis demonstrated a clear association between surgical resection and enhanced OS in GCLM patients. Nevertheless, further research endeavors should be undertaken to identify specific prognostic factors that aid in the selection of optimal candidates for surgical resection.

Concurrent Versus Sequential Adjuvant Capecitabine-Based Chemoradiation in Residual Triple-Negative Breast Cancer After Neoadjuvant-Chemotherapy: A Multicenter Comparative Study.

Given the aggressive nature and poor prognosis of triple-negative breast cancer (TNBC), adjuvant capecitabine has been the standard therapy for residual disease after preoperative systemic therapy (PST). However, the optimal sequence of postoperative radiation therapy (RT) and capecitabine remains unclear. This study evaluated the efficacy and safety of concurrent RT and capecitabine (RT+CAP) versus sequential RT followed by capecitabine (RT→CAP) in patients with residual TNBC after PST. In this multicenter retrospective study, data from 491 patients treated at 14 tertiary hospitals were analyzed. The patients received either postoperative RT→CAP (n = 255) or RT+CAP (n = 236). Survival outcomes were analyzed using the Kaplan-Meier method, and multivariable Cox regression was used to adjust for potential confounders. There were no significant differences in the baseline characteristics between the 2 groups. With a median follow-up of 41.8 months, the 4-year rates of disease-free survival (DFS) and overall survival (OS) were 68.8% and 82.4%, respectively. The RT+CAP group demonstrated improvements in DFS (74.6% vs 63.7%, P = .045) and OS (86.8% vs 78.3%, P = .006) compared with the RT→CAP group. Specifically, RT+CAP showed superior DFS and OS outcomes in patients with a low disease burden (ypT0-1, ypN0/axillar level I only, or Ki67 <15%). Additionally, the incidence of ≥grade 2 toxicities and discontinuation of capecitabine because of toxicity did not differ, indicating that RT+CAP was well tolerated. RT+CAP offers improvements in oncologic outcomes without an increase in adverse events compared with RT→CAP, suggesting it is a promising treatment option for patients with residual TNBC after PST.

Real-World Survival Outcomes in Non-Small Cell Lung Cancer: The Impact of Genomic Testing and Targeted Therapies in a Latin American Middle-Income Country.

Targeted therapies are indicated for patients with non-small cell lung cancer (NSCLC) and driver tumor mutations. However, real-world studies on the survival benefits of these agents are limited. This study aimed to evaluate the effect of targeted therapies matched to a genomic alteration on the survival of patients with NSCLC. This retrospective study included 446 patients with advanced NSCLC who underwent next-generation sequencing between 2016 and 2023 at the Instituto Nacional de Cancerología in Mexico. The primary outcomes were progression-free survival (PFS) and overall survival (OS). For the entire cohort, the PFS and OS were 10.71 months (95% CI, 9.35 to 12.06) and 47.77 months (95% CI, 29.67 to 65.86). PFS was significantly longer in patients with actionable mutations treated with targeted therapies (19.41 months [95% CI, 14.27 to 24.55]; P < .001) than in patients without actionable mutations (6.4 months [95% CI, 4.4 to 8.4]) or not treated with targeted therapies (6.6 months [95% CI, 5.3 to 7.89]). Similarly, OS was significantly longer in patients with actionable mutations treated with targeted therapies (89.69 months [95% CI, 45.54 to 133.84]; P < .001) than in patients without actionable mutations (17.11 months [95% CI, 8.65 to 25.57]) or not treated with targeted therapies (22.3 months [95% CI, 12.48 to 32.1]). Survival gains were driven by significant improvements in PFS and OS in patients with EGFR and ALK mutations. This real-world data analysis demonstrated that targeted therapies improve the survival of patients with NSCLC with actionable mutations, which supports a recommendation for widening access to broad-based genomic testing and targeted therapies.

Efficacy and Safety Evaluation of Immune Checkpoint Inhibitors in Combination With Chemotherapy for Extensive Small Cell Lung Cancer: Real-World Evidence.

Extensive small cell lung cancer (ES-SCLC) are currently managed using first-line chemotherapy options, including atezolizumab (Atezo) plus etoposide and carboplatin (CE) or durvalumab (Durva) plus etoposide with either cisplatin (PE) or carboplatin (CE). However, a definitive distinction in therapeutic effects between Atezo and Durva in these regimens remains unestablished. We analyzed data from 100 patients diagnosed with ES-SCLC who received immune checkpoint inhibitors (ICIs) as first-line chemotherapy. Among them, 70 were administered Atezo + CE, 12 received Durva + PE, and 18 received Durva + CE. We assessed the efficacy of the two ICIs across various factors. The progression-free survival (PFS) and overall survival (OS) did not significantly differ between Atezo + CE and Durva + CE/PE as first-line chemotherapy treatments for SCLC. We observed no significant differences in age, sex, performance status (PS), liver metastasis, bone metastasis, or platinum-based agent usage between the treatment cohorts. However, a marked improvement in PFS and OS was observed in the solitary patient with brain metastasis treated with Atezo + CE. The primary distinction between these treatments was observed in the management of patients with brain metastasis. The literature lacks comparative studies on the effects of first-line ICI treatment on the central nervous system, rendering our findings significant in clinical practice. Despite the retrospective nature of this study and the potential for various biases, we recommend the preferential use of Atezo + CE in patients with brain metastasis to potentially enhance prognosis.

Salvage Therapy with Second-Generation Inhibitors for FLT3 Mutated Acute Myeloid Leukemia: A Real-World Study by the CETLAM and PETHEMA Groups.

Patients with relapsed/refractory (R/R) AML with FLT3 mutation (FLT3mut) have a dismal prognosis. FLT3mut offers a target for therapy in these patients. Gilteritinib (gilter) and quizartinib (quizar) have demonstrated efficacy as single agents in two phase 3 clinical trials. We retrospectively analyzed the characteristics, treatments, and outcomes of 50 patients with R/R FLT3mut AML who received gilter or quizar as monotherapy in 27 Spanish centers before their commercial availability. Forty-four patients were treated with gilter and six with quizar. The median age was 62.5 years, and 52% were women. Most patients presented with FLT3-ITD mutations (80%); 46% had refractory disease and 54% had relapsed disease at treatment initiation. First-line treatment was chemotherapy in 80% of patients, with 40% of these also receiving midostaurin. Twenty-five patients (50%) had previously received FLT3 inhibitor, and twenty-eight (56%) had received more than one line treatment before starting gilter/quizar. The rates of complete remission (CR), CR without hematological recovery (CRi), and partial remission were 22%, 18%, and 16%, respectively. The median overall survival (OS) and disease-free survival were 4.74 months and 2.99 months, respectively. We observed a significant improvement in OS in patients who had received only one prior line of therapy compared to those who had received two or more therapies (10.77 months vs. 4.24 months, p = 0.016). Multivariate analysis identified failure to achieve CR/CRi, receiving more than one prior line of therapy, age, and white blood cells count as independent prognostic factors for OS. The most common toxicities were febrile neutropenia, liver function abnormalities, and QT interval prolongation. Gilter/quizar monotherapy are effective and tolerable options for patients with R/R FLT3mut AML in a real-world setting. Response and toxicity rates are similar to those reported in the phase 3 trials, despite the more heterogeneous nature of the study population.

Evaluation of Gemtuzumab Ozogamicin and Anthracycline Dosing for Favorable Risk Acute Myeloid Leukemia.

Gemtuzumab ozogamicin (GO) is a CD33-targeting antibody-drug conjugate approved for the treatment of CD33-positive de novo and relapsed and refractory acute myeloid leukemia (AML). Subset analyses have demonstrated improved clinical outcomes in patients with favorable-risk disease. It is unclear whether the addition of GO to cytarabine and anthracycline chemotherapy (7+3) improves clinical outcomes compared with other conventional regimens for AML. We evaluated the real-world experience with GO added to 7+3 chemotherapy for patients with favorable risk AML. This retrospective analysis included 174 patients with de novo favorable risk AML undergoing induction chemotherapy between 2010 and 2020. The primary outcome was overall survival (OS) and secondary outcomes included rates of remission, measurable residual disease (MRD), and toxicity. Eighteen patients received GO, 37 received a high-dose (HD) anthracycline, and 119 received an intermediate-dose anthracycline. Composite complete remission was achieved in 162 patients (93.1%). Among the 54 patients who were assessed for MRD at remission, 66.7% were undetectable. An improvement in OS was seen for patients who received GO and those treated with HD anthracycline, which was better explained by differences in patient performance status and comorbidities. Patients who received GO did not show increased toxicity.

Analysis of linear accelerator-based fractionated stereotactic radiotherapy in brain metastases: efficacy, safety, and dose tolerances.

To assess the efficacy and safety of linear accelerator-based fractionated stereotactic radiotherapy (LINAC-FSRT) in patients with brain metastases (BM). We retrospectively analyzed 214 patients treated with LINAC-FSRT, categorized based on biologically effective dose (BED10, α/β = 10) into two groups (≤55 Gy, >55 Gy). Stratified analyses were conducted based on targeted therapy to compare survival outcomes. To examine brain tissue dose-tolerance volume, patients were divided into two groups: the standard Hypofractionated Treatment Effects in the Clinic (HyTEC) protocol group and an adjusted HyTEC protocol group where dose-volume restrictions exclude the planning target volume (PTV). Results as of December 2023 showed median intracranial progression-free survival (iPFS) at 12.4 months, with median overall survival (OS) not reached and a one-year local control (LC) rate of 68.7%. Mild to moderate toxicity affected 17.3% of patients, while severe toxicity occurred in 2.8%. Multivariate Cox analysis indicated that uncontrolled extracranial disease significantly reduced iPFS (HR = 2.692, 95%CI:1.880-3.853, P < 0.001) and OS (HR = 3.063, 95%CI:1.987-4.722, P < 0.001). BED10 >55 Gy (HR = 0.656, 95%CI:0.431-0.998, P = 0.049) improved OS, showing statistical significance (P = 0.037) without affecting iPFS or CNS toxicity (P = 0.127, P = 0.091). Stratified analysis highlighted nearly significant OS improvements with high-dose FSRT and targeted therapy (P = 0.054), while concurrent therapy markedly enhanced iPFS (P = 0.027). No significant differences were observed in intracranial local failure (ILF-which represents progression in previously treated areas during follow-up), one-year LC rates, iPFS, or OS between dose-volume groups. Adjusting HyTEC volume restrictions did not significantly increase CNS adverse reactions (P = 0.889). LINAC-FSRT is safe and effective in BM. BED10>55 Gy notably enhances OS post-LINAC-FSRT and may benefit LC. High BED10 FSRT with targeted therapy likely boosts synergy, and concurrent targeted therapy significantly improves iPFS. Diminishing dose volume constraints at different fractions based on the HyTEC guidelines is feasible.

Reappraising the prognostic relevance of cytogenetic risk in patients with acute myeloid leukemia undergoing allogeneic hematopoietic cell transplantation.

This study aimed to investigate the prognostic relevance of cytogenetic risk in 9826 adults with acute myeloid leukemia (AML) who underwent allogeneic hematopoietic cell transplantation (HCT) during the first or second complete remission. The 5-year probabilities of overall survival (OS) were 66%, 61%, and 47% (P < 0.001), the cumulative incidences of relapse were 14%, 19%, and 32% (P < 0.001), and the cumulative incidences of non-relapse mortality (NRM) were 23%, 23%, and 25% (P = 0.208) in patients with favorable (n = 1418), intermediate (n = 6747), and poor cytogenetic risk (n = 1661), respectively. The significant effect of cytogenetic risk on OS was strong in all subgroups stratified by age, sex, performance status, disease status, donor type, conditioning intensity, graft-versus-host disease prophylaxis, and transplantation period (P < 0.001 for all). The evaluation of trends in posttransplant outcomes for patients in each cytogenetic risk category indicated that the risk of relapse declined in patients with favorable and intermediate cytogenetics and that the risk of NRM decreased in those with intermediate and poor cytogenetics. Therefore, patients with intermediate cytogenetics experienced the best OS improvement. These results confirm cytogenetic risk as a universal prognostic factor in patients with AML undergoing allogeneic HCT while highlighting the requirement for further improvements in posttransplant OS by reducing NRM in patients with favorable cytogenetics and by reducing relapse in patients with poor cytogenetics.