Cancer最新文献

Background: Herein, we present the results of the phase 2 IMMUNOSARC study (NCT03277924), investigating sunitinib and nivolumab in adult patients with advanced bone sarcomas (BS).

Methods: Progressing patients with a diagnosis of BS were eligible. Treatment was comprised of sunitinib (37.5 mg/day on days 1-14, 25 mg/day afterword) plus nivolumab (3 mg/kg every 2 weeks). Primary end point was progression-free survival rate (PFSR) at 6 months based on central radiology review. Secondary end points were overall survival (OS), overall response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, and safety.

Results: A total of 46 patients were screened, 40 patients entered the study, and 38 underwent central radiological review and were evaluable for primary end point. Median age was 47 years (range, 21-74). Histologies include 17 (43%) osteosarcoma, 14 chondrosarcoma (35%, 10 conventional, four dedifferentiated [DDCS]), eight (20%) Ewing sarcoma, and one (2%) undifferentiated pleomorphic sarcoma. The PFSR at 6 months was 42% (95% confidence interval [CI], 27-58). With a median follow-up of 39.8 months (95% CI, 37.9-41.7), the median PFS and OS were 3.8 months (95% CI, 2.7-4.8) and 11.9 months (95% CI, 5.6-18.2). ORR by RECIST was 5%, with two of 38 partial responses (one of four DDCS and one of 17 osteosarcoma), 19 of 38 (50%) stable disease, and 17 of 38 (45%) progressions. Grade ≥3 adverse events were neutropenia (six of 40, 15%), anemia (5/40, hypertension (6/40, 15%), 12.5%), ALT/AST elevation (5/40, 12.5%), and pneumonitis (1/40, 2.5%). Seventeen percent of patients discontinued treatment due to toxicity, including a treatment-related grade 5 pneumonitis CONCLUSION: The trial met its primary end point in the BS cohort with >15% of patients progression-free at 6 months. However, the toxicity profile of this regimen was relevant.

Background: From 2007 to 2017, sorafenib was the sole systemic therapy for hepatocellular carcinoma (HCC), but nine new therapies were approved from 2017 to 2022. No studies have yet examined population-level treatment patterns for HCC since these approvals.

Methods: For this retrospective cohort, Surveillance, Epidemiology, and End Results (SEER)-Medicare data were used to identify patients who had HCC diagnosed between 2014 and 2019 with claims through 2020. The authors examined patient characteristics, comorbidities, and receipt of local (e.g., transplantation, resection, embolization) and systemic (e.g., sorafenib, lenvatinib, atezolizumab plus bevacizumab) therapies. Cohort characteristics, treatment patterns, and overall survival (OS) were analyzed, and χ² tests and t-tests were used to compare treatments between the 2014-2017 and 2018-209 cohorts. Adjusted Cox models were used to compare median OS between treatment groups.

Results: Among 11,766 patients (men, 69.2%; White, 76.9%; median age, 71 years), 60.5% received treatment within 1 year, which remained stable over time (2014-2017, 60.4%; 2018-2019, 61.0%; p = .84). The use of local therapy also remained stable (2014-2017, 52.1%; 2018-2019, 52.8%; p = .43), whereas the use of systemic therapy slightly decreased (2014-2017, 17.0%; 2018-2019, 15.2%; p = .01). First-line systemic treatments shifted significantly, with sorafenib use dropping from 84.5% (2014-2017) to 41.3% (2018-2019). The median OS among patients who received no treatment, systemic therapies first, or local therapies first was 2.2, 12.0, and 23.6 months, respectively. Patients who were diagnosed in 2019 had better OS (hazard ratio [HR], 0.80; 95% confidence interval [CI], 0.74-0.86) as did those who received systemic therapy first (HR, 0.33; 95% CI, 0.18-0.61), but survival was worse for those who received local therapy first (HR, 1.41; 95% CI, 1.08-1.84) compared with those who were diagnosed in 2014.

Conclusions: Local therapy patterns remained stable, but novel therapies replaced sorafenib as the preferred first-line treatment, improving survival.

Background: Myeloproliferative neoplasms represent a heterogeneous group of acquired hematopoietic stem cell diseases in which chronic inflammation is essential for both clonal evolution and thrombotic complications. The neutrophil-to-lymphocyte ratio (NLR), reflecting the imbalance between systemic inflammation and immunity, is emerging as a prognostic biomarker in several diseases, including hematological ones.

Methods: A total of 473 patients with essential thrombocythemia (ET), the relationship between NLR value at diagnosis and the risk of thrombotic events in the follow-up, in addition to conventional clinical and biological variables, were retrospectively analyzed.

Results: A total of 78 thrombotic events were reported for an incidence rate of 1.8 × 100 patients/year. In multivariate analysis, NLR value ≥4 at diagnosis was associated with higher cumulative thrombotic risk (hazard ratio [HR], 2.05; 95% CI, 1.29-2.28; p = .0001) as well International Prognostic Score for Thrombosis in Essential Thrombosis score intermediate-high (HR, 2.69; 95% CI, 1.27-5.72; p = .01) and diabetes (HR, 2.49; 95% CI, 1.23-3.05; p = .010). Concerning arterial thrombotic events, in multivariate analysis, NLR value at diagnosis ≥4 was predictive for thrombosis (HR, 2.13; 95% CI, 1.31-4.04; p = .001 as well diabetes (HR, 2.44; 95% CI, 1.05-5.68; p = .04) and hypertension (HR, 2.46; 95% CI, 1.05-5.68; p = .01). About venous thrombotic events, NLR value ≥5 was a marker predictive for venous thrombosis (HR, 2.99; 95% CI, 2.45-6.48; p = .01) as well age >60 years old (HR, 2.26; 95% CI, 1.0-5.10; p = .05).

Conclusion: NLR value is a simple, cost-effective, and easy-to-obtain inflammatory marker that can predict a diagnosis the risk of thrombosis in ET. Our results suggest that NLR value could be integrated into conventional cardiovascular risk scores, to better classify high-risk patients who are candidates for cytoreductive therapy. Further larger and prospective studies are warranted.

Background: In acute myeloid leukemia (AML), further investigation is warranted to integrate measurable residual disease (MRD) with genetic characteristics for formulating a dynamic prognostic system for predicting response and selecting appropriate postremission therapeutic strategies.

Methods: The authors incorporated MRD with genetic risk classification and assessed its impact on transplantation decision making within different risk cohorts, comprising 769 patients with newly diagnosed AML across three clinical trials. Only patients who achieved complete remission (CR) within two courses of chemotherapy were selected.

Results: In the favorable-risk and intermediate-risk groups, patients who underwent transplantation according to the protocol experienced significant 3-year overall survival (OS) benefits compared with those who did not (favorable-risk group: hazard ratio [HR], 0.38; 95% confidence interval [CI], 0.20-0.73l p = .004; intermediate-risk group: HR, 0.53; 95% CI, 0.33-0.85; p = .008). In the intermediate-risk group, early detection of MRD positivity, even after the initial course of chemotherapy, was associated with a significantly elevated cumulative incidence of relapse (47.2% vs. 36.0%; p = .009) and a notable extension of OS with allogeneic hematopoietic stem cell transplantation (HR, 0.47; 95% CI, 0.28-0.79; p = .004). Conversely, patients who achieved MRD negativity at either of the two time points had comparable OS in the favorable-risk and intermediate-risk groups, regardless of whether they underwent transplant or not. In the adverse-risk group, allogeneic hematopoietic stem cell transplantation led to improvements in OS irrespective of MRD status (HR, 0.51; 95% CI, 0.38-0.69; p < .001).

Conclusions: Early clearance of MRD demonstrated significant prognostic value, particularly for patients in the favorable-risk and intermediate-risk groups. Positive MRD status after two courses of intensive chemotherapy were associated with a higher relapse rate and inferior OS, necessitating allogeneic hematopoietic stem cell transplantation.

Background: Isolated limb infusion and perfusion (ILI/ILP) has been a mainstay treatment for unresectable melanoma in-transit metastases (ITM), but increased use of immune checkpoint inhibitors (ICI) and intralesional therapy (talimogene laherparepvec [TVEC]) introduced several different management options. This study compares first-line ILI/ILP, ICI, and TVEC.

Methods: Retrospective review from 12 international institutions included patients treated from 1990 to 2022 with first-line ILI/ILP, ICI, or TVEC for unresectable melanoma ITM.

Results: A total of 551 patients were treated, with ILI/ILP (n = 356), ICI (n = 125), and TVEC (n = 70) with median follow-up of 5.5 years. Tumor burden was highest with ILI/ILP and lowest with TVEC (p = .002). Breslow thickness was lowest with TVEC (p = .007). TVEC was mostly used in stage IIIB disease versus IIIC for ILI/ILP and ICI (p = .01). Using ICI as the reference category, TVEC had the highest odds of a complete response (CR) (odds ratio, 1.96; p = .029) and a longer local progression-free survival (PFS) (hazard ratio [HR], 0.40; p = .003). ILI/ILP had shorter local PFS (HR, 1.72; p = .012), PFS (HR, 1.79; p < .001), distant metastasis-free survival (DMFS) (HR, 1.75; p = .014), overall survival (HR, 1.82; p = .009), and melanoma-specific survival (HR, 2.29; p = .004). Stage IIIB disease had longer DMFS (HR, 0.24; p < .001) compared to IIIC/D.

Conclusions: TVEC as first-line therapy for unresectable melanoma ITM was associated with superior CR rates and local PFS. Notably, TVEC was used in patients with a lower Breslow thickness, disease stage, and tumor burden. Therefore, when compared to ILI/ILP and ICI, TVEC should be considered as first-line therapy for unresectable stage IIIB melanoma ITM with minimal tumor burden and lower Breslow thickness.