Analysis of the Radiotherapy Strategies of the CWS-96 and CWS-2002P Studies and SoTiSaR Registry.

[Posted 6/Nov/2023]

AUDIENCE: Oncology, Pediatric

KEY FINDINGS: RT can be omitted in patients with IRS I eRMS. RT improves LCS and EFS in IRS II and III. RT improves OS in patients with HN-PM, with proton RT comparable with photon RT. Doses of 32 Gy (HART) or 36 and 41.4 Gy (CFRT) had comparable efficacy in patients with favorable risk profiles and 44.8 Gy (HART) or 50.4 and 55.8 Gy (CFRT) in the unfavorable groups.

BACKGROUND: Objective of this study is to analyze and compare the indications, doses, and application methods of radiotherapy (RT) and their influence on prognosis of patients with localized rhabdomyosarcoma (RMS). Radiotherapy (RT) is one of the local control modalities in patients with rhabdomyosarcoma (RMS) but is associated with severe acute and late toxicities. Authors have analyzed and compared the indications, doses, and application methods of RT and their influence on prognosis for patients with localized RMS.

DETAILS: One thousand four hundred seventy patients with localized RMS 21 years and younger entered on CWS-96, CWS-2002P, and SoTiSaR were eligible for the analysis. The median follow-up was 6.5 years (IQR, 3.3-9.5). The 5-year event-free survival (EFS) and local control survival (LCS) for 910 (62%) irradiated versus nonirradiated patients were 71% versus 69% and 78% versus 73% (P = .03), respectively. Ninety-five percent of patients in IRS I (90% embryonal RMS [eRMS]) were nonirradiated (EFS, 87%). Irradiated patients with IRS II had improved LCS (91% v 80%; P = .01) and EFS (not significant). In IRS III, EFS and LCS were significantly better for RT patients: 71% versus 56% (P = 3.1e-06) and 76% versus 61% (P = 4.1e-07). Patients with tumors in the head and neck region (orbita, parameningeal, and nonparameningeal) and in other sites had significantly better EFS and LCS and in parameningeal also overall survival (OS). The efficacy of low RT doses of 32 Gy (hyperfractionated, accelerated RT [HART]) and 36 and 41.4 Gy (conventional fractionated RT [CFRT]) in the favorable groups and higher doses of 44.8 Gy (HART) and 50.4 and 55.4 Gy (CFRT) in the unfavorable groups was comparable. Proton RT was used predominantly in head/neck-parameningeal (HN-PM) tumors, with similar EFS and LCS to photon RT.

Copyright © American Society of Clinical Oncology. All rights reserved.

Source: Koscielniak, E., Timmermann, B., Munter, M., et al. (2023). Which Patients With Rhabdomyosarcoma Need Radiotherapy? Analysis of the Radiotherapy Strategies of the CWS-96 and CWS-2002P Studies and SoTiSaR Registry. J Clinical Oncology. 2023; 41(31): 4916-4926.Published: November 1, 2023. DOI: 10.1200/JCO.22.02673.

[Posted 2/Sep/2026]

AUDIENCE: Hematology, Oncology

KEY FINDINGS: In this phase II study, azacitidine, venetoclax, and gilteritinib produced high remission rates and encouraging long-term survival in patients with newly diagnosed FLT3-mutated AML who were unfit for intensive chemotherapy. The 3-year RFS and OS rates were 43% and 46%, respectively, although outcomes were less favorable in patients with FLT3-ITD mutations and baseline RAS pathway mutations. Most evaluable relapses were FLT3-negative, suggesting that resistance may involve mechanisms beyond persistent FLT3-mutated disease. Dose or duration reductions were frequently required during consolidation, primarily reflecting the challenge of managing myelosuppression. Randomized studies are needed to establish the role of this triplet regimen relative to current standard approaches.

BACKGROUND: Relapse after frontline azacitidine and venetoclax remains a major challenge in patients with FLT3-mutated acute myeloid leukemia (AML), with relapse often associated with expansion of FLT3-mutated clones. This phase II study evaluated the long-term efficacy and safety of adding the FLT3 inhibitor gilteritinib to azacitidine and venetoclax in adults with newly diagnosed FLT3-mutated AML who were considered unfit for intensive chemotherapy.

DETAILS: Thirty patients with newly diagnosed FLT3-mutated AML were treated with the azacitidine, venetoclax, and gilteritinib triplet regimen. The median age was 71 years, and 22 (73%) patients had FLT3-ITD mutations. Fourteen patients (47%) proceeded to allogeneic hematopoietic stem cell transplantation in first remission. The median follow-up was 41.5 months.

The complete remission or complete remission with incomplete hematologic recovery rate was 96%. Eleven patients (37%) subsequently relapsed, and among evaluable relapses, the FLT3 mutation was no longer detectable in 67%, indicating that relapse mechanisms were not necessarily driven by persistent FLT3-mutated disease.

The median relapse-free survival (RFS) was 23.4 months and median overall survival (OS) was 29.7 months. At 3 years, RFS was 43% and OS was 46%. Among patients with FLT3-ITD-mutated AML, median RFS and OS were 17.0 months and 21.8 months, respectively, with 3-year RFS and OS rates of 32% and 36%. Baseline RAS pathway mutations were associated with poorer outcomes.

Survival outcomes were similar regardless of whether patients underwent allogeneic hematopoietic stem cell transplantation in first remission. Among patients receiving at least one consolidation cycle, 68% required a reduction in the dose or duration of at least one study drug, highlighting the need to manage treatment-related myelosuppression during prolonged therapy.

Copyright © Skyscape. All rights reserved.

Source: Short, N. J., Kantarjian, H. M., Daver, N., et al. Long-Term Outcomes of Azacitidine, Venetoclax and Gilteritinib in Newly Diagnosed FLT3-Mutated AML. Blood Advances.. 2026; 10(17): 5743–5750. Published: May 27, 2026. DOI: 10.1182/bloodadvances.2026019841.

[Posted 2/Sep/2026]

AUDIENCE: Hematology, Oncology

KEY FINDINGS: In this phase II study, azacitidine, venetoclax, and gilteritinib produced high remission rates and encouraging long-term survival in patients with newly diagnosed FLT3-mutated AML who were unfit for intensive chemotherapy. The 3-year RFS and OS rates were 43% and 46%, respectively, although outcomes were less favorable in patients with FLT3-ITD mutations and baseline RAS pathway mutations. Most evaluable relapses were FLT3-negative, suggesting that resistance may involve mechanisms beyond persistent FLT3-mutated disease. Dose or duration reductions were frequently required during consolidation, primarily reflecting the challenge of managing myelosuppression. Randomized studies are needed to establish the role of this triplet regimen relative to current standard approaches.

BACKGROUND: Relapse after frontline azacitidine and venetoclax remains a major challenge in patients with FLT3-mutated acute myeloid leukemia (AML), with relapse often associated with expansion of FLT3-mutated clones. This phase II study evaluated the long-term efficacy and safety of adding the FLT3 inhibitor gilteritinib to azacitidine and venetoclax in adults with newly diagnosed FLT3-mutated AML who were considered unfit for intensive chemotherapy.

DETAILS: Thirty patients with newly diagnosed FLT3-mutated AML were treated with the azacitidine, venetoclax, and gilteritinib triplet regimen. The median age was 71 years, and 22 (73%) patients had FLT3-ITD mutations. Fourteen patients (47%) proceeded to allogeneic hematopoietic stem cell transplantation in first remission. The median follow-up was 41.5 months.

The complete remission or complete remission with incomplete hematologic recovery rate was 96%. Eleven patients (37%) subsequently relapsed, and among evaluable relapses, the FLT3 mutation was no longer detectable in 67%, indicating that relapse mechanisms were not necessarily driven by persistent FLT3-mutated disease.

The median relapse-free survival (RFS) was 23.4 months and median overall survival (OS) was 29.7 months. At 3 years, RFS was 43% and OS was 46%. Among patients with FLT3-ITD-mutated AML, median RFS and OS were 17.0 months and 21.8 months, respectively, with 3-year RFS and OS rates of 32% and 36%. Baseline RAS pathway mutations were associated with poorer outcomes.

Survival outcomes were similar regardless of whether patients underwent allogeneic hematopoietic stem cell transplantation in first remission. Among patients receiving at least one consolidation cycle, 68% required a reduction in the dose or duration of at least one study drug, highlighting the need to manage treatment-related myelosuppression during prolonged therapy.

Copyright © Skyscape. All rights reserved.

Source: Short, N. J., Kantarjian, H. M., Daver, N., et al. Long-Term Outcomes of Azacitidine, Venetoclax and Gilteritinib in Newly Diagnosed FLT3-Mutated AML. Blood Advances.. 2026; 10(17): 5743–5750. Published: May 27, 2026. DOI: 10.1182/bloodadvances.2026019841.

A Nationwide Analysis

[Posted 26/Aug/2026]

AUDIENCE: Hospice & Palliative Nursing, Oncologys

KEY FINDINGS: Among adults with cancer approaching death, hospice utilization was associated with less frequent and lower-intensity broad-spectrum antibiotic exposure, particularly during the final days of life. The findings are consistent with a transition toward comfort-focused care, although they do not establish that hospice care itself caused the reduction. Hospice initiation occurred relatively close to death, with a mean interval of 39.9 days and a median of 22.0 days, and some antibiotic treatment may have preceded hospice enrollment. In addition, cancer stage, treatment status, infection severity, microbiological findings, functional status, symptom burden, and treatment intent were unavailable in the claims data.

BACKGROUND: Antibiotic treatment remains common during end-of-life care for patients with cancer, despite uncertain benefits for survival and potential burdens including drug toxicity, intravenous administration, adverse effects, and antimicrobial resistance. This retrospective cohort study evaluated whether hospice involvement was associated with differences in broad-spectrum antibiotic use among adults with cancer during the final 3 months of life.

DETAILS: Investigators analyzed Korean National Health Insurance Service claims data for adults aged ≥18 years who died between January 1, 2018, and December 31, 2021, with one of the 10 leading cancer-related causes of death. Hospice users had received inpatient, home-based, or consultation-based hospice care before death. Broad-spectrum antibiotic exposure included anti-pseudomonal penicillins, anti-pseudomonal cephalosporins, carbapenems, and glycopeptides. The final 90 days of life were divided into four intervals: 1–3 months before death, 1 week to 1 month before death, the final week, and the final 3 days. Antibiotic exposure was assessed by the proportion of patients receiving antibiotics and by days of therapy (DOT) per 1,000 patient-days. Propensity score matching was performed at a 1:2 ratio.

After matching, 38,102 hospice users and 75,736 non-hospice users were analyzed. During the final 3 months of life, 74.6% of hospice users and 79.0% of non-hospice users received at least one broad-spectrum antibiotic (P0.001). Antibiotic use was initially slightly higher among hospice users during the period 1–3 months before death, at 34.0% versus 32.2% (P0.001), but became consistently lower among hospice users thereafter. From 1 week to 1 month before death, use was 31.1% versus 32.8%; during the final week, 11.3% versus 18.5%; and during the final 3 days, 4.8% versus 10.3% among hospice and non-hospice users, respectively (all P0.001).

Days of therapy per 1,000 patient-days were also consistently lower among hospice users, with the greatest differences occurring during the final week and final 3 days of life. Carbapenems and glycopeptides demonstrated particularly pronounced differences between the groups. In cancer-specific analyses, patients with hematologic malignancies had the highest overall antibiotic exposure, followed by those with pancreatobiliary and gastric cancers, while exposure was comparatively lower among patients with breast and liver cancers.

Copyright © Skyscape. All rights reserved.

Source: Jeung, Y. S., Kim, H. J., Yu, J., et al. Comparison of Broad-Spectrum Antibiotic Use According to Hospice Utilization Among Patients with Cancer at the End of Life in South Korea: A Nationwide Analysis. Journal of Hospice and Palliative Care. 2026; 29(2): 41-50. Published: June 1, 2026. DOI: 10.14475/jhpc.2026.29.2.41.

[Posted 24/Aug/2026]

AUDIENCE: Gastroenterology, Oncology, Internal Medicine

KEY FINDINGS: In a prospective multicenter validation study of 1,268 adults with cirrhosis, HelioLiver Dx demonstrated greater sensitivity than ultrasound for HCC detection, including small lesions. Sensitivity was 47.8% versus 28.3% for all HCC and 28.6% versus 0% for lesions ≤2 cm. Although specificity was lower with HelioLiver Dx, the test met prespecified criteria for superior sensitivity and non-inferior specificity.

BACKGROUND: Patients with cirrhosis who are at high risk for hepatocellular carcinoma (HCC) are recommended to undergo biannual abdominal ultrasound surveillance. However, ultrasound has limited sensitivity for small HCC lesions, and adherence to surveillance can be poor. A multianalyte cell-free DNA (cfDNA)-based blood test, HelioLiver Dx, was developed to facilitate HCC detection in this high-risk population.

DETAILS: This cross-sectional, prospective, blinded, multicenter validation study evaluated HelioLiver Dx and abdominal ultrasound in adults with cirrhosis. Participants underwent both tests, while multiphasic magnetic resonance imaging (MRI) served as the reference standard for determining HCC status. The study included 1,268 evaluable participants from 42 clinical sites in the United States.

HelioLiver Dx combines cfDNA methylation features with patient age and sex and serum concentrations of alpha-fetoprotein (AFP), AFP-L3, and des-gamma-carboxy prothrombin (DCP). The test provides a qualitative positive or negative result, with its algorithm and cutoffs established before testing of the validation cohort.

The co-primary endpoints compared HelioLiver Dx with ultrasound for sensitivity and specificity in detecting HCC. Superiority required the lower bound of the 95% confidence interval for the sensitivity difference to exceed a prespecified 5% margin, while noninferiority for specificity required the lower bound to remain above −10%.

Of the 1,268 evaluable participants, 46 (3.6%) had HCC identified by MRI. Among these, 46% had small HCC lesions ≤2 cm in diameter. HelioLiver Dx detected HCC with a sensitivity of 47.8% (95% CI 32.9-63.1), compared with 28.3% (95% CI 16.0-43.5) for ultrasound.

For HCC lesions ≤2 cm, HelioLiver Dx had a sensitivity of 28.6% (95% CI 11.3-52.2), whereas ultrasound detected 0% (95% CI 0.0-16.1). Specificity was 87.6% (95% CI 85.6-89.4) for HelioLiver Dx and 93.9% (95% CI 92.5-95.2) for ultrasound.

The HelioLiver Dx test met the prespecified co-primary endpoints for superior sensitivity and non-inferior specificity compared with ultrasound. The study also found that the blood test identified more HCC lesions overall and more early lesions than ultrasound.

Copyright © Skyscape. All rights reserved.

Source: Taggart, D. J., Mahajan, S., Gallant, M. A., et al. A Multi-Analyte cfDNA-Based Blood Test for Early Detection of Hepatocellular Carcinoma. Journal of Hepatology. 2026; 85(3): 528-536. Published: September, 2026. DOI: 10.1016/j.jhep.2026.04.012.

[Posted 12/Aug/2026]

AUDIENCE: Oncology, Dermatology

KEY FINDINGS: FDA approval of Tudriqev introduces an engineered viral immunotherapy option for adults with treatment-resistant advanced melanoma. By combining direct tumor destruction with immune activation, this therapeutic approach expands the available immunotherapy landscape for patients with limited options after progression on standard treatments. Continued evaluation through confirmatory studies will determine its long-term clinical role in melanoma management.

BACKGROUND: Patients with advanced melanoma whose disease progresses despite available systemic therapies have limited treatment options and significant unmet clinical needs. The U.S. Food and Drug Administration (FDA) approved a new engineered viral immunotherapy designed to provide a treatment option for adults with advanced melanoma that is resistant to prior therapies.

DETAILS: The FDA approved Tudriqev (vusolimogene oderparepvec, formerly RP1), an engineered oncolytic viral immunotherapy developed by Replimune, for adults with unresectable or metastatic melanoma that has progressed following treatment with an anti–PD-1 therapy and, when appropriate, targeted therapy for BRAF-mutated disease. Tudriqev is an engineered herpes simplex virus type 1 (HSV-1)-based therapy administered through intratumoral injection. The treatment is designed to selectively replicate within tumor cells, promote tumor cell destruction, and stimulate an immune response against cancer cells. The FDA approval was based on clinical evidence demonstrating tumor responses in patients with advanced melanoma who had limited therapeutic alternatives. The therapy represents an additional immunotherapeutic approach that uses direct tumor targeting combined with immune system activation. In clinical evaluation, Tudriqev demonstrated tumor reduction or elimination in 24.2% of treated patients, with a median duration of response of 14.1 months. The FDA approval provides a new treatment option for patients with advanced melanoma whose disease has become resistant to prior immunotherapy approaches. A confirmatory Phase III study is ongoing to further evaluate the therapy’s clinical benefit and long-term outcomes.

Copyright © Skyscape. All rights reserved.

Source: FDA Approves New Engineered Viral Immunotherapy for Patients with Treatment-Resistant Advanced Melanoma. Food and Drug Administration. 2026; Published: August 6, 2026.

[Posted 6/Aug/2026]

AUDIENCE: Oncology, Ob/Gyn

KEY FINDINGS: This study demonstrates that gut microbiome imbalance may contribute to HR+ breast cancer progression through systemic metabolic and inflammatory mechanisms. Dysbiosis-associated elevation of primary bile acids was shown to promote mammary inflammation and tumor dissemination through PGE2 signaling. Clinical database analyses further suggested that bile acid pathway modulation, including bile acid sequestrant use, may be associated with improved survival outcomes in metastatic disease. These findings highlight the potential importance of microbiome-derived metabolites in cancer biology and future precision oncology strategies.

BACKGROUND: Breast cancer metastasis remains a major clinical challenge, particularly in hormone receptor-positive (HR+) tumors, which represent the most common metastatic breast cancer subtype. Emerging evidence suggests that alterations in the gut microbiome may influence systemic inflammation and cancer progression. This study investigated whether commensal dysbiosis alters bile acid metabolism and contributes to mammary gland inflammation and HR+ breast tumor dissemination.

DETAILS: Researchers evaluated the relationship between gut microbiome alterations, bile acid signaling, inflammation, and breast cancer progression using experimental models and human genomic and clinical datasets. Metabolomic profiling demonstrated increased primary bile acids in dysbiotic microbiomes. Additional mechanistic studies using bile acid sequestration and supplementation approaches examined how altered bile acid levels influenced mammary inflammation and tumor dissemination.

The investigators further analyzed The Cancer Genome Atlas (TCGA) data to evaluate associations between bile acid-related signatures, insulin resistance, prostaglandin E2 (PGE2) signaling, and survival outcomes in patients with HR+ breast tumors. Electronic health record data from the Epic Cosmos database were also examined to assess associations between bile acid sequestrant use and outcomes among patients with metastatic disease.

Commensal dysbiosis increased primary bile acid levels by disrupting microbial bile acid metabolism. Elevated primary bile acids promoted mammary gland inflammation and enhanced HR+ breast tumor dissemination through a prostaglandin E2 (PGE2)-dependent pathway.

TCGA analysis demonstrated that gene signatures related to bile acids, insulin resistance, and PGE2 signaling were associated with reduced survival in patients with HR+ tumors. In complementary clinical data analysis, bile acid sequestrant use was associated with longer restricted mean survival time among patients with metastatic disease.

These findings identify gut microbiome–bile acid signaling as a potential biological pathway linking intestinal dysbiosis with breast cancer progression and suggest that modulation of bile acid pathways may represent an area for future therapeutic investigation.

Copyright © Skyscape. All rights reserved.

Source: Putelo, A. M., Bajgai, S., Poblete, M. K., et al. Commensal Dysbiosis Alters Primary Bile Acid Signaling to Drive Mammary Gland Inflammation and Breast Tumor Dissemination. Cancer Research. 2026; Published: June 2, 2026. DOI: 10.1158/0008-5472.CAN-25-4466