Resectable Pediatric Nonrhabdomyosarcoma Soft Tissue Sarcoma: Which Patients Benefit from Adjuvant Radiation Therapy and How Much?

It remains unclear which children and adolescents with resected nonrhabdomyosarcoma soft tissue sarcoma (NRSTS) benefit from radiation therapy, as well as the optimal dose, volume, and timing of radiotherapy when used with primary surgical resection. This paper reviews the sparse literature from clinical trials and retrospective studies of resected pediatric NRSTS to discern local recurrence rates in relationship to the use of radiation therapy

Uterine Leiomyosarcoma with FN1-Anaplastic Lymphoma Kinase Fusion Responsive to Alectinib and Lorlatinib

Uterine leiomyosarcoma (LMS) is a rare malignant neoplasm of the female genital tract poorly responsive to conventional chemotherapy and radiotherapy, with an overall poor prognosis. Pazopanib is at the moment the only FDA-approved targeted molecular therapy for uterine LMS, given the exceedingly rare occurrence of actionable genetic mutations in this type of cancer. Here, we describe the first reported case of metastatic uterine LMS with an FN1-anaplastic lymphoma kinase (ALK) fusion mutation occurring in a 63-year-old woman with a history of uterine leiomyomas. The patient progressed on several lines of therapy, including conventional chemotherapy, pazopanib, and the first-generation ALK inhibitor crizotinib. Interestingly, the patient showed a remarkable 16-month response to second generation ALK inhibitors alectinib and lorlatinib. This case demonstrates that ALK inhibitors can be an effective therapeutic strategy for patients with ALK fusion-positive uterine LMS that has progressed on conventional chemotherapy

Deep Functional and Molecular Characterization of a High-Risk Undifferentiated Pleomorphic Sarcoma.

Nonrhabdomyosarcoma soft-tissue sarcomas (STSs) are a class of 50+ cancers arising in muscle and soft tissues of children, adolescents, and adults. Rarity of each subtype often precludes subtype-specific preclinical research, leaving many STS patients with limited treatment options should frontline therapy be insufficient. When clinical options are exhausted, personalized therapy assignment approaches may help direct patient care. Here, we report the results of an adult female STS patient with relapsed undifferentiated pleomorphic sarcoma (UPS) who self-drove exploration of a wide array of personalized Clinical Laboratory Improvement Amendments (CLIAs) level and research-level diagnostics, including state of the art genomic, proteomic

Shaping success: clinical implementation of a 3D-printed electron cutout program in external beam radiation therapy

PurposeThe integration of 3D-printing technology into radiation therapy (RT) has allowed for a novel method to develop personalized electron field-shaping blocks with improved accuracy. By obviating the need for handling highly toxic Cerrobend molds, the clinical workflow is significantly streamlined. This study aims to expound upon the clinical workflow of 3D-printed electron cutouts in RT and furnish one year of in-vivo dosimetry data.Methods and materials3D-printed electron cutouts for 6x6 cm, 10x10 cm, and 15x15 cm electron applicators were designed and implemented into the clinical workflow after dosimetric commissioning to ensure congruence with the Cerrobend cutouts. The clinical workflow consisted of four parts: i) the cutout aperture was extracted from the treatment planning system (TPS). A 3D printable cutout was then generated automatically through custom scripts; ii) the cutout was 3D-printed with PLA filament, filled with tungsten ball bearings, and underwent quality assurance (QA) to verify density and dosimetry; iii) in-vivo dosimetry was performed with optically stimulated luminescence dosimeters (OSLDs) for a patient’s first treatment and compared to the calculated dose in the TPS; iv) after treatment completion, the 3D-printed cutout was recycled.ResultsQA and in-vivo OSLD measurements were conducted (n=40). The electron cutouts produced were 6x6 cm (n=3), 10x10 cm (n=30), and 15x15 cm (n=7). The expected weight of the cutouts differed from the measured weight by 0.4 + 1.1%. The skin dose measured with the OSLDs was compared to the skin dose in the TPS on the central axis. The difference between the measured and TPS doses was 4.0 + 5.2%.ConclusionThe successful clinical implementation of 3D-printed cutouts reduced labor, costs, and removed the use of toxic materials in the workplace while meeting clinical dosimetric standards

Alveolar Rhabdomyosarcoma with Regional Nodal Involvement: Results of a Combined Analysis from Two Cooperative Groups

BACKGROUND: Treatment of children and adolescents with alveolar rhabdomyosarcoma (ARMS) and regional nodal involvement (N1) have been approached differently by North American and European cooperative groups. In order to define the better therapeutic strategy, we analyzed two studies conducted between 2005 and 2016 by the European paediatric Soft tissue sarcoma Study Group (EpSSG) and Children’s Oncology Group (COG). METHODS: We retrospectively identified patients with ARMS-N1 enrolled in either EpSSG RMS2005 or in COG ARST0531. Chemotherapy in RMS2005 comprised IVADo (ifosfamide, vincristine, dactinomycin, doxorubicin), IVA and maintenance (vinorelbine, cyclophosphamide); in ARST0531 it consisted on either VAC (vincristine, dactinomycin, cyclophosphamide) or VAC alternating with VI (vincristine, irinotecan). Local treatment was similar in both protocols. RESULTS: The analysis of the clinical characteristics of 239 patients showed some differences between study groups: in RMS2005, advanced IRS Group and large tumors predominated. There were no differences in outcomes between the two groups: 5-year event-free survival (EFS), 49%(95%CI=39–59) and 44%(95%CI=30–58), and overall survival (OS), 51%(95%CI=41–61) and 53.6%(95%CI=40–68), in RMS2005 and ARST0531, respectively. In RMS2005, EFS of patients with FOXO1-positive tumors was significantly inferior to those FOXO1-negative (49.3% vs 73%, p=0.034). In contrast, in ARST0531, EFS of patients with FOXO1-positive tumors was 45% compared with 43.8% for those FOXO1-negative. CONCLUSIONS: The outcome of patients with ARMS N1 was similar in both protocols. However, patients with FOXO1 fusion-negative tumors enrolled in RMS2005 showed a significantly better outcome, suggesting that different strategies of chemotherapy may have an impact in the outcome of this subgroup of patients

Local Control For High-Grade Nonrhabdomyosarcoma Soft Tissue Sarcoma Assigned to Radiation Therapy on ARST0332: A Report From the Childrens Oncology Group

PURPOSE: The ARST0332 trial for pediatric and young adults with nonrhabdomyosarcoma soft tissue sarcoma (NRSTS) used risk-based treatment including primary resection with lower-than-standard radiation doses to optimize local control (LC) while minimizing long-term toxicity in those requiring radiation therapy (RT). RT for high-grade NRSTS was based on extent of resection (R0: negative margins, R1: microscopic margins, R2/U: gross disease/unresectable); those with \u3e 5 cm tumors received chemotherapy (CT; ifosfamide/doxorubicin). This analysis evaluates LC for patients assigned to RT and prognostic factors associated with local recurrence (LR). METHODS AND MATERIALS: Patients aged \u3c 30 years with high-grade NRSTS received RT (55.8 Gy) for R1 \u3c /=5 cm tumor (arm B); RT (55.8 Gy)/CT for R0/R1 \u3e 5 cm tumor (arm C); or neoadjuvant RT (45 Gy)/CT plus delayed surgery, CT, and postoperative boost to 10.8 Gy R0 \u3c 5 mm margins/R1 or 19.8 Gy for R2/unresected tumors (arm D). RESULTS: One hundred ninety-three eligible patients had 24 LRs (arm B 1/15 [6.7%], arm C 7/65 [10.8%], arm D 16/113 [14.2%]) at median time to LR of 1.1 years (range, 0.11-5.27). Of 95 eligible for delayed surgery after neoadjuvant therapy, 89 (93.7%) achieved R0/R1 margins. Overall LC after RT were as follows: R0, 106 of 109 (97%); R1, 51 of 60 (85%); and R2/unresectable, 2 of 6 (33%). LR predictors include extent of delayed resection (P \u3c .001), imaging response before delayed surgery (P \u3c .001), histologic subtype (P \u3c .001), and no RT (P = .046). The 5-year event-free survival was significantly lower (P = .0003) for patients unable to undergo R0/R1 resection. CONCLUSIONS: Risk-based treatment for young patients with high-grade NRSTS treated on ARST0332 produced very high LC, particularly after R0 resection (97%), despite lower-than-standard RT doses. Neoadjuvant CT/RT enabled delayed R0/R1 resection in most patients and is preferred over adjuvant therapy due to the lower RT dose delivered