Dana L. Casey

Predicting Outcome in Patients with Rhabdomyosarcoma: Role of [18F]Fluorodeoxyglucose Positron Emission Tomography

PURPOSE To evaluate whether [(18)F]fluorodeoxyglucose positron emission tomography (FDG-PET) response of the primary tumor after induction chemotherapy predicts outcomes in rhabdomyosarcoma (RMS). METHODS AND MATERIALS After excluding those with initial tumor resection, 107 patients who underwent FDG-PET after induction chemotherapy at Memorial Sloan Kettering Cancer Center from 2002 to 2013 were reviewed. Local control (LC), progression-free survival (PFS), and overall survival (OS) were calculated according to FDG-PET response and maximum standardized uptake value (SUV) at baseline (PET1/SUV1), after induction chemotherapy (PET2/SUV2), and after local therapy (PET3/SUV3). Receiver operator characteristic curves were used to determine the optimal cutoff for dichotomization of SUV1 and SUV2 values. RESULTS The SUV1 (<9.5 vs ≥9.5) was predictive of PFS (P=.02) and OS (P=.02), but not LC. After 12 weeks (median) of induction chemotherapy, 45 patients had negative PET2 scans and 62 had positive scans: 3-year PFS was 72% versus 44%, respectively (P=.01). The SUV2 (<1.5 vs ≥1.5) was similarly predictive of PFS (P=.005) and was associated with LC (P=.02) and OS (P=.03). A positive PET3 scan was predictive of worse PFS (P=.0009), LC (P=.05), and OS (P=.03). CONCLUSIONS [(18)F]fluorodeoxyglucose positron emission tomography is an early indicator of outcomes in patients with RMS. Future prospective trials may incorporate FDG-PET response data for risk-adapted therapy and early assessment of new treatment regimens.

Late Toxicities of Intensity-Modulated Radiation Therapy for Head and Neck Rhabdomyosarcoma.

To examine the late effects of intensity‐modulated radiation therapy (IMRT) in pediatric patients with rhabdomyosarcoma of the head and neck.

Ewing sarcoma in adults treated with modern radiotherapy techniques.

BACKGROUND AND PURPOSE To evaluate local control and survival outcomes in adults with Ewing sarcoma (ES) treated with radiotherapy (RT). MATERIAL AND METHODS Retrospective review of all 109 patients age ⩾18 treated for ES with RT to the primary site at Memorial Sloan Kettering Cancer Center between 1990 and 2011. RT was used as the definitive local control modality in 44% of patients, preoperatively for 6%, and postoperatively for 50%. RESULTS Median age at diagnosis was 27years (range, 18-67). The 5-year local failure (LF) was 18%. Differences in LF were not identified when evaluated by modality of local control (RT versus combined surgery and RT), RT dose, fractionation, and RT technique. However, margin status at time of resection significantly predicted LF. The 5-year event-free survival and overall survival rates were 44% and 66% for patients with localized disease, compared with 16% and 26% for metastatic disease (p=0.0005 and 0.0002). Tumor size, histopathologic response to chemotherapy, and treatment on or according to a protocol were also significantly associated with survival. CONCLUSIONS This series of adults treated with modern chemotherapy and RT had prognostic factors and outcomes similar to adolescents with ES. All adults with ES should be treated with an aggressive, multidisciplinary approach.

Favorable outcomes after whole abdominopelvic radiation therapy for pediatric and young adult sarcoma

Current Childrens Oncology Group (COG) guidelines recommend 24 Gy whole abdominopelvic radiation therapy (WAP‐RT) for pediatric patients with sarcoma with peritoneal dissemination and/or malignant ascites. However, WAP‐RT has never been described for pediatric sarcoma excluding desmoplastic small round‐cell tumor (DSRCT). The objective of this study was to evaluate feasibility, outcomes, and toxicity of WAP‐RT in children with sarcoma and peritoneal dissemination.

Radiation for bone metastases in Ewing sarcoma and rhabdomyosarcoma

The role, optimal dose, and efficacy of radiotherapy (RT) for the treatment of bone metastases in rhabdomyosarcoma (RMS) and Ewing sarcoma (ES) are unclear.

Whole Lung Irradiation for Adults With Pulmonary Metastases From Ewing Sarcoma

PURPOSE To evaluate feasibility and patterns of failure in adult patients with Ewing sarcoma (ES) treated with whole lung irradiation (WLI) for pulmonary metastases. METHODS AND MATERIALS Retrospective review of all ES patients treated at age 18 or older with 12-15 Gy WLI for pulmonary metastases at a single institution between 1990 and 2014. Twenty-six patients met the study criteria. RESULTS The median age at WLI was 23 years (range, 18-40). The median follow-up time of the surviving patients was 3.8 years (range, 1.0-9.6). The 3-year cumulative incidence of pulmonary relapse (PR) was 55%, with a 3-year cumulative incidence of PR as the site of first relapse of 42%. The 3-year event-free survival (EFS) and overall survival (OS) were 38 and 45%, respectively. Patients with exclusively pulmonary metastases had better outcomes than did those with extrapulmonary metastases: the 3-year PR was 45% in those with exclusively lung metastases versus 76% in those with extrapulmonary metastases (P=.01); the 3-year EFS was 49% versus 14% (P=.003); and the 3-year OS was 61% versus 13% (P=.009). Smoking status was a significant prognostic factor for EFS: the 3-year EFS was 61% in nonsmokers versus 11% in smokers (P=.04). Two patients experienced herpes zoster in the radiation field 6 and 12 weeks after radiation. No patients experienced pneumonitis or cardiac toxicity, and no significant acute or late sequelae were observed among the survivors. CONCLUSION WLI in adult patients with ES and lung metastases is well tolerated and is associated with freedom from PR of 45% at 3 years. Given its acceptable toxicity and potential therapeutic effect, WLI for pulmonary metastases in ES should be considered for adults, as it is in pediatric patients. All patients should be advised to quit smoking before receiving WLI.

Second cancer risk in childhood cancer survivors treated with intensity-modulated radiation therapy (IMRT)

Treatment with radiotherapy (RT) is associated with an increased risk of second malignant neoplasms (SMNs) in childhood cancer survivors; it is unclear how treatment with intensity‐modulated radiation therapy (IMRT) impacts this risk. We provide the first report of SMN risk in a cohort of childhood cancer survivors treated with IMRT.

Patterns of Failure for Rhabdomyosarcoma of the Perineal and Perianal Region

PURPOSE To analyze prognostic factors and patterns of failure for rhabdomyosarcoma of the perineal and perianal region (PRMS), with an emphasis on radiation therapy for locoregional control. METHODS AND MATERIALS Detailed records of all 14 patients treated for PRMS at Memorial Sloan-Kettering Cancer Center between 1998 and 2012 were reviewed. The Kaplan-Meier method was used to assess the event-free survival (EFS) and overall survival (OS), and a competing-risks analysis was used to assess the cumulative incidence of local, regional, and distant failures. RESULTS Median age was 15.8 years (range, 1.1-31.9 years). High-risk features were identified: 9 of 14 patients (64%) had group 3 disease and 3 of 14 (21%) had group 4; 11 of 14 tumors (78%) were alveolar; 12 of 14 tumors (86%) were ≥5 cm; and 9 of 14 patients (64%) had involved lymph nodes (N1). Of those aged ≥10 years at diagnosis, 9 of 10 (90%) had alveolar histology, all had tumors ≥5 cm, and 8 of 10 (80%) presented with N1 disease. The rates of local, regional, and distant failure at 5 years were 17%, 31%, and 52%, respectively. Although 3 of the 4 patients with regional failure received nodal irradiation, only one of the nodal failures occurred in the radiation therapy field. The 5-year EFS was 33%, and OS was 39%. Age ≥10 years was associated with poor outcomes: EFS was 13% in patients aged ≥10 years, compared with 75% in those aged <10 years (P=.04); the OS was 13% in patients aged ≥10 years, compared with 100% in those aged <10 years (P=.04). CONCLUSIONS Patients with PRMS, especially those aged ≥10 years, present with poor prognostic features and continue to have poor outcomes. Given the high incidence of regional node recurrence, we recommend prophylactic ilioinguinal lymph node irradiation for all patients aged ≥10 years. For children aged <10 years, nodal evaluation is essential to determine the role for lymph node irradiation.

Rhabdomyosarcoma of the Head and Neck: A Multimodal Approach

&NA; Head and neck rhabdomyosarcoma (HNRMS) is a uniquely challenging site to treat given the young patient age and critical anatomy of the head and neck region. We review the characteristics, management, and future directions in the treatment of HNRMS. Most patients who present with HNRMS have unresectable disease due to functional and/or cosmetic constraints. However, surgical resection and brachytherapy serve a critical role in select patients. The treatment paradigm for the majority of patients with HNRMS consists of definitive chemotherapy and radiation therapy. As the incidence of late toxicities increases with improved survival, modern efforts must focus on ways to decrease long‐term morbidity. We recommend a multimodal approach emphasizing the preservation of form and function for the treatment of HNRMS.

Dose-escalation is needed for gross disease in high-risk neuroblastoma

Locoregional failure is common after subtotal resection in high‐risk neuroblastoma. Although a dose of 21 Gy radiation therapy (RT) is standard for treatment of high‐risk neuroblastoma after gross total resection, the dose needed for local control of patients with gross residual disease at the time of RT is unknown. We sought to evaluate local control after 21–36 Gy RT in patients with high‐risk neuroblastoma undergoing subtotal resection.