PURPOSE: To define the maximum tolerated dose (MTD) of a SHort-course Accelerated whole brain RadiatiON therapy (SHARON) in the treatment of patients with multiple brain metastases. METHODS AND MATERIALS: A phase 1 trial in 4 dose-escalation steps was designed: 12 Gy (3 Gy per fraction), 14 Gy (3.5 Gy per fraction), 16 Gy (4 Gy per fraction), and 18 Gy (4.5 Gy per fraction). Eligibility criteria included patients with unfavorable recursive partitioning analysis (RPA) class>or=2 with at least 3 brain metastases or metastatic disease in more than 3 organ systems, and Eastern Cooperative Oncology Group (ECOG) performance status≤3. Treatment was delivered in 2 days with twice-daily fractionation. Patients were treated in cohorts of 6-12 to define the MTD. The dose-limiting toxicity (DLT) was defined as any acute toxicity≥grade 3, according to the Radiation Therapy Oncology Group scale. Information on the status of the main neurologic symptoms and quality of life were recorded. RESULTS: Characteristics of the 49 enrolled patients were as follows: male/female, 30/19; median age, 66 years (range, 23-83 years). ECOG performance status was <3 in 46 patients (94%). Fourteen patients (29%) were considered to be in recursive partitioning analysis (RPA) class 3. Grade 1-2 acute neurologic (26.4%) and skin (18.3%) toxicities were recorded. Only 1 patient experienced DLT (neurologic grade 3 acute toxicity). With a median follow-up time of 5 months (range, 1-23 months), no late toxicities have been observed. Three weeks after treatment, 16 of 21 symptomatic patients showed an improvement or resolution of presenting symptoms (overall symptom response rate, 76.2%; confidence interval 0.95: 60.3-95.9%). CONCLUSIONS: Short-course accelerated radiation therapy in twice-daily fractions for 2 consecutive days is tolerated up to a total dose of 18 Gy. A phase 2 study has been planned to evaluate the efficacy on overall survival, symptom control, and quality of life indices.
PURPOSE: To define the maximum tolerated dose (MTD) of a SHort-course Accelerated whole brain RadiatiON therapy (SHARON) in the treatment of patients with multiple brain metastases. METHODS AND MATERIALS: A phase 1 trial in 4 dose-escalation steps was designed: 12 Gy (3 Gy per fraction), 14 Gy (3.5 Gy per fraction), 16 Gy (4 Gy per fraction), and 18 Gy (4.5 Gy per fraction). Eligibility criteria included patients with unfavorable recursive partitioning analysis (RPA) class>or=2 with at least 3 brain metastases or metastatic disease in more than 3 organ systems, and Eastern Cooperative Oncology Group (ECOG) performance status≤3. Treatment was delivered in 2 days with twice-daily fractionation. Patients were treated in cohorts of 6-12 to define the MTD. The dose-limiting toxicity (DLT) was defined as any acute toxicity≥grade 3, according to the Radiation Therapy Oncology Group scale. Information on the status of the main neurologic symptoms and quality of life were recorded. RESULTS: Characteristics of the 49 enrolled patients were as follows: male/female, 30/19; median age, 66 years (range, 23-83 years). ECOG performance status was <3 in 46 patients (94%). Fourteen patients (29%) were considered to be in recursive partitioning analysis (RPA) class 3. Grade 1-2 acute neurologic (26.4%) and skin (18.3%) toxicities were recorded. Only 1 patient experienced DLT (neurologic grade 3 acute toxicity). With a median follow-up time of 5 months (range, 1-23 months), no late toxicities have been observed. Three weeks after treatment, 16 of 21 symptomatic patients showed an improvement or resolution of presenting symptoms (overall symptom response rate, 76.2%; confidence interval 0.95: 60.3-95.9%). CONCLUSIONS: Short-course accelerated radiation therapy in twice-daily fractions for 2 consecutive days is tolerated up to a total dose of 18 Gy. A phase 2 study has been planned to evaluate the efficacy on overall survival, symptom control, and quality of life indices.
Authors: Jenny Capuccini; Gabriella Macchia; Eleonora Farina; Milly Buwenge; Domenico Genovesi; Luciana Caravatta; Nam P Nguyen; Silvia Cammelli; Savino Cilla; Tigeneh Wondemagegnhu; A F M Kamal Uddin; Mostafà Aziz Sumon; Francesco Cellini; Vincenzo Valentini; Francesco Deodato; Alessio G Morganti Journal: Clin Exp Metastasis Date: 2018-08-18 Impact factor: 5.150
Authors: Alessio G Morganti; Gabriella Macchia; Francesco Cellini; Francesco Deodato; Alice Zamagni; Giambattista Siepe; Milly Buwenge Journal: Front Oncol Date: 2022-02-23 Impact factor: 6.244
Authors: Alexander Fabian; Justus Domschikowski; Anne Letsch; Claudia Schmalz; Sandra Freitag-Wolf; Juergen Dunst; David Krug Journal: JAMA Netw Open Date: 2022-09-01