A phase I study of short-course accelerated whole brain radiation therapy for multiple brain metastases.
OBJECTIVE
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
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.
Department of Radiation Oncology, Fondazione di Ricerca e Cura Giovanni Paolo II, Università Cattolica del S. Cuore, and Department of Oncology, A. Cardarelli Hospital, Campobasso, Italy.
Luciana
L
Caravatta
Francesco
F
Deodato
Marica
M
Ferro
Gabriella
G
Macchia
Mariangela
M
Massaccesi
Savino
S
Cilla
Gilbert D A
GD
Padula
Samantha
S
Mignogna
Rosa
R
Tambaro
Francesco
F
Carrozza
Mariano
M
Flocco
Giampaolo
G
Cantore
Andrea
A
Scapati
Milly
M
Buwenge
Giovanna
G
Sticca
Vincenzo
V
Valentini
Numa
N
Cellini
Alessio G
AG
Morganti
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000528:radiation effects; D001932:Brain Neoplasms / Q000532:radiotherapy* / Q000556:secondary*; D015331:Cohort Studies; D019583:Dose Fractionation, Radiation; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D015999:Multivariate Analysis; D011788:Quality of Life; D011832:Radiation Injuries / Q000150:complications / Q000473:pathology; D011880:Radiotherapy Planning, Computer-Assisted / Q000379:methods; D012720:Severity of Illness Index; D012867:Skin / Q000528:radiation effects; D055815:Young Adult