Dose-escalation of whole-brain radiotherapy for brain metastasis in patients with a favorable survival prognosis.

BACKGROUND: Patients with brain metastases who have a favorable survival prognosis may benefit from intensive treatments, including neurosurgery and radiosurgery. However, many patients cannot receive such treatments, and whole-brain radiotherapy (WBRT) alone is their only option. The most common WBRT schedule is 30 grays (Gy) in 10 fractions. In this retrospective study, the authors investigated whether these patients benefit from a dose escalation beyond 30 Gy. METHODS: Data from 109 patients who received 30 Gy in 10 fractions were compared with 75 patients who received 40 Gy in 20 fractions. All patients had a favorable survival prognosis. Both groups were compared for local control (LC) and overall survival (OS). Subgroup analyses were performed for patients who had less radiosensitive tumors (N = 27) and for other patients (N = 157). RESULTS: The LC rate at 1 year was 28% after 30 Gy and 44% after 40 Gy (P = .064). On multivariate analysis, the 40 Gy dose was associated with improved LC (P = .047). The survival rate at 1 year was 50% after 30 Gy and 61% after 40 Gy (P = .007). On multivariate analysis, the 40 Gy dose was associated with improved OS (P = .008). On subgroup analysis of patients who had less radiosensitive tumors, the 1-year LC rate was 7% after 30 Gy and 38% after 40 Gy (P = .031); and the 1-year OS rate was 40% and 73%, respectively (P = .008). On subgroup analysis of patients who had other tumor types, the 1-year LC rate was 31% after 30 Gy and 45% after 40 Gy (P = .26); and the 1-year OS rate was 52% and 59%, respectively (P = .08). CONCLUSIONS: Escalation of the WBRT dose beyond 30 Gy resulted in better outcomes, particularly for patients who had less radiosensitive tumors.

Dose escalation of radiotherapy for metastatic spinal cord compression (MSCC) in patients with relatively favorable survival prognosis.

BACKGROUND AND PURPOSE: Local control of metastatic spinal cord compression (MSCC) is particularly important for long-term survivors. Radiotherapy alone is the most common treatment for MSCC. The most frequently used schedule world wide is 30 Gy/10 fractions. This study investigated whether patients with favorable survival prognoses benefit from a dose escalation beyond 30 Gy. PATIENTS AND METHODS: Data from 191 patients treated with 30 Gy/10 fractions were matched to 191 patients (1:1) receiving higher doses (37.5 Gy/15 fractions or 40 Gy/20 fractions). All patients had favorable survival prognoses based on a validated scoring system and were matched for age, gender, tumor type, performance status, number of involved vertebrae, visceral or other bone metastases, interval from tumor diagnosis to radiotherapy, ambulatory status, and time developing motor deficits. Both groups were compared for local control, progression-free survival, overall survival, and functional outcome. RESULTS: Local control rates at 2 years were 71% after 30 Gy and 92% after higher doses (p=0.012). Two-year progression-free survival rates were 68% and 90%, respectively (p=0.013). Two-year overall survival rates were 53% and 68%, respectively (p=0.032). Results maintained significance in the multivariate analyses (Cox proportional hazards model; stratified model) with respect to local control (p=0.011; p=0.012), progression-free survival (p=0.010; p=0.018), and overall survival (p=0.014; p=0.015). Functional outcome was similar in both groups. Motor function improved in 40% of patients after 30 Gy and 41% after higher doses (p=0.98). CONCLUSION: Escalation of the radiation dose beyond 30 Gy resulted in significantly better local control, progression-free survival, and overall survival in patients with favorable survival prognoses.

Outcomes After Radiotherapy Alone for Metastatic Spinal Cord Compression in Patients with Oligo-metastatic Breast Cancer.

BACKGROUND/AIM: Patients with oligo-metastatic breast cancer are a unique patient subgroup with more favourable outlook than most patients with metastatic disease. Prognostic factors in these patients with metastatic spinal cord compression (MSCC) were evaluated. PATIENTS AND METHODS: In 159 patients irradiated for MSCC from oligo-metastatic breast cancer, seven characteristics were retrospectively analyzed including age, interval between breast cancer diagnosis and irradiation of MSCC, time developing motor deficits, ambulatory status, involved vertebrae, performance score (ECOG-PS) and radiotherapy regimen. RESULTS: Improvement of motor function was significantly associated with time developing motor deficits (p=0.017), post-radiotherapy ambulatory status with pre-radiotherapy ambulation (p=0.012) and ECOG-PS 1-2 (p=0.029). Radiation doses of 39-40 Gy (equivalent doses) resulted in 1- and 2-year local control of 100% and 95%. On multivariate analyses, higher doses were associated with local control (p=0.011). Pre-radiotherapy ambulatory status (p=0.001) and ECOG-PS 1-2 (p=0.002) were associated with survival. CONCLUSION: Significant prognostic factors were identified for patients with MSCC from oligo-metastatic breast cancer. Higher radiation doses improved local control.

Phase I Study of Definitive Radio-chemotherapy with Cisplatin, 5-Fluorouracil and Cetuximab for Unresectable Locally Advanced Esophageal Cancer.

BACKGROUND/AIM: Prognoses of patients receiving radio-chemotherapy with 5-fluorouracil (5-FU) and cisplatin for unresectable esophageal cancer may be improved with the addition of cetuximab. This phase I study aimed to define the maximum tolerated dose of 5-FU when combined with cisplatin, cetuximab and radiotherapy. PATIENTS AND METHODS: Treatment included 59.4 Gy of radiotherapy concurrently with two courses of cisplatin (20 mg/m2, d1-4) and 5-FU (dose level 0: 500 mg/m2, dose level 1: 750 mg/m2, d1-4; dose level 2: 1,000 mg/m2, d1-4), followed by two courses of chemotherapy. Cetuximab was given for 14 weeks (400 mg/m2 loading dose followed by 250 mg/m2 weekly). RESULTS: At dose level 1 (n=3) and 2 (n=3), no patient experienced a dose-limiting toxicity. Minor treatment modifications were due to organization or request by physicians/patients. At dose level 2, only five grade 3 adverse events occurred. CONCLUSION: Dose level 2 appears safe and is used in a subsequent randomized phase II study.