M. Casale

8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression: Results of a phase III randomized multicentre Italian trial

BACKGROUND AND PURPOSE In a previous randomized trial we showed that the short-course radiotherapy (RT) regimen of 8 Gy x 2 was feasible in patients with metastatic spinal cord compression (MSCC) and short life expectancy. This phase III trial was planned to determine whether in the same category of patients 8 Gy single-dose is as effective as 8 Gy x 2. MATERIALS AND METHODS Three hundred and twenty-seven patients with MSCC and short life expectancy were randomly assigned to a short-course of 8 Gy x 2 or to 8 Gy single-dose RT. Median follow-up was 31 months (range, 4-58). RESULTS A total of 303 (93%) patients are assessable, 150 treated with the short-course and 153 with the single-dose RT. No difference in response was found between the two RT schedules adopted. Median duration of response was 5 and 4.5 months for short-course and single-dose RT (p=0.4), respectively. The median overall survival was 4 months for all cases. Light acute toxicity was registered in a minority of cases. Late toxicity was never recorded. CONCLUSIONS Both RT schedules adopted were effective. As already shown in several trials evaluating RT regimens in uncomplicated painful bone metastases, also MSCC patients may achieve palliation with minimal toxicity and inconvenience with a single-dose of 8 Gy.

Treatment of recurrent glioblastoma with stereotactic radiotherapy: long-term results of a mono-institutional trial

AIMS AND BACKGROUND Few clinical data exist concerning normal brain tissue tolerance to re-irradiation. The present study evaluated long-term outcome of 22 recurrent glioblastoma patients re-irradiated with radiosurgery or fractionated stereotactic radiotherapy. METHODS Twenty-two patients were treated with radiosurgery (13, 59%) or fractionated stereotactic radiotherapy (9, 41%) for 24 lesions of recurrent glioblastoma. The male/female ratio was 14:8, median age 55 years (range, 27-81), and median Karnofsky performance status 90 (range, 70-100). The majority of the cases (77%) was in recursive partitioning analysis classes III or IV Radiosurgery or fractionated stereotactic radiotherapy was chosen according to lesion size and location. RESULTS Median time between primary radiotherapy and re-irradiation was 9 months. Median doses were 17 Gy and 30 Gy, whereas median cumulative normalized total dose was 141 Gy and 98 Gy for radiosurgery and fractionated stereotactic radiotherapy, respectively. All patients submitted to radiosurgery had a cumulative normalized total dose of more than 100 Gy, whereas only a few (44%) of fractionated stereotactic radiotherapy patients had a cumulative normalized total dose exceeding 100 Gy. Median follow-up from re-irradiation was 54 months. At the time of analysis, all patients had died. After re-irradiation, 1 (4%) lesion was in partial remission, 16 (67%) lesions were stable, and the remaining 7 (29%) were in progression. Median duration of response was 6 months, and median survival from re-irradiation 11 months. Three of 13 (23%) patients submitted to radiosurgery developed asymptomatic brain radionecrosis. The cumulative normalized total dose for the 3 patients was 122 Gy, 124 Gy, and 141 Gy, respectively. In one case, the volume of the lesion was large (14 cc), and in the other 2 the interval between the first and second cycle of radiotherapy was short (5 months). CONCLUSIONS Re-irradiation with radiosurgery and fractionated stereotactic radiotherapy is feasible and effective in recurrent glioblastoma patients. Apart from the importance of an accurate patient selection, cumulative radiotherapy dose and a correct indication for radiosurgery or fractionated stereotactic radiotherapy must be taken into account to avoid brain toxicity.

Reirradiation of brain metastases with radiosurgery

PURPOSE To assess the outcome of reirradiation with stereotactic radiosurgery (SRS) of brain metastases (BM) recurring after whole brain radiotherapy (WBRT). METHODS AND MATERIALS Between September 2001 and October 2008, 69 patients who recurred after WBRT were re-irradiated with SRS using a linear accelerator. The dose prescription was generally chosen according to maximum diameter of the tumor as suggested by Radiation Therapy Oncology Group (RTOG) 90-05 protocol. Patients were stratified by Karnofsky Performance Status (KPS), Neurologic Functional Score (NFS), RTOG Recursive Partitioning Analysis (RPA), Score Index for Radiosurgery (SIR), primary disease, dimension and number of BM, and time to first brain recurrence after WBRT. Response, survival, and toxicity were analyzed. RESULTS At time of this retrospective analysis all patients had died. The 69 patients reirradiated with SRS had 150 metastases. Median interval between prior WBRT and SRS was 11 months and median SRS prescribed dose was 20 Gy. Response was obtained in 91% of lesions with 1-year local control rate of 74±4%. Significantly longer duration of response was associated with higher doses (≥23 Gy) and response achieved after SRS (complete and partial response better than stable disease). Cause of death was brain failure only in 36 (52%) patients. Median overall survival after reirradiation was 10 months. Variables which significantly conditioned survival were KPS and NFS. Four (6%) patients had asymptomatic radionecrosis that developed prevalently when lesion diameters were larger and cumulative doses exceeded the values recommended by RTOG 90-05 protocol. About three-fourth of the patients had a good KPS and NFS after reirradiation. CONCLUSIONS Reirradiation of BM with SRS resulted feasible and effective. A correct patient selection and an accurate evaluation of the cumulative irradiation dose were suggested.

Definitive three-dimensional high-dose-rate brachytherapy for inoperable endometrial cancer

Purpose To report our experience on high-dose-rate brachytherapy (HDR-BT) in patients with stage I-III endometrial cancer unfit to surgery. Material and methods Seventeen patients underwent HDR-BT as definitive treatment. Median age was 79 years (range, 60-95), median Karnofsky performance status 90% (range, 60-100). Histology was endometrial adenocarcinoma in 14 (82%), and non-endometrial in 3 (18%) patients. In 15 (88%) patients, clinical stage was I and in remaining 2 (12%) was III. All patients were evaluated with computed tomography (CT) and endometrial biopsy. Using the Fletcher applicator, a CT-based planning HDR-BT was delivered. Local control (LC) was obtained when there was an interruption of vaginal bleeding in absence of CT-imaging progression. Results Fourteen patients underwent HDR-BT alone and three external beam radiotherapy (EBRT) combined with HDR-BT. All patients had a clinical LC, after a median follow-up of 53 months (range, 6-131), 3 and 6 years LC rates were 86% and 69%, respectively. Cancer specific survival (CSS) at 1, 2, and 6 years was 93%, 85%, and 85%, respectively. Age, stage, dose, and type of radiotherapy did not result significant prognostic factors for LC and CSS. Only histology significantly influenced LC: for high-risk histology (i.e., non-endometrial carcinoma or grade [G] 3 endometrial adenocarcinoma) LC was 73% at 1 year and 36% at 6 years; for low-risk histology (i.e., G1-2 endometrial adenocarcinoma) was 100% at 1 and 6 years (p = 0.05). Two (12%) patients had G2 acute toxicity and two others (12%) G1 late toxicity. Conclusions Although some limitations of our analysis (relatively few number of patients recruited, retrospective evaluation, and consequent suboptimal patient selection), it confirms effectiveness and safety of definitive HDR-BT for medically inoperable stage I-III endometrial cancer. The best LC was obtained in stage I low-risk histology.