Significant Hemorrhage Rate Reduction after Gamma Knife Radiosurgery in Symptomatic Cavernous Malformations: Long-Term Outcome in 95 Case Series and Literature Review.

BACKGROUND: The natural history of cavernous malformations (CMs) has remained unclear. This lack of knowledge has made treatment decisions difficult. Indeed, the use of stereotactic radiosurgery is nowadays controversial. The purpose of this paper is to throw light on the effectiveness of Gamma Knife radiosurgery (GKRS) therapy. METHODS: The authors reviewed data collected from a prospectively maintained database. A total of 95 patients (57 female and 38 male) underwent GKRS for high-surgical-risk CMs. A total of 76 cavernomas were deeply located (64 lesions in the brainstem and 12 lesions in the thalamus). All of them were located in eloquent regions. The median malformation volume was 1,570 mm3. The median tumor margin dose was 11.87 Gy, and the mean tumor maximum dose was 19.56 Gy. RESULTS: Ninety-five cavernous CMs were managed from 1994 to 2014. All patients had experienced at least 1 symptomatic bleeding incident before treatment (only 1 hemorrhage event in 81%). The median length of follow-up review was 78 months. The pretreatment annual hemorrhage rate was 3.06% compared with 1.4% during the first 3-year latency interval, and 0.16% thereafter (p = 0.004). Four patients developed new location-dependent neurological deficits, and 3 patients had edema-related headache after radiosurgery. All of them presented full recovery. CONCLUSIONS: The best dosage range for preventing bleeding was identified as between 11 and 12 Gy in our series. Although the efficacy of radiosurgery in CMs remains impossible to quantify, a very significant reduction in the bleeding rate occurs after a 3-year latency interval. No permanent neurological morbidity is reported in our series. These results defend the safety of GKRS in surgical high-risk CM from the first bleeding event.

Neoadjuvant chemoradiation with tegafur in cancer of the pancreas: initial analysis of clinical tolerance and outcome.

The early institutional experience in the neoadjuvant treatment of potentially resectable pancreatic carcinoma using oral Tegafur as radioenhancing agent is analyzed. Fifteen patients (10 male and 5 female, mean age of 61 years) were treated over a 30-month period. Tegafur dose was 1,200 mg/d along the external radiotherapy period (45-55 consecutive days). Preoperative radiotherapy achieved a total dose of 45 to 50 Gy (1.8 Gy/d). Intraoperative electron boost (10-15 Gy) was delivered at the time of surgery. Hematologic tolerance showed a significant decrease of neutrophil and platelet counts from the outset to the end of the neoadjuvant period (p = 0.001 and p = 0.004, respectively). Five grade III vomiting episodes (33%) were also registered. In 9 patients (60%), surgical resection was performed after chemoradiation. Three complete pathologic responses (pT0 specimens) were identified; in seven cases, the resection achieved tumor-free surgical margins of the specimen. With a median follow-up of 21 months, median survival time was 17 months, with actuarial rates of 45% at 1 year and 24% at 3 years. Median survival for the resected patients was 23 months, and for the unresected patients median survival was 8 months (p = 0.02). The overall median survival in completely resected patients was 28 months, with a 71% survival rate at 1 and 3 years. It is concluded that the treatment scheme described is feasible and acceptably tolerated. The use of oral Tegafur seems to induce results similar to those of other therapeutic protocols using intravenous radioenhancing chemotherapy.

Intraoperative presacral electron boost following preoperative chemoradiation in T3-4Nx rectal cancer: initial local effects and clinical outcome analysis.

BACKGROUND AND PURPOSE: To analyze early results of a single institution experience using adjuvant intraoperative electron radiation therapy (IOERT) presacral boost in locally advanced rectal cancer following preoperative chemoradiation. MATERIALS AND METHODS: In a 63 month period (March 1995-June 2000), 100 consecutive T(3-4)N(x) rectal cancer patients were treated with preoperative chemoradiation (45-50 Gy plus oral Tegafur or 5-Fluorouracil continuous intravenous infusion), radical surgery and IOERT presacral boost (mean dose, 12.5 Gy; range, 10-15 Gy). Adjuvant chemotherapy (5-FU-leucovorin: 4-6 cycles) was given to 52 patients. The median age was 63 years, and 39 patients were >or=70 years old (65 males). Clinical staging was performed with computed tomography (94%) and/or endorectal ultrasound (71%) categorizing 90 cT(3), 10 cT(4), 20 cN(x), and 36 cN(+). Abdomino-perineal resection was performed in 41 cases. RESULTS: The IOERT cancellation rate was 6%. With a median follow-up of 23 months in IOERT treated patients, three developed pelvic recurrence: one anastomotic and one in the posterior vaginal wall (simultaneously with distant metastatic disease); and one presacral (in-field IOERT) as the only site of initial failure. Distant metastasis has been observed in 14 patients (exceptionally in pT(0-1) downstaged patients: 1/20; 5%). Overall treatment tolerances, including neoadjuvant and surgical segments, were acceptable. The actuarial 4-year estimations of local control, disease-free and overall survival are 94, 75 and 65%, respectively. CONCLUSIONS: IOERT electron boost to the presacral region is feasible to integrate systematically in the intensive combined treatment of locally advanced rectal cancer, including neoadjuvant chemoradiation segment. Topography of pelvic recurrences identified 2/3 relapses located in non-IOERT boosted anatomic intrapelvic sites: posterior vaginal wall and anastomotic suture. Presacral recurrence in locally advanced rectal cancer seems to be of low incidence, in a non-subspecialized academic surgical practice coordinated with a multidisciplinary oncology evaluation context, if an IOERT boost is included as a component of treatment together with preoperative chemoradiation.