CT-guided interstitial HDR-brachytherapy for recurrent glioblastoma multiforme: a 20-year single-institute experience.

PURPOSE: To report our results of computed tomography-guided interstitial high-dose-rate (HDR) brachytherapy (BRT) in the treatment of patients with recurrent inoperable glioblastoma multiforme (GBM). PATIENTS AND METHODS: Between 1995 and 2014, 135 patients were treated with interstitial HDR BRT for inoperable recurrent GBM located within previously irradiated volumes. Patient's median age was 57.1 years (14-82 years). All patients were pretreated with surgery, postoperative external beam radiation therapy (EBRT) and systemic chemotherapy (ChT). The median recurrent tumor volume was 42 cm3 (2-207 cm3). The prescribed HDR dose was median 40 Gy (30-50 Gy) delivered in twice-daily fractions of 5.0 Gy over consecutive days. No repeat surgery or ChT was administered in conjunction with BRT. Survival from BRT, progression-free survival (PFS), toxicity as well as the impact of several prognostic factors were evaluated. RESULTS: At a median follow-up of 9.2 months, the median overall survival following BRT and the median PFS were 9.2 and 4.6 months, respectively. Of the prognostic variables evaluated in univariate analysis, extent of surgery at initial diagnosis, tumor volume at recurrence, as well as time from EBRT to BRT reached statistical significance, retained also in multivariate analysis. Eight patients (5.9%) developed treatment-associated complications including intracerebral bleeding in 4 patients (2.9%), symptomatic focal radionecrosis in 3 patients (2.2%), and severe convulsion in 1 patient (0.7%). CONCLUSIONS: For patients with recurrent GBM, interstitial HDR BRT is an effective re-irradiation method for even larger tumors providing palliation without excessive toxicity.

Long-term results of targeted intraoperative radiotherapy (Targit) boost during breast-conserving surgery.

PURPOSE: We have previously shown that delivering targeted radiotherapy to the tumour bed intraoperatively is feasible and desirable. In this study, we report on the feasibility, safety, and long-term efficacy of TARGeted Intraoperative radioTherapy (Targit), using the Intrabeam system. METHODS AND MATERIALS: A total of 300 cancers in 299 unselected patients underwent breast-conserving surgery and Targit as a boost to the tumor bed. After lumpectomy, a single dose of 20 Gy was delivered intraoperatively. Postoperative external beam whole-breast radiotherapy excluded the usual boost. We also performed a novel individualized case control (ICC) analysis that computed the expected recurrences for the cohort by estimating the risk of recurrence for each patient using their characteristics and follow-up period. RESULTS: The treatment was well tolerated. The median follow up was 60.5 months (range, 10-122 months). Eight patients have had ipsilateral recurrence: 5-year Kaplan Meier estimate for ipsilateral recurrence is 1.73% (SE 0.77), which compares well with that seen in the boosted patients in the European Organization for Research and Treatment of Cancer study (4.3%) and the UK STAndardisation of breast RadioTherapy study (2.8%). In a novel ICC analysis of 242 of the patients, we estimated that there should be 11.4 recurrences; in this group, only 6 recurrences were observed. CONCLUSIONS: Lumpectomy and Targit boost combined with external beam radiotherapy results in a low local recurrence rate in a standard risk patient population. Accurate localization and the immediacy of the treatment that has a favorable effect on tumour microenvironment may contribute to this effect. These long-term data establish the long-term safety and efficacy of the Targit technique and generate the hypothesis that Targit boost might be superior to an external beam boost in its efficacy and justifies a randomized trial.

Targeted intraoperative radiotherapy (TARGIT) yields very low recurrence rates when given as a boost.

PURPOSE: Patients undergoing breast-conserving surgery were offered boost radiotherapy with targeted intraoperative radiotherapy (TARGIT) using the Intrabeam system to test the feasibility, safety, and efficacy of the new approach. METHODS AND MATERIALS: We treated 302 cancers in 301 unselected patients. This was not a low-risk group. One-third of patients (98/301) were younger than 51 years of age. More than half of the tumors (172, 57%) were between 1 cm and 2 cm, and one-fifth (62, 21%) were >2 cm; 29% (86) had a Grade 3 tumor and, in 29% (87), axillary lymph nodes contained metastasis. After primary surgery, 20 Gy was delivered intraoperatively to the surface of the tumor bed, followed by external-beam radiotherapy (EBRT), but excluding the usual boost. RESULTS: The treatment was well tolerated. The follow-up ranged from 3 to 80 months (164 and 90 patients completed 2 and 3 years follow-up, respectively). Four patients (1.3%) had local recurrence. The Kaplan-Meier estimate of local recurrence is 2.6% (SE = 1.7) at 5 years. This compares favorably with the 4.3% recurrence rate in boosted patients from the EORTC boost study, in which only 8.1% patients were node-positive, as opposed to 29% in our series. CONCLUSION: Targeted intraoperative radiotherapy combined with EBRT results in a low local recurrence rate. This could be attributed to both accurate targeting and timeliness of the treatment. These data support the need for a randomized trial to test whether the TARGIT boost is superior to conventional external boost, especially in high-risk women.

TARGeted Intraoperative radiotherapy (TARGIT): an innovative approach to partial-breast irradiation.

A revolution is challenging the dogma that local treatment for all patients with breast cancer treated with breast conservation therapy must include postoperative radiotherapy delivered to the whole breast. Such prolonged postoperative radiotherapy is a burden to patients and hospitals and forces many women to chose mastectomy instead. Furthermore, for patients receiving chemotherapy, the start of conventional radiotherapy may be delayed so long as to increase the risk of local relapse. These problems might be eliminated if effective radiotherapy could be given as a single treatment intraoperatively, immediately after the surgery. Local recurrence after breast-conserving surgery usually occurs in the portion of the breast in the immediate proximity of the tumor, even when radiotherapy is omitted. Therefore, it should usually be possible to restrict radiotherapy to only the area adjacent to the tumor in selected women. Based on this premise, we have devised a new technique of partial breast irradiation, with the intention of completing all local treatment in a single session. In this article, we elaborate on the rationale and on the different methods of delivering intraoperative radiotherapy. If this approach is validated in ongoing randomized trials, it could save time, money, and breasts.

Intraoperative radiotherapy for breast cancer.

Postoperative radiotherapy, which forms part of breast-conserving therapy, may not need to encompass the whole breast. Apart from the consumption of huge resources and patients' time, postoperative radiotherapy deters many women from receiving the benefits of breast-conserving surgery, forcing them to choose a mastectomy instead. If radiotherapy could be given in the operating theatre immediately after surgery, many of these disadvantages could be overcome. One striking fact about local recurrence after breast-conserving surgery is that most occurs in the area of breast immediately next to the primary tumour; this is despite the finding that two-thirds of mastectomy samples have microscopic tumours distributed throughout the breast, even when radiotherapy is omitted. Thus, only the area adjacent to the tumour may need treatment with radiotherapy. On the basis of this premise, clinical scientists have used new technology to administer radiotherapy to the area at greatest risk of local recurrence, with the aim of completing the whole local treatment in one sitting. In this review, we have elaborated on the rationale and different methods of delivery of intraoperative radiotherapy. If this approach is validated by the results of current randomised trials, it could save time, money, and breasts.

Use of low-energy X-rays in the treatment of superficial nonmelanomatous skin cancers.

The Photon Radiosurgery System (PRS), developed by the Photoelectron Corporation in Lexington, Massachusetts, produces low-energy x-rays from the tip of a needle-like probe at a high dose-rate. This portable device can be located directly over the target volume, delivering a uniform dose while sparing surrounding normal structures. To evaluate its radiotherapeutic profile, a prospective phase I Food and Drug Administration trial was performed utilizing this device in the management of nonmelanomatous skin cancers. Target doses ranged from 10 Gray in one fraction to 30 Gray in three weekly fractions. Thirty-eight lesions in 18 patients were treated. The overall completed response rate for all histologies at 12 months was 83%. No significant acute or late morbidity was encountered. Our results to date demonstrate that low-energy x-rays produced by the PRS were as effective in managing nonmelanomatous skin tumors as other radiation treatment modalities without the need for cumbersome shielding or radiation precautions.