Radiosurgery for Five to Fifteen Brain Metastases: A Single Centre Experience and a Review of the Literature.

Purpose: Stereotactic radiosurgery (SRS) is now mainstream for patients with 1-4 brain metastases however the management of patients with 5 or more brain metastases remains controversial. Our aim was to evaluate the clinical outcomes of patients with 5 or more brain metastases and to compare with published series as a benchmarking exercise. Methods: Patients with 5 or more brain metastases treated with a single isocentre dynamic conformal arc technique on a radiosurgery linac were identified from the institutional database. Endpoints were local control, distant brain failure, leptomeningeal disease and overall survival. Dosimetric data were extracted from the radiosurgery plans. Series reporting outcomes following SRS for multiple brain metastases were identified by a literature search. Results: 36 patients, of whom 35 could be evaluated, received SRS for 5 or more brain metastases between February 2015 and October 2021. 25 patients had 5-9 brain metastases (group 1) and 10 patients had 10-15 brain metastases (group 2). The mean number of brain metastases in group 1 was 6.3 (5-9) and 12.3 (10-15) in group 2. The median cumulative irradiated volume was 4.6 cm3 (1.25-11.01) in group 1 and 7.2 cm3 (2.6-11.1) in group 2. Median follow-up was 12 months. At last follow-up, local control rates per BM were 100% and 99.8% as compared with a median of 87% at 1 year in published series. Distant brain failure was 36% and 50% at a median interval of 5.2 months and 7.4 months after SRS in groups 1 and 2 respectively and brain metastasis velocity at 1 year was similar in both groups (9.7 and 11). 8/25 patients received further SRS and 7/35 patients received whole brain radiotherapy. Median overall survival was 10 months in group 1 and 15.7 months in group 2, which compares well with the 7.5 months derived from the literature. There was one neurological death in group 2, leptomeningeal disease was rare (2/35) and there were no cases of radionecrosis. Conclusion: With careful patient selection, overall survival following SRS for multiple brain metastases is determined by the course of the extracranial disease. SRS is an efficacious and safe modality that can achieve intracranial disease control and should be offered to patients with 5 or more brain metastases and a constellation of good prognostic factors.

Successful salvage of recurrent leptomeningeal disease in large cell neuroendocrine lung cancer with stereotactic radiotherapy.

A 70-year old male with stage I large cell neuroendocrine carcinoma (LCNEC) of the lung underwent resection of a metachronous 5 cm brain metastasis and received postoperative hypofractionated stereotactic radiotherapy (hfSRT). Five sequential nodular leptomeningeal metastases up to 5.3 cm in diameter were diagnosed on MRI within 10 months and were treated with SRT. Currently the patient has no evidence of intracranial disease 24 months after last irradiation without chemotherapy or whole brain radiotherapy. This is the first report of sustained complete remission of multiple large leptomeningeal metastases achieved with hfSRT, highlighting this brain-sparing approach in selected patients with LCNEC lung cancer.

Early results and volumetric analysis after spot-scanning proton therapy with concomitant hyperthermia in large inoperable sacral chordomas.

OBJECTIVE: Large inoperable sacral chordomas show unsatisfactory local control rates even when treated with high dose proton therapy (PT). The aim of this study is assessing feasibility and reporting early results of patients treated with PT and concomitant hyperthermia (HT). METHODS:: Patients had histologically proven unresectable sacral chordomas and received 70 Gy (relative biological effectiveness) in 2.5 Gy fractions with concomitant weekly HT. Toxicity was assessed according to CTCAE_v4. A volumetric tumor response analysis was performed. RESULTS:: Five patients were treated with the combined approach. Median baseline tumor volume was 735 cc (range, 369-1142). All patients completed PT and received a median of 5 HT sessions (range, 2-6). Median follow-up was 18 months (range, 9-26). The volumetric analysis showed an objective response of all tumors (median shrinkage 46%; range, 9-72). All patients experienced acute Grade 2-3 local pain. One patient presented with a late Grade 3 iliac fracture. CONCLUSION: Combining PT and HT in large inoperable sacral chordomas is feasible and causes acceptable toxicity. Volumetric analysis shows promising early results, warranting confirmation in the framework of a prospective trial. ADVANCES IN KNOWLEDGE:: This is an encouraging first report of the feasibility and early results of concomitant HT and PT in treating inoperable sacral chordoma.

Quality assurance guidelines for superficial hyperthermia clinical trials: I. Clinical requirements.

Quality assurance guidelines are essential to provide uniform execution of clinical trials and treatment in the application of hyperthermia. This document provides definitions for a good hyperthermia treatment and identifies the clinical conditions where a certain hyperthermia system can or cannot adequately heat the tumour volume. It also provides brief description of the characteristics and performance of the current electromagnetic (radiative and capacitive), ultrasound and infra-red heating techniques. This information helps to select the appropriate heating technique for the specific tumour location and size, and appropriate settings of the water bolus and thermometry. Finally, requirements of staff training and documentation are provided. The guidelines in this document focus on the clinical application and are complemented with a second, more technical quality assurance document providing instructions and procedure to determine essential parameters that describe heating properties of the applicator for superficial hyperthermia. Both sets of guidelines were developed by the ESHO Technical Committee with participation of senior STM members and members of the Atzelsberg Circle.

Hyperthermia and reirradiation for locoregional recurrences in preirradiated breast cancers: a single institutional experience.

QUESTIONS UNDER STUDY: The aim of this retrospective analysis was to evaluate the safety and efficacy of local hyperthermia (HT) and reirradiation (ReRT) in the management of preirradiated locoregional recurrent breast cancers at Kantonsspital Aarau, Switzerland. METHODS: Twenty-four previously irradiated patients who had developed locoregional recurrences in the chest wall or breast, with or without regional lymph node involvement, were reirradiated to a mean dose of 36.8 Gy (range 20-50 Gy) delivered at a mean dose per fraction of 2.33 Gy (range 1.8-4.0 Gy). All patients received local HT at 41 to 43 °C, once or twice a week prior to radiotherapy. Online thermometry was carried out during the hyperthermia sessions. RESULTS: An overall objective response rate of 91.7% (22/24) with a complete response in 66.7% (16/24) of patients and partial response in 25% (6/24) of patients was observed. Post-thermoradiotherapy follow-up ranged from 1 to 38 months (median 10 months). The 3-year actuarial local control rate was 59.7%. More patients who attained complete response had sustained locoregional control until their death or last follow-up when compared with those who were partial or non-responders (median local disease-free survival for complete responders not reached; for partial and non-responders 4 months; p <0.001). Post-retreatment median overall survival for all 24 patients was 10 months. Grade III/IV acute toxicity was seen in only one patient and no patient had any significant late morbidity. CONCLUSIONS: ReRT and HT is an effective and a safe modality to treat locoregional recurrences in previously irradiated breast cancers. The approach can lead to sustainable long-term palliation with minimal morbidity.

Quality assurance for clinical studies in regional deep hyperthermia.

BACKGROUND: A guideline is provided for the implementation of regional deep hyperthermia treatments under strict rules of quality assurance. The objective is to guarantee a comparable and comprehensible method in the treatment and scientific analysis of hyperthermia. The guideline describes regional deep hyperthermia (RHT) and MR-controlled partial body hyperthermia (PBH) of children, young and adult patients. According to this guideline, hyperthermia treatment is always applied in combination with chemotherapy and/or radiotherapy. METHODS: The guideline is based on practical experience from several hyperthermia centers. The procedure allows applying jointly coordinated standards and quality control in hyperthermia for studies. RESULTS: The guideline contains recommendations for hyperthermia treatments, including indication, preparation, treatment, and standardized analysis.

Gamma Knife surgery after fractionated radiotherapy for acromegaly.

OBJECT: Acromegaly that has not been cured by microsurgery is usually treated with fractionated radiotherapy; however, it is not possible to repeat such a treatment with effective radiation doses if it should fail. The authors pose the question: Can stereotactic radiosurgery be used as an effective, alternative method for retreatment by irradiation? METHODS: A retrospective study of 12 patients was performed to compare patients treated with Gamma Knife surgery (GKS) after initial, failed radiotherapy and 37 patients treated with GKS only. The mean dose for the initial fractionated radiotherapy was 44.6 Gy (range 40-54 Gy). The mean maximum GKS dose was 45.1 Gy (range 27-50 Gy) in the pretreated group and 49.5 Gy (range 25-70 Gy) in the group undergoing GKS alone. The mean interval between the two treatments was 10.6 years (range 3-20.6 years). The age-related insulin-like growth factor-I (IGF-I), assessed at 3-month intervals, was the main follow-up parameter. An IGF-I normalization rate of more than 80% was achieved in both patient groups; however, the latency of endocrinological normalization was longer in the patients who had undergone failed fractionated radiotherapy (median time to cure 35.4 months compared with 13.5 months). CONCLUSIONS: Treatment with GKS is successful in patients with acromegaly even after failed fractionated radiotherapy; GKS represents a therapeutic tool in patients with no therapeutic options life-long octreotide. It must be noted that the incidence of neurological complications is higher (p < 0.01, 2 x 2 crosstab). The remaining dose fraction after previous fractionated radiotherapy appears to be approximately 50%. Maintenance of other endocrinological functions may be better after GKS alone; however, the difference is not significant.

Quantifying the degree of conformity in radiosurgery treatment planning.

PURPOSE: To compare different parameters used to quantify the quality of a treatment plan and to evaluate the dose conformity and coverage clinically achieved using gamma knife radiosurgery. METHODS AND MATERIALS: Various existing parameters for coverage and conformity are reviewed. Additionally, a modified conformity index (CI) has been defined as the ratio of the volume within the target irradiated to at least the prescription isodose over the total volume enclosed by the prescription isodose. These parameters are calculated for all the 551 evaluable patient treatment plans. RESULTS: The median CI for all targets is 0.75, with a median target coverage of 94.6%. Regardless of the conformity parameter chosen, the conformity is seen to vary depending on the type of tumor and its location, reflecting the treatment planning philosophy. For tumors with volumes smaller than about 1 cm(3), the conformity parameter is also seen to be dependent on the target volume. CONCLUSION: With gamma knife radiosurgery, it is possible to achieve highly conformal dose distributions. A single parameter for the quantification of a plan, though desirable, is not realistic, because of the competing components of high dose to the target and low dose to normal tissue. Thus, we propose the use of the CI, together with the target volume coverage.