Adaptive Staged-Dose Gamma Knife Radiosurgery for the Treatment of Large Brain Metastases: Report of 40 Consecutive Cases and Analysis of Literature.

Background: Brain metastases are the most common brain tumors, being one of the most frequent neurological complications of systemic cancer and an important cause of morbidity and mortality. Stereotactic radiosurgery is efficacious and safe in the treatment of brain metastases, with good local control rates and low adverse effects rate. Large brain metastases present some issues in balancing local control and treatment-related toxicity. Objective: Demonstrating adaptive staged-dose Gamma Knife radiosurgery (ASD-GKRS) being a safe and effective treatment for large brain metastases. Materials and Methods: We retrospectively analyzed our series of patients treated with two-stage Gamma Knife radiosurgery for large brain metastases in [BLINDED], between February 2018 and May 2020. Results: Forty patients with large brain metastases underwent adaptive staged-dose Gamma Knife radiosurgery, with median prescription dose of 12 Gy and a median interval between stages of 30 days. At three-month follow-up, the survival rate was 75.0% with a local control rate of 100%. At six-month follow-up, the survival rate was 75.0% with a local control rate of 96.7%. The mean volume reduction was 21.81 cm3 (16.76-26.86; 95% CI). The difference between baseline volume and six-month follow-up volume was statistically significant. Conclusions: Adaptive staged-dose Gamma Knife radiosurgery is a safe, non-invasive and effective treatment for brain metastases, with a low rate of side effects. Large prospective trials are needed to strengthen data obtained about the effectiveness and safety of this technique in managing large brain metastases.

Stereotactic Radiosurgery with Gamma Knife in Recurrent Rathke's Cleft Cyst: Case Report and Literature Analysis.

Background: Rathke's cleft cyst is a benign expansive lesion of the sella turcica. If related to clinical disorders, the patient needs surgical treatment. Objective: To demonstrate the efficacy of radiosurgery in the treatment of relapse of Rathke's cleft cyst as an alternative to surgery. Methods and Material: The stereotactic radiosurgical treatment was performed at the Gamma Knife Center of the Niguarda Hospital in a patient with Rathke's cleft cyst subjected to two subsequent neurosurgical resections with early regrowth of the cyst. The cyst underwent radiosurgery with a prescription dose of 12 Gy at 50% (minimum dose 9.8, mean 17.3 and maximum 24.4). Results: Three years after stereotactic radiosurgical treatment the patient is asymptomatic and does not present disorders of the hypothalamic-pituitary axis or further visual alterations. The control MRI shows a reduction of the cyst's volume. Conclusions: Stereotactic radiosurgery resulted in a reduction of the cyst's volume and avoided further recourse to surgery.

Gamma Knife Radiosurgery for Treatment of Brain Metastases during the COVID-19 Outbreak.

INTRODUCTION: The WHO declared 2019 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) a public health emergency of international concern. The National and Regional Health System has been reorganized, and many oncological patients died during this period or had to interrupt their therapies. This study summarizes a single-centre experience, during the COVID-19 period in Italy, in the treatment of brain metastases with Gamma Knife stereotactic radiosurgery (GKRS). METHODS: We retrospectively analysed our series of patients with brain metastases who underwent GKRS at the Niguarda Hospital from February 24 to April 24, 2020. RESULTS: We treated 30 patients with 66 brain metastases. A total of 22 patients came from home and 8 patients were admitted to the emergency room for urgent neurological symptoms. Duration of stay was limited to 0-1 day in 17 patients. We chose to treat a cluster of 9 patients, whose greater lesion exceeded 10 cm3, with 2-stage modality GKRS to minimize tumour recurrence and radiation necrosis. CONCLUSION: Due to the COVID-19 pandemic, the whole world is at a critical crossroads about the use of health care resources. During the COVID-19 outbreak, the deferral of diagnostic and therapeutic procedures and a work backlog in every medical specialty are the natural consequences of reservation of resources for COVID-19 patients. GKRS improved symptoms and reduced the need for open surgeries, allowing many patients to continue their therapeutic path and sparing beds in ICUs. Neurosurgeons have to take into account the availability of stereotactic radiosurgery to reduce hospital stay, conciliating safety for patients and operators with the request for health care coming from the oncological patients and their families.

Radiotherapy for oligometastatic cancer: a survey among radiation oncologists of Lombardy (AIRO-Lombardy), Italy.

AIMS: To evaluate the use of radiotherapy (RT) for oligometastatic cancer (OMC) among radiation oncologists in Lombardy, Italy. METHODS AND STUDY DESIGN: A survey with 12 items regarding data of 2016 was sent to all 34 Lombardy RT centers. The survey included six general items and six specific items regarding patient/disease/treatment characteristics. RESULTS: Thirteen centers answered the survey (38%). All centers responded to general items and 12 centers submitted patient/disease/treatment data. General items The majority of centers (8/13) consider OMC if metastases number is less than 5. The most commonly prescribed dose/fraction is 5-10 Gy (8/13) using schedules of 3-5 fractions (11/13). Patient data items A total of 15.681 patients were treated in 2016 with external beam RT in 12 responding centers, and 1.087 patients were treated for OMC (7%). Primary tumor included lung, prostate, breast, colorectal and other malignancies in 33%, 21%, 12%, 9% and 25% of all OMC patients, respectively. Brain, lymph node, lung, bone, liver and others were the most common treated sites (24%, 24%, 22%, 17%, 8% and 5%, respectively). One and more than one metastasis were treated in 75 and 25% of patients, respectively. The vast majority of patients (95%) were treated with image-guided intensity-modulated RT or stereotactic RT. CONCLUSIONS: Seven percent of all RT patients in Lombardy are treated for OMC. Extreme hypofractionation and high-precision RT are commonly employed. The initiative of multicenter and multidisciplinary collaboration has been undertaken in order to prepare the platform for prospective and/or observational studies in OMC.

Pattern of care and outcome in elderly patients with glioblastoma: Data in 151 patients from 3 Lombardia Hospitals.

The appropriate treatment approach for elderly patients with glioblastoma multiforme (GBM) is unclear, although different studies suggest survival benefit in fit patients treated with radiotherapy and chemiotherapy after surgery. We performed a retrospective analysis of 151 patients older than 65years with GBM treated in 3 Lombardia Hospitals. In univariate regression analysis higher KPS (p=0.02), macroscopical total resection (p<0.003), radiotherapy (p<0.0001), chemotherapy (p<0.0001) and second line chemotheraphy (p=0.02) were of positive prognostic value. On the contrary older age (>70years), presence of seizure at onset and additional resection after tumor recurrence did not influence OS. Multivariate analysis revealed radiotherapy (HR 0.2 p<0.0001) and extent of surgery (HR 0.3, p=0,0063) as positive independent prognostic factors. Patients receiving radio-chemiotherapy displayed more treatment-related toxicities with a slightly prolonged OS versus those receiving hypofractionated radiotherapy. With the limits of a retrospective study, our data suggest that in elderly fit patients extensive surgery should be considered, moreover adjuvant treatments led to an increase in OS. Randomized controlled study are needed to develop treatment guidelines for elderly GBM patients and to assess whether the combination of post-surgical radio and chemiotherapy may be superior to hypofractionated radiotherapy and chemiotherapy in fit patients.

Impact of radiotherapy technique on the outcome of early breast cancer treated with conservative surgery: A multicenter observational study on 1,176 patients.

PURPOSE: To quantify the impact of radiotherapy technique on cosmetic outcome and on 5-year local control rate of early breast cancer treated with conservative surgery and adjuvant radiation. METHODS AND MATERIALS: A total of 1,176 patients irradiated to the breast in 1997 were entered by eight centers into a prospective, observational study. Surgical procedure was quadrantectomy in 97% of patients, with axillary dissection performed in 96%; pT-stage was T1 in 81% and T2 in 19% of cases; pN-stage was N0 in 71%, N + (1-3) in 21%, and N + (>3) in 8% of cases. An immobilization device was used in 17% of patients; external contour-based and computed tomography-based treatment planning were performed in 20% and 72% of cases, respectively; 37% of patients were treated with a telecobalt unit and 63% with a linear accelerator; portal verification was used in 55% of patients; a boost dose to the tumor bed was delivered in 60% of cases. RESULTS: With a median follow-up of 6.2 years, local, regional, and distant control rates at 5 years are 98%, 99%, and 92%, respectively. Use of less sophisticated treatment technique was associated with a less favorable cosmetic outcome. Local control was comparable between centers despite substantial technical differences. In a multivariate analysis including clinical and technical factors, only older age and prescription of medical adjuvant treatment significantly predicted for better local control, whereas use of portal verification was of borderline significance. CONCLUSIONS: Radiation technical factors impacted negatively on cosmetic outcome, but had relatively small effects on local control compared with other clinical factors.

Are international guidelines for the prescription of adjuvant treatment for early breast cancer followed in clinical practice? Results of a population-based study on 1547 patients.

AIMS AND BACKGROUND: The results of several randomized trials and meta-analyses have been reported on adjuvant treatment for early breast cancer and treatment guidelines have been defined accordingly, but detailed data are lacking on the appropriateness of treatment prescription in clinical practice. METHODS: We performed a prospective, observational, multicenter study to monitor the prescription, delivery and effectiveness of radiotherapy following conservative surgery for early breast cancer; 1610 patients treated with postoperative radiation to the breast in 1997 were entered by 12 centers in Lombardy, Italy. Here we report the results of a secondary analysis focused on the prescription of medical adjuvant treatment (1547 eligible patients). RESULTS: Chemotherapy only was prescribed to 526 patients (33%), hormonal therapy only to 539 (33%), and both treatments to 85 patients (5%); 460 women (29%) received no medical adjuvant treatment. We compared the collected data with guidelines defined in 1995 by the St Gallen Consensus Conference. Undertreatment was most frequent in node-negative patients at intermediate/high risk, no treatment (instead of tamoxifen or chemotherapy) being prescribed in 21-45% of cases. Node-negative patients at low risk, on the other hand, were overtreated with tamoxifen in 31% of cases. In node-positive, premenopausal women compliance with guidelines was far better, with a 91-96% rate of chemotherapy prescription. In node-positive, postmenopausal, estrogen receptor-positive patients chemotherapy was unduly prescribed in as many as 56% of cases. Comparison of clinical practice with the next version of the guidelines (1998) showed a somewhat better compliance. CONCLUSIONS: Despite the availability of official and authoritative guidelines, adjuvant treatment prescription for early breast cancer in Lombardy in 1997 was suboptimal, especially in well-defined subgroups of patients.