Quality of life and sexual functioning among endometrial cancer patients treated with one week adjuvant high-dose-rate vaginal brachytherapy schedule.

Purpose: To examine quality of life (QOL) and sexual functioning in a series of patients with intermediate- and high-intermediate risk endometrial cancer, treated with exclusive adjuvant one week high-dose-rate (HDR) vaginal brachytherapy (VBT) schedule. Material and methods: Between July 2008 and October 2013, 55 patients with diagnosis of endometrial cancer were treated with adjuvant exclusive VBT. All patients had undergone surgical treatment with a laparotomy approach before VBT. Post-operative VBT was administered 6-8 weeks after surgery. Treatment was delivered to vaginal vault using Nucletron HDR unit with iridium-192 source at a dose of 21 Gy/3 fractions of 7 Gy each, three times a week, every other day, prescribed at 0.5 cm depth of vaginal wall, and 3 cm in length from the apex. QOL was assessed using European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire Core-30 (QLQ-C30), and EORTC cancer-specific quality of life questionnaire (QLQ-CX24). Results: Median follow-up time was 92 months (range, 42-162 months). Questionnaires were carried out respectively at 1, 3, 6, 12, 24, 36, 48, and 60 months after the end of BT. Response rate to questionnaires was 100% (n = 55). Nineteen patients (35%) answered all the questions of surveys, while 36 patients (65%) completed the surveys, except for questions on sex activity, vaginal function, and sex enjoyment. Longitudinal analysis during 5-year follow-up period showed a statistically significant trend towards worsening of fatigue, constipation, and diarrhea. Overall physical functioning and role functioning was not impaired after VBT. Over the time, sex enjoyment improved, except for elderly patients. For emotional functioning, sex worry and social functioning presented no significant time-related effect. Conclusions: One week brachytherapy schedule to vaginal cuff is generally well-tolerated. QOL does not worsen after applying vaginal brachytherapy.

Adjuvant chemotherapy after severe myelotoxicity during chemoradiation phase in malignant gliomas. Is it feasibile? Results from AINO study (Italian Association for Neuro-Oncology).

BACKGROUND: Malignant gliomas (MG) are aggressive brain tumours in adults. The standard of care is concurrent radiation plus temozolomide (TMZ) [chemo-radiotherapy (CRT)] followed by TMZ maintenance up to 6 months. TMZ is considered to have a low toxicity profile, but several studies reported occurrence of severe myelosuppression, especially during the concomitant phase. Toxicity may be prolonged, thus treatment should be discontinued. PURPOSE: To evaluate the risk of recurrente myelotoxicity during adjuvant chemotherapy (CT) in patients who recovered from severe myelotoxicity during CRT. METHODS: We retrospectively collected data on patients with MG who developed and recovered from severe myelotoxicity during CRT from eight Italian neuro-oncology centers. RESULTS: We included 87 patients. Histology was Glioblastoma (GBM) in 78 patients (89.7%); 60% of patients were female. After myelotoxicity recovery, 54 (62%) received treatment. The majority of them (82%, n = 44) received adjuvant TMZ and 18% (n = 10) others treatments. Out of 44 patients who received adjuvant TMZ, 34% experienced the re-occurrence of grade 3-4 myelotoxicity which required permanent CT discontinuation in 6 (13%) cases. Patients who received TMZ or other treatments had longer overall (OS) (adjusted HR 0.46, p = 0.008) and progression free survival (PFS) (adjusted HR 0.57, p = 0.034) than those who remained untreated. CONCLUSION: Our study suggests that after severe myelotoxicity the majority of patients received treatment, particularly with TMZ. Only a fraction of patients experienced toxicity recurrence, suggesting that TMZ is well tolerated and had an impact on PFS and OS.

Long-term metabolic evolution of brain metastases with suspected radiation necrosis following stereotactic radiosurgery: longitudinal assessment by F-DOPA PET.

BACKGROUND: The evolution of radiation necrosis (RN) varies depending on the combination of radionecrotic tissue and active tumor cells. In this study, we characterized the long-term metabolic evolution of RN by sequential PET/CT imaging with 3,4-dihydroxy-6-[18F]-fluoro-l-phenylalanine (F-DOPA) in patients with brain metastases following stereotactic radiosurgery (SRS). METHODS: Thirty consecutive patients with 34 suspected radionecrotic brain metastases following SRS repeated F-DOPA PET/CT every 6 months or yearly in addition to standard MRI monitoring. Diagnoses of local progression (LP) or RN were confirmed histologically or by clinical follow-up. Semi-quantitative parameters of F-DOPA uptake were extracted at different time points, and their diagnostic performances were compared with those of corresponding contrast-enhanced MRI. RESULTS: Ninety-nine F-DOPA PET scans were acquired over a median period of 18 (range: 12-66) months. Median follow-up from the baseline F-DOPA PET/CT was 48 (range 21-95) months. Overall, 24 (70.6%) and 10 (29.4%) lesions were classified as RN and LP, respectively. LP occurred after a median of 18 (range: 12-30) months from baseline PET. F-DOPA tumor-to-brain ratio (TBR) and relative standardized uptake value (rSUV) increased significantly over time in LP lesions, while remaining stable in RN lesions. The parameter showing the best diagnostic performance was rSUV (accuracy = 94.1% for the optimal threshold of 1.92). In contrast, variations of the longest tumor dimension measured on contrast-enhancing MRI did not distinguish between RN and LP. CONCLUSION: F-DOPA PET has a high diagnostic accuracy for assessing the long-term evolution of brain metastases following SRS.

Initial Experience With Single-Isocenter Radiosurgery to Target Multiple Brain Metastases Using an Automated Treatment Planning Software: Clinical Outcomes and Optimal Target Volume Margins Strategy.

PURPOSE: Our purpose was to assess the clinical outcomes and target positioning accuracy of frameless linear accelerator single-isocenter multiple-target (SIMT) dynamic conformal arc (DCA) stereotactic radiosurgery (SRS) for multiple brain metastases (BM). METHODS AND MATERIALS: Between October 2016 and September 2018, 31 consecutive patients ≥18 years old with 204 BM <3 cm in maximum size receiving SIMT DCA SRS were retrospectively evaluated. All plans were created using a dedicated automated treatment planning software (Brainlab, Munich, Germany), and treatments were performed with a Truebeam STx or a Novalis Tx (Brainlab and Varian Medical Systems, CA). The accuracy of setup and interfraction patient repositioning was assessed by Brainlab ExacTrac radiograph 6-dimensional image system and the risk of compromised target dose coverage evaluated. Brain control and overall survival were estimated by Kaplan-Meier method calculated from the time of SRS. RESULTS: Fourteen patients were treated for 4 to 6 and 17 patients for 7 to 10 BM. The mean gross tumor volume (GTV) was 0.65 cm3 and the mean planning target volume (PTV) was 0.89 cm3. Mean V95 (the volume of the PTV covered by 95% of the prescription dose) and D95 (the prescription dose covering 95% of the PTV) were 99.5% and 21.1 Gy, respectively. With a median clinical follow-up of 11 months (range, 4-26 months), the 1-year survival was 68% and local control was 89%. As a consequence of plan isocenter residual errors, a loss of target coverage, defined as V95 < 95%, occurred in 28 PTVs (10 patients); using a 1 mm GTV-to-PTV margin, adequate dose coverage was maintained for all lesions. CONCLUSIONS: SIMT DCA SRS represents a fast and effective approach for patients with up to 10 BM. The dosimetric effects of residual set-up and intrafraction positioning errors are modest, although a GTV-to-PTV margin of 1 mm is recommended.

Stereotactic reirradiation with temozolomide in patients with recurrent aggressive pituitary tumors and pituitary carcinomas.

OBJECTIVES: To evaluate the efficacy of a second course of fractionated stereotactic radiotherapy (re-SRT) and temozolomide (TMZ) as salvage treatment option in patients with aggressive pituitary tumors (APTs) and pituitary carcinomas (PCs). PATIENTS AND METHODS: Twenty-one patients with recurrent or progressive APTs (n = 17) and PCs (n = 4) who received combined TMZ and re-SRT, 36 Gy/18fractions or 37.5 Gy/15fractions, were retrospectively evaluated. TMZ was given at a dose of 75 mg/m2 given concurrently to re-SRT, and then 150-200 mg/m2/day for 5 days every 4 weeks or 50 mg/m2 daily for 12 months. Local control (LC) and overall survival (OS) were calculated from the time of re-SRT by Kaplan-Meier method. RESULTS: With a median follow-up of 27 months (range 12-58 months), 2-year and 4-year LC rates were 73% and 65%, respectively; 2-year and 4-year survival rates were 82% and 66%, respectively. A complete response was achieved in 2 and partial response in 11 patients. Six patients recurred with a median time to progression of 14 months. O(6)-Methylguanine-DNA methyltransferase (MGMT) status and tumor volume emerged as prognostic factors. Grade 3 radiation-related toxicities occurred in 3 (14%) patients. Grade 2 or 3 hematologic toxicities during chemotherapy occurred in 8 (38%) patients. CONCLUSION: Re-SRT and TMZ is a safe treatment offering high LC in patients with progressive APTs and PCs. The potential advantages of combined chemoradiation as up-front or salvage treatment need to be explored in prospective trials.

Metabolic Evolution of Brain Metastasis After Stereotactic Radiosurgery: Mismatch Between F-DOPA and FDG PET.

The differentiation between radiation-induced changes and tumor recurrence is a major pitfall of magnetic resonance imaging, which can be overcome by the use of PET. Although amino-acid PET tracers showed several advantages over F-fluorodeoxyglucose in neurooncology, studies comparing these 2 types of radiopharmaceuticals in previously irradiated brain metastases are lacking. Here, we demonstrated a mismatch between 3,4-dihydroxy-6-[F]-fluoro-L-phenylalanine (F-DOPA) and FDG in the first report of a previously irradiated brain metastasis undergoing a longitudinal evaluation by sequential double tracer PET imaging.

Neurological outcome and memory performance in patients with 10 or more brain metastases treated with frameless linear accelerator (LINAC)-based stereotactic radiosurgery.

PURPOSE: To assess the neurocognitive function and neurological toxicity of frameless linear accelerator (LINAC)-based stereotactic radiosurgery (SRS) in patients with 10 or more brain metastases (BM). PATIENTS AND METHODS: Forty consecutive adult patients who received SRS for ten or more 10 BM < 3 cm in maximum size were evaluated. All plans were generated using a single-isocenter multiple-target (SIMT) SRS technique with doses of 22 Gy for lesions < 2 cm and 16-18 Gy for those ≥ 2 cm in size. Survival analyses were estimated by Kaplan-Meier method from the date of SRS. Neurocognitive function using the Hopkins verbal learning test-revised (HVLT-R) and activity of daily living scale (ADLS) were collected prospectively at baseline and at 3,6 and 12-month follow-up. Toxicity was assessed by the National Cancer Institute Common Toxicity Criteria for Adverse Events (Version 5.0). RESULTS: With a median follow-up of 10.8 months, 1-year survival and local control rates were 65% and 86%, respectively. Grade 2 or 3 toxicity occurred in eleven patients, being associated with radiological changes suggestive of radiation necrosis in seven patients. Three months after SRS, the mean relative decline was 14.2% for HVLT-R delayed recall, 12.3% for HVLT-R recognition, and 9.8% for HVLT-R total recall. A significant deterioration of HVLT-R scores ranged from 5.5 to 18.7% of patients at different time points. ADLS scores declined over time, but changes were not significant. CONCLUSIONS: SRS is an effective and safe approach for patients with 10 or more BM able to maintain the pretreatment neurocognitive function in the majority of patients.

Comparative effectiveness of multi-fraction stereotactic radiosurgery for surgically resected or intact large brain metastases from non-small-cell lung cancer (NSCLC).

PURPOSE: to investigate clinical outcomes in patients with large brain metastases from non-small-cell lung cancer (NSCLC) who received surgical resection and postoperative stereotactic radiosurgery or SRS alone. PATIENTS AND METHODS: Two hundred and twenty-two patients with 241 large brain metastases (2-4 cm in size) who received surgery and multi-fraction SRS (mfSRS) to the resection cavity or mfSRS alone were analyzed. For all lesions the delivered dose was 3 x 9 Gy over three consecutive days. Primary endpoint of the study was local control (LC). Secondary endpoints included early improvement of neurological deficits, changes in performance status, treatment-related toxicity, radiation-induced brain necrosis (RN), distant brain failure (DBF), and overall survival (OS). Kaplan-Meier analysis and cumulative incidence function were used for comparing the probability of failure. RESULTS: At a median follow-up of 13 months, median OS times and 1-year survival rates were comparable: 13.5 months and 59% for patients receiving surgery and postoperative mfSRS to the resection cavity and 15.2 months and 68% for those treated with mfSRS alone (p = 0.2). Median DBF did not differ significantly between groups (surgery and mfSRS,12 months; mfSRS,14 months). Eighteen patients receiving surgery and mfSRS and 17 patients treated with mfSRS alone recurred locally (p = 0.2); respective 6-month and 12-month LC rates were 87% and 83% and 96% and 91% (p = 0.15). The 1-year cumulative incidence rates of RN were 15% and 7% after postoperative mfSRS and mfSRS alone (p = 0.03), respectively. CONCLUSIONS: In conclusion, mfSRS is an effective treatment for patients with large brain metastases from NSCLC resulting in equivalent LC and lower RN and risk of leptomeningeal spread compared to surgery and mf-SRS to the resection cavity. Surgery is an effective treatment option for patients with large symptomatic brain metastases who require rapid relief of neurological symptoms caused by tumor mass effect.

18F-DOPA uptake does not correlate with IDH mutation status and 1p/19q co-deletion in glioma.

OBJECTIVE: The role of amino acid positron emission tomography (PET) in glioma grading and outcome prognostication has not yet been well established. This is particularly true in the context of the new WHO 2016 classification, which introduced a definition of glioma subtypes primarily based on molecular fingerprints. The aim of the present study was to correlate 3,4­dihydroxy­6­[18F]­fluoro-L­phenylalanine (F-DOPA) uptake parameters with IDH mutation, 1p/19q status, and survival outcomes in patients with glioma. METHODS: The study population consisted of 33 patients (17 M/16 F, mean age: 46 ± 13 years) who underwent F-DOPA PET/CT for the evaluation of tumor extent before the start of chemo or radiotherapy. The presence of IDH mutation and 1p/19q status was assessed in all the cases. Tumor volume and semiquantitative uptake parameters, namely SUVmax, tumor-to-normal brain ratio and tumor-to-normal striatum ratio, were calculated for each tumor. Imaging-derived parameters were compared between patients stratified according to molecular fingerprints, using parametric or non-parametric tests, where appropriate. The Kaplan-Meier method was used to assess differences of overall survival (OS) and progression-free survival (PFS) between groups. PET parameters were also tested as prognostic factors in univariate Cox survival regression models. RESULTS: There were 12 IDH-wild-type and 21 IDH-mutant patients. Stratification according to 1p/19q co-deletion resulted in 20 non-co-deleted and 13 co-deleted patients. Median follow-up time from PET/CT exam was 30.5 months (range 3.5-74 months). Semiquantitative uptake parameters did correlate neither with IDH mutation nor with 1p/19q status. Uptake was similar in low-grade and high-grade tumors, respectively. In addition, F-DOPA uptake parameters, macroscopic tumor volume, or tumor grade did not stratify OS, while a correlation between SUVmax and PFS was shown in the subgroup of astrocytomas. On the other hand, IDH mutation status and presence of 1p/19q co-deletion had a significant impact on survival outcomes. The prognostic value of IDH mutation status was also confirmed in the subgroup of patients with astrocytic tumors. CONCLUSIONS: F-DOPA uptake parameters do not correlate with tumor molecular and histological characteristics. The predictive value of PET-derived parameters on outcomes of survival is limited.

Technical Advances in Radiation Therapy for Brain Tumors.

Radiation therapy plays a critical role in the management of brain tumors. Recent advances in radiation techniques include the use of intensity-modulated radiotherapy (IMRT), volumetric-modulated arc therapy (VMAT) and stereotactic radiosurgery (SRS). All of these techniques allow the delivery of higher radiation doses to the target volume, at the same time reducing the risk of toxicity to normal tissues as compared with conventional 3D conformal radiotherapy (3D-CRT). Proton therapy may represent a treatment alternative to photon irradiation, due to the more favorable dose distribution to the target volume. This review summarizes current developments in radiation therapy and their clinical impact on the management of patients with brain tumors.

18F-DOPA uptake parameters in glioma: effects of patients' characteristics and prior treatment history.

OBJECTIVE: In amino acid positron emission tomography brain tumour imaging, tumour-to-background uptake parameters are often used for treatment monitoring. We studied the effects of patients' characteristics and anticancer treatments on 18F-fluoro-l-phenylalanine uptake of normal brain and tumour lesions, with particular emphasis on temozolomide (TMZ) chemotherapy. METHODS: 155 studies from 120 patients with glioma were analysed. Average uptake of normal background (standardized uptake value, SUVbckgr) and basal ganglia (SUVbg), as well as tumour-to-brain ratios (TBR) were compared between positron emission tomography/CT studies acquired before (Group A, n = 48), after (Group B, n = 50) or during (Group C, n = 57) TMZ treatment, using analysis of variance. RESULTS: Overall, mean SUVbckgr and mean SUVbg were 1.06 ± 0.26 and 2.12 ± 0.47, respectively. Female had significantly higher SUVbckgr (p = 0.002) and SUVbg (p = 0.012) than male patients. Age showed a positive correlation with SUVbg (p = 0.001). In the overall cohort, there were significant effects of TMZ on SUVbckgr (p = 0.0237) and TBR (p = 0.0138). In particular, SUVbckgr was lower in Group C than in Group B (1.00 ± 0.25 vs 1.14 ± 0.31, p = 0.0173). Significant variations of SUVbckr could be observed in female only. TBR was significantly higher in Group C than in Group B (2.37 ± 0.54 vs 2.06 ± 0.38, p = 0.010). Variations of SUVbg between groups slightly missed significance (p = 0.0504). CONCLUSION: Temozolomide chemotherapy and patients' characteristics, including gender and age, affect physiological [18F]-fluoro-l-phenylalanine uptake and, consequently, the calculation of TBRs. Advances in knowledge: For the first time, the effects of past or concurrent temozolomide chemotherapy on brain physiological amino acid uptake have been investigated. Such effects are relevant and should be taken into account when evaluating tumour-to-background ratios.

Multiparametric evaluation of low grade gliomas at follow-up: comparison between diffusion and perfusion MR with (18)F-FDOPA PET.

OBJECTIVE: To compare MRI using perfusion and diffusion techniques with 6-[(18)F]-fluoro-L-3,4-dihydroxyphenylalanine ((18)F-FDOPA) positron emission tomography (PET) in the follow-up of low-grade gliomas (LGGs) and to identify the best imaging parameter to differentiate patients with different prognosis. METHODS: Between 2010 and 2015, 12 patients with a pathology-proven diagnosis of LGG and MR (with perfusion and diffusion sequences) and a PET study during their follow-up were retrospectively included in our study. Cerebral blood volume (CBV) and apparent diffusion coefficient (ADC) maps on MR studies and PET images were evaluated using a region of interest-based method. All patients were categorized as stable or as having progressive disease at 1-year follow-up. Statistical analysis was performed using Pearson's correlation test and multivariate analysis of variance (p < 0.05). RESULTS: No significant correlations were found between PET parameters [maximum tumour-to-controlateral normal brain ratio (T/Nmax) and tumour-to-striatum ratio] and ADC or relative CBV values measured in both PET hotspot regions and areas of maximum signal alterations. T/Nmax demonstrated a good sensitivity (83%) and specificity (100%) for differentiating two subgroups of patients with different outcomes at 1-year-follow-up (p < 0.05). CONCLUSION: Perfusion and diffusion MR images provide different information compared with (18)F-FDOPA PET in LGGs during follow-up and therefore, they should be considered as complementary tools in the evaluation of these tumours. (18)F-FDOPA PET showed a significant prognostic role in the follow-up of LGGs and appeared to be a better tool than MR advanced techniques for outcome prediction. These results need to be confirmed with longitudinal studies on a larger population. ADVANCES IN KNOWLEDGE: This is the first study that compared (18)F-FDOPA PET with perfusion and diffusion MR in LGGs during follow-up. These preliminary results highlight the importance of a multimodality approach in this field and evidence a potential role for (18)F-FDOPA PET to predict patients at risk for tumour progression.

(18)F-DOPA Positron Emission Tomography in Medulloblastoma: 2 Case Reports.

BACKGROUND: Medulloblastoma (MDB) is an aggressive embryonal brain tumor, with underlying altered genetics and biological pathways that account for very heterogeneous natural histories and clinical behaviors. Positron emission tomography (PET) using radiolabeled amino acids provides important metabolic information for the diagnosis of cerebral glioma but only a few data are available on amino acid PET in MDB. In particular, no cases of MDB imaging with 6-[(18)F]-fluoro-L-3,4-dihydroxyphenylalanine (F-DOPA) have previously been described. CASE DESCRIPTION: Two patients with different histologic subtypes of MDB were referred for F-DOPA PET to define the extent and metabolic degree of their diseases. The patients had a newly diagnosed large-cell/anaplastic MDB and a fourth relapse of classic MDB, respectively. F-DOPA PET was unremarkable in the first case; F-DOPA uptake was low in the second patient with the tumor/background ratio as high as 1.29. Comparison was made with magnetic resonance imaging, which showed fluid-attenuated inversion recovery positive diseases. Aggressive tumor growth was shown in the clinical course of both patients. CONCLUSIONS: The 2 cases reported here suggest that sensitivity of F-DOPA PET in MDB can be low. However, more comprehensive data are needed to conclude on the overall accuracy of F-DOPA PET in MDB.

Stereotactic radiotherapy and radiosurgery for non-functioning and secreting pituitary adenomas.

Radiotherapy (RT) is frequently employed in patients with residual or recurrent pituitary adenoma with excellent rates of tumor control and remission of hormonal hypersecretion. Advances in RT have improved with the use of stereotactic techniques either as fractionated stereotactic radiotherapy (FSRT) or stereotactic radiosurgery (SRS), all aiming to improve the dose distribution to the tumor while reducing the amount of normal brain receiving significant doses of radiation. We provide an overview of the recent published literature on the long-term efficacy and adverse effects of stereotactic irradiation in nonfunctioning and secreting pituitary adenomas. Both techniques are associated with excellent clinical outcomes; however, advantages and drawbacks of each of these techniques in terms of local control, hormonal excess normalization, and radiation-induced toxicity remain a matter of debate. In clinical practice, single-fraction SRS may represent a convenient approach to patients with small and medium-sized pituitary adenoma away at least 2 mm from the optic chiasm, whereas FSRT is preferred over SRS for lesions >2.5-3 cm in size and/or involving the anterior optic pathway.

Single-Fraction Versus Multifraction (3 × 9 Gy) Stereotactic Radiosurgery for Large (>2 cm) Brain Metastases: A Comparative Analysis of Local Control and Risk of Radiation-Induced Brain Necrosis.

PURPOSE: To investigate the local control and radiation-induced brain necrosis in patients with brain metastases >2 cm in size who received single-fraction or multifraction stereotactic radiosurgery (SRS); factors associated with clinical outcomes and the development of brain radionecrosis were assessed. METHODS AND MATERIALS: Two hundred eighty-nine consecutive patients with brain metastases >2.0 cm who received SRS as primary treatment at Sant'Andrea Hospital, University of Rome Sapienza, Rome, Italy, were analyzed. Cumulative incidence analysis was used to compare local control and radiation-induced brain necrosis between groups from the time of SRS. To achieve a balanced distribution of baseline covariates between treatment groups, a propensity score analysis was used. RESULTS: The 1-year cumulative local control rates were 77% in the single-fraction SRS (SF-SRS) group and 91% in the multifraction SRS (MF-SRS) group (P=.01). Recurrences occurred in 25 and 11 patients who received SF-SRS or MF-SRS (P=.03), respectively. Thirty-one patients (20%) undergoing SF-SRS and 11 (8%) subjected to MF-SRS experienced brain radionecrosis (P=.004); the 1-year cumulative incidence rate of radionecrosis was 18% and 9% (P=.01), respectively. Significant differences between the 2 groups in terms of local control and risk of radionecrosis were maintained after propensity score adjustment. CONCLUSIONS: Multifraction SRS at a dose of 27 Gy in 3 daily fractions seems to be an effective treatment modality for large brain metastases, associated with better local control and a reduced risk of radiation-induced radionecrosis as compared with SF-SRS.

Repeated stereotactic radiosurgery for patients with progressive brain metastases.

In the present study we have evaluated the efficacy and toxicity of repeated stereotactic radiosurgery (SRS) in patients with recurrent/progressive brain metastases. Between March 2006 and October 2014, 43 patients (21 men and 22 women) with 47 lesions received a second course of SRS given in three daily fractions of 7-8 Gy. With a follow-up study of 19 months, the 1- and 2-year survival rates from repeated SRS were 37 and 20%, respectively, and the 1- and 2-year local control rates were 70 and 60%, respectively. Actuarial local control was significantly better for breast and lung metastases as compared with melanoma metastases; specifically, 1-year local control rates were 38% for melanoma, 78% for breast carcinoma and 73% for non-small cell lung cancer (NSCLC) metastases (p = 0.01). The cause of death was progressive systemic disease in 25 patients and progressive brain disease in 11 patients. Stable extracranial disease (p = 0.01) and Karnofsky performance status (KPS; p = 0.03) were predictive of longer survival. Radiologic changes suggestive of brain radionecrosis were observed in 9 (19%) out of 47 lesions, with an actuarial risk of 34% at 12 months. Neurological deficits (RTOG Grade 2 or 3) associated with brain necrosis occurred in 14% of patients. In conclusion, a second course of SRS given in three daily fractions is a feasible treatment for selected patients with recurrent/progressive brain metastases. Further studies are needed to explore the efficacy and safety of different dose-fractionation schedules, especially in patients with melanoma or large metastases.

A Mobile Health Service to Manage Diabetic Foot in Homeless Patients.

BACKGROUND: Homeless people live in poverty, with limited access to public health services. They are likely to experience chronic medical conditions, such as diabetes mellitus; however, they do not always receive the necessary services to prevent complications. This study was designed to determine the effectiveness of a volunteer health service outreach to reduce disparity in diabetic foot care for homeless people. METHODS: The research was conducted on 21 patients with diabetic ulcers of 930 homeless people visited between 2008 and 2013. Each ulcer was treated with regular medication every week for a mean ± SD of 17.6 ± 12 months. The inclusion criteria were 1) homeless with a previous diagnosis of diabetes or a blood glucose level greater than 126 mg/dL at first check and 2) foot ulcer caused by diabetic vasculopathy or neuropathy. The efficacy of the interventions was assessed against the number of successfully cured diabetic feet based on a reduced initial Wagner classification score for each ulcer. RESULTS: Clinical improvement was observed in 18 patients (86%), whose pathologic condition was completely resolved after 3 years and, therefore, no longer needed medication. One patient died of septic shock and kidney failure, and two patients needed amputation owing to clinical worsening of ulcers (Wagner class 4 at the last visit). CONCLUSIONS: Most homeless people who have diabetes and diabetic foot encounter many difficulties managing their disease, and a volunteer health-care unit could be a suitable option to bridge these gaps.

Multifraction radiotherapy for palliation of painful bone metastases: 20 Gy versus 30 Gy.

AIMS AND BACKGROUND: To compare 2 multifraction radiotherapy schedules in the palliation of painful bone metastases. METHODS AND STUDY DESIGN: We retrospectively analyzed clinical data of 105 patients with a total of 140 painful bone metastases who were treated with 20 Gy in 5 fractions or 30 Gy in 10 fractions. The primary tumors were breast (30%), lung (28%), and prostate (14%). The main sites of irradiation were spine (n = 79) and sacrum or pelvis (n = 39). Pain was graded by patients according to the pain numeric rating scale just before and 1 month after radiotherapy. Pain progression was defined as an increase ≥2 on pain scale after an initial response. RESULTS: The overall response rate at 1 month was 88.6%. Overall response rate was 89.6% in the 20-Gy arm and 87.3% in the 30-Gy arm (p = 0.669). The rate of complete response was statistically better in patients treated with 30 Gy (p = 0.019). The mean reduction in pain was 3.2 in the 20-Gy group and 3.6 in the 30-Gy group. Pain progression was 6.5% and 1.6%, respectively. The incidence of acute toxicity was statistically significantly higher in the 30-Gy arm (23.8%) than in the 20-Gy arm (2.6%) (p = 0.001). One pathologic fracture of the irradiated bone was observed in the 30-Gy arm. Two lesions, one in each group, were re-irradiated for pain recurrence. Pain progression was found in 6.5% of the irradiated lesions in the 20-Gy arm and in 1.6% in the 30-Gy arm. CONCLUSIONS: In our series, both regimens achieved high rate of pain relief, although the group treated with higher total dose reported better complete response rate. The 30-Gy arm had a significantly higher rate of acute toxicity.

Radiation-induced malignant meningioma following proton beam therapy for a choroidal melanoma.

We report a woman with malignant meningioma diagnosed 9 years after the treatment of a choroidal melanoma with proton beam therapy. The risk of secondary cancers is a well-known adverse late effect of radiation therapy, especially with the use of advanced techniques such as intensity-modulated radiation therapy. However, this risk may be less with the use of proton beam therapy. A 79-year-old woman presented with symptoms of enophthalmos, ptosis and paralysis of the left medial rectus muscle. She had previously been successfully treated for a choroidal melanoma of the left eye with proton beam therapy (total dose: 60 cobalt gray equivalents) following local resection. MRI showed a lesion in the left cavernous sinus with extension into the orbit and a subsequent biopsy revealed a papillary meningioma. The cavernous tumor was treated with photon radiotherapy (total dose: 54Gy) which achieved an initial partial response. However, 8 months later the tumor extensively metastasized to the skull and the spine and the patient died 1 year after the treatment. The incidence of secondary malignancies after proton beam therapy is low but not negligible, therefore, it must be taken into account when planning a treatment as secondary tumors may present with a highly aggressive behaviour.