Management and long-term clinical outcomes of patients with stage IVA cervical cancer with bladder involvement.

OBJECTIVE: To describe the long-term outcomes of patients with stage IVA cervical cancer, a rare and deadly disease for which long-term toxicity data are scarce, to guide clinician counseling and survivorship support. METHODS: In a retrospective review of a prospectively maintained database, we identified 76 patients with stage IVA cervical cancer with biopsy- or MRI-proven bladder mucosal involvement who received definitive radiotherapy (external beam radiotherapy [EBRT] alone or EBRT plus brachytherapy) with or without chemotherapy at our institution between 2000 and 2020. We used Kaplan-Meier modeling to estimate recurrence-free survival (RFS) and overall survival (OS) and used proportional hazard modeling to identify clinical variables associated with recurrence or survival. We performed actuarial competing risk modeling for severe late toxicity (grades 3 to 5, occurring >6 months of follow-up) and vesicovaginal fistulae (VVF), censoring for pelvic recurrence and death, and made comparisons between potential predictors using Gray's test and binary logistic regression. RESULTS: The median follow-up time was 76 months (interquartile range 58-91). The median OS duration was 35 months (range, 18-not reached), and the 2- and 5-year OS rates were 53.6% and 40.9%, respectively. OS and RFS did not differ significantly between patients who received EBRT alone (N = 18) or EBRT plus brachytherapy (N = 49). Current smoking was a strong predictor of severe late toxicity, whose incidence was 14% at 2 years and 17% at 10 years. The VVF incidence was 24% at 2 years and 32% at 10 years. CONCLUSION: Patients with stage IVA cervical cancer, even those who receive EBRT alone, can have long-term survival. These patients should be followed closely for late radiation-related toxicity.

Acute and Chronic Complications After Treatment of Locoregional Anal Cancer: Prevention and Management Strategies.

Definitive chemoradiotherapy (CRT) for anal cancer spares patients the morbidity of a colostomy surgery and optimizes cancer outcomes. CRT, however, has introduced a unique acute and chronic toxicity profile, which has greatly improved over the years with the introduction of advanced radiotherapy techniques. This article provides the multidisciplinary care team with practical tools to mitigate and manage acute and chronic complications from definitive treatment of anal cancer.

Ultrasound-Based Grading System for Radiation-Induced Acute Breast Toxicity.

OBJECTIVES: To introduce an ultrasound-based scoring system for radiation-induced breast toxicity and test its reliability. METHODS: Breast ultrasound (BUS) was performed on 32 patients receiving breast radiotherapy (RT) to assess the radiation-induced acute toxicity. For each patient, both the untreated and irradiated breasts were scanned at five locations: 12:00, 3:00, 6:00, 9:00, and tumor bed to evaluate for heterogenous responses to radiation within the entire breast. In total, 314 images were analyzed. Based on ultrasound findings such as skin thickening, dermis boundary irregularity, and subcutaneous edema, a 4-level, Likert-like grading scheme is proposed: none (G0), mild (G1), moderate (G2), and severe (G3) toxicity. Two ultrasound experts graded the severity of breast toxicity independently and reported the inter- and intra-observer reliability of the grading system. Imaging findings were compared with standard clinical toxicity assessments using Common Terminology Criteria for Adverse Events (CTCAE). RESULTS: The inter-observer Pearson correlation coefficient (PCC) was 0.87 (95% CI: 0.83-0.90, P < .001). For intra-observer repeatability, the PCC of the repeated scores was 0.83 (95% CI: 0.78-0.87, P < .001). Imaging findings were compared with standard clinical toxicity assessments using CTCAE scales. The PCC between BUS scores and CTCAE results was 0.62 (95% CI: 0.35-0.80, P < .001). Among all locations, 6:00 and tumor bed showed significantly greater toxicity compared with 12:00 (P = .04). CONCLUSIONS: BUS can investigate the cutaneous and subcutaneous tissue changes after RT. This BUS-based grading system can complement subjective clinical assessments of radiation-induced breast toxicity with cutaneous and subcutaneous sonographic information.

How many brain metastases can be treated with stereotactic radiosurgery before the radiation dose delivered to normal brain tissue rivals that associated with standard whole brain radiotherapy?

INTRODUCTION: Clinical trial data comparing outcomes after administration of stereotactic radiosurgery (SRS) or whole-brain radiotherapy (WBRT) to patients with brain metastases (BM) suggest that SRS better preserves cognitive function and quality of life without negatively impacting overall survival. Here, we estimate the maximum number of BM that can be treated using single and multi-session SRS while limiting the dose of radiation delivered to normal brain tissue to that associated with WBRT. METHODS: Multiple-tumor SRS was simulated using a Monte Carlo - type approach and a pre-calculated dose kernel method. Tumors with diameters ≤36 mm were randomly placed throughout the contoured brain parenchyma until the brain mean dose reached 3 Gy, equivalent to the radiation dose delivered during a single fraction of a standard course of WBRT (a total dose of 30 Gy in 10 daily fractions of 3 Gy). Distribution of tumor sizes, dose coverage, selectivity, normalization, and maximum dose data used in the simulations were based on institutional clinical metastases data. RESULTS: The mean number of tumors treated, mean volume of healthy brain tissue receiving > 12 Gy (V12) per tumor, and total tumor volume treated using mixed tumor size distributions were 12.7 ± 4.2, 2.2 cc, and 12.9 cc, respectively. Thus, we estimate that treating 12-13 tumors per day over 10 days would deliver the dose of radiation to healthy brain tissue typically associated with a standard course of WBRT. CONCLUSION: Although in clinical practice, treatment with SRS is often limited to patients with ≤15 BM, our findings suggest that many more lesions could be targeted while still minimizing the negative impacts on quality of life and neurocognition often associated with WBRT. Results from this in silico analysis require clinical validation.

Germline genetic biomarkers to stratify patients for personalized radiation treatment.

BACKGROUND: Precision medicine incorporating genetic profiling is becoming a standard of care in medical oncology. However, in the field of radiation oncology there is limited use of genetic profiling and the impact of germline genetic biomarkers on radiosensitivity, radioresistance, or patient outcomes after radiation therapy is poorly understood. In HNSCC, the toxicity associated with treatment can cause delays or early cessation which has been associated with worse outcomes. Identifying potential biomarkers which can help predict toxicity, as well as response to treatment, is of significant interest. METHODS: Patients with HNSCC who received RT and underwent next generation sequencing of somatic tumor samples, transcriptome RNA-seq with matched normal tissue samples were included. Patients were then grouped by propensity towards increased late vs. early toxicity (Group A) and those without (Group B), assessed by CTCAE v5.0. The groups were then analyzed for association of specific germline variants with toxicity and clinical outcomes. RESULTS: In this study we analyzed 37 patients for correlation between germline variants and toxicity. We observed that TSC2, HLA-A, TET2, GEN1, NCOR2 and other germline variants were significantly associated with long term toxicities. 34 HNSCC patients treated with curative intent were evaluated for clinical outcomes. Group A had significantly improved overall survival as well as improved rates of locoregional recurrence and metastatic disease. Specific variants associated with improved clinical outcomes included TSC2, FANCD2, and PPP1R15A, while the HLA-A and GEN1 variants were not correlated with survival or recurrence. A group of five HLA-DMA/HLA-DMB variants was only found in Group B and was associated with a higher risk of locoregional recurrence. CONCLUSIONS: This study indicates that germline genetic biomarkers may have utility in predicting toxicity and outcomes after radiation therapy and deserve further investigation in precision radiation medicine approaches.

Dental extraction, intensity-modulated radiotherapy of head and neck cancer, and osteoradionecrosis : A systematic review and meta-analysis.

OBJECTIVE: To seek evidence for osteoradionecrosis (ORN) after dental extractions before or after intensity-modulated radiotherapy (IMRT) for head and neck cancer (HNC). METHODS: Medline/PubMed, Embase, and Cochrane Library were searched from 2000 until 2020. Articles on HNC patients treated with IMRT and dental extractions were analyzed by two independent reviewers. The risk ratios (RR) and odds ratios (OR) for ORN related to extractions were calculated using Fisher's exact test. A one-sample proportion test was used to assess the proportion of pre- versus post-IMRT extractions. Forest plots were used for the pooled RR and OR using a random-effects model. RESULTS: Seven of 630 publications with 875 patients were eligible. A total of 437 (49.9%) patients were treated with extractions before and 92 (10.5%) after IMRT. 28 (3.2%) suffered from ORN after IMRT. ORN was associated with extractions in 15 (53.6%) patients, eight related to extractions prior to and seven cases related to extractions after IMRT. The risk and odds for ORN favored pre-IMRT extractions (RR = 0.18, 95% CI: 0.04-0.74, p = 0.031, I2 = 0%, OR = 0.16, 95% CI: 0.03-0.99, p = 0.049, I2 = 0%). However, the prediction interval of the expected range of 95% of true effects included 1 for RR and OR. CONCLUSION: Tooth extraction before IMRT is more common than after IMRT, but dental extractions before compared to extractions after IMRT have not been proven to reduce the incidence of ORN. Extractions of teeth before IMRT have to be balanced with any potential delay in initiating cancer therapy.

Ionizing Radiation from Radiopharmaceuticals and the Human Gut Microbiota: An Ex Vivo Approach.

This study aimed to determine the effect of three widely used radiopharmaceuticals with intestinal excretion on selected relevant bacteria that are part of the human gut microbiota, using an ex vivo approach. Fecal samples obtained from healthy volunteers were analyzed. Each sample was divided into four smaller aliquots. One served as the non-irradiated control. The other three were homogenized with three radiopharmaceutical solutions ([131I]NaI, [99mTc]NaTcO4, and [223Ra]RaCl2). Relative quantification of each taxa was determined by the 2-ΔΔC method, using the ribosomal gene 16S as an internal control (primers 534/385). Twelve fecal samples were analysed: three controls and nine irradiated. Our experiment showed fold changes in all analyzed taxa with all radiopharmaceuticals, but results were more significant with I-131, ranging from 1.87-83.58; whereas no relevant differences were found with Tc-99m and Ra-223, ranging from 0.98-1.58 and 0.83-1.97, respectively. This study corroborates limited existing research on how ionizing radiation changes the gut microbiota composition, providing novel data regarding the ex vivo effect of radiopharmaceuticals. Our findings justify the need for future larger scale projects.

Intraoperative radiation therapy for early-stage breast cancer: a single-institution experience.

Background: To assess outcomes and toxicity after low-energy intraoperative radiotherapy (IORT) for early-stage breast cancer (ESBC). Materials and methods: We reviewed patients with unilateral ESBC treated with breast-conserving surgery and 50-kV IORT at our institution. Patients were prescribed 20 Gy to the surface of the spherical applicator, fitted to the surgical cavity during surgery. Patients who did not meet institutional guidelines for IORT alone on final pathology were recommended adjuvant treatment, including additional surgery and/or external-beam radiation therapy (EBRT). We analyzed ipsilateral breast tumor recurrence, overall survival, recurrence-free survival and toxicity. Results: Among 201 patients (median follow-up, 5.1 years; median age, 67 years), 88% were Her2 negative and ER positive and/or PR positive, 98% had invasive ductal carcinoma, 87% had grade 1 or 2, and 95% had clinical T1 disease. Most had pathological stage T1 (93%) N0 (95%) disease. Mean IORT applicator dose at 1-cm depth was 6.3 Gy. Post-IORT treatment included additional surgery, 10%; EBRT, 11%; adjuvant chemotherapy, 9%; and adjuvant hormonal therapy, 74%. Median total EBRT dose was 42.4 (range, 40.05-63) Gy and median dose per fraction was 2.65 Gy. At 5 years, the cumulative incidence of ipsilateral breast tumor recurrence was 2.7%, the overall survival rate was 95% with no breast cancer-related deaths, and the recurrence-free survival rate was 96%. For patients who were deemed unsuitable for postoperative IORT alone and did not receive recommended risk-adapted EBRT, the IBTR rate was 4.7% versus 1.7% (p = 0.23) for patients who were either suitable for IORT alone or unsuitable and received adjuvant EBRT. Cosmetic toxicity data was available for 83%, with 7% experiencing grade 3 breast toxicity and no grade 4-5 toxicity. Conclusions: IORT for select patients with ESBC results in acceptable outcomes in regard to ipsilateral breast tumor recurrence and toxicity.

The impact of hyperbaric oxygen therapy on late radiation toxicity and quality of life in breast cancer patients.

PURPOSE: To evaluate symptoms of late radiation toxicity, side effects, and quality of life in breast cancer patients treated with hyperbaric oxygen therapy (HBOT). METHODS: For this cohort study breast cancer patients treated with HBOT in 5 Dutch facilities were eligible for inclusion. Breast cancer patients with late radiation toxicity treated with ≥ 20 HBOT sessions from 2015 to 2019 were included. Breast and arm symptoms, pain, and quality of life were assessed by means of the EORTC QLQ-C30 and -BR23 before, immediately after, and 3 months after HBOT on a scale of 0-100. Determinants associated with persistent breast pain after HBOT were assessed. RESULTS: 1005/1280 patients were included for analysis. Pain scores decreased significantly from 43.4 before HBOT to 29.7 after 3 months (p < 0.001). Breast symptoms decreased significantly from 44.6 at baseline to 28.9 at 3 months follow-up (p < 0.001) and arm symptoms decreased significantly from 38.2 at baseline to 27.4 at 3 months follow-up (p < 0.001). All quality of life domains improved at the end of HBOT and after 3 months follow-up in comparison to baseline scores. Most prevalent side effects of HBOT were myopia (any grade, n = 576, 57.3%) and mild barotrauma (n = 179, 17.8%). Moderate/severe side effects were reported in 3.2% (n = 32) of the patients. Active smoking during HBOT and shorter time (i.e., median 17.5 vs. 22.0 months) since radiotherapy were associated with persistent breast pain after HBOT. CONCLUSION: Breast cancer patients with late radiation toxicity reported reduced pain, breast and arm symptoms, and improved quality of life following treatment with HBOT.

Evaluating predictive factors for toxicities experienced by head & neck cancer patients undergoing radiotherapy.

PURPOSE: The purpose of this study was to evaluate if HPV status serves as an independent predictor of early and late dysphagia outcomes when considered alongside standard patient characteristics and dose metrics for head and neck cancer patients treated with radiotherapy. METHODS AND MATERIALS: The age, sex, smoking history, cancer type (oropharyngeal vs non-oropharyngeal), HPV status, and early and late dysphagia outcomes were obtained for 99 retrospective head and neck cancer patients treated at our clinic with radiotherapy. Additionally for each patient, the mean radiation dose to the pharynx, superior/middle/inferior pharyngeal constrictor muscles, and cricopharyngeus was calculated. The predictive power of these clinical characteristics and radiation metrics was evaluated using chi-square tests for categorical variables and t-tests for continuous variables. Then multi-variate logistic models were built for each outcome using a single dose metric at a time, and either HPV status, cancer type, or both. Multi-variate models were built using both top-down and bottom-up technique to establish the most predictive independent covariates. RESULTS: In the univariate analysis for early dysphagia, cancer type (p = 0.04) and four dose metrics (p ≤ 0.02) were significantly associated with outcome, while for late dysphagia, only cancer type (p = 0.04) was associated with outcome. In the multivariate analysis for early dysphagia, cancer type, smoking history, and mean dose to the five structures were consistently selected as covariates. For late dysphagia, either HPV status or cancer type was selected in each model and the mean dose to the cricopharyngeus was selected in one model. CONCLUSION: While HPV is a known contributing factor for tumor prognosis in oropharyngeal cancers, its role in normal tissue toxicities for head and neck cancers has not previously been evaluated. Our results indicate having an oropharyngeal cancer may increase a patient's risk of high-grade early and late dysphagia while HPV status was seldom selected.

Gene alterations as predictors of radiation-induced toxicity in head and neck squamous cell carcinoma.

BACKGROUND: Optimizing the therapeutic ratio for radiation therapy (RT) in head and neck squamous cell carcinoma (HNSCC) is uniquely challenging owing to high rates of early and late toxicity involving nearby organs at risk. These toxicities have a profound impact on treatment compliance and quality of life. Emerging evidence suggests that RT dose alone cannot fully account for the variable severity of RT-related adverse events (rtAEs) observed in HNSCC patients. Next-generation sequencing has become an increasingly valuable tool with widespread use in the oncology field and is being robustly explored for predicting rtAEs beyond dosimetric data. METHODS: Patients who had Foundation Medicine sequencing data and received RT for primary or locally recurrent HNSCC were selected for this study. Early and late toxicity data were collected and reported based on Common Terminology Criteria for Adverse Events version 5.0. Dosimetric parameters were collected for pertinent structures. RESULTS: A total of HNSCC 37 patients were analyzed in this study. Genetic alterations in BRCA2, ERBB3, NOTCH1 and CCND1 were all associated with higher mean grade of toxicity with BRCA2 alteration implicated in all toxicity parameters evaluated including mucositis, early dysphagia, xerostomia and to a lesser extent, late dysphagia. Interestingly, patients who exhibited alterations in both BRCA2 and ERBB3 experienced a twofold or greater increase in early dysphagia, early xerostomia and late dysphagia compared to ERBB3 alteration alone. Furthermore, several gene alterations were associated with improved toxicity outcomes. Within an RT supersensitive patient subset, alterations were found in TNFAIP3, HNF1A, SPTA1 and CASP8. All of these alterations were not found in the RT insensitive patient subset. We found 17 gene alterations in the RT insensitive patient subset that were not found in the RT supersensitive patient subset. CONCLUSION: Despite consistent RT dosimetric parameters, patients with HNSCC experience heterogeneous patterns of rtAEs. Identifying factors associated with toxicity outcomes offers a new avenue for personalized precision RT therapy and prophylactic management. Here, next-generation sequencing in a population of HNSCC patients correlates several genetic alterations with severity of rtAEs. Further analysis is urgently needed to identify genetic patterns associated with rtAEs in order to reduce harmful outcomes in this challenging population.

Single- and hypofractionated stereotactic radiosurgery for large (> 2 cm) brain metastases: a systematic review.

PURPOSE: Since frameless stereotactic radiosurgery (SRS) techniques have been recently introduced, hypofractionated SRS (HF-SRS) for large brain metastases (BMs) is gradually increasing. To verify the efficacy and safety of HF-SRS for large BMs, we aimed to perform a systematic review and compared them with SF-SRS. METHODS: We systematically searched the studies regarding SF-SRS or HF-SRS for large (> 2 cm) BM from databases including PubMed, Embase, and the Cochrane Library on July 31, 2018. Biologically effective dose with the α/ß ratio of 10 (BED10), 1-year local control (LC), and radiation necrosis (RN) were compared between the two groups, with the studies being weighted by the sample size. RESULTS: The 15 studies with 1049 BMs that described 1-year LC and RN were included. HF-SRS tended to be performed in larger tumors; however, higher mean BED10 (50.1 Gy10 versus 40.4 Gy10, p < 0.0001) was delivered in the HF-SRS group, which led to significantly improved 1-year LC (81.6 versus 69.0%, p < 0.0001) and 1-year overall survival (55.1 versus 47.2%, p < 0.0001) in the HF-SRS group compared to the SF-SRS group. In contrast, the incidence of radiation toxicity was significantly decreased in the HF-SRS group compared to the SF-SRS group (8.0 versus 15.6%, p < 0.0001). CONCLUSION: HF-SRS results in better LC of large BMs while simultaneously reducing RN compared to SF-SRS. Thus, HF-SRS should be considered a priority for SF-SRS in patients with large BMs who are not suitable to undergo surgical resection.

Radiotherapy of the oldest old-feasibility and institutional analysis.

PURPOSE: Little is known about efficacy and toxicity of radiation therapy in the elderly, as the vast majority of prospective trials excluded patients aged over 70 years. The aim of this study was to investigate the outcome of radiation therapy in a group of so-called oldest old cancer patients (≥85 years). MATERIALS AND METHODS: We retrospectively reviewed data from patients aged ≥85 years, treated between 2010 and 2015 for any tumor histology at the University Hospital Zurich, Switzerland. Overall survival (OS), relapse-free survival (RFS), performance status (ECOG), Charlson comorbidity index (CCI) and treatment tolerance were assessed. RESULTS: We identified and included 100 patients with a mean age of 88 years (range: 85-102 years). Most patients received a curative-intent treatment (n = 64, 64%). About one third received palliative radiation therapy for symptomatic metastatic disease (n = 36, 36%). Curative treatment was well tolerated, with no high-grade acute toxicities (≥grade 4). Median OS was 52.6 and 13.1 months for the curative and palliative treated patient groups, respectively. 5­year OS for all patients was 39.5% (95% CI: 23.6-54.5%). The Charlson comorbidity index (CCI) had a predictive value for overall survival (CCI > 10, p = 0.0001) in the curative group. CONCLUSION: The number of older cancer patients will increase considerably in the next decades because of demographic changes. Our analysis supports the notion that radiation therapy for this patient group of oldest old cancer patients is feasible in general. Treatment decisions should not be based on chronological age but rather on comorbidities and functional status.

Neurologic Complications of Cranial Radiation Therapy and Strategies to Prevent or Reduce Radiation Toxicity.

PURPOSE OF REVIEW: Radiation therapy is an important treatment for patients with brain tumors but can have significant neurologic complications. This review highlights the broad spectrum of short-term and long-term neurologic complications that can occur in patients receiving cranial radiation therapy, and strategies to prevent and treat such complications. RECENT FINDINGS: Despite significant improvements in radiotherapy delivery, there are neurologic complications that can result from treatment. With increased recognition and understanding of these neurologic complications, novel strategies to prevent and mitigate them are an area of active research with early promising results. Intensive efforts are ongoing to address the risk of radiation-induced neurocognitive changes through advances in radiation technique and therapies targeting relevant molecular pathways. Neurologic complications from radiation therapy are an important consideration in counseling, treatment, and post-treatment management of patients with brain tumors.

Lethal outcome after pelvic salvage radiotherapy in a patient with prostate cancer due to increased radiosensitivity : Case report and literature review.

BACKGROUND: In general, late side effects after salvage radiotherapy (RT) for prostate cancer are below 10%. Patients with impaired DNA repair ability and genetic instability can have significantly increased reactions after RT. CASE, CLINICAL FOLLOW-UP, AND EXAMINATION: We present a patient who experienced severe side effects after additive RT for prostate cancer and died from the complications 25 months after RT. Imaging (MR) is shown as well as three-color fluorescence in situ hybridization. The blood sample testing revealed that radiosensitivity was increased by 35-55%. We undertook a review of the literature to give an overview over the tests established that are currently considered useful. CONCLUSION: This case highlights that the identification of patients with increased radiosensitivity is an important task in radiation protection. Groups of patients who should be screened have to be found and corresponding research facilities have to be set up.

Stereotactic radiosurgery and ipilimumab for patients with melanoma brain metastases: clinical outcomes and toxicity.

INTRODUCTION: There is evidence that the combination of ipilimumab and stereotactic radiosurgery (SRS) for brain metastases improves outcomes. We investigated clinical outcomes, radiation toxicity, and impact of ipilimumab timing in patients treated with SRS for melanoma brain metastases. METHODS: We retrospectively identified 91 patients treated with SRS at our institution for melanoma brain metastases from 2006 to 2015. Concurrent ipilimumab administration was defined as within ± 4 weeks of SRS procedure. Acute and late toxicities were graded with CTCAE v4.03. Overall survival (OS), local failure, distant brain failure, and failure-free survival were analyzed with the Kaplan-Meier method. OS was analyzed with Cox regression. RESULTS: Twenty-three patients received ipilimumab concurrent with SRS, 28 patients non-concurrently, and 40 patients did not receive ipilimumab. The median age was 62 years and 91% had KPS ≥ 80. The median follow-up time was 7.4 months. Patients who received ipilimumab had a median OS of 15.1 months compared to 7.8 months in patients who did not (p = 0.02). In multivariate analysis, ipilimumab (p = 0.02) and diagnosis-specific graded prognostic assessment (p = 0.02) were associated with OS. There were no differences in intracranial control by ipilimumab administration or timing. The incidence of radiation necrosis was 5%, with most events occurring in patients who received ipilimumab. CONCLUSIONS: Patients who received ipilimumab had improved OS even after adjusting for prognostic factors. Ipilimumab did not appear to increase risk for acute toxicity. The majority of radiation necrosis events, however, occurred in patients who received ipilimumab. Our results support the continued use of SRS and ipilimumab as clinically appropriate.

Quantification of patient-reported outcome measures of radiation-induced skin reactions for use in clinical trial design.

PURPOSE: Skin toxicity is a common effect from radiotherapy, although difficult to predict on an individual basis, and there is little evidence-based management. This study aimed to quantify inter-patient variation in patient-reported outcome measures for radiation-induced skin reactions (RISR) to enable the determination of the number of patients required for adequate power in a comparative trial of RISR management strategies. METHODS: The study included 154 patients scheduled to receive breast cancer radiotherapy. Patients filled in a weekly questionnaire during and up to 4 weeks following the end of radiotherapy scoring five aspects of their experience of RISR: skin redness, and bother from redness like itching, burning sensation and tenderness/pain. RESULTS: Assessment of patients' reported experience of their RISR was shown to be feasible, with 91 % of patients returning at least two questionnaires. The mean score increase between weeks 1 and 4 was 25 points (p value <0.0001, 95 % CI 21-29), and the estimated standard deviation at 4 weeks was 18 (95 % CI 16-21). CONCLUSIONS: Patients' assessment of their reaction was not predicted on the basis of treatment and patient-related characteristics. Based on the observed variance in scores at 4 weeks, we could calculate the sample size required for a comparative study of two RISR management policies would be 200 patients to have statistical power to detect a clinically significant difference in patient-rated scores of their skin reactions. A trial employing this tool would help provide an evidence base to guide policy in advising patients how to manage their RISR.

Evaluating Critical Brain Radiation Doses in the Treatment of Multiple Brain Lesions with Gamma Knife Radiosurgery.

BACKGROUND: Treatment of patients with multiple brain metastases has shifted to stereotactic radiosurgery, withholding whole-brain (WB) radiation therapy. However, radiation toxicity to the brain is a concern when treating multiple brain lesions with single-fraction stereotactic radiosurgery. OBJECTIVE: The purpose of this study was to determine the changes in brain radiation doses when treating various numbers of targets and lesion volumes. METHODS: We simulated different treatment plans with different combinations of varying tumor volumes including 0.1, 0.5, 1, 2, and 5 cm3, and tumor numbers including 1, 3, 5, 10, 15, 20, and 25. Treatment planning was performed for all combinations in a computerized tomography of the head of a patient, using Leksell GammaPlan version 10.1.1 (Elekta AB, Stockholm, Sweden). Two different dosing strategies were used. In the lower-prescription dosing schedule, a marginal dose was given to the 50% isodose line, and 20 Gy were used when the number of lesions was less than 15 and 18 Gy were applied when the number of lesions was equal to or more than 15. In the higher-prescription dosing schedule, a marginal dose of 24 Gy was used for lesions of less than 5 cm3 and 20 Gy were applied for lesions equal to 5cm3. The mean WB dose, the WB integral dose, and the volume of brain receiving 12 Gy (V12 Gy) were calculated for each scenario. Also, the beam-on time of the Gamma Knife 4C unit was reported for all treatment scenarios. RESULTS: Regression analysis showed that the total tumor volume was a more significant predictor of V12 Gy than the number of lesions, and a linear correlation between the total tumor volume and V12 Gy was found. We also found that the total tumor volume was a more significant predictor of the mean WB dose and the WB integral dose compared to the number of lesions. CONCLUSION: Our results suggest that multiple small to mid-sized lesions could be safely treated with a single-fraction gamma knife.

Radiotherapy-related intracranial aneurysm: case presentation of a 17-year male and a meta-analysis based on individual patient data.

PURPOSE: The aim of this study was to investigate the incidence, clinical profiles, latency, and outcomes of radiotherapy (RT)-related intracranial aneurysms, rare but often fatal complications of cranial irradiation. METHODS: We reviewed all published individual patient data regardless of language, using survival analysis to make statistical inferences. RESULTS: We examined a total of 58 patients with RT-related intracranial aneurysms, including one unpublished case presented here, of whom 74.1 % presented with rupture. In the study, 29.3 % were younger than 18 years. The mean age at which patients received the first course of RT was 34.8 ± 22.8 years old. The mean latency between initiating RT and presenting with aneurysm was 10.4 ± 8.5 years. Rapid death ensured in 24 % shortly after presentation. The only significant predictor of death was rupture. In those with a single aneurysm, 43.1 % were located at the internal carotid artery, while 15.5 % of patients had multiple aneurysms. A male-to-female ratio of 1.87, 0.5, and 1.32 was found in patients younger than age 52, 52 years of age or older, and all 58 patients, respectively. Older age when receiving RT and presentation with ruptured aneurysm were significantly associated with shorter latency. CONCLUSIONS: RT-related intracranial aneurysms presented differently from classical ones based on age, sex, site, multiplicity, and type. Sex ratios differed with age. The younger age group showed a longer latency of occurrence of an aneurysm. Older patients and those who develop ruptured aneurysms presented earlier. Since rupture may affect outcome, early detection of aneurysms before rupture may save lives.

Is current clinical practice modified about intraoperative breast irradiation?

After the results obtained in the two randomized clinical trial, the ELIOT trial and the TARGIT-A trial, a heated debate is going on concerning the question of applying intraoperative radiotherapy (IORT) instead of postoperative whole breast irradiation (WBI) after breast conservative treatment. Currently, many centers are applying the IORT following the strict selection criteria dictated by the working groups American Society for Radiation Oncology (ASTRO) and Groupe Européen de Curiethérapie-European Society for Therapeutic Radiology and Oncology (GEC-ESTRO) and monitoring the oncological outcome together with radiation toxicity on breast tissue. The clinical experience of the Geneva University Hospital regarding the use of the Intrabeam system is evaluated and compared with current evidences.