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Purpose/Objective(s): Merkel cell carcinoma (MCC) radiation treatment has historically consisted of standard 1.8–2 Gy fractions treated daily over 4–6 weeks. Hypofractionated treatment regimens have demonstrated tumor control and toxicity equivalence to standard fractionation regimens for common cutaneous malignancies such as basal cell and squamous cell carcinomas. Herein we report the outcomes of hypofractionated versus standard fractionation radiotherapy for MCC at our institution. Materials/Methods: The study involved a retrospective review of MCC patients treated with radiotherapy. Treatment characteristics and patient outcomes, including acute toxicities, disease recurrence and survival data were collected. The cumulative incidence of local and distant failures was estimated, with death as a competing risk. Results: A total of 29 treatment courses for 24 patients were included, of which 13 involved standard fractionation with curative intent, 10 involved hypofractionated radiotherapy with curative intent, and 6 involved single fraction (8 Gy) palliative radiation. Half the patients were treated to a head/neck site. A subset of patients treated adjuvantly with curative intent included 8 standard fractionation and 8 hypofractionated radiotherapy patients. No statistically significant differences in local and/or distant failure or overall survival was observed between the patient groups. Conclusion: Hypofractionated radiotherapy for MCC was associated with similar treatment outcomes relative to standard fractionation. In our limited patient sample, hypofractionated radiation treatment achieved similar results with similar toxicity and fewer treatments. Further analysis of a larger patient population with longer follow up is needed to confirm treatment tolerability and efficacy. [ABSTRACT FROM AUTHOR]

Background: The effectiveness and safety of moderately hypofractionated radiotherapy (HFRT) in patients undergoing breast-conserving surgery (BCS) has been demonstrated in several pivotal randomized trials. However, the feasibility of applying simultaneous integrated boost (SIB) to the tumor bed and regional node irradiation (RNI) using modern radiotherapy techniques with HFRT needs further evaluation. Methods: This prospective, multi-center, randomized controlled, non-inferiority phase III trial aims to determine the non-inferiority of HFRT combined with SIB (HFRTsib) compared with conventional fractionated radiotherapy with sequential boost (CFRTseq) in terms of five-year locoregional control rate in breast cancer patients undergoing upfront BCS. A total of 2904 participants will be recruited and randomized in a 1:1 ratio into the HFRTsib and CFRTseq groups. All patients will receive whole breast irradiation, and those with positive axillary nodes will receive additional RNI, including internal mammary irradiation. The prescribed dose for the HFRTsib group will be 40 Gy in 15 fractions, combined with a SIB of 48 Gy in 15 fractions to the tumor bed. The CFRTseq group will receive 50 Gy in 25 fractions, with a sequential boost of 10 Gy in 5 fractions to the tumor bed. Discussion: This trial intends to assess the effectiveness and safety of SIB combined with HFRT in early breast cancer patients following BCS. The primary endpoint is locoregional control, and the results of this trial are expected to offer crucial evidence for utilizing HFRT in breast cancer patients after BCS. Trial registration: This trial was registered at ClincalTrials.gov (NCT04025164) on July 18, 2019. [ABSTRACT FROM AUTHOR]

Background: Oncologic surgical resection is the standard of care for extremity and truncal soft tissue sarcoma (STS), often accompanied by the addition of pre- or postoperative radiation therapy (RT). Preoperative RT may decrease the risk of joint stiffness and fibrosis at the cost of higher rates of wound complications. Hypofractionated, preoperative RT has been shown to provide acceptable outcomes in prospective trials. Proton beam therapy (PBT) provides the means to decrease dose to surrounding organs at risk, such as the skin, bone, soft tissues, and adjacent joint(s), and has not yet been studied in patients with extremity and truncal sarcoma. Methods: Our study titled "PROspective phase II trial of preoperative hypofractionated protoN therapy for extremity and Truncal soft tissue sarcOma (PRONTO)" is a non-randomized, prospective phase II trial evaluating the safety and efficacy of preoperative, hypofractionated PBT for patients with STS of the extremity and trunk planned for surgical resection. Adult patients with Eastern Cooperative Group Performance Status ≤ 2 with resectable extremity and truncal STS will be included, with the aim to accrue 40 patients. Treatment will consist of 30 Gy radiobiological equivalent of PBT in 5 fractions delivered every other day, followed by surgical resection 2–12 weeks later. The primary outcome is rate of major wound complications as defined according to the National Cancer Institute of Canada Sarcoma2 (NCIC-SR2) Multicenter Trial. Secondary objectives include rate of late grade ≥ 2 toxicity, local recurrence-free survival and distant metastasis-free survival at 1- and 2-years, functional outcomes, quality of life, and pathologic response. Discussion: PRONTO represents the first trial evaluating the use of hypofractionated PBT for STS. We aim to prove the safety and efficacy of this approach and to compare our results to historical outcomes established by previous trials. Given the low number of proton centers and limited availability, the short course of PBT may provide the opportunity to treat patients who would otherwise be limited when treating with daily RT over several weeks. We hope that this trial will lead to increased referral patterns, offer benefits towards patient convenience and clinic workflow efficiency, and provide evidence supporting the use of PBT in this setting. Trial registration: NCT05917301 (registered 23/6/2023). [ABSTRACT FROM AUTHOR]

Background: Paucity and low evidence-level data on proton therapy (PT) represent one of the main issues for the establishment of solid indications in the PT setting. Aim of the present registry, the POWER registry, is to provide a tool for systematic, prospective, harmonized, and multidimensional high-quality data collection to promote knowledge in the field of PT with a particular focus on the use of hypofractionation. Methods: All patients with any type of oncologic disease (benign and malignant disease) eligible for PT at the European Institute of Oncology (IEO), Milan, Italy, will be included in the present registry. Three levels of data collection will be implemented: Level (1) clinical research (patients outcome and toxicity, quality of life, and cost/effectiveness analysis); Level (2) radiological and radiobiological research (radiomic and dosiomic analysis, as well as biological modeling); Level (3) biological and translational research (biological biomarkers and genomic data analysis). Endpoints and outcome measures of hypofractionation schedules will be evaluated in terms of either Treatment Efficacy (tumor response rate, time to progression/percentages of survivors/median survival, clinical, biological, and radiological biomarkers changes, identified as surrogate endpoints of cancer survival/response to treatment) and Toxicity. The study protocol has been approved by the IEO Ethical Committee (IEO 1885). Other than patients treated at IEO, additional PT facilities (equipped with Proteus®ONE or Proteus®PLUS technologies by IBA, Ion Beam Applications, Louvain-la-Neuve, Belgium) are planned to join the registry data collection. Moreover, the registry will be also fully integrated into international PT data collection networks. [ABSTRACT FROM AUTHOR]

Background: Dose fractionation of a coronavirus disease 2019 (COVID-19) vaccine could effectively accelerate global vaccine coverage, while supporting evidence of efficacy, immunogenicity, and safety are unavailable, especially with emerging variants. Methods: We systematically reviewed clinical trials that reported dose-finding results and estimated the dose-response relationship of neutralizing antibodies (nAbs) of COVID-19 vaccines using a generalized additive model. We predicted the vaccine efficacy against both ancestral and variants, using previously reported correlates of protection and cross-reactivity. We also reviewed and compared seroconversion to nAbs, T cell responses, and safety profiles between fractional and standard dose groups. Results: We found that dose fractionation of mRNA and protein subunit vaccines could induce SARS-CoV-2-specific nAbs and T cells that confer a reasonable level of protection (i.e., vaccine efficacy > 50%) against ancestral strains and variants up to Omicron. Safety profiles of fractional doses were non-inferior to the standard dose. Conclusions: Dose fractionation of mRNA and protein subunit vaccines may be safe and effective, which would also vary depending on the characteristics of emerging variants and updated vaccine formulations. [ABSTRACT FROM AUTHOR]

Purpose: Boosting dominant intra-prostatic lesions (DILs) has the potential to increase the therapeutic ratio in prostate cancer radiotherapy. In this study, employing 5-fraction stereotactic ablative radiotherapy (SABR) volumetric modulated arc therapy (VMAT) to deliver 40 Gy to the prostate clinical target volume (CTV) while boosting the DIL up to 50 Gy was evaluated for patients before and after rectal spacer insertion.Materials and Methods: 24 Computed Tomography (CT) scans of 12 prostate cancer patients with unfavourable intermediate or high risk prostate cancer were employed in this study. At least two treatment plans were generated for each patient to compare pre- and post-spacer insertion plans. Plans were evaluated for target coverage, organs-at-risk doses, and the achievable boost dose level.Results: The CTV coverage was significantly better in plans with a spacer, V40Gy 98.4% versus 97.0% (p = 0.012). Using spacers significantly reduced rectal dose in all 12 patients in this study. It was possible to boost DIL to 50 Gy to without violating dose constraints in 6 of 12 patients and to 47.5 Gy in 3 patients post-spacer insertion. For 3 patients (25%) it was not possible to boost DIL above 45 Gy even with a spacer in situ. Without a spacer, for 6 patient (50%) clinically acceptable plan were only achieved when the DIL dose was lowered to 45 Gy. In five of these 6 patients the dose limiting structure was the urethra (urethra planning risk volume V45Gy [cc] ≤ 0.1 cc constraint).Conclusions: Clinically acceptable plans for 5 fraction SABR, 40 Gy to the prostate CTV, with a SIB to DIL (45-50 Gy) were achieved. The boost dose achieved was DIL location dependent and primarily affected by DIL's proximity to the urethra. Compared to plans before spacer insertion, higher DIL dose were achieved with spacer in situ for 25% of the patients. Moreover, significant reduction in rectal dose and better target coverage were also achieved for all patients with spacers in situ. [ABSTRACT FROM AUTHOR]

Background: Common symptoms of oesophageal cancer are dysphagia, pain, and bleeding. These symptoms can be relieved with palliative radiotherapy. The aim of this study was to analyse the outcome of two different palliative radiotherapy schedules.Methods: We conducted a retrospective cohort study on palliative radiotherapy for oesophageal cancer given at Karolinska University Hospital. Patients included were treated with either short-course (20 Gy in 4 Gy fractions daily, 5 consecutive workdays) or long-course (30-39 Gy in 3 Gy fractions, 10-13 consecutive workdays) palliative external beam radiotherapy between January 2009 and December 2013. The primary endpoint was dysphagia relief and secondary endpoints were adverse events, re-interventions, and overall survival. Cox regression analyses were used to estimate the effect of treatment schedule on survival.Results: A total of 128 patients received external beam radiotherapy under the study period, of these 75 (58.6%) received short-course radiotherapy and 53 (41.4%) long-course radiotherapy. Sixteen (30.8%) patients experienced dysphagia relief after short-course radiotherapy and 9 (22.0%) patients after long-course radiotherapy (p = 0.341). Acute toxicity was less frequent after short-course radiotherapy than after long-course radiotherapy, particularly oesophagitis (35.4% vs. 56.0%, p = 0.027) and nausea/emesis (18.5% vs. 36.0% p = 0.034). Re-interventions tended to be more common after short-course radiotherapy (32.0%) than after long-course radiotherapy (18.9%) (p = 0.098). There was no difference in overall survival between the two groups.Conclusions: Short- and long-course palliative radiotherapy for oesophageal cancer were equally effective to relieve dysphagia and no difference was seen in overall survival. Acute toxicity was, however, more frequent and more severe after long-course radiotherapy. Our results suggest that short-course radiotherapy is better tolerated with equal palliative effects as long-course radiotherapy. [ABSTRACT FROM AUTHOR]

Background: Hypofractionated post-prostatectomy radiotherapy is emerging practice, however with no randomized evidence so far to support it's use. Additionally, patients with persistent PSA after prostatectomy may have aggressive disease and respond less well on standard salvage treatment. Herein we report outcomes for conventionally fractionated (CFR) and hypofractionated radiotherapy (HFR) in patients with persistent postprostatectomy PSA who received salvage radiotherapy to prostate bed.Methods: Single institution retrospective chart review was performed after Institutional Review Board approval. Between May 2012 and December 2016, 147 patients received salvage postprostatectomy radiotherapy. PSA failure-free and metastasis-free survival were calculated using Kaplan-Meier method. Cox regression analysis was performed to test association of fractionation regimen and other clinical factors with treatment outcomes. Early and late toxicity was assessed using Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0.Results: Sixty-nine patients who had persistent PSA (≥ 0.1 ng/mL) after prostatectomy were identified. Median follow-up was 67 months (95% CI 58-106 months, range, 8-106 months). Thirty-six patients (52.2%) received CFR, 66 Gy in 33 fractions, 2 Gy per fraction, and 33 patients (47.8%) received HFR, 52.5 Gy in 20 fractions, 2.63 Gy per fraction. Forty-seven (68%) patients received androgen deprivation therapy (ADT). 5-year PSA failure- and metastasis-free survival rate was 56.9% and 76.9%, respectively. Thirty patients (43%) experienced biochemical failure after salvage radiotherapy and 16 patients (23%) experienced metastatic relapse. Nine patients (13%) developed metastatic castration-resistant disease and died of advanced prostate cancer. Median PSA failure-free survival was 72 months (95% CI; 41-72 months), while median metastasis-free survival was not reached. Patients in HFR group were more likely to experience shorter PSA failure-free survival when compared to CFR group (HR 2.2; 95% CI 1.0-4.6, p = 0.04). On univariate analysis, factors significantly associated with PSA failure-free survival were radiotherapy schedule (CFR vs HFR, HR 2.2, 95% CI 1.0-4.6, p = 0.04), first postoperative PSA (HR 1.02, 95% CI 1.0-1.04, p = 0.03), and concomitant ADT (HR 3.3, 95% CI 1.2-8.6, p = 0.02). On multivariate analysis, factors significantly associated with PSA failure-free survival were radiotherapy schedule (HR 3.04, 95% CI 1.37-6.74, p = 0.006) and concomitant ADT (HR 4.41, 95% CI 1.6-12.12, p = 0.004). On univariate analysis, factors significantly associated with metastasis-free survival were the first postoperative PSA (HR 1.07, 95% CI 1.03-1.12, p = 0.002), seminal vesicle involvement (HR 3.48, 95% CI 1.26-9.6,p = 0.02), extracapsular extension (HR 7.02, 95% CI 1.96-25.07, p = 0.003), and surgical margin status (HR 2.86, 95% CI 1.03-7.97, p = 0.04). The first postoperative PSA (HR 1.04, 95% CI 1.00-1.08, p = 0.02) and extracapsular extension (HR 4.24, 95% CI 1.08-16.55, p = 0.04) remained significantly associated with metastasis-free survival on multivariate analysis. Three patients in CFR arm (8%) experienced late genitourinary grade 3 toxicity.Conclusions: In our experience, commonly used hypofractionated radiotherapy regimen was associated with lower biochemical control compared to standard fractionation in patients with persistent PSA receiving salvage radiotherapy. Reason for this might be lower biological dose in HFR compared to CFR group. However, this observation is limited due to baseline imbalances in ADT use, ADT duration and Grade Group distribution between two radiotherapy cohorts. In patients with persistent PSA post-prostatectomy, the first postoperative PSA is an independent risk factor for treatment failure. Additional studies are needed to corroborate our observations. [ABSTRACT FROM AUTHOR]

Background: This work addresses a basic inconsistency in the way dose is accumulated in radiotherapy when predicting the biological effect based on the linear quadratic model (LQM). To overcome this inconsistency, we introduce and evaluate the concept of the total biological dose, bEQDd.Methods: Daily computed tomography imaging of nine patients treated for prostate carcinoma with intensity-modulated radiotherapy was used to compute the delivered deformed dose on the basis of deformable image registration (DIR). We compared conventional dose accumulation (DA) with the newly introduced bEQDd, a new method of accumulating biological dose that considers each fraction dose and tissue radiobiology. We investigated the impact of the applied fractionation scheme (conventional/hypofractionated), uncertainties induced by the DIR and by the assigned α/β-value.Results: bEQDd was systematically higher than the conventionally accumulated dose with difference hot spots of 3.3-4.9 Gy detected in six out of nine patients in regions of high dose gradient in the bladder and rectum. For hypofractionation, differences are up to 8.4 Gy. The difference amplitude was found to be in a similar range to worst-case uncertainties induced by DIR and was higher than that induced by α/β.Conclusion: Using bEQDd for dose accumulation overcomes a potential systematic inaccuracy in biological effect prediction based on accumulated dose. Highest impact is found for serial-type late responding organs at risk in dose gradient regions and for hypofractionation. Although hot spot differences are in the order of several Gray, in dose-volume parameters there is little difference compared with using conventional or biological DA. However, when local dose information is used, e.g. dose surface maps, difference hot spots can potentially change outcomes of dose-response modelling and adaptive treatment strategies. [ABSTRACT FROM AUTHOR]

Background: Glioblastoma multiforme (GBM) has a poor prognosis despite a multi modal treatment that includes normofractionated radiotherapy. So, various hypofractionated alternatives to normofractionated RT have been tested to improve such prognosis. There is need of systematic review and meta-analysis to analyse the literature properly and maybe generalised the use of hypofractionation. The aim of this study was first, to perform a meta-analysis of all controlled trials testing the impact of hypofractionation on survival without age restriction and secondly, to analyse data from all non-comparative trials testing the impact of hypofractionation, radiosurgery and hypofractionated stereotactic RT in first line.Materials/methods: We searched Medline, Embase and Cochrane databases to identify all publications testing the impact of hypofractionation in glioblastoma between 1985 and March 2020. Combined hazard ratio from comparative studies was calculated for overall survival. The impact of study design, age and use of adjuvant temozolomide was explored by stratification. Meta-regressions were performed to determine the impact of prognostic factors.Results: 2283 publications were identified. Eleven comparative trials were included. No impact on overall survival was evidenced (HR: 1.07, 95%CI: 0.89-1.28) without age restriction. The analysis of non-comparative literature revealed heterogeneous outcomes with limited quality of reporting. Concurrent chemotherapy, completion of surgery, immobilization device, isodose of prescription, and prescribed dose (depending on tumour volume) were poorly described. However, results on survival are encouraging and were correlated with the percentage of resected patients and with patients age but not with median dose.Conclusions: Because few trials were randomized and because the limited quality of reporting, it is difficult to define the place of hypofactionation in glioblastoma. In first line, hypofractionation resulted in comparable survival outcome with the benefit of a shortened duration. The method used to assess hypofractionation needs to be improved. [ABSTRACT FROM AUTHOR]

Background: This retrospective German and Italian multicenter analysis aimed to compare the role of normofractionated stereotactic radiotherapy (nFSRT) to CyberKnife-based hypofractionated stereotactic radiotherapy (CK-hFSRT) for skull base meningiomas.Methods: Overall, 341 patients across three centers were treated with either nFSRT or CK-hFSRT for skull base meningioma. Treatment planning was based on computed tomography (CT) and magnetic resonance imaging (MRI) following institutional guidelines. Most nFSRT patients received 33 × 1.8 Gy, and most CK-hFSRT patients received 5 × 5 Gy. The median follow-up time was 36 months (range: 1-232 months).Results: In the CK-hFSRT group, the 1-, 3-, and 10-year local control (LC) rates were 99.4, 96.8, and 80.3%, respectively. In the nFSRT group, the 1-, 3-, and 10-year LC rates were 100, 99, and 79.1%, respectively. There were no significant differences in LC rates between the nFSRT and CK-hFSRT groups (p = 0.56, hazard ratio = 0.76, 95% confidence interval, 0.3-1.9). In the CK-hFSRT group, only one case (0.49%) of severe toxicity (CTCAE 4.0 ≥ 3) was observed. In the nFSRT group, three cases (2.1%) of grade III toxicity were observed.Conclusion: This analysis of pooled data from three centers showed excellent LC and low side effect rates for patients treated with CK-hFSRT or nFSRT. The efficacy, safety, and convenience of a shortened treatment period provide a compelling case for the use of CK-hFSRT in patients with moderate size skull base meningioma and provided that OAR constraints are met. [ABSTRACT FROM AUTHOR]

Background: The 2-week schedule of hypofractionated radiotherapy as a salvage treatment for hepatocellular carcinoma (HCC) has previously exhibited promising results; this study aimed to assess its long-term clinical outcomes in patients with recurrent HCC ineligible for curative treatments.Methods: We retrospectively enrolled 77 patients (84 lesions) with HCC who were treated with hypofractionated radiotherapy between December 2008 and July 2013. Primary inclusion criteria were HCC unsuitable for curative treatments and HCC located within 2 cm of a critical normal organ. We administered 3.5-5 Gy/fraction for 2 weeks, resulting in a total dose of 35-50 Gy.Results: The median follow-up period was 33.6 (range, 4.8-78.3) months. The 3- and 5-year overall survival rates were 52.3% and 40.9%, respectively, and local control rates were 79.5% and 72.6% in all treated lesions, respectively. The 5-year local control rate was better in the higher radiation dose group than in the lower radiation dose group (50 Gy: 79.7% vs. < 50 Gy: 66.1%); however, the difference was not statistically significant (P = 0.493). We observed grade ≥ 3 hepatic toxicity in 2 (2.6%) patients and grade 3 gastrointestinal bleeding in 1 (1.3%) patient. However, grade ≥ 4 toxicity was not observed after hypofractionated radiotherapy.Conclusions: The 2-week schedule of hypofractionated radiotherapy for recurrent HCC exhibited good local control and acceptable treatment-related toxicity during the long-term follow-up period. Thus, this fractionation schedule can be a potential salvage treatment option for recurrent HCC, particularly for tumors located close to a radiosensitive gastrointestinal organ. [ABSTRACT FROM AUTHOR]

Background: Local recurrences after breast conserving treatment are mainly close to the original tumor site, and as such shorter fractionation strategies focused on and nearest mammary gland, i.e. accelerated partial breast irradiation (APBI), have been developed. Stereotactic APBI has been attempted, although there is little experience using CyberKnife (CK) for early breast cancer.Methods: This pilot study was designed to assess the feasibility of CK-APBI on 20 evaluable patients of 29 eligible, followed for 2 years. The primary endpoint was acute/sub-acute toxicity; secondary endpoints were late toxicity and the cosmetic result.Results: Mean pathological tumor size was 10.5 mm (±4.3, range 3-18), 8 of these patients were classified as LumA-like, 11 as LumB-like, and 1 as LumB-HER2-enriched. Using CK-APBI with Iris, the treatment time was approximately 60 min (range~ 35 to ~ 120). All patients received 30 Gy in five fractions delivered to the PTV. The median number of beams was 180 (IQR 107-213; range:56-325) with a median PTV isodose prescription of 86.0% (IQR 85.0-88.5; range:82-94). The median PTV was 88.1 cm3 (IQR 63.8-108.6; range:32.3-238.8). The median breast V100 and V50 was 0.6 (IQR 0.1-1.5; range:0-13) and 18.6 (IQR 13.1-21.7; range:7.5-37), respectively. The median PTV minimum dose was 26.2 Gy (IQR 24.7-27.6; range 22.3-29.3). Mild side effects were recorded during the period of observation. Cosmetic evaluations were performed by three observers from the start of radiotherapy up to 2 years. Patients' evaluation progressively increase from 60% to 85% of excellent rating; this trend was similar to that of external observer.Conclusions: These preliminary results showed the safe feasibility of CK-APBI in early breast cancer, with mild acute and late toxicity and very good cosmetic results.Trial Registration: The present study is registered at Clinicaltrial.gov ( NCT02896322 ). Retrospectively egistered August 4, 2016. [ABSTRACT FROM AUTHOR]

Background: Using propensity score matching method (PSM) to evaluate the feasibility and clinical outcomes of simultaneous modulated accelerated radiation therapy (SMART) using helical tomotherapy (HT) in patients with nasopharyngeal carcinoma (NPC).Methods: Between August 2007 and January 2016, 381 newly diagnosed NPC patients using HT were enrolled in pre-PSM cohort, including 161 cases in a prospective phase II study (P67.5 study, with a prescription dose of 67.5Gy in 30 fractions to the primary tumour and positive lymph nodes) and 220 cases in a retrospective study (P70 study, with a prescription dose of 70Gy in 33 fractions to the primary tumour and positive lymph nodes). Acute and late toxicities were assessed according to the established RTOG/EORTC criteria and Common Terminology Criteria for Adverse Events (CTCAE) V 3.0. Survival rate were assessed with Kaplan-Meier method, log-rank test and Cox regression.Results: After matching, 148 sub-pairs of 296 patients were generated in post-PSM cohort. The incidence of grade 3-4 leukopenia, thrombocytopenia and anemia in the P67.5 group was significantly higher than in the P70 study, but no significant different was found in other acute toxicities or late toxicities between the two groups. The median follow-up was 33 months in the P67.5 and P70 group, ranging 12-54 months and 6-58 months, respectively. No significant differences in 3-year local-regional recurrence free survival (LRRFS), distant metastasis-free survival (DMFS), disease free survival (DFS) and overall survival (OS) were observed between the 2 groups. Univariate analysis showed that age, T stage, clinical stage were the main factors effecting survival. Cox proportional hazards model showed that 67.5Gy/30F pattern seemed superior in 3-year OS (HR = 0.476, 95% CI: 0.236-0.957).Conclusions: Through increasing fraction dose and shortening treatment time, the P67.5 study achieved excellent short-term outcomes and potential clinical benefits, with acceptable acute and late toxicities.Trial Registration: The trial was registered at Chinese Clinical Trial Registry on 5 July 2014 with a registration code of ChiCTRONC-14,004,895. [ABSTRACT FROM AUTHOR]

Background: Solitary plasmacytoma of the liver is a very rare and aggressive form of plasma cell dyscrasia. To the best of our knowledge, very few cases have been reported without systemic disease. We reported a rare case of hepatic solitary plasmacytoma that successfully responded to fractionated stereotactic radiotherapy.Case Presentation: A 64-year-old white French man had monoclonal gammopathy of the immune globulin G lambda type; he developed a cholestasis and cytolysis with the discovery of a subscapular nodule. A biopsy showed plasma cells and, for several reasons, the decision was made to use the fractionated stereotactic radiotherapy strategy. After 20 months, he is asymptomatic and the immune globulin G component has completely disappeared.Conclusion: We suggest considering Cyberknife® radiosurgery as an option for the treatment of hepatic solitary plasmacytoma. [ABSTRACT FROM AUTHOR]

Background: The purpose of the study was to evaluate the impact of multiple prognostic factors on the acute skin reaction in adjuvant breast cancer radiotherapy, in particular the impact of hypofractionation (HF) compared to conventional fractionation (CF) and tangential beam (TB) IMRT compared to three-dimensional conformal radiotherapy (3DCRT).Methods: Two-hundred and sixty-six breast cancer patients with postoperative radiotherapy after breast conserving surgery or mastectomy were retrospectively evaluated. Patients were treated with HF (15 fractions of 2.67 Gy; n = 121) or CF (28 fractions of 1.8 Gy or 25 fractions of 2.0 Gy; n = 145) and TB-IMRT (n = 151) or 3DCRT (n = 115). The acute skin reactions were prospectively assessed using the CTCAE v4 grading scale. Ordinal regression analysis was used to assess the impact of possible prognostic factors on the maximal acute skin reaction.Results: Grade 2 skin reactions were observed in 19 % of the patients treated with CF compared to 2 % treated with HF. On univariate analysis, the fractionation regimen, the PTV (breast versus chest wall), the volume of the PTV and the body mass index were significant prognostic factors for the maximum acute skin reaction. On multivariate analysis, the fractionation regimen (p < 0.00001) and the volume of the PTV (p = 0.0002) remained as independent significant factors.Conclusions: Our data suggest that HF is associated with a significantly reduced maximal acute skin reaction compared to CF. [ABSTRACT FROM AUTHOR]

Background: Electrogram-guided ablation procedures have been proposed as an alternative strategy consisting of either mapping and ablating focal sources or targeting complex fractionated electrograms in atrial fibrillation (AF). However, the incomplete understanding of the mechanism of AF makes difficult the decision of detecting the target sites. To date, feature extraction from electrograms is carried out mostly based on the time-domain morphology analysis and non-linear features. However, their combination has been reported to achieve better performance. Besides, most of the inferring approaches applied for identifying the levels of fractionation are supervised, which lack of an objective description of fractionation. This aspect complicates their application on EGM-guided ablation procedures.Methods: This work proposes a semi-supervised clustering method of four levels of fractionation. In particular, we make use of the spectral clustering that groups a set of widely used features extracted from atrial electrograms. We also introduce a new atrial-deflection-based feature to quantify the fractionated activity. Further, based on the sequential forward selection, we find the optimal subset that provides the highest performance in terms of the cluster validation. The method is tested on external validation of a labeled database. The generalization ability of the proposed training approach is tested to aid semi-supervised learning on unlabeled dataset associated with anatomical information recorded from three patients.Results: A joint set of four extracted features, based on two time-domain morphology analysis and two non-linear dynamics, are selected. To discriminate between four considered levels of fractionation, validation on a labeled database performs a suitable accuracy (77.6 %). Results show a congruence value of internal validation index among tested patients that is enough to reconstruct the patterns over the atria to located critical sites with the benefit of avoiding previous manual classification of AF types.Conclusions: To the best knowledge of the authors, this is the first work reporting semi-supervised clustering for distinguishing patterns in fractionated electrograms. The proposed methodology provides high performance for the detection of unknown patterns associated with critical EGM morphologies. Particularly, obtained results of semi-supervised training show the advantage of demanding fewer labeled data and less training time without significantly compromising accuracy. This paper introduces a new method, providing an objective scheme that enables electro-physiologist to recognize the diverse EGM morphologies reliably. [ABSTRACT FROM AUTHOR]

Background: The primary components of lignocellulosic biomass such as sorghum bagasse are cellulose, hemicellulose, and lignin. Each component can be utilized as a sustainable resource for producing biofuels and bio-based products. However, due to their complicated structures, fractionation of lignocellulosic biomass components is required. Organosolv pretreatment is an attractive method for this purpose. However, as organosolv pretreatment uses high concentrations of organic solvents (>50 %), decreasing the concentration necessary for fractionation would help reduce processing costs. In this study, we sought to identify organic solvents capable of efficiently fractionating sorghum bagasse components at low concentrations. Results: Five alcohols (ethanol, 1-propanol, 2-propanol, 1-butanol, and 1-pentanol) were used for organosolv pretreatment of sorghum bagasse at a concentration of 12.5 %. Sulfuric acid (1 %) was used as a catalyst. With 1-butanol and 1-pentanol, three fractions (black liquor, liquid fraction containing xylose, and cellulose-enriched solid fraction) were obtained after pretreatment. Two-dimensional nuclear magnetic resonance analysis revealed that the lignin aromatic components of raw sorghum bagasse were concentrated in the black liquor fraction, although the major lignin side-chain (β-O-4 linkage) was lost. Pretreatment with 1-butanol or 1-pentanol effectively removed p-coumarate, some guaiacyl, and syringyl. Compared with using no solvent, pretreatment with 1-butanol or 1-pentanol resulted in two-fold greater ethanol production from the solid fraction by Saccharomyces cerevisiae. Conclusions: Our results revealed that a low concentration (12.5 %) of a highly hydrophobic solvent such as 1-butanol or 1-pentanol can be used to separate the black liquor from the solid and liquid fractions. The efficient delignification and visible separation of the lignin-rich fraction possible with this method simplify the fractionation of sorghum bagasse. [ABSTRACT FROM AUTHOR]

Purpose: A method is presented to radiobiologically compare sequential (SEQ) and simultaneously integrated boost (SIB) breast radiotherapy.Methods: The method is based on identically prescribed biologically effective dose (iso-BED) which was achieved by different prescribed doses due to different fractionation schemes. It is performed by converting the calculated three-dimensional dose distribution to the corresponding BED distribution taking into consideration the different number of fractions for generic α/β ratios. A cumulative BED volume histogram (BEDVH) is then derived from the BED distribution and is compared for the two delivery schemes. Ten breast cancer patients (4 right-sided and 6 left-sided) were investigated. Two tangential intensity modulated whole breast beams with two other oblique (with different gantry angles) beams for the boost volume were used. The boost and the breast target volumes with either α/β = 10 or 3 Gy, and ipsi-lateral and contra-lateral lungs, heart, and contra-lateral breast as organs at risk (OARs) with α/β = 3 Gy were compared.Results: Based on the BEDVH comparisons, the use of SIB reduced the biological breast mean dose by about 3 %, the ipsi-lateral lung and heart by about 10 %, and contra-lateral breast and lung by about 7 %.Conclusion: BED based comparisons should always be used in comparing plans that have different fraction sizes. SIB schemes are dosimetrically more advantageous than SEQ in breast target volume and OARs for equal prescribed BEDs for breast and boost. [ABSTRACT FROM AUTHOR]

Background: Sonodynamic therapy (SDT) is a new approach for cancer treatment. Repair by reoxygenation induces cell damage in all treatment which uses photo- and sonosensitizers. In this study, the in vivo antitumor effect of dual-frequency sonication is investigated at low-level intensity and hematoporphyrin (Hp). It is used for the treatment of spontaneous breast adenocarcinoma of Balb/c mice with a variety of dose repetition and fractionation regimes. Methods: Eighty tumor-bearing mice were divided into eight groups, the control group (A); the sham group (B); the injection of Hp alone group (C); 30-min dual-frequency sonication with Hp injection in one repetition at the first day group (D); two repetitions at the first and sixth days group (E); three repetitions at the first, sixth, and twelfth days group (F); four repetitions at the first, sixth, twelfth, and eighteenth days (30 min/repetition) group (G); and the fractional treatment group treated by dual-frequency sonication and Hp injection at the first, third, sixth, and ninth days (7.5 min/fraction) (H). For each group, the tumor growth delay was calculated during 30 days after treatment. These tumors were studied histopathologically. Results: The results show that the treatment with ultrasound dose repetition in two, three, and four times (E, F, and G groups) were effective in delaying tumor growth compared with one-time sonication (D group) (p < 0.05). Also, the ultrasound dose fractionation is more effective in decreasing the tumor growth rate compared with the ultrasound dose repetition in four repeats and in one repeat from the 12th to the 30th day (p < 0.05). Histopathological studies indicated that the mitotic activity of tumor cells was reduced following treatment with four fraction and four repetition protocols. Conclusion: The ultrasound dose fractionation and repetition technique with dual-frequency sonication can have a useful therapeutic effect in sonodynamic therapy with the possibility of use in future clinical applications. [ABSTRACT FROM AUTHOR]

Background: Radiation-induced rib fracture after stereotactic body radiotherapy (SBRT) for lung cancer has been recently reported. However, incidence of radiation-induced rib fracture after SBRT using moderate fraction sizes with a long-term follow-up time are not clarified. We examined incidence and risk factors of radiation-induced rib fracture after SBRT using moderate fraction sizes for the patients with peripherally located lung tumor. Methods: During 2003-2008, 41 patients with 42 lung tumors were treated with SBRT to 54-56 Gy in 9-7 fractions. The endpoint in the study was radiation-induced rib fracture detected by CT scan after the treatment. All ribs where the irradiated doses were more than 80% of prescribed dose were selected and contoured to build the dose-volume histograms (DVHs). Comparisons of the several factors obtained from the DVHs and the probabilities of rib fracture calculated by Kaplan-Meier method were performed in the study. Results: Median follow-up time was 68 months. Among 75 contoured ribs, 23 rib fractures were observed in 34% of the patients during 16-48 months after SBRT, however, no patients complained of chest wall pain. The 4-year probabilities of rib fracture for maximum dose of ribs (Dmax) more than and less than 54 Gy were 47.7% and 12.9% (p = 0.0184), and for fraction size of 6, 7 and 8 Gy were 19.5%, 31.2% and 55.7% (p = 0.0458), respectively. Other factors, such as D2cc, mean dose of ribs, V10-55, age, sex, and planning target volume were not significantly different. Conclusions: The doses and fractionations used in this study resulted in no clinically significant rib fractures for this population, but that higher Dmax and dose per fraction treatments resulted in an increase in asymptomatic grade 1 rib fractures. [ABSTRACT FROM AUTHOR]

Background The aim of the present analysis was to evaluate the recurrence pattern in patients with recurrent malignant glioma after re-irradiation in combination with bevacizumab as there is limited data on how to optimally choose dose, fractionation and delineation margins. Methods Thirty-one patients with recurrent malignant glioma treated with re-irradiation and bevacizumab after previous chemoradiotherapy (concurrent temozolomide 75 mg/m2/d according to the EORTC/NCIC trial) and [18 F]FET-PET and/or MRI confirmed recurrence were retrospectively analyzed. Bevacizumab was applied twice during fractionated reirradiation (10 mg/kg, d1 + d15, median 36 Gy, conventionally fractionated). Recurrence patterns were assessed by means of [18 F]FET-PET and/or MRI. Results Median follow-up was 34.0 months for all patients [95%-CI, 27.7-40.3] and median postrecurrence survival 10.8 months [95%-CI, 9.2-12.4]. Concerning the recurrence patterns, 61.3% of these were located in-field (19 patients), 22.6% were marginal (7 patients) and 16.1% ex-field (5 patients). No influence on the recurrence pattern was observed according to sex, WHO grade, maintenance chemotherapy or MGMT methylation status whereas planning target volume (PTV) size had a significant influence on the recurrence pattern (p = 0.032). PTV sizes > 75 ml were associated with a higher in-field recurrence rate and lower median post-recurrence progression-free survival (8.5 vs. 4.9 months, p = 0.016). Conclusions After the administration of re-irradiation with bevacizumab the recurrence pattern seems to be mainly centrally located. The PTV size was the main predictor for a marginal/ex-field recurrence. [ABSTRACT FROM AUTHOR]

Background Stereotactic body radiotherapy (SBRT) for non-small-cell lung cancer (NSCLC) has led to promising local control and overall survival for fractionation schemes with increasingly high fractional doses. A point has however been reached where the number of fractions used might be too low to allow efficient local inter-fraction reoxygenation of the hypoxic cells residing in the tumour. It was therefore the purpose of this study to investigate the impact of hypoxia and extreme hypofractionation on the tumour control probability (TCP) from SBRT. Methods A three-dimensional model of tumour oxygenation able to simulate oxygenation changes on the microscale was used. The TCP was determined for clinically relevant SBRT fractionation schedules of 1, 3 and 5 fractions assuming either static tumour oxygenation or that the oxygenation changes locally between fractions due to fast reoxygenation of acute hypoxia without an overall reduction in chronic hypoxia. Results For the schedules applying three or five fractions the doses required to achieve satisfying levels of TCP were considerably lower when local oxygenation changes were assumed compared to the case of static oxygenation; a decrease in D50 of 17.7 Gy was observed for a five-fractions schedule applied to a 20% hypoxic tumour when fast reoxygenation was modelled. Assuming local oxygenation changes, the total doses required for a tumor control probability of 50% were of similar size for one, three and five fractions. Conclusions Although attractive from a practical point of view, extreme hypofractionation using just one single fraction may result in impaired local control of hypoxic tumours, as it eliminates the possibility for any kind of reoxygenation. [ABSTRACT FROM AUTHOR]

Purpose Urinary incontinence (UI) following prostate radiotherapy is a rare toxicity that adversely affects a patient's quality of life. This study sought to evaluate the incidence of UI following stereotactic body radiation therapy (SBRT) for prostate cancer. Methods Between February, 2008 and October, 2010, 204 men with clinically localized prostate cancer were treated definitively with SBRT at Georgetown University Hospital. Patients were treated to 35-36.25 Gray (Gy) in 5 fractions delivered with the CyberKnife (Accuray). UI was assessed via the Expanded Prostate Index Composite (EPIC)-26. Results Baseline UI was common with 4.4%, 1.0% and 3.4% of patients reporting leaking > 1 time per day, frequent dribbling and pad usage, respectively. Three year post treatment, 5.7%, 6.4% and 10.8% of patients reported UI based on leaking > 1 time per day, frequent dribbling and pad usage, respectively. Average EPIC UI summary scores showed an acute transient decline at one month post-SBRT then a second a gradual decline over the next three years. The proportion of men feeling that their UI was a moderate to big problem increased from 1% at baseline to 6.4% at three years post-SBRT. Conclusions Prostate SBRT was well tolerated with UI rates comparable to conventionally fractionated radiotherapy and brachytherapy. More than 90% of men who were pad-free prior to treatment remained pad-free three years following treatment. Less than 10% of men felt post-treatment UI was a moderate to big problem at any time point following treatment. Longer term followup is needed to confirm late effects. [ABSTRACT FROM AUTHOR]

Background Microglial cells are resident macrophages of the central nervous system and important cellular mediators of the immune response and neuroinflammatory processes. In particular, microglial activation and communication between microglia, astrocytes, and neurons are hallmarks of the pathogenesis of several neurodegenerative diseases. Membrane proteins and their N-linked glycosylation mediate this microglial activation and regulate many biological process including signal transduction, cell-cell communication, and the immune response. Although membrane proteins and N-glycosylation represent a valuable source of drug target and biomarker discovery, the knowledge of their expressed proteome in microglia is very limited. Results To generate a large-scale repository, we constructed a membrane proteome and Nglycoproteome from BV-2 mouse microglia using a novel integrated approach, comprising of crude membrane fractionation, multienzyme-digestion FASP, N-glyco-FASP, and various mass spectrometry. We identified 6928 proteins including 2850 membrane proteins and 1450 distinct N-glycosylation sites on 760 N-glycoproteins, of which 556 were considered novel N-glycosylation sites. Especially, a total of 114 CD antigens are identified via MS-based analysis in normal conditions of microglia for the first time. Our bioinformatics analysis provides a rich proteomic resource for examining microglial function in, for example, cell-tocell communication and immune responses. Conclusions Herein, we introduce a novel integrated proteomic approach for improved identification of membrane protein and N-glycosylation sites. To our knowledge, this workflow helped us to obtain the first and the largest membrane proteomic and N-glycoproteomic datesets for mouse microglia. Collectively, our proteomics and bioinformatics analysis significantly expands the knowledge of the membrane proteome and N-glycoproteome expressed in microglia within the brain and constitutes a foundation for ongoing proteomic studies and drug development for various neurological diseases. [ABSTRACT FROM AUTHOR]

Background: The accuracy of the two dose calculation engines available for RapidArc planning (both released for clinical use) is investigated in comparison to the COMPASS data. Methods: Two dose calculation algorithms (Acuros-XB and Anisotropic Analytic Algorithm (AAA)) were used to calculate RA plans and compared to calculations with the Collapsed Cone Convolution algorithm (CC) from the COMPASS system (IBA Dosimetry). CC calculations, performed on patient data, are based on experimental fluence measurements with a 2D array of ion chambers mounted on the linac head. The study was conducted on clinical cases treated with RA. Five cases for each of the following groups were included: Brain, Head and Neck, Thorax, Pelvis and stereotactic body radiation therapy for hypo-fractionated treatments with small fields. COMPASS measurements were performed with the iMatrixx-2D array. RapidArc plans were optimized for delivery using 6MVphotons from a Clinac-iX (Varian, Palo Alto, USA). Accuracy of the RA calculation was appraised by means of: 1) comparison of Dose Volume histograms (DVH) metrics; 2) analysis of differential dose distributions and determination of mean dose differences per organ; 3) 3D gamma analysis with distance-to-agreement and dose difference thresholds set to 3%/3 mm or 2%/2 mm fortargets, organs at risks and for the volumes encompassed by the 50 and 10% isodoses. Results: For almost all parameters, the better agreement was between Acuros-XB and COMPASS independently from the anatomical site and fractionation. The same result was obtained from the mean dose difference per organ with Acuros-CC average differences below 0.5% while for AAA-CC data, average deviations exceeded 0.5% and in the case of the pelvis 1%. Relevance of observed differences determined with the 3D gamma analysis resulted ina pass rate exceeding 99.5% for Acuros-CC and exceeding 97.5% for AAA-CC. Conclusions: This study demonstrated that i) a good agreement exists between COMPASS-CC calculations basedon measured fluences with respect to dose distributions obtained with both Acuros-XB and AAA algorithms; ii) 3D dose distributions reconstructed from actual delivery coincide very precisely with the planned data; iii) a slight preference in favor of Acuros-XB was observed suggesting the preference for this algorithm in clinical applications. [ABSTRACT FROM AUTHOR]

Background: Hypofractionated Radiosurgery (HR) is a therapeutic option for delivering partial brain radiotherapy (RT) to large brain metastases or resection cavities otherwise not amenable to single fraction radiosurgery (SRS). The use, safety and efficacy of HR for brain metastases is not well characterized and the optimal RT dosefractionation schedule is undefined. Methods: Forty-two patients treated with HR in 3-5 fractions for 20 (48%) intact and 22 (52%) resected brain metastases with a median maximum dimension of 3.9 cm (0.8-6.4 cm) between May 2008 and August 2011 were reviewed. Twenty-two patients (52%) had received prior radiation therapy. Local (LC), intracranial progression free survival (PFS) and overall survival (OS) are reported and analyzed for relationship to multiple RT variables through Cox-regression analysis. Results: The most common dose-fractionation schedules were 21 Gy in 3 fractions (67%), 24 Gy in 4 fractions (14%) and 30 Gy in 5 fractions (12%). After a median follow-up time of 15 months (range 2-41), local failure occurred in 13 patients (29%) and was a first site of failure in 6 patients (14%). Kaplan-Meier estimates of 1 year LC, intracranial PFS, and OS are: 61% (95% CI 0.53 - 0.70), 55% (95% CI 0.47 - 0.63), and 73% (95% CI 0.65 - 0.79), respectively. Local tumor control was negatively associated with PTV volume (p = 0.007) and was a significant predictor of OS (HR 0.57, 95% CI 0.33 - 0.98, p = 0.04). Symptomatic radiation necrosis occurred in 3 patients (7%). Conclusions: HR is well tolerated in both new and recurrent, previously irradiated intact or resected brain metastases. Local control is negatively associated with PTV volume and a significant predictor of overall survival, suggesting a need for dose escalation when using HR for large intracranial lesions. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via the original article. [ABSTRACT FROM AUTHOR]

Background: It has been reported that radiation therapy (RT) followed by procarbazine, lomustine, and vincristine (PCV) chemotherapy could improve progression-free survival (PFS) and overall survival (OS) in patients with high-risk World Health Organization (WHO) grade 2 gliomas after surgery. However, procarbazine is not available in China. In clinical practice, Chinese doctors often use radiotherapy combined with temozolomide (TMZ) to treat these patients, although large-scale prospective studies are lacking. This trial aims to confirm whether RT combined with temozolomide can improve PFS and OS in high-risk patients with low-grade gliomas (LGGs).Methods/design: This is a two-group, randomized controlled trial (RCT) enrolling patients who have LGGs (WHO grade 2) and are aged 40 years or older without regard to the extent of resection or are aged younger than 40 years old with subtotal resection or biopsy. An estimated 250 patients will be enrolled. Eligible participants will be randomly assigned to receive RT alone or RT plus TMZ chemotherapy in a 1:1 ratio. The same RT will be given to all eligible participants regardless of whether they are randomly assigned to the RT group or the chemoradiotherapy (CRT) group. While in the CRT group, patients will receive adjuvant TMZ with or without concurrent radiochemotherapy. The primary outcome of this trial is PFS, and it will be analyzed by the intention-to-treat approach. Secondary outcomes include OS, adverse events, and cognitive function.Discussion: The objective of our research is to assess the effect of radiotherapy coupled with TMZ in high-risk patients with LGGs after surgery, compared with RT alone. Different histological types and molecular subtypes will be examined, and a corresponding subgroup analysis will be conducted. Our data can provide evidence for postoperative adjuvant therapy in patients with high-risk LGGs in China.Trial Registration: Chinese Clinical Trial Registry, ChiCTR1800015199. Registered on 13 March 2018. [ABSTRACT FROM AUTHOR]

Background: Until 50% of patients with renal cancer or melanoma, develop brain metastases during the course of their disease. Stereotactic radiotherapy has become a standard of care for patients with a limited number of brain metastases. Given the radioresistant nature of melanoma and renal cancer, optimization of the fractionation of stereotactic radiotherapy is needed. The purpose of this retrospective study was to elucidate if hypofractionated stereotactic radiotherapy (HFSRT) impacts local control of brain metastases from radioresistant tumors such as melanoma and renal cancer, in comparison with radiosurgery (SRS).Methods: Between 2012 and 2016, 193 metastases, smaller than 3 cm, from patients suffering from radioresistant primaries (melanoma and renal cancer) were treated with HFSRT or SRS. The primary outcome was local progression free survival (LPFS) at 6, 12 and 18 months. Overall survival (OS) and cerebral progression free survival (CPFS) were secondary outcomes, and were evaluated per patient. Objective response rate and radionecrosis incidence were also reported. The statistical analysis included a supplementary propensity score analysis to deal with bias induced by non-randomized data.Results: After a median follow-up of 7.4 months, LPFS rates at 6, 12 and 18 months for the whole population were 83, 74 and 70%, respectively. With respect to fractionation, LPFS rates at 6, 12 and 18 months were 89, 79 and 73% for the SRS group and 80, 72 and 68% for the HFSRT group. The fractionation schedule was not statistically associated with LPFS (HR = 1.39, CI95% [0.65-2.96], p = 0.38). Time from planning MRI to first irradiation session longer than 14 days was associated with a poorer local control rate. Over this time, LPFS at 12 months was reduced from 86 to 70% (p = 0.009). Radionecrosis occurred in 7.1% for HFSRT treated metastases to 9.6% to SRS treated metastases, without any difference according to fractionation (p = 0.55). The median OS was 9.6 months. Six, 12 and 18 months CPFS rates were 54, 24 and 17%, respectively.Conclusion: Fractionation does not decrease LPFS. Even for small radioresistant brain metastases (< 3 cm), HFSRT, with 3 or 6 fractions, leads to an excellent local control rate of 72% at 1 year with a rate of 7.1% of radionecrosis. HFSRT is a safe and efficient alternative treatment to SRS. [ABSTRACT FROM AUTHOR]

Background: To evaluate the clinical outcomes of patients treated with 3D conformal Hypo-fractionated, deep Inspiratory breath-hold (DIBH), Partial breast radiotherapy, termed "HIP." HIP was implemented to merge the schedule of once-daily breast hypofractionation with partial breast treatment.Methods: We identified 38 breast cancers in 37 patients from 2013 to 2014 treated at our institution with HIP following lumpectomy for early stage breast cancer. Patients received a hypo-fractionated course (≤ 20 fractions) of once daily radiation to the partial breast (lumpectomy cavity + margin) utilizing DIBH regardless of laterality. Clinical and treatment-related characteristics were obtained, including target volume and organ at risk (OAR) dosimetric characteristics. Patients were followed clinically and with at least yearly mammograms for up to 36 months (range 5-36 months). Acute and late toxicity was scored using the Common Terminology Criteria for Adverse Events (CTCAE) v4.03.Results: Patients received a median dose of 42.56 Gy in 16 Fractions (Fx) (range 40.05-53.2 Gy; and 15-20 Fx). OAR doses were low, with a mean heart dose of 0.37 Gy, an ipsilateral lung V20 mean of 4%, and a contralateral lung V5 of 1%. Acute toxicity (≤ grade 2) was present in 79% (n = 30) of the cases, with dermatitis being the most common finding (63%). Late grade 1-2 toxicity was present in 42% (n = 16) of the cases, with hyperpigmentation being the most common finding (n = 9). There were no severe acute or late toxicities (≥ grade 3). At a median follow up of 21 months, there were no local, regional, or distant failures.Conclusions: We report limited toxicity in this low risk cohort of patients with early stage breast cancer treated with HIP, a unique and logical combination of 3-D conformal external beam radiotherapy, moderate hypo-fractionation, and DIBH. [ABSTRACT FROM AUTHOR]

Background: Good radiotherapy reporting in clinical trials of prostate radiotherapy is important because it will allow accurate reproducibility of radiotherapy treatment and minimize treatment variations that can affect patient outcomes. The aim of our study is to assess the quality of prostate radiotherapy (RT) treatment reporting in randomized controlled trials in prostate cancer.Methods: We searched MEDLINE for randomized trials of prostate cancer, published from 1996 to 2016 and included prostate RT as one of the intervention arms. We assessed if the investigators reported the ten criteria adequately in the trial reports: RT dose prescription method; RT dose-planning procedures; organs at risk (OAR) dose constraints; target volume definition, simulation procedures; treatment verification procedures; total RT dose; fractionation schedule; conduct of quality assurance (QA) as well as presence or absence of deviations in RT treatment planning and delivery. We performed multivariate logistic regression to determine the factors that may influence the quality of reporting.Results: We found 59 eligible trials. There was significant variability in the quality of reporting. Target volume definition, total RT dose and fractionation schedule were reported adequately in 97% of included trials. OAR constraints, simulation procedures and presence or absence of deviations in RT treatment planning and delivery were reported adequately in 30% of included trials. Twenty-four trials (40%) reported seven criteria or more adequately. Multivariable logistic analysis showed that trials that published their quality assurance results and cooperative group trials were more likely to have adequate quality in reporting in at least seven criteria.Conclusion: There is significant variability in the quality of reporting on prostate radiotherapy treatment in randomized trials of prostate cancer. We need to have consensus guidelines to standardize the reporting of radiotherapy treatment in randomized trials. [ABSTRACT FROM AUTHOR]