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• Boost dose is beneficial for young patients affected by breast cancer. • Intraoperative electrons (IOERT) boost and hypofractionated whole breast irradiation (HWBI) represent a suitable modality. • Local control with IOERT/HWBI was excellent, even in very young patients. • High tumor bed fibrosis was observed due to high cumulative EQD2 boost dose. To evaluate outcome of intraoperative electron boost (IOERT) and hypofractionated whole breast irradiation (HWBI) for breast cancer (BC) in young women. Women aged ≤ 48 with pT1-2 N0-1 BC received 12 Gy IOERT boost during conservative surgery followed by 3-dimensional conformal HWBI in 13 fractions (2.85 Gy/die). Local relapses (LR) and survival (disease-free, DFS; specific, BCSS; overall, OS) were analyzed. 481 consecutive BC patients, mostly node negative, with median age of 42 were treated between 2004 and 2014. Median tumor size was 1.48 cm and median IOERT collimator was 4 cm. After 25-day mean interval, HWBI was delivered. At a median follow-up of 9.6 years, there were 23 LRs (4.8 %, 9 of which were in the boost region). Ten-year LR cumulative incidence was 4.1 % (95 %CI, 2.5–6.3). Over time, local control rate decreased for Luminal A and HER2 positive with negative hormonal receptors, while remained steady for triple negative. At multivariate analysis, LR predictors included age < 40, extensive intraductal component and the use of 4-cm IOERT collimator size. Ten-year survival outcomes were as follows: DFS 80.0 % (95 % CI, 75.8–83.5), BCSS 97.5 % (95 % CI, 95.5–98.6 %), OS 96.5 % (95 % CI, 94.3–97.9). Luminal B HER2 negative had the worse survival outcomes. Perioperative complications were uncommon (16.4 %), acute toxicity was mild (<2% Grade 3), but moderate/severe fibrosis was described in 40.8 % of the cases. Cosmesis was scored as excellent/good in 86 % of the cases. ELIOT boost and HWBI achieved an excellent local control at the cost of tumor bed fibrosis. IOERT boost dose lower than 12 Gy is advisable. [ABSTRACT FROM AUTHOR]

• The role of an additional boost to the tumor bed in DCIS is still unknown. • Severity of acute skin toxicities is significantly increased by tumor bed boost. • Smoking history and large breast CTV are predictive factors of acute toxicities. • Dummy run before patients' inclusion reduced the risk of major TP deviations. To describe the quality assurance (QA) program and early toxicities in the phase III randomized trial BONBIS (NCT00907868) on the role of a localized radiation boost in ductal carcinoma in situ (DCIS). From November 2008 to July 2014, 2004 patients were randomized in arm A (only whole breast radiotherapy, WBRT) and arm B (WBRT + boost). The QA program involved 44 participant centers that performed the dummy run (DR). Compliance and uniformity of clinical target volume (CTV) delineations, and dose prescription and delivery according to the BONBIS trial radiotherapy guidelines were analyzed. Acute toxicities (during and up to 3 months after radiotherapy completion, NCI-CTCAE v3.0 classification) were evaluated in 1929 patients. The differences in whole breast CTV (CTV1) and planning target volume (PTV1) were ≤10%, and the differences in boost CTV (CTV2) and PTV (PTV2) were ≥20% compared with the reference DR values; 95% of the prescribed dose encompassed 98.7% and 100% of the median CTV1 and CTV2. Grade ≥2 breast erythema (38.3% vs. 22.4% of grade 2 and 5.4% vs. 2.1% of grade 3, p < 0.001), grade ≥2 dermatitis (2.8% vs. 0.7%, p < 0.001), and grade 2 hyperpigmentation (6.9% vs. 3.6%, p = 0.005) were more frequent in arm B than arm A. No acute lung or cardiac toxicity was observed. Smoking history, large breast size, and large breast CTV were strong predictive factors of grade ≥2 acute skin toxicities. The QA program showed deviations in breast and tumor bed delineation. The boost significantly increased acute skin toxicities. [ABSTRACT FROM AUTHOR]

• First-in-human application of a weekly online adaptive MR-guided radiotherapy boost. • Rectal ultrasound gel filling facilitated excellent tumor visualization and sparing of healthy mucosa. • Treatment was very well tolerated with only minimal toxicity. Dose escalated radiotherapy has previously been investigated as a strategy to increase complete response rates in rectal cancer. However large safety margins are required using cone-beam computed tomography guided radiotherapy leading to high doses to organs at risk or insufficient target volume coverage in order to keep dose constraints. We herein present the first clinical application of a new technique for dose escalation in rectal cancer using online magnetic resonance (MR)-guidance and rectal ultrasound gel filling. A 73-year-old patient with distal cT3a cN0 cM0 rectal cancer was referred for definitive radiochemotherapy with the goal of organ preservation after multidisciplinary discussion. A dose of 45 Gy in 25 fractions with a stereotactic integrated boost to the primary tumor of 50 Gy with concomitant 5-fluorouracil was prescribed. Furthermore, a boost to the primary tumor with 3 Gy per fraction using the adapt-to-shape workflow on a 1.5 T MR-Linac was planned once weekly. For the boost fractions 100 cc of ultrasound gel was applied rectally in order to improve tumor visibility and distancing of uninvolved rectal mucosa. In order to determine the required planning target volume margin diagnostic scans of ten rectal cancer patients conducted with rectal ultrasound gel filling were studied. Based on the ten diagnostic scans an average isotropic margin of 4 mm was found to be sufficient to cover 95% of the target volume during an online adaptive workflow. Three boost fractions were applied, mean treatment duration was 22:34 min. Treatment was well tolerated by the patient with no more than PRO-CTCAE grade I° toxicity of any kind. The rectal ultrasound gel filling resulted in superior visibility of the tumor and reduced the dose to the involved mucosa especially in the high dose range compared with a boost plan calculated without any filling. A considerable tumor shrinkage was observed during treatment from 17.43 cc at baseline to 4 cc in week four. This novel method appears to be a simple but effective strategy for dose escalated radiotherapy in rectal cancer. Based on the encouraging observation, a prospective trial is currently under preparation. [ABSTRACT FROM AUTHOR]

• 12 year results confirm HDR boost improves prostate cancer relapse free survival. • No difference in overall survival is seen. • No excess toxicity is seen in the HDR boost arm. A randomised phase-III trial compared external beam radiotherapy (EBRT) alone with EBRT combined with high-dose-rate brachytherapy boost (HDR-BTb) in localised prostate adenocarcinoma. Previous analysis, at median follow up of 85 months, demonstrated improved relapse free survival (RFS) with EBRT + HDR-BTb. This data has now been updated with a median follow up of 131 months. From December 1997 to August 2005, patients were assigned either to EBRT alone delivering 55 Gy in 20 fractions over 4 weeks or EBRT followed by a temporary high-dose-rate implant delivering 2 × 8·5 Gy over 24 h. The primary endpoint was RFS defined by a PSA rise ≥2.0 µg/l above nadir, clinical progression or death. Actuarial survival rates and Hazard Ratios (HRs) were calculated using the Kaplan–Meier method and Cox's Proportional Hazard Model, respectively. Secondary endpoints were overall survival (OS), urinary and bowel toxicity. One hundred and six patients received EBRT alone and 110 EBRT + HDR-BTb. Median time to relapse was 137 months in the HDR-BTb arm compared to 82 months for EBRT alone (p = 0·01). A 27% risk of recurrence with EBRT alone was observed (p = 0·001), resulting in a 21% improvement in RFS at 12 years with EBRT + HDR-BTb. In multivariate analysis treatment arm, risk category and no androgen deprivation therapy were significant covariates for risk of relapse. Differences in overall survival were not significant. At 12 years there remains a significant improvement in RFS after EBRT + HDR-BTb; both treatments were equitoxic for severe late urinary and bowel events and urethral strictures. [ABSTRACT FROM AUTHOR]

• Overall treatment tolerance of HWBI plus IOERT as a boost is excellent. • Acute and late toxicity are mild. • Postoperative cosmetic appearance is not impaired. • T-size, tube diameter, age and fibrosis are negative predictors for breast cosmesis. To assess the role of intraoperative radiation with electrons (IOERT) as tumor bed boost followed by hypofractionated whole breast irradiation (HWBI) after breast conserving surgery (BCS) of patients with low to intermediate risk breast cancer focusing on acute/late toxicity and cosmetic outcome. In 2011, a prospective multicenter trial (NCT01343459) was started. Treatment consisted of BCS, IOERT (11.1 Gy) and HWBI (40.5 Gy in 15 fractions). In a single-arm design, 5-year IBR-rates are benchmarked by a sequential ratio test (SQRT) against best published evidences in 3 age groups (35–40 y, 41–50 y, >50 y). Acute/late toxicity and cosmesis were evaluated by validated scorings systems. Of 627 eligible patients, 44 were excluded, leaving 583 to analyze. After a median follow-up (FUP) of 45 months (range 0–74), for acute effects CTCAE-score 0/1 was noted in 91% (end of HWBI) and 92% (4 weeks later), respectively. Late toxicity Grading 0/1 (mean values, ranges) by LENT-SOMA criteria were observed in 92.7% (89–97.3) at 4/5 months, rising to 96.5% (91–100) at 6 years post HWBI. Baseline cosmesis after wound healing prior to HWBI was scored as excellent/good in 86% of cases by subjective (patient) and in 74% by objective (doctor) assessment with no impairment thereafter. Acute and late treatment tolerance of a combined Boost-IOERT/HWBI regimen is excellent in short/mid-term assessment. Postoperative cosmetic appearance is not impaired after 3 years FUP. [ABSTRACT FROM AUTHOR]

• This data can be used to determine margins for radiotherapy boosting for rectal cancer. • 80% of rectal tumors showed no microscopic intramural spread after neoadjuvant chemoradiation. • To treat all MIS in 95% of patients, a 5.5 mm margin around visible residual tumor would suffice. • Exploratory analysis showed that ypT stage was predictive for extent of MIS. • Exploratory analysis showed: longer interval between chemoradiation and surgery gives more MIS. In selected rectal cancer patients with residual local disease following neoadjuvant chemoradiation (CRT) and the preference of an organ preservation pathway, additional treatment with dose escalation by endoluminal radiotherapy (RT) may ultimately result in a clinical complete response. To date, the widespread introduction of selective endoluminal radiation techniques is hampered by a lack of evidence-based guidelines that describe the radiation treatment volume in relation to the residual tumor mass. In order to convert an incomplete response into a complete one with additional treatment such as dose-escalation with endoluminal RT from a theoretical perspective, it seems important to treat all remaining microscopic tumor cells after CRT. In this setting, residual tumor extension beneath normal appearing mucosa (microscopic intramural spread – MIS) becomes relevant for accurate tumor volume and margin estimation. With the goal of providing evidence-based guidelines that define an appropriate treatment volume and patient selection, we present results from a meta-analysis based on individual patient data of studies that have assessed the extent or range of MIS of rectal cancers after neoadjuvant CRT. This meta-analysis should provide an estimate of the residual tumor volume/extension that needs to be targeted by any additional radiation therapy boost in order to achieve complete tumor eradication after initial incomplete or near-complete response following standard CRT. A PubMed search was performed. Additional articles were selected based on identification from reference lists. Papers were eligible when reporting MIS in patients who were treated by total mesorectal excision or local excision/transanal endoscopic microsurgery (TEM) after neo-adjuvant long-course CRT. The mean MIS was calculated for the entire group along with the 70th until 95th percentiles. Additional exploratory subgroup analyses were performed. Individual patient data from 349 patients with residual disease from five studies were analyzed. 80% of tumors showed no MIS. In order to appropriately treat MIS in 95% of rectal cancer patients after CRT, a margin of 5.5 mm around the macroscopic tumor would suffice. An exploratory subgroup analysis showed that T-stage after CRT (ypT) and time interval between neoadjuvant CRT and surgery are significant factors predicting the extent of MIS (p < 0.001.) The group of ypT1 had the smallest MIS, followed by the ypT3-4 group, while the ypT2 group had the largest MIS (p < 0.001). Regarding time interval between CRT and surgery, a statistically significant difference was seen when comparing the three time-interval groups (less than 8 weeks, 8–12 weeks, and more than 12 weeks), where waiting more than 12 weeks after CRT resulted in the largest MIS (p < 0.0001). Based on this meta-analysis, in order to treat the MIS for 95% of rectal cancer patients after CRT, a Clinical Target Volume (CTV) margin of 5.5 mm from the lateral most edge of the macroscopic tumor would suffice. 80% of tumors showed no MIS and would not require an extra CTV margin for treatment. These findings support the feasibility of localized radiotherapy boosts for dose-escalation to improve response among patients with incomplete response after standard CRT and can also be applied in the surgical setting. [ABSTRACT FROM AUTHOR]

• Cosmetic outcomes of BCS for DCIS were independent of treating centre geography. • Conventional and hypofractionated WBI achieved similar 3-year cosmesis. • Tumour bed boost (16 Gy in 8 fractions) doubled the risk of cosmetic deterioration. • The adverse impact of a tumour bed boost was independent of WBI fractionation. To assess the cosmetic impact of breast conserving surgery (BCS), whole breast irradiation (WBI) fractionation and tumour bed boost (TBB) use in a phase III trial for women with ductal carcinoma in situ (DCIS) of the breast. Baseline and 3-year cosmesis were assessed using the European Organization for Research and Treatment of Cancer (EORTC) Cosmetic Rating System and digital images in a randomised trial of non-low risk DCIS treated with postoperative WBI +/− TBB. Baseline cosmesis was assessed for four geographic clusters of treating centres. Cosmetic failure was a global score of fair or poor. Cosmetic deterioration was a score change from excellent or good at baseline to fair or poor at three years. Odds ratios for cosmetic deterioration by WBI dose-fractionation and TBB use were calculated for both scoring systems. 1608 women were enrolled from 11 countries between 2007 and 2014. 85–90% had excellent or good baseline cosmesis independent of geography or assessment method. TBB (16 Gy in 8 fractions) was associated with a >2-fold risk of cosmetic deterioration (p < 0.001). Hypofractionated WBI (42.5 Gy in 16 fractions) achieved statistically similar 3-year cosmesis compared to conventional WBI (50 Gy in 25 fractions) (p ≥ 0.18). The adverse impact of a TBB was not significantly associated with WBI fractionation (interaction p ≥ 0.30). Cosmetic failure from BCS was similar across international jurisdictions. A TBB of 16 Gy increased the rate of cosmetic deterioration. Hypofractionated WBI achieved similar 3-year cosmesis as conventional WBI in women treated with BCS for DCIS. [ABSTRACT FROM AUTHOR]

Highlights • First available report on randomized study about intensification of radiochemotherapy by either radiotherapy dose escalation or multidrug chemosensibilisation, for Low-located cT2N0–2M0, cT3N0–2M0 (up to 12 cm from anal verge). • Major pathological response rates (i.e.: TRG 1-2) were significantly improved in the RT dose escalated arm (Xelac arm 61.7% vs. Xelox 52.3%). • Pathological complete response rates (primary outcome) did not differ between 2 arms. • Xelox arm (multidrug chemosensibilisation) presented higher G ≥ 3 haematologic, upper gastrointestinal and neurologic toxicity. • Patients achieving both major and pathological complete response presented significantly better clinical outcome (disease free and overall survival) irrespective of the treatment arm. Abstract Background and purpose Capecitabine-based radiochemotherapy (cbRCT) is standard for preoperative long-course radiochemotherapy of locally advanced rectal cancer. This prospective, parallel-group, randomised controlled trial investigated two intensification regimens. cT4 lesions were excluded. Primary objective: pathological outcome (TRG 1-2) among arms. Materials and methods Low-located cT2N0–2M0, cT3N0–2M0 (up to 12 cm from anal verge) presentations were treated with cbRCT randomly intensified by either radiotherapy boost (Xelac arm) or multidrug concomitant chemotherapy (Xelox arm). Xelac: concomitant boost to bulky site (45 Gy/1.8 Gy/die, 5 sessions/week to the pelvis, +10 Gy at 1 Gy twice/week to the bulky) plus concurrent capecitabine (1650 mg/mq/die). Xelox: 45 Gy to the pelvis + 5.4 Gy/1.8 Gy/die, 5 sessions/week to the bulky site + concurrent capecitabine (1300 mg/mq/die) and oxaliplatin (130 mg/mq on days 1,19,38). Surgery was planned 7–9 weeks after radiochemotherapy. Results From June 2005 to September 2013, 534 patients were analysed: 280 in Xelac, 254 in Xelox arm. Xelox arm presented higher G ≥ 3 haematologic (p = 0.01) and neurologic toxicity (p < 0.001). Overall, 98.5% patients received curative surgery. The tumour regression grade distribution did not differ between arms (p = 0.102). TRG 1+2 rate significantly differed: Xelac arm 61.7% vs. Xelox 52.3% (p = 0.039). Pathological complete response (ypT0N0) rates were 24.4 and 23.8%, respectively (p non-significant). Median follow-up:5.62 years. Five-year disease-free survival rate were 74.7% (Xelac) and 73.8% (Xelox), respectively (p = 0.444). Five-year overall survival rate were 80.4% (Xelac) and 85.5% (Xelox), respectively (p = 0.155). Conclusion Xelac arm significantly obtained higher TRG1-2 rates. No differences were found about clinical outcome. Because of efficacy on TRG, inferior toxicity and good compliance, Xelac schedules or similar radiotherapy dose intensification schemes could be considered as reference treatments for cT3 lesions. [ABSTRACT FROM AUTHOR]

Background and purpose Platinum based chemoradiotherapy is the standard of care for inoperable non-small cell lung cancer (NSCLC). With evidence that NSCLC can have a dose dependent response with stereotactic ablative radiotherapy (SABR), we hypothesize that a SABR boost on residual tumor treated with chemoradiotherapy could increase treatment efficacy. The purpose of this study was to determine feasibility of such an approach. Material and methods A prospective phase I trial was performed including 26 patients. Time-to-event continual reassessment method (TITE-CRM) was used for dose escalation which ranged from 3 × 7 to 3 × 12 Gy for the stereotactic boost, after 46 Gy (2 Gy per day) of chemoradiotherapy. Results Median follow-up was of 37.1 months (1.7–60.7), and 3, 4, 3, 3, 9 and 4 patients were included at the dose levels 1, 2, 3, 4, 5 and 6, respectively. During chemoradiotherapy, 9 patients experienced grade 3 toxicity. After stereotactic radiotherapy, 1 patient experienced an esophageal fistula (with local relapse) at the 3 × 11 Gy level, and 1 patient died from hemoptysis at the 3 × 12 Gy level. The 2-year rate of local control, locoregional free survival, metastasis-free survival, and overall survival was 70.3%, 55.5%, 44.5% and 50.8%, respectively. Conclusion In the treatment of NSCLC with chemoradiotherapy followed by a stereotactic boost, the safe recommended dose in our protocol was a boost dose of 3 × 11 Gy. [ABSTRACT FROM AUTHOR]

Purpose Breast conserving treatment, consisting of lumpectomy followed by whole-breast irradiation, is considered the standard of care in early-stage breast cancer. Randomized studies have reported that delivering boost doses to tumor bed improves local control rates, particularly in young women. This study sought to evaluate local control and cosmetic results of delivering boost doses using a high-dose-rate (HDR) brachytherapy (HDRBT) in breast cancer conservative treatment. Methods We included 621 T1–T2, N0–N1 breast cancer patients who underwent lumpectomy, external irradiation (44 Gy over 5 weeks), and a boost dose of two fractions of 5 Gy to the tumor bed by means of HDR iridium brachytherapy. Implantation was performed during the lumpectomy or 2–3 weeks after external irradiation. Population characteristics were as follows: pTis = 11.6%; pT1 = 63.4%; pT2 = 25.0%; median tumor size = 1.5 cm; histology: ductal carcinoma in situ (DCIS): 72 (11.6%); infiltrative ductal carcinoma (IDC): 471 (75.8%); other: 78 (12.6%). For IDCs, the surgical margins were positive in 38 cases (6.2%) and an extensive intraductal component was present in 254 cases. Results With a median follow-up of 10.3 years, 47 local relapses were observed (10-year local relapse rate: 7.4%). Small-volume implantation (V100 < 45 cc) and ductal carcinoma in situ histology both significantly correlated with local relapse. The 10-year overall survival was 91%. Cosmetic results were evaluated in 264 patients, proving excellent in 58 (22%), good in 153 (58%), fair in 40 (15%), and poor in 13 (5%). Conclusions Small implant volume and ductal carcinoma in situ histology significantly correlated with local relapse following HDR brachytherapy dose boost in breast cancer conservative treatment. Modern image-guided breast brachytherapy techniques using surgical clips as a guide may decrease potential treatment targeting errors, consequently improving local control without increasing toxicity. [ABSTRACT FROM AUTHOR]

Background and purpose Breast radiotherapy (RT) for elderly women with estrogen receptor positive early stage breast cancer (ER + ESBC) improves local recurrence (LR) rates without benefitting overall survival. Breast boost is a common practice, although the absolute benefit decreases with age. Consequently, an analysis of its cost-effectiveness in the elderly ESBC populations is warranted. Material and methods A Markov model was used to compare cost-effectiveness of RT with or without a boost in elderly ER + ESBC patients. The ten-year probability of LR with boost was derived from the CALGB 9343 trial and adjusted by the hazard ratio for LR from boost radiotherapy trial data, yielding the LR rate without boost. Remaining parameters were estimated using published data. Results Boost RT was associated with an increase in mean cost ($7139 vs $6193) and effectiveness (5.66 vs 5.64 quality adjusted life years; QALYs) relative to no boost. The incremental cost-effectiveness ratio (ICER) for boost was $55,903 per QALY. On one-way sensitivity analysis, boost remained cost-effective if the hazard ratio of LR with boost was <0.67. Conclusions Boost RT for ER + ESBC patients was cost-effective over a wide range of assumptions and inputs over commonly accepted willingness-to pay-thresholds, but particularly in women at higher risk for LR. [ABSTRACT FROM AUTHOR]

Objective The aim was to develop a delineation guideline for target definition for APBI or boost by consensus of the Breast Working Group of GEC-ESTRO. Proposed recommendations Appropriate delineation of CTV (PTV) with low inter- and intra-observer variability in clinical practice is complex and needs various steps as: (1) Detailed knowledge of primary surgical procedure, of all details of pathology, as well as of preoperative imaging. (2) Definition of tumour localization before breast conserving surgery inside the breast and translation of this information in the postoperative CT imaging data set. (3) Calculation of the size of total safety margins. The size should be at least 2 cm. (4) Definition of the target. (5) Delineation of the target according to defined rules. Conclusion Providing guidelines based on the consensus of a group of experts should make it possible to achieve a reproducible and consistent definition of CTV (PTV) for Accelerated Partial Breast Irradiation (APBI) or boost irradiation after breast conserving closed cavity surgery, and helps to define it after selected cases of oncoplastic surgery. [ABSTRACT FROM AUTHOR]

Purpose The purpose of this meta-analysis is to summarize the current evidence on the role of boost and the efficacy of hypofractionated radiotherapy in patients with ductal cancer in situ (DCIS) after surgery and grade the quality of evidence. Materials and methods A comprehensive systematic electronic search through MEDLINE and the Cochrane Library as well as through the major international congresses’ proceedings was conducted. Studies were considered eligible if they investigated the efficacy of hypofractionated vs. standard radiotherapy or the efficacy of boost vs. no boost in patients with DCIS. The outcome of interest was the number of local recurrences. Pooled estimates were calculated by using standard meta-analytic procedures. Results Thirteen trials were considered eligible and were further analyzed. No difference in the risk of local recurrence was observed between the patients that received boost vs. no boost in the general cohort (12 studies, 6943 patients; Odds Ratio (OR): 0.91, 95% confidence interval (CI): 0.77–1.08, very low level of evidence). However, we found a reduced risk for local recurrence when boost was administered in patients with positive margins compared to no boost (6 studies, 811 patients; OR: 0.56, 95% CI: 0.36–0.87, very low level of evidence). No difference in local recurrence rate between patients who received hypofractionated versus standard radiotherapy was observed (4 studies, 2534 patients; OR: 0.78, 95% CI: 0.58–1.03, low level of evidence). Conclusion Hypofractionated radiotherapy seems to be a safe option in patients with DCIS after breast-conserving surgery while the addition of boost reduces the risk for local recurrence in the presence of positive margins. However, the level of evidence for these observations ranges between very low and low and the results of the ongoing randomized trials are necessary to confirm the results with higher level of evidence. [ABSTRACT FROM AUTHOR]

Purpose To evaluate the efficacy and toxicity of external beam radiation therapy (EBRT) plus high-dose-rate brachytherapy (HDRB) as a boost in patients (pts) with intermediate or high-risk prostate cancer. Methods and materials From 2002 to July 2012, 377 pts with a diagnosis of intermediate or high-risk prostate cancer were treated with EBRT plus HDRB. Median patient age was 66 years (range, 41–86). Most patients (347 pts; 92%) were classified as high-risk (stage T2c–T3, or PSA > 20 ng/mL, or GS ⩾ 8), with 30 patients (8%) considered intermediate risk. All patients underwent EBRT at a prescribed dose of 60.0 Gy (range, 45–70 Gy) to the prostate and seminal vesicles. A total of 120 pts (31%) received a dose of 46 Gy (45–50 Gy) to the true pelvis. All pts received a single-fraction 9 Gy (9–15 Gy) HDR boost. Most patients (353; 94%) were prescribed complete androgen deprivation therapy (ADT). Overall survival (OS), cause-specific survival (CSS), and biochemical relapse-free survival (BRFS) rates were calculated. In the case of BRFS, patients with <26 months of follow-up ( n = 106) were excluded to minimize the impact of ADT. Results The median follow-up for the entire sample was 50 months (range, 12–126), with 5-year actuarial OS and CSS, respectively, of 88% (95% confidence interval [CI]: 84–92) and 98% (95% CI: 97–99). The 5-year BRFS was 91% (95% CI: 87–95) in the 271 pts with ⩾26 months (median, 60 months) of follow-up. Late toxicity included grade 2 and 3 gastrointestinal toxicity in 17 (4.6%) and 6 pts (1.6%), respectively, as well as grades 2 and 3 genitourinary toxicity in 46 (12.2%) and 3 pts (0.8%), respectively. Conclusion These long-term outcomes confirm that EBRT plus a single-fraction HDRB boost provides good results in treatment-related toxicity and biochemical control. In addition to the excellent clinical results, this fractionation schedule reduces physician workload, treatment-related expenses, patient discomfort and risks associated with anaesthesia. We believe these findings support the use of single-fractionation boost techniques. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: Linac-based intraoperative radiotherapy with electrons (IOERT) was implemented to prevent local recurrences after breast conserving therapy (BCT) and was delivered as an intraoperative boost to the tumor bed prior to whole breast radiotherapy (WBI). A collaborative analysis has been performed by European ISIORT member institutions for long term evaluation of this strategy. Material and methods: Until 10/2005, 1109 unselected patients of any risk group have been identified among seven centers using identical methods, sequencing and dosage for intra- and postoperative radiotherapy. A median IOERT dose of 10Gy was applied (90% reference isodose), preceding WBI with 50–54Gy (single doses 1.7–2Gy). Results: At a median follow up of 72.4months (0.8–239), only 16 in-breast recurrences were observed, yielding a local tumor control rate of 99.2%. Relapses occurred 12.5–151months after primary treatment. In multivariate analysis only grade 3 reached significance (p =0.031) to be predictive for local recurrence development. Taking into account patient age, annual in-breast recurrence rates amounted 0.64%, 0.34%, 0.21% and 0.16% in patients <40years; 40–49years; 50–59years and ⩾60years, respectively. Conclusion: In all risk subgroups, a 10Gy IOERT boost prior to WBI provided outstanding local control rates, comparing favourably to all trials with similar length of follow up. [Copyright &y& Elsevier]

Abstract: Purpose: We conducted a retrospective population-based study to examine the survival outcomes in patients with brain metastases treated with salvage stereotactic radiosurgery (SRS), compared to boost SRS, after previous whole brain radiotherapy (WBRT). Methods and materials: From January 2000 to June 2011, 191 patients treated with WBRT and SRS for brain metastases in British Columbia were studied. Patients were divided into a boost cohort and a salvage cohort. The criteria used to determine eligibility for SRS were: 1–3 metastases, ⩽4cm size, Karnofsky performance status ⩾70, and control of extracranial disease. Results: Diagnosis by primary site was 84 lung, 47 breast, 15 melanoma, 12 renal, 9 colorectal, and 24 other. There were 113 patients (59%) in the boost cohort and 78 patients (41%) in the salvage cohort. The median overall survival from WBRT for the whole population was 17.7months: 12.1months for the boost cohort and 22.7months for the salvage cohort. There was no difference in median survival after SRS for the boost and salvage cohorts (11.2 vs. 11.2months, p =0.78). Conclusions: In selected patients with brain metastases treated with WBRT, survival following salvage SRS is as good as survival after WBRT+boost SRS. [Copyright &y& Elsevier]

Abstract: Introduction: Dominant cancer foci within the prostate are associated with sites of local recurrence post radiotherapy. In this systematic review we sought to address the question: “what is the clinical evidence to support differential boosting to an imaging defined GTV volume within the prostate when delivered by external beam or brachytherapy”. Materials and methods: A systematic review was conducted to identify clinical series reporting the use of radiation boosts to imaging defined GTVs. Results: Thirteen papers describing 11 unique patient series and 833 patients in total were identified. Methods and details of GTV definition and treatment varied substantially between series. GTV boosts were on average 8Gy (range 3–35Gy) for external beam, or 150% for brachytherapy (range 130–155%) and GTV volumes were small (<10ml). Reported toxicity rates were low and may reflect the modest boost doses, small volumes and conservative DVH constraints employed in most studies. Variability in patient populations, study methodologies and outcomes reporting precluded conclusions regarding efficacy. Conclusions: Despite a large cohort of patients treated differential boosts to imaging defined intra-prostatic targets, conclusions regarding optimal techniques and/or efficacy of this approach are elusive, and this approach cannot be considered standard of care. There is a need to build consensus and evidence. Ongoing prospective randomized trials are underway and will help to better define the role of differential prostate boosts based on imaging defined GTVs. [Copyright &y& Elsevier]

Abstract: Purpose: We reviewed our seven year single institution experience with pulsed dose rate brachytherapy dose escalation study in patients with intermediate and high risk prostate cancer. Materials and methods: We treated a total of 130 patients for intermediate and high risk prostate cancer at our institution between 2000 and 2007 using PDR-brachytherapy as a boost after conformal external beam radiation therapy to 50.4Gy. The majority of patients had T2 disease (T1c 6%, T2 75%, T3 19%). Seventy three patients had intermediate-risk and 53 patients had high-risk disease according to the D’Amico classification. The dose of the brachytherapy boost was escalated from 25 to 35Gy – 33pts. received 25Gy (total dose 75Gy), 63pts. 30Gy (total dose 80Gy) and 34pts. 35Gy, (total dose 85Gy) given in one session (dose per pulse was 0.60Gy or 0.70Gy/h, 24h per day, night and day, with a time interval of 1h between two pulses). PSA-recurrence-free survival according to Kaplan–Meier using the Phoenix definition of biochemical failure was calculated and also late toxicities according to Common Toxicity Criteria scale were assessed. Results: At the time of analysis with a median follow-up of 60months biochemical control was achieved by 88% of patients – only 16/130 patients (12.3%) developed a biochemical relapse. Biochemical relapse free survival calculated according to Kaplan–Meier for all patients at 5years was 85.6% (83.9% for intermediate-risk patients and 84.2% for high-risk patients) and at 9years’ follow up it was 79.0%. Analysing biochemical relapse free survival separately for different boost dose levels, at 5years it was 97% for the 35Gy boost dose and 82% for the 25 and 30Gy dose levels. The side effects of therapy were negligible: There were 18 cases (15%) of grade 1/2 rectal proctitis, one case (0.8%) of grade 3 proctitis, 18 cases (15%) of grade 1/2 cystitis, and no cases (0%) with dysuria grade 3. No patient had a bulbourethral stricture requiring dilation or new onset incontinence. Conclusions: Image-guided conformal PDR-brachytherapy using up to 35Gy as boost dose after 50Gy of external beam radiation therapy (total dose up to 85Gy) is a very effective treatment option with very low morbidity in patients with intermediate or high risk prostate cancer. Further dose escalation seems possible. [Copyright &y& Elsevier]

Abstract: Background and purpose: The EORTC 22881-10882 trial showed that for patients treated with breast conserving therapy (BCT), a 16Gy boost dose significantly improved local control, but increased the risk of breast fibrosis. A model to estimate the risk of ipsilateral breast relapse (IBR) already exists, but now a model has been developed which takes boost treatment into account and is based on centrally reviewed pathology. Materials and methods: A Cox model was developed based on central pathology review data and clinical data of 1603 patients from the EORTC 22881-10882 trial with a median follow-up of 11.5years. From a predefined set of variables, predictors with a maximal effect on 10-year IBR rate >4% were retained in the model. Bootstrap re-sampling was used to assess model calibration and discrimination. The results are presented in the form of a nomogram. Results: Apart from young age and no boost, presence of DCIS adjacent to the invasive tumor was associated with increased risk of IBR (HR 1.96, p =0.001). Patients with high grade invasive tumors were younger than patients with low/intermediate grade (p <0.0001). The nomogram includes histologic grade, DCIS, tumor diameter, age, tamoxifen, chemotherapy, and boost with a concordance probability estimate of 0.68. Conclusions: The nomogram for predicting IBR 10years after BCT includes seven factors, with young age, presence of DCIS and boost treatment as the most dominant factors. The nomogram estimates IBR and confirms the importance of a boost dose. Combined with a model to predict fibrosis published previously, the nomogram presented here may assist in decision making for individual patients. [Copyright &y& Elsevier]

Abstract: Background and purpose: To measure the distance between surgical clips and edge of CT-defined seroma in a coronal plane in women who have undergone wide local excision of breast cancer and to evaluate dosimetric coverage of CT-defined boost volumes by conventional clip-based electron fields. Materials and methods: Planning CT images of 30 lumpectomy cavities from 30 patients were reviewed. All seroma cavities had at least 4 clips and Cavity Visualization Score ⩾3. Distances between clips and seroma edge (D c–s) were measured at the radial margins for each patient. Clips-based electron fields were generated by including all the clips with 2cm margin in the coronal plane and three-dimensional conformal radiotherapy plans (3D-CRT) were devised based on CT tumor beds (CT-TBs). The parameters of dose–volume histogram between the two boost treatment plans were analyzed. Results: The mean seroma edge extended beyond the clips by 0.3–0.5cm. In all 120 D c–ss, 76.7% were ⩽0.5cm, 8.3% were >1cm and 15% were between 0.5 and 1cm. Twenty patients (20/30) had D c–smax (The maximal D c–s of each patient)>0.5cm and 7 patients had D c–smax >1cm. With the electron fields, only 46.7% (14/30) had D 90 (The minimal dose received by 90% of the planning target volume (PTV))>90% and geographical miss (any portion of the PTV receiving <50% of the prescribed dose) was found in 36.7% (11/30). D c–smax >0.5cm was associated with D 90 <90% (P <0.001) and >1cm was associated with geographic miss (P =0.001). Conclusions: Surgical clips are not always consistent with the edge of seroma. Electron boost field based on clips leads to insufficient dose coverage to the CT-TB. 3D-CRT planning should be considered to ameliorate the dose coverage to the tumor bed. [Copyright &y& Elsevier]

Abstract: Background and purpose: The purpose of this study was to investigate the effect of CT-based delineation and planning on the irradiated boost volume. For this specific purpose we used the data as derived from 2 prospective phase III randomised trials. Patients and methods: Data from 1331 patients (⩽50 years) were analyzed with a reported boost volume from a simulation-based treatment plan (EORTC boost vs no boost trial, n =922), and a CT-scan-based treatment plan (Young Boost Trial, n =409) group. Tumour diameter, irradiation technique (photons vs electrons), lumpectomy size, and age were used as covariates. Results: Median V 95% in the conventional simulation-based treatment plans was 99 cc (range 9–628) for photons and was 98 cc (13–651) for electrons, whereas in the CT-planned patients, these figures were 178 cc (37–2699) and 150 cc (43–1272), respectively. Multivariable analysis showed an association of the irradiated boost volume with tumour size (p <0.0067), lumpectomy size (p <0.0002), and boost technique (p <0.0004). The use of a CT-scan for volume delineation and treatment planning remained significant (p <0.0001). Conclusions: The use of a CT-scan for delineation and treatment planning led to a significant increase of the irradiated boost volume by a factor of 1.5–1.8, compared to conventional simulator-based plans. [Copyright &y& Elsevier]

Abstract: Purpose: To assess the impact of the boost dose in patients with involved surgical margins. Patients and methods: In the EORTC “boost versus no boost” trial, 251 patients with a microscopically incomplete tumour excision were randomised to receive either a low boost dose of 10Gy (126 patients) or a high boost dose of 26Gy (125 patients). Overall survival and the cumulative incidence of local recurrence as first event were compared by Logrank and Gray test, respectively (2-sided α =0.05), with a median follow-up of 11.3 years. The planned sample size was 660 patients, but only 251 were recruited. Results: The median age at randomisation was 54 years. Thirty-seven patient initially relapsed locally. At 10 years, the cumulative incidence of local recurrence was 17.5% (95% CI: 10.4–24.6%) versus 10.8% (95% CI: 5.2–16.4%) for the low and high boost dose groups, respectively (HR=0.83, 95% CI: 0.43–1.57, Gray p >0.1). Overall, 64 patients have died (25.5%), 47 of them of breast cancer, without a difference in duration of survival between the two groups (HR=0.97, 95% CI=0.59–1.5, p >0.1). Severe fibrosis was palpated in the breast in 1% versus 5% and in the boost area in 3% versus 13% in the low and high boost dose groups, respectively. Conclusions: There was no statistically significant difference in local control or survival between the high boost dose of 26Gy and the low boost dose of 10Gy in patients with microscopically incomplete excision of early breast cancer. Fibrosis, however, was noted significantly more frequently in cases treated with the high boost dose. [Copyright &y& Elsevier]

Abstract: Purpose: To determine whether the effect of an additional “boost” radiation after breast conservative therapy (BCT) on local control depends on age and evaluate the impact of a treatment policy with a threshold for age. Patients and methods: We used data from EORTC 22881-10882 trial, with median follow-up of 77.4 months. Patients receiving BCT and 50Gy whole breast irradiation were randomized to no boost and 16Gy boost (N =5318). Results: In univariate analysis, a boost reduced local failure by a factor of 2 (P <0.0001). Multivariate analysis showed local control increased with age (P =0.0003). There was no evidence that the relative effect of a boost on local control depends on age (P =0.97) However in younger patients the 5-year local failure was higher, therefore the absolute reduction was greater. If the threshold-age for boost treatment were set at 40 years, 8.4% of the study population would receive a boost, resulting in a 5-year local failure of 6.1% in the study population. Changing the threshold-age to 60 years, 67% of the study population would receive a boost and the 5-year local failure would be reduced to 4.4%. Conclusions: In younger patients a boost dose resulted in a greater absolute reduction of local failure. The relative risk reduction was however similar for all ages. Applying a treatment policy with a threshold-age of 60 would result in 0.6% increase in local failure in the total study population, while sparing the boost to 1/3 of the patients. [Copyright &y& Elsevier]