Abstract Purpose The aim was to assess changes of tumour hypoxia during primary radiochemotherapy (RCT) for head and neck cancer (HNC) and to evaluate their relationship with treatment outcome. Material and methods Hypoxia was assessed by FMISO-PET in weeks 0, 2 and 5 of RCT. The tumour volume (TV) was determined using FDG-PET/MRI/CT co-registered images. The level of hypoxia was quantified on FMISO-PET as TBRmax (SUVmaxTV/SUVmean background). The hypoxic subvolume (HSV) was defined as TV that showed FMISO uptake ⩾1.4 times blood pool activity. Results Sixteen consecutive patients (T3–4, N+, M0) were included (mean follow-up 31, median 44 months). Mean TBRmax decreased significantly (p < 0.05) from 1.94 to 1.57 (week 2) and 1.27 (week 5). Mean HSV in week 2 and week 5 (HSV2 = 5.8 ml, HSV3 = 0.3 ml) were significantly (p < 0.05) smaller than at baseline (HSV1 = 15.8 ml). Kaplan–Meier plots of local recurrence free survival stratified at the median TBRmax showed superior local control for less hypoxic tumours, the difference being significant at baseline and after 2 weeks (p = 0.031, p = 0.016). Conclusions FMISO-PET documented that in most HNC reoxygenation starts early during RCT and is correlated with better outcome.

Abstract Introduction The HERBERT study evaluated a high-dose-rate endorectal brachytherapy boost (HDREBT) after EBRT in medically inoperable/elderly patients with rectal cancer. The response-rates are promising but not without risk of toxicity. The current analysis provides a comprehensive overview of patient reported, physician reported and endoscopically observed toxicity. Material and methods A brachytherapy dose finding study was performed in 38 inoperable/elderly patients with T2-T4N0-1 rectal cancer. Patients received EBRT (13 × 3 Gy) followed by three weekly HDREBT applications (5–8 Gy). Toxicity was assessed via three methods: patient and physician (CTCAEv3) reported rectal symptoms and endoscopically. Wilcoxon’s signed rank test, paired t-test and Spearman’s correlation were used. Results Patient reported bowel symptoms showed a marked increase at the end of EBRT and two weeks after HDREBT. Acute grade 2 and 3 proctitis occurred in 68.4% and 13.2% respectively while late grade 2 and ≥3 proctitis occurred in 48% and 40%. Endoscopic evaluation mainly showed erythema and telangiectasia. In three patients frank haemorrhage or ulceration occurred. Most severe toxicity was observed 12–18 months after treatment. Conclusion For elderly patients with rectal cancer, definitive radiotherapy can provide good tumour response but has a substantial risk of toxicity. The potential benefit and risks of a HDREBT boost above EBRT alone must be further evaluated.

Abstract Background/purpose To perform a large analysis of Stage I endometrioid-type endometrial cancer patients to determine the impact of adjuvant radiotherapy (ART) on survival. Material/methods 132,976 FIGO Stage I endometrioid-type endometrial cancer patients treated surgically were identified within the National Cancer Database (NCDB) comprising Commission on Cancer facilities in the United States. Patients were categorized as observation (OBS) or ART (vaginal brachytherapy, external beam radiotherapy, or both). Univariable generalized linear mixed effects models were used to estimate the odds of receiving ART, and a multivariable frailty survival model was used to estimate the instantaneous hazard of death for those receiving OBS versus ART. Due to the presence of a significant interaction, these estimates were stratified by PORTEC-based low, low-intermediate, high-intermediate, and high risk groups. Results 104,645 (79%) underwent OBS while 28,331 (21%) received ART. Of those receiving ART, 12,913 (46%) received VBT alone, 12,857 (45%) received EBRT alone, and 2561 (9%) received EBRT + VBT. On univariable analysis, increasing stage/myometrial invasion, higher grade, older age, presence of lymphovascular space invasion, and larger tumor size predicted poorer survival (all p < 0.01). On multivariable analysis, patients at high-intermediate risk and high risk experienced improved survival with ART with a hazard ratio of 0.796 (95% CI: 0.731–0.867; p < 0.001) and 0.783 (95% CI: 0.693–0.885; p < 0.001), respectively. There was no survival benefit for ART among patients at low or low-intermediate risk. Conclusions In Stage I high-intermediate and high risk endometrioid-type endometrial cancer patients, ART significantly improves overall survival.

Abstract Breast cancer patients are typically advised to avoid antiperspirants for fear of increasing radiation dermatitis in the axilla. We hypothesized that antiperspirants would have minimal effect on skin dose. We found no difference in surface dose ± antiperspirants using 6 MV photons at gantry angles of 0°/30°/60°/90° regardless of aluminum concentration.

Abstract Background and purpose To compare early side effects and patient compliance of accelerated partial breast irradiation (APBI) with multicatheter brachytherapy to external beam whole breast irradiation (WBI) in a low-risk group of patients with breast cancer. Material and methods Between April 2004 and July 2009, 1328 patients with UICC stage 0–IIA breast cancer were randomized to receive WBI with 50 Gy and a boost of 10 Gy or APBI with either 32.0 Gy/8 fractions, or 30.1 Gy/7 fractions (HDR-brachytherapy), or 50 Gy/0.60–0.80 Gy per pulse (PDR-brachytherapy). This report focuses on early side-effects and patient compliance observed in 1186 analyzable patients. ClinicalTrials.gov identifier: NCT00402519. Results Patient compliance was excellent in both arms. Both WBI and APBI were well tolerated with moderate early side-effects. No grade 4 toxicity had been observed. Grade 3 side effects were exclusively seen for early skin toxicity (radiation dermatitis) with 7% vs. 0.2% (p < 0.0001), and breast infection with 0% vs. 0.2% (p = n.s.) for patients treated with WBI and APBI. The incidence of grades 1–2 early side effects for WBI and APBI was 86% vs. 21% (p < 0.0001) for skin toxicity, 2% vs. 20% (p < 0.0001) for mild hematoma, and 2% vs. 5% (p = 0.01) for mild breast infection rates, respectively. No differences had been found regarding grades 1–2 early breast pain (26% vs. 29%, p = 0.23). Conclusions APBI with interstitial multicatheter brachytherapy was tolerated very well and dramatically reduced early skin toxicity in comparison to standard WBI.

Abstract Background and purpose To evaluate high-dose-rate brachytherapy (HDR BT) as a salvage modality for locally recurrent prostate cancer after primary radiotherapy failure. Materials and methods Eighty-three prostate cancer patients, who locally relapsed after radiotherapy, were treated with salvage HDR BT. The schedule was three implantations, every two weeks, with 10 Gy per implant, to a total dose of 30 Gy. Acute and late toxicity rates were evaluated. Overall survival (OS) and biochemical control were calculated using Kaplan–Meier method. Results Median follow-up after salvage HDR was 41 months. The 3-year and 5-year OS were 93% and 86%, respectively. The 3-year and 5-year biochemical disease-free survival (bDFS) were 76% and 67%, respectively. The single factor associated with biochemical control was time to achieve salvage PSA nadir (p-.006). OS was linked significantly with primary nadir level (p-.001) while primary biochemical relapse interval was of borderline significance (p-.07). Conclusions Salvage HDR BT is a promising treatment option for patients with localized relapse of previously irradiated prostate cancer. Lower PSA nadir after primary radiotherapy and longer primary disease-free interval influence the outcome.

Abstract Background and purpose Pre-clinical data have shown that PARP inhibitors (PARPi) may increase the efficacy of radiotherapy in prostate cancer. However, it is uncertain as to whether PARPi lead to clonogenic kill when combined with radiotherapy (RT). Material and methods We tested the PARP inhibitor AZD-2281 as a radiosensitizing agent under oxic and hypoxic conditions for clonogenic survival in vitro and in vivo using the human prostate cancer cell line, 22Rv1. In addition, the effects of PARPi + RT on normal tissue were investigated using a crypt clonogenic assay. Results AZD-2281 inhibited cellular PARP activity under both oxic and hypoxic conditions. The addition of AZD-2281 radiosensitized 22Rv1 cells under oxia, acute hypoxia and chronic hypoxia in vitro. The combination of AZD-2281 with fractionated radiotherapy resulted in a significant growth delay and clonogenic kill in vivo. No increased gut toxicity was observed using this combined PARPi + radiotherapy regimen. Conclusions This is the first preclinical study to demonstrate direct clonogenic kill in vivo by the addition of AZD-2281 to radiotherapy. As we did not observe gut toxicity, the use of PARPi in the context of prostate cancer radiotherapy warrants further investigation in clinical trials.

Abstract Objective To examine the clinical results of a preoperative image-guided pulse-dose-rate brachytherapy (PDR-BT) in early stage cervical cancer. Materials/methods We examined the outcome of consecutive patients with early stage cervical cancer undergoing preoperative image-guided PDR-BT between 2004 and 2013 because of risk factors (lymphovascular embols and/or tumour > 2 cm). The objective was to deliver 60 Gy to 100% of the intermediate risk clinical target volume. Brachytherapy was followed, 6–8 weeks later, by a radical hysterectomy/bilateral salpingo-oophorectomy plus pelvic +/− para-aortic lymph node dissection. Patients with positive lymph nodes had postoperative chemoradiation. Results 77 patients met the above criteria of preoperative PDR-BT. On hysterectomy specimen, 54 (70.1%) presented a complete histological response. Four (5.2%) had a tumour residuum ⩾ 1 cm. Median follow-up was 46.8 months. 5-Year disease-free survival (DFS) rate was 84.4%. Only one local recurrence was observed. The presence of lymph nodal metastases, a tumour size > 3 cm and a brachytherapy/surgery time interval ⩾ 9 weeks correlated with a poorer DFS. Six postoperative complications were encountered (7.8%). Total reference air kerma correlated with late vaginal toxicity (p = 0.02). Conclusions A preoperative image-guided PDR-BT was safe and effective. Predictive factors for survival and toxicity were evidenced.

Abstract Background and purpose To identify rectal subregions at risks (SRR) highly predictive of 3-year rectal bleeding (RB) in prostate cancer IMRT. Materials and methods Overall, 173 prostate cancer patients treated with IMRT/IGRT were prospectively analyzed, divided into “training” (n = 118) and “validation” cohorts (n = 53). Dose–volume histograms (DVHs) were calculated in three types of rectal subregions: “geometric”, intuitively defined (hemi-rectum,…); “personalized”, obtained by non-rigid registration followed by voxel-wise statistical analysis (SRRp); “generic”, mapped from SRRps, located within 8 × 8 rectal subsections (SRRg). DVHs from patients with and without RB were compared and used for toxicity prediction. Results Training cohort SRRps were primarily within the inferior anterior hemi-rectum and upper anal canal, with 3.8 Gy mean dose increase for Grade ⩾ 1 RB patients. The SRRg, representing 15% of the absolute rectal volume, was located in 10 inferior–anterior rectal subsections. V18–V70 for SRRps and V58–V65 for SRRg were significantly higher for RB patients than non-RB. Maximum areas under the curve (AUCs) for SRRp and SRRg RB prediction were 71% and 64%, respectively. The validation cohort confirmed the predictive value of SRRg for Grade ⩾ 1 RB. The total cohort confirmed the predictive value of SRRg for Grade ⩾ 2 RB. Geometrical subregions were not RB predictors. Conclusion The inferior–anterior hemi anorectum was highly predictive of RB.

Abstract Purpose In oropharyngeal cancer adaptive radiation therapy (ART), this study aimed to quantify the dosimetric benefit of numerous replanning strategies, defined by various numbers and timings of replannings, with regard to parotid gland (PG) sparing. Material and methods Thirteen oropharyngeal cancer patients had one planning and then six weekly CT scans during the seven weeks of IMRT. Weekly doses were recalculated without replanning or with replanning to spare the PG. Sixty-three ART scenarios were simulated by considering all the combinations of numbers and timings of replanning. The PG cumulated doses corresponding to “standard” IMRT and ART scenarios were estimated and compared, either by calculating the average of weekly doses or using deformable image registration (DIR). Results Considering average weekly doses, the mean PG overdose using standard IMRT, compared to the planned dose, was 4.1 Gy. The mean dosimetric benefit of 6 replannings was 3.3 Gy. Replanning at weeks 1, 1–5, 1–2–5, 1–2–4–5 and 1–2–4–5–6 produced the lowest PG mean doses, 94% of the maximum benefit being obtained with 3 replannings. The percentage of patients who had a benefit superior to 5 Gy for the contralateral PG was 31% for the three-replannings strategy. The same conclusions were found using DIR. Conclusion Early replannings proved the most beneficial for PG sparing, three replannings (weeks 1–2–5), representing an attractive combination for ART in oropharyngeal cancer.