Abstract Purpose To compare late genitourinary (GU) and gastrointestinal (GI) toxicity following different prostate cancer treatment modalities. Materials and methods This study included 1084 consecutive prostate cancer patients treated with conventional radiotherapy, intensity-modulated radiotherapy (IMRT), permanent iodine-125 implantation (PI) alone, and PI combined with external beam radiotherapy (PI + EBRT). The effects of treatment- and patient-related factors on late grade ⩾ 2 (G2+) GU/GI toxicity risk were assessed. Results The median follow-up was 43 months (range, 12–97 months). Compared to the PI + EBRT, there was significantly less G2+ GU toxicity in the conventional radiotherapy (hazard ratio [HR] = 0.39; 95% CI, 0.20–0.77) and the IMRT (HR = 0.45, 95% CI, 0.27–0.73). Compared to the PI + EBRT, there was significantly more G2+ GI toxicity in the IMRT (HR = 2.38; 95% CI, 1.16–4.87). In PI-related groups, prostate equivalent dose in 2 Gy fractions was a significant predictor of G2+ GU toxicity (p = 0.001), and the rectal volume receiving more than 100% of the prescribed dose was a significant predictor of G2+ GI toxicity (p = 0.001). Conclusion The differences in the late G2+ GU/GI risk cannot be explained by the differences in treatment modalities themselves, but by the total radiation dose to the GU/GI tract, which had a causal role in the development of late G2+ GU/GI toxicity across all treatment modality groups.

Abstract Background and purpose Late anorectal toxicity influences quality of life after external beam radiotherapy (EBRT) for prostate cancer. A daily inserted endorectal balloon (ERB) during EBRT aims to reduce anorectal toxicity. Our goal is to objectify anorectal function over time after prostate intensity-modulated radiotherapy (IMRT) with ERB. Material and methods Sixty men, irradiated with IMRT and an ERB, underwent barostat measurements and anorectal manometry prior to EBRT and 6 months, one year and 2 years after radiotherapy. Primary outcome measures were rectal distensibility and rectal sensibility in response to stepwise isobaric distensions and anal pressures. Results Forty-eight men completed all measurements. EBRT reduced maximal rectal capacity 2 years after EBRT (250 ± 10 mL vs. 211 ± 10 mL; p < 0.001), area under the pressure–volume curve (2878 ± 270 mL mmHg vs. 2521 ± 305 mL mmHg; p = 0.043) and rectal compliance (NS). Sensory pressure thresholds for first sense and first urge (both p < 0.01) increased. Anal maximum pressure diminished after IMRT (p = 0.006). Conclusions Rectal capacity and sensory function are increasingly affected over time after radiotherapy. There is an indication that these reductions are affected less with IMRT + ERB compared to conventional radiation techniques.

Abstract Background and purpose Patients with breast cancer receiving mastectomy in our institution are offered immediate breast reconstruction (IBR). IBR may have an impact on the optimisation of radiation therapy (RT). Therefore, we aimed to evaluate the clinical target volume (CTV) dose coverage when disregarding the dose received by the breast implant in women treated for breast cancer. Furthermore, to investigate the safety of immediate breast reconstruction (IBR) with an implant (IBR+) in terms of recurrence and survival compared to patients without an implant (IBR−). Patients and methods This matched-cohort included 128 patients with IBR+ and 252 IBR− patients (controls). The potential confounding effects of tumour stage and treatment were controlled for. For IBR+ patients, the implant volume was excluded from the CTV in the RT planning images, and the RT target coverage (V95%: CTV covered by ≥the 95% isodose) was compared between the IBR+ and IBR− groups. Results A limited under dosage was observed in patients without lymph-node irradiation; the V95% mean values for the CTV subtracting the implant were 84% and 92%, for IBR+ and IBR− groups, respectively. Median follow-up duration was 5.8 years (0.1–7.5 years). In comparing IBR+ and IBR− groups, no statistically significant differences were found in the incidence of recurrence rate ratios or recurrence free survival (log-rank p = 0.142), overall survival (log-rank p = 0.096), or breast cancer specific survival (log-rank p = 0.147). Conclusions Post-mastectomy radiation therapy and implant-based reconstruction lead to minor under dosage of the target, due to the projection of the subcutaneous tissue in the presence of the implant. However, recurrence and survival rates were equally distributed among IBR+ and IBR− patients indicating that the overall treatment protocol used in our institution is safe.

Abstract Background and purpose To determine if there are differences between dose to pelvic bone marrow (PBM) using intensity modulated radiotherapy (IMRT) under UK guidance versus conformal radiotherapy (CRT) per ACT II protocol and if differences translate to rates of early haematological adverse events grade 3 or greater (HT3+). Methods and materials Two groups of 20+ patients, treated under IMRT and CRT regimes respectively, were identified. All patients underwent weekly blood cell count: haemoglobin (HgB), white cell count (WCC), absolute neutrophil count (ANC) and platelets (plats). Percent volume of PBM and sub structures receiving 5–25 Gy were tested for statistical significance. Regression models were used to test for correlation to blood counts. NTCP modeling was also performed. Results PMB dose metrics showed a significant increase in the IMRT group. Regression analysis showed iliac and lumbosacral PBM dose metrics to associate with reduced nadir ANC and WCC. NTCP at HT3+ was 0.13 using IMRT relative to 0.07 using CRT (p < 0.05). Conclusion Whilst this is a relatively small retrospective study and lacks information on the distribution of active PBM, IMRT treatment has been shown to significantly increase PMB irradiation. PBM dose metrics have been shown to be predictive of WCC and ANC suppression. NTCP modeling predicts much high risk of HT3+. Paradoxically, actual rates of HT3+ were comparable suggesting that differences in the distributions of dose metrics maybe a significant factor and/or that there are insufficiency in the NTCP modeling.

Abstract Purpose To validate a novel deformable image registration (DIR) method for online adaptation of planning organ-at-risk (OAR) delineations to match daily anatomy during hypo-fractionated RT of abdominal tumors. Materials and methods For 20 liver cancer patients, planning OAR delineations were adapted to daily anatomy using the DIR on corresponding repeat CTs. The DIR’s accuracy was evaluated for the entire cohort by comparing adapted and expert-drawn OAR delineations using geometric (Dice Similarity Coefficient (DSC), Modified Hausdorff Distance (MHD) and Mean Surface Error (MSE)) and dosimetric (Dmax and Dmean) measures. Results For all OARs, DIR achieved average DSC, MHD and MSE of 86%, 2.1 mm, and 1.7 mm, respectively, within 20 s for each repeat CT. Compared to the baseline (translations), the average improvements ranged from 2% (in heart) to 24% (in spinal cord) in DSC, and 25% (in heart) to 44% (in right kidney) in MHD and MSE. Furthermore, differences in dose statistics (Dmax, Dmean and D2%) using delineations from an expert and the proposed DIR were found to be statistically insignificant (p > 0.01). Conclusion The validated DIR showed potential for online-adaptive radiotherapy of abdominal tumors as it achieved considerably high geometric and dosimetric correspondences with the expert-drawn OAR delineations, albeit in a fraction of time required by experts.

Abstract Diagnostic imaging continues to evolve, and now has unprecedented accuracy for detecting small nodal metastasis. This influences the tumor load in elective target volumes and subsequently has consequences for the radiotherapy dose required to control disease in these volumes. Small metastases that used to remain subclinical and were included in elective volumes, will nowadays be detected and included in high-dose volumes. Consequentially, high-dose volumes will more often contain low-volume disease. These target volume transformations lead to changes in the tumor burden in elective and “gross” tumor volumes with implications for the radiotherapy dose prescribed to these volumes. For head and neck tumors, nodal staging has evolved from mere palpation to combinations of high-resolution imaging modalities. A traditional nodal gross tumor volume in the neck typically had a minimum diameter of 10–15 mm, while nowadays much smaller tumor deposits are detected in lymph nodes. However, the current dose levels for elective nodal irradiation were empirically determined in the 1950s, and have not changed since. In this report the radiobiological consequences of target volume transformation caused by modern imaging of the neck are evaluated, and theoretically derived reductions of dose in radiotherapy for head and neck cancer are proposed. The concept of target volume transformation and subsequent strategies for dose adaptation applies to many other tumor types as well. Awareness of this concept may result in new strategies for target definition and selection of dose levels with the aim to provide optimal tumor control with less toxicity.

Abstract Soft tissue sarcomas (STS) are rare and heterogeneous tumours. A correct definition of STS is imperative from the very beginning of disease management, to guide the diagnostic and imaging work-up, and help to establish the prognosis on which the therapeutic strategy will be based. Over the last few years, many efforts have been made to identify characteristics that could predict disease behaviour and to enrich the therapeutic armamentarium against the advanced disease, that is still characterised by poor prognosis. Surgery remains the milestone of treatment for localised STS, whereas many uncertainties regarding the role of adjuvant and neoadjuvant treatment persist. Some controlled evidence is available, but often conflicting and insufficient to make chemotherapy (CT) a standard practice and, currently, a common and shared strategy does not exist. The biggest question concerns the prospective identification of the subgroup of patients who would benefit the most from (neo)adjuvant therapies. In light of the growing understanding of different biologies and sensitivities of the various sarcoma subtypes, the value of histology in the selection of peri-operative treatments is one of the most intriguing topics under discussion. In this perspective, a new generation of neoadjuvant trials have been planned and are currently ongoing. The aim of this review was to rekindle interest in the long-standing topic of (neo)adjuvant CT in localised STS, providing an update on its role in sarcomas' management and highlighting future directions and consequential factors needed to further improve outcomes in this disease.

Abstract Background It has been estimated that half of all cancer patients should receive radiotherapy during the course of the disease. Actual Radiotherapy Utilization (RTU) rates are usually lower than the optimal rates. Methods Data were collected from all radiotherapy departments (RTD) in New South Wales (NSW) and the Australian Capital Territory (ACT) for the period 2004–06 and were linked to Central Cancer Registries. Geographic Information System (GIS) software was used to calculate road distance between patient residence and the closest RTD. Patients were excluded from the study if their nearest RTD was outside NSW. Results The overall RTU rate was 26%. The RTU rates decreased with increasing travel distance from patient residence to the nearest RTD (p < 0.0001). Multivariate logistic regression shows that male gender, younger age and shorter travel distance were significantly associated with receiving radiotherapy. Patients were 10% less likely to receive radiotherapy for each additional 100 km distance from the nearest RTD (p < 0.001). Conclusions There was a statistically significant reduction in radiotherapy access with longer road distance between patient residence and radiotherapy department.

Abstract Immune checkpoint inhibitors (ICIs) are antibodies that target key signalling pathways such as programmed death 1 (PD1)/programmed death-ligands 1 and 2 (PDL1 and PDL2) to improve anti-tumour immune responses. Until recently, nivolumab was the only ICI validated for advanced non-small-cell lung cancer (NSCLC) in a second-line treatment setting. Results from recent phase II and phase III randomised trials testing other ICIs have been presented. In Keynote-024, pembrolizumab, an anti-PD1 antibody, was reported to have great efficacy in the first-line treatment of PDL1 ≥ 50% tumours (30% of screened tumours), with a progression-free survival (PFS, median) of 10.4 months versus 6.0 months with chemotherapy (CT; hazard ratio [HR] = 0.50; 95% confidence interval [95% CI] 0.37–0.68, P < 0.001), overall response rate (ORR) of 45% versus 28% with CT (P = 0.0011), and a 1-year overall survival (OS) of around 70%. In contrast, Checkmate-026 reported that nivolumab failed to show any benefit compared with standard platinum-based CT, with a PFS (median) in the PDL1 ≥ 5% NSCLC group of 4.2 months (nivolumab) versus 5.9 months (CT; HR = 1.15: 95% CI 0.91–1.45, P = 0.25). No benefit was observed in the PDL1 ≥ 50% subgroup. An encouraging report of the efficacy of pembrolizumab in addition to CT in first-line treatment in unselected NSCLC was also presented (Keynote-021) with an ORR of 55% versus 29% with CT alone (P = 0.0016). Atezolizumab, an anti-PDL1 antibody, showed efficacy for second-line treatment compared with docetaxel (OAK phase III study) with an OS (median) of 13.8 months versus 9.6 months with docetaxel. These results suggest a new paradigm for the treatment of advanced NSCLC using pembrolizumab for the first-line treatment of PDL1 ≥ 50% tumours.

Abstract Background Little is known about the joint impact of C-reactive protein (CRP) and cardiorespiratory fitness (CRF) in lung cancer risk. The aim of this study is to examine the joint impact of CRF and CRP in predicting lung cancer risk. Methods A population-based cohort study of 2276 men with no history of cancer was carried out. Baseline measures of CRP and CRF were divided into median values and categorised. During an average follow-up of 21-years, 73 cases of lung cancer occurred. Results In a multivariate model, men with the combination of high CRP (>50% 1.24 mg/l) and low CRF (maximal oxygen uptake (VO2max) 50% 30.08 ml/kg/min). Furthermore, men categorised in high CRP and combined with either low/high CRF, had an increased risk for lung cancer as compared to reference group. In further separate independent analysis for CRP and CRF, lung cancer risk was threefold for high CRP (RR 3.22, 95% CI 1.44–7.20, p 2.38 mg/l) and CRF (>35.15 ml/kg/min). Conclusions In this study, the joint impact of CRP and CRF is a strong risk marker for lung cancer. Furthermore, men with an increase in CRP were at higher risk for lung cancer than men with low CRP and high CRF may reduce the risk.