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Background: Current standard for most of the locally advanced rectal cancers is preoperative chemoradiotherapy, and, variably per institution, postoperative adjuvant chemotherapy. Short-course preoperative radiation with delayed surgery has been shown to induce tumour down-staging in both randomized and observational studies. The concept of neo-adjuvant chemotherapy has been proven successful in gastric cancer, hepatic metastases from colorectal cancer and is currently tested in primary colon cancer., Methods and Design: Patients with rectal cancer with high risk features for local or systemic failure on magnetic resonance imaging are randomized to either a standard arm or an experimental arm. The standard arm consists of chemoradiation (1.8 Gy x 25 or 2 Gy x 25 with capecitabine) preoperatively, followed by selective postoperative adjuvant chemotherapy. Postoperative chemotherapy is optional and may be omitted by participating institutions. The experimental arm includes short-course radiotherapy (5 Gy x 5) followed by full-dose chemotherapy (capecitabine and oxaliplatin) in 6 cycles before surgery. In the experimental arm, no postoperative chemotherapy is prescribed. Surgery is performed according to TME principles in both study arms. The hypothesis is that short-course radiotherapy with neo-adjuvant chemotherapy increases disease-free and overall survival without compromising local control. Primary end-point is disease-free survival at 3 years. Secondary endpoints include overall survival, local control, toxicity profile, and treatment completion rate, rate of pathological complete response and microscopically radical resection, and quality of life., Discussion: Following the advances in rectal cancer management, increased focus on survival rather than only on local control is now justified. In an experimental arm, short-course radiotherapy is combined with full-dose chemotherapy preoperatively, an alternative that offers advantages compared to concomitant chemoradiotherapy with or without postoperative chemotherapy. In a multi-centre setting this regimen is compared to current standard with the aim of improving survival for patients with locally advanced rectal cancer., Trial Registration: ClinicalTrials.gov NCT01558921.

• Significant association of blood biomarkers and radiation DVH parameters in esophageal cancer. • Significant association of blood biomarkers and clinical events after CRT for esophageal cancer. • HS TNT and Pro BNP can be useful in radiotherapy prediction models for cardiac events. The aim of this study was to test the hypothesis that the levels of High Sensitive Troponin T (HS-TNT) and N-terminal Brain Natriuretic Peptide (NT-ProBNP) increase after radiation therapy in a dose dependent way and are predictive for clinical cardiac events. Blood samples during and after radiotherapy of 87 esophageal cancer patients were analysed regarding the course of HS-TNT and NT-ProBNP levels and their relationship with clinical toxicity endpoints and radiation dose volume parameters. HS-TNT values at the end of treatment correlated with the mean heart dose (p = 0.02), whereas the rise of NT-ProBNP correlated with the mean lung dose (p = 0.01). Furthermore, the course of both HS-TNT (p < 0.001) and NT-ProBNP (p < 0.01) levels were significantly different for patients who developed new cardiac events as opposed to those without new cardiac events. Significant correlations were found for both biomarkers with radiation dose and clinical toxicity endpoints after treatment. Therefore, these markers might be of additional value in NTCP models for cardiac events and might help us unravelling the mechanisms behind these toxicity endpoints. [ABSTRACT FROM AUTHOR]

[Display omitted] • Proton therapy can be as robust as photon therapy to inter-fraction motion. • Proton therapy significantly reduces organ at risk doses compared to photon therapy. • Two ITV-based treatment planning techniques for PBS-PT presented. Large-field photon radiotherapy is current standard in the treatment of cervical cancer patients. However, with the increasing availability of Pencil Beam Scanning Proton Therapy (PBS-PT) and robust treatment planning techniques, protons may have significant advantages for cervical cancer patients in the reduction of toxicity. In this study, PBS-PT and photon Volumetric Modulated Arc Therapy (VMAT) were compared, examining target coverage and organ at risk (OAR) dose, taking inter- and intra-fraction motion into account. Twelve cervical cancer patients were included in this in-silico planning study. In all cases, a planning CT scan, five weekly repeat CT scans (reCTs) and an additional reCT 10 min after the first reCT were available. Two-arc VMAT and robustly optimised two- and four-field (2F and 4F) PBS-PT plans were robustly evaluated on planCTs and reCTs using set-up and range uncertainty. Nominal OAR doses and voxel-wise minimum target coverage robustness were compared. Average voxel-wise minimum accumulated doses for pelvic target structures over all patients were adequate for both photon and proton treatment techniques (D98 > 95%, [91.7–99.3%]). Average accumulated dose of the para-aortic region was lower than the required 95%, D98 > 94.4% [91.1–98.2%]. With PBS-PT 4F, dose to all OARs was significantly lower than with VMAT. Major differences were observed for mean bowel bag V 15Gy : 60% [39–70%] for VMAT vs 30% [10–52%] and 32% [9–54%] for PBS-PT 2F and 4F and for mean bone marrow V 10Gy : 88% [82–97%] for VMAT vs 66% [60–73%] and 67% [60–75%] for PBS-PT 2F and 4F. Robustly optimised PBS-PT for cervical cancer patients shows equivalent target robustness against inter- and intra-fraction variability compared to VMAT, and offers significantly better OAR sparing. [ABSTRACT FROM AUTHOR]

Purpose: In recent years several papers have been published on radiation-induced cardiac toxicity, especially in breast cancer patients. However, in esophageal cancer patients the radiation dose to the heart is usually markedly higher. To determine whether radiation-induced cardiac toxicity is also a relevant issue for this group, we conducted a review of the current literature. Methods: A literature search was performed in Medline for papers concerning cardiac toxicity in esophageal cancer patients treated with radiotherapy with or without chemotherapy. Results: The overall crude incidence of symptomatic cardiac toxicity was as high as 10.8%. Toxicities corresponded with several dose–volume parameters of the heart. The most frequently reported complications were pericardial effusion, ischemic heart disease and heart failure. Conclusion: Cardiac toxicity is a relevant issue in the treatment of esophageal cancer. However, valid Normal Tissue Complication Probability models for esophageal cancer are not available at present. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To assess the effectiveness of definitive radiation therapy in patients with potentially curable esophageal cancer and to evaluate the side-effects of this treatment. Methods and materials: Sixty-two patients with esophageal cancer, who were treated with definitive, curatively intended radiotherapy consisting of external radiotherapy (60Gy in 30 fractions), preceded and followed by LDR or HDR intraluminal brachy (12Gy in 2 fractions) were retrospectively analyzed. Results: Recurrences were reported in 38 patients (61%), of which 25 (64%) failed locally first. The overall survival rates at 1, 2 and 5years were 57%, 34% and 11%, respectively. The median overall survival was 15months. No prognostic factors could be identified. Most frequently reported treatment related toxicities were esophagitis, ulcerations, (11%) and strictures (16%). In 10 patients (16%) severe toxicities, were reported including grade III ulceration (2 cases), stricture (1 case), radiation pneumonitis (1 case), perforation (1 case), esophageal-pleural-tracheal fistula (1 case), and acute esophageal bleeding (4 cases). A history of gastrectomy was significantly associated with the development of severe toxicity. Conclusion: Curatively intended radiotherapy alone can be offered to esophageal cancer patients, even when surgery and/or chemotherapy are not feasible. However, we observed severe toxicity in a substantial part of the patients. Given the relatively high rate of severe complications and the uncertainties regarding dose escalation, the addition of brachytherapy, with consequently high surface doses, should be limited to well-selected patients. [Copyright &y& Elsevier]

Abstract: Purpose: This review analyses the literature concerning the influence of the patient position (supine, prone and prone on a belly board device (BB) on the irradiated small-bowel-volume (SB-V)) and the resulting morbidity of radiation therapy (RT) in pelvic malignancies. Methods: A literature search was performed in MEDLINE, web of science and Scopus. Results: Forty-six full papers were found, of which 33 met the eligibility criteria. Fifteen articles focussed on the irradiated SB-V using dose volume histograms (DVHs). Twenty-seven articles studied the patient setup in different patient positions. This review showed that a prone treatment position can result in a lower irradiated SB-V as compared to a supine position, but a more significant reduction of the SB-V can be reached by the additional use of a BB in prone position, for both 3D-CRT and IMRT treatment plans. This reduction of the irradiated SB-V might result in a reduced GI-morbidity. The patient position did not influence the required PTV margins for prostate and rectum. Conclusions: The irradiated SB-V can be maximally reduced by the use of a prone treatment position combined with a BB for both 3D-CRT and IMRT, which might individually result in a reduction of GI-morbidity. [Copyright &y& Elsevier]