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Aims: To report late toxicity and long-term outcomes of intensity-modulated radiotherapy (IMRT)-based stereotactic ablative body radiotherapy (SABR) in patients with ultra-central lung tumours., Materials and Methods: This is a single-institution retrospective analysis of patients treated with SABR for ultra-central tumours between May 2008 and April 2016. Ultra-central location was defined as tumour (GTV) abutting or involving trachea, main or lobar bronchi. Respiratory motion management and static-field dynamic-IMRT were used, with dose prescribed homogeneously (maximum <120%). Descriptive analysis, Kaplan-Meier method, log-rank test and Cox regression were used to assess outcomes., Results: Sixty-five per cent of patients had inoperable primary non-small cell lung cancer and 35% had lung oligometastases. The median age was 72 (range 34-85) years. The median gross tumour volume and planning target volume (PTV) were 19.6 (range 1.7-203.3) cm 3 and 57.4 (range 7.7-426.6) cm 3 , respectively. The most commonly used dose fractionation was 60 Gy in eight fractions (n = 51, 87.8%). Median BED 10 for D98%PTV and D2%PTV were 102.6 Gy and 115.06 Gy, respectively. With a median follow-up of 26.5 (range 3.2-100.5) months, fatal haemoptysis occurred in five patients (8.7%), of which two were directly attributable to SABR. A statistically significant difference was identified between median BED 3 for 4 cm 3 of airway, for patients who developed haemoptysis versus those who did not (147.4 versus 47.2 Gy, P = 0.005). At the last known follow-up, 50 patients (87.7%) were without local recurrence. Freedom from local progression at 2 and 4 years was 92 and 79.8%, respectively. The median overall survival was 34.3 (95% confidence interval 6.1-61.6) months. Overall survival at 2 and 4 years was 55.1 and 41.2%, respectively., Conclusion: In patients with high-risk ultra-central lung tumours, IMRT-based SABR with homogenous dose prescription achieves high local control, similar to that reported for peripheral tumours. Although fatal haemoptysis occurred in 8.7% of patients, a direct causality with SABR was evident in only 3%. Larger studies are warranted to ascertain factors associated with outcomes, especially toxicity, and identify patients who would probably benefit from this treatment., (Copyright © 2021 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Aims: Stereotactic ablative radiation therapy (SABR) is a standard of care for medically inoperable early stage non-small cell lung carcinoma. Tumours greater than 5 cm have been excluded from randomised trials using SABR and, hence, it is not used as a standard for larger lung tumours. However, improvements in radiation therapy techniques and the success of SABR in treatment of early stage disease may allow safe delivery of ablative doses to larger tumours. We analysed our experience with tumours ≥5 cm to determine the efficacy and toxicity profile of SABR in this setting., Materials and Methods: We evaluated survival, control rates, patterns of failure and toxicity in patients with a tumour diameter larger than 5 cm that had no nodal or distant metastases treated with SABR technology. Patients had been treated in two centres since 2009 and were retrospectively analysed. All patients had positron emission tomography staging, were discussed at a tumour board and were documented to have no nodal or distant metastatic disease. Treatment outcomes were analysed using Kaplan-Meier estimates and compared using the Log-rank test. Cox regression was used to investigate the association between the survival outcomes and predictor variables., Results: In total, 86 patients were identified. Six patients had no follow-up imaging. Therefore, 80 patients were available for analysis. All patients were reclassified according to the updated AJCC eighth edition. The median follow-up was 19.6 months. No patients received neoadjuvant or concurrent systemic therapy. One patient received adjuvant systemic therapy. The median age at treatment was 77 years (range 58-91). Eighty-four per cent were stage T3N0M0 and 16% were staged T4N0M0. The median tumour diameter was 5.8 cm (range 5.0-9.3 cm). The median gross tumour volume, measured on a single phase of the respiratory cycle, was 45.7 cm 3 (range 12.1-203.3 cm 3 ). The median overall survival was 20.9 months (95% confidence interval 12.6-29.1 months). One-, 2- and 3-year overall survival was 71%, 48% and 32%, respectively. The median local failure-free survival was 19.5 months (95% confidence interval 14.4-24.6). The median disease-free survival was 15.1 months (95% confidence interval 9.9-20.4 months). Local control at 1, 2 and 3 years was 85% (95% confidence interval 76-94%), 71% (95% confidence interval 58-84%) and 57% (95% confidence interval 40-74%), respectively. Forty-four patients (55%) had any treatment failure (local, mediastinal, intrapulmonary or distant metastases). Out-of-field intrapulmonary disease progression was the most common mode of failure, occurring in 21 patients (26%). Local failure occurred in 19 patients (24%) - alone or in combination with other progression. Distant metastases occurred in 20 patients (25%). Neither histological subtype, tumour size nor gross tumour volume had a statistically significant effect on local failure-free survival. Two patients experienced grade 3 late dyspnoea. There were no other reported grade 3 or higher acute or late toxicities., Conclusion: SABR for larger lung tumours ≥5 cm results in high local control and acceptable survival in patients with medically inoperable large non-small cell lung carcinoma treated with radiation alone. Such patients should be considered for SABR owing to fewer treatment fractions and acceptable toxicity. Local control analysis reveals a sustained pattern of local failure emphasising the need for long-term follow-up. Improvements in technical strategies are required to further improve local control., (Copyright © 2020 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Aims: The objective of this phase II clinical trial was to prospectively evaluate the safety and efficacy of accelerated hypofractionated three-dimensional conformal radiation therapy (3DCRT) in localised non-resectable/non-operable non-small cell lung cancer (NSCLC)., Materials and Methods: Sixty patients with stage I-III NSCLC were enrolled in a prospective single-arm All Ireland Co-operative Oncology Research Group (ICORG 99-09) toxicity end point phase II trial. The protocol allocated patients between three radiation schedule dose levels (60, 66 or 72 Gy, in 20, 22 and 24 fractions, respectively, 3 Gy daily, five fractions per week) according to combined lung V 25Gy (V 25Gy  ≤ 30%) with built-in early stopping toxicity rules. The primary end point was toxicity with evaluation of dose-limiting toxicity. The secondary objectives included radiological tumour response rate at 3 months after the completion of radiation therapy and the thoracic progression-free survival time., Results: Sixty patients were recruited from August 1999 to June 2009. Forty-nine patients were included in the primary per-protocol analysis. Eleven patients were not evaluable. In the first 30 evaluable patient cohort, severe oesophageal toxicity was reported in two patients (2/49; 4% experiencing grade 5 oesophageal late toxicity, related to the 97% oesophageal length). The trial was temporarily closed and was then reopened to validate an oesophageal dose volume constraint (DVC) of limiting the length of oesophagus fully encompassed by the 97% isodose to less than 1 cm (applied to 21 patients). The trial prospectively showed the safety of the oesophageal DVC, with no oesophageal toxicity above grade 3 thereafter. Thirty-nine per cent of patients had disease progression at 3-4 months after radiotherapy, 22% had stable disease, 20% had a complete response and 14% had a partial response. The median overall survival was 13.6 months (95% confidence interval 10.5-16.7) and overall survival at 1 and 3 years was 57% and 29%, respectively., Conclusion: A strategy using accelerated hypofractionated 3DCRT is feasible and reasonably safe for patients with inoperable NSCLC. It is safe to deliver for centrally located tumours if DVCs are applied to the oesophagus, which is the primary dose-limiting toxicity. Further studies are required to assess the efficacy of hypofractionated regimens for centrally located tumours using an oesophageal DVC and monitoring for oesophageal toxicity., (Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Aim: The feasibility and improved efficacy of six conventional fractions per week has previously been proven in a Danish randomized trial. We tested the tolerance and efficacy of seven conventional fractions per week using a concomitant boost technique., Methods: From September 1996 to May 1998, 20 patients with squamous cancer of the head and neck were treated with radiation alone. The site of disease was oropharynx in 35%, larynx in 30%, oral cavity 20%, and hypopharynx in 15%. All patients had stage III (10%)/IV (90%) disease. The planned total dose to gross disease was 66 Gy delivered in 33 fractions of 2 Gy each in 31 days. Large volumes were treated to 46 Gy, 2 Gy per fraction, once each morning, Monday-Friday. Boosts to gross disease consisted of 20 Gy in 10 fractions > or = 6 h after the morning dose on Tuesday and Thursday., Results: Acute toxicity > or = grade 3 was mucous membrane 75%, pharynx 60%, skin 65%, and larynx 35%. One acute toxicity was fatal. Chronic toxicity > or = grade 3 (three patients) was mucous membrane 5%, pharynx 10%, skin 5%, salivary 15%, and larynx 5%. All patients with grade III or greater late toxicity had grade III acute toxicity in each toxicity category. At 30 months Kaplan-Meier survival is 55%, and local control is 39%., Conclusions: Without increasing resource utilization this scheme accelerates treatment by 30%. As expected acute toxicity is high but manageable. Chronic toxicity appears comparable to other altered fractionation strategies however the median follow up is only 30 months more toxicity may emerge as the data matures. We plan further trials using 1.8 Gy fractions to reduce toxicity.

We performed this analysis to document the rate and severity of complications both during and after local field irradiation for localized prostate cancer and to assess the influence of three-dimensional conformal radiation therapy (3DCRT) on these complications. Bowel, urinary and cutaneous toxicities were noted in all patients treated with primary radiotherapy (RT) for prostate cancer using Radiation Therapy Oncology Group/European Organization for Research on Treatment of Cancer scores. Evaluations were performed weekly during RT, 6 weeks after RT and 3 monthly thereafter. Data on 111 were analysed. We also compared the complications of conventional and 3DCRT. The serious complication rates identified in this study compare favourably with those reported in the literature. Only 3.6%, 0.8% and 0% had acute grade 3 or 4 urinary, bowel or skin reactions respectively. Only two patients had chronic grade 3 or 4 urinary complications. Thus far no patients have developed chronic bowel or skin complications greater than grade 2. Despite dose escalation from 66 Gy to 70 Gy (with 3DCRT), there was a trend towards reduced toxicity when 3DCRT was compared with conventional radiation. RT is a well-tolerated treatment for early stage carcinoma of the prostate and our complication rates are compatible with international experiences. Further follow-up is required to determine the efficacy of treatment, the incidence of impotence and the final number of late complications.

Over the past 20 years, it has become evident that limb preservation is possible in the management of soft tissue sarcomas of the extremities. Amputation has been generally replaced by more conservative operations that preserve limb function, followed by radiation therapy. Although external beam irradiation has been the most commonly applied adjuvant, there has been increasing interest in using brachytherapy instead of external beam therapy. The reasons for this tren include the apparent equivalence of local control for properly selected patients using brachytherapy, improved patient convenience, shorter treatment time, and lower cost. A recently published report of a prospective randomized trail shows statistically significant improvement in local control when brachytherapy is added to surgery for high grade sarcomas. The treatment concepts used when using brachytherapy challenge many of the orginal teachings for external beam irradiation with regard to field size, volume irradiated, and the tissues that require treatment in the postoperative setting. This article addresses thse controversies, as well as reviews the evolving role of brachytherapy in the management of soft tissue sarcomas. Issues such as patient selection, integration with other local therapies, and complications are highlighted, and special situations are discussed.

High dose rate brachytherapy for lung and esophageal cancer is performed by placing a high activity Iridium 192 source into the lumen of the airway of esophagus. Because of the high activity of the source it remains in place for only a matter of minutes, and fractionated treatments are feasible. Before this development, conventional dose rate brachytherapy required hospitalization with attendant patient discomfort, expense, and complicated radiation safety requirements. The development of high activity remote afterloading machines has removed these practical disadvantages and has led to a great interest in the use of this technology for radical treatment and palliation of obstructing malignancies. There are several unresolved issues concerning this modality for both lung and esophageal cancer. For both diseases, optimal dose and fractionation schemes are not well defined but the palliative benefits for recurrent lung cancer have been clearly shown. The use of a brachytherapy boost following radical external beam radiation therapy of lung cancer is not proven to be advantageous. For esophageal cancer, the value of brachytherapy for palliation is not established. However, there are preliminary data to suggest that it can improve outcome when used routinely after radical treatment with external beam radiation therapy.