UK 2022 Consensus on Normal Tissue Dose-Volume Constraints for Oligometastatic, Primary Lung and Hepatocellular Carcinoma Stereotactic Ablative Radiotherapy.

The use of stereotactic ablative radiotherapy (SABR) in the UK has expanded over the past decade, in part as the result of several UK clinical trials and a recent NHS England Commissioning through Evaluation programme. A UK SABR Consortium consensus for normal tissue constraints for SABR was published in 2017, based on the existing literature at the time. The published literature regarding SABR has increased in volume over the past 5 years and multiple UK centres are currently working to develop new SABR services. A review and update of the previous consensus is therefore appropriate and timely. It is hoped that this document will provide a useful resource to facilitate safe and consistent SABR practice.

Stereotactic Body Radiotherapy for Large Unresectable Hepatocellular Carcinomas - A Single Institution Phase II Study.

AIMS: To evaluate the safety and efficacy of liver stereotactic body radiotherapy (SBRT) in the treatment of unresectable hepatocellular carcinomas (HCC) measuring >5 cm. MATERIALS AND METHODS: Between November 2013 and February 2016, 13 patients with unresectable HCC (>5 cm), ineligible for other local treatments, with a Child-Pugh score (CPS) ≤ B7, were enrolled into a single-institution phase II study. SBRT was delivered by volumetric-modulated arc radiotherapy. Radiological response was reported using modified Response Evaluation Criteria in Solid Tumours criteria and toxicities graded by Common Terminology Criteria for Adverse Events v4 criteria. RESULTS: Sixteen hepatomas (median size 7.5 cm, range 5.1-9.7 cm) were treated in 13 patients. The baseline CPS was A5/6 in nine patients (69%) and B7 in four patients (31%). Five patients (38%) received previous liver-directed treatment. The median prescribed dose was 45 Gy (range 40-45 Gy) in five fractions. The median follow-up was 17.7 months. The 1-year local control rate was 92%. The median overall survival was 17.7 months and the 1-year overall survival was 62%. The median time to local progression was not reached. Five patients (39%) had an increase in CPS by two or more points at 3 months. Overall, there were 10 grade 3 acute toxicities occurring in seven patients, of which six were haematological. Quality of life remained clinically stable or improved at 3 months in 61.5% and 53.8% of patients based on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 Global Health Score and Functional Assessment of Cancer Therapy - Hepatobiliary version 4 score, respectively. CONCLUSIONS: In our cohort, SBRT to unresectable large HCC tumours provided excellent local control with acceptable toxicities. Regional recurrence remained the major cause of failure. Further studies are warranted to examine the role for SBRT in combination with other modalities to maximise disease control in the liver.

Whole Brain Radiotherapy Versus Stereotactic Radiosurgery in Poor-Prognosis Patients with One to 10 Brain Metastases: A Randomised Feasibility Study.

AIMS: A significant proportion of patients with brain metastases have a poor prognosis, with a life expectancy of 3-6 months. To determine the optimal radiotherapeutic strategy for brain metastases in this population, we conducted a randomised feasibility study of whole brain radiotherapy (WBRT) versus stereotactic radiosurgery (SRS). MATERIALS AND METHODS: Patients with a life expectancy of 3-6 months and between one and 10 brain metastases with a diameter ≤4 cm were enrolled at six Canadian cancer centres. Patients were randomly assigned (1:1) to receive either WBRT (20 Gy in five fractions) or SRS (15 Gy in one fraction). The primary end point was the rate of accrual per month. Secondary feasibility and clinical end points included the ratio of accrued subjects to screened subjects. This trial is registered with ClinicalTrials.gov (number NCT02220491). RESULTS: In total, 210 patients were screened to enrol 22 patients into the trial; 20 patients were randomised between the two arms. Two patients did not receive treatment because one patient died and another patient withdrew consent after being enrolled. Patients were accrued between January 2015 and November 2017; the accrual rate was 0.63 patients/month. The most common reasons for exclusion were anticipated median survival outside the required range (n = 40), baseline Karnofsky Performance Score below 70 (n = 28) and more than 10 brain metastases (n = 28). The median follow-up was 7.0 months and the median survival was 7.0 months for all patients in the trial. The median intracranial progression-free survival was 1.8 months in the SRS arm and 9.2 months in the WBRT arm. There were five grade 3+ toxicities in the SRS arm and one grade 3+ toxicity in the WBRT arm; no grade 5 toxicities were observed. The cumulative rates of retreatment were 40% in the SRS arm and 40% in the WBRT arm. CONCLUSIONS: A randomised trial evaluating WBRT versus SRS in patients with one to 10 metastases and a poor prognosis is feasible. A slower than expected accrual rate and difficulties with accurate prognostication were identified as issues in this feasibility study. A larger phase III randomised trial is planned to determine the optimal treatment in this patient population.

Stereotactic Body Radiotherapy for Small Unresectable Hepatocellular Carcinomas.

AIMS: Stereotactic body radiotherapy (SBRT) is an option for the treatment of hepatocellular carcinoma (HCC) in patients ineligible for standard local therapies. This study reports on the safety and efficacy of SBRT in small HCC tumours (≤5 cm) in the province of British Columbia. MATERIALS AND METHODS: Between March 2011 and July 2015, 31 patients with Child-Pugh Class A or B, with small HCCs measuring ≤5 cm were treated with SBRT at our institution. Primary end points were local control, progression-free survival, overall survival and toxicity. RESULTS: Thirty-four hepatomas (median size 3.3 cm, range 1.3-5.0 cm) were treated. The median follow-up was 18.3 months. Twenty-six patients (84%) had received previous liver-directed treatments. Most patients (88%) were treated with 45 Gy in three or five fractions. Six patients (19%) had worsened Child-Pugh score by two or more points during follow-up; overall 32% of patients experienced ≥ grade 3 + toxicities. One-year local control and overall survival were 94 and 84%, respectively. One-year progression-free survival was 49%; 81% of patients with disease progression received further HCC therapy. On univariate analysis, small tumour size predicted for improved overall survival (P = 0.01) whereas prescription biological equivalent dose (BED10) ≥100Gy10 approached significance (P = 0.06). CONCLUSION: SBRT provides high local control to small inoperable HCC. SBRT can be delivered safely even after previous liver-directed therapies and further liver therapies can follow treatment with SBRT. Although overall 32% of patients experienced ≥ grade 3 + toxicities, and 19% had a deterioration in Child-Pugh score of two or more points, these changes were mainly transient with minimal clinical impact. Despite excellent local control, disease progression outside of the irradiated site remains prominent. Further studies are warranted to examine combined therapy approaches to maximise disease control.

Head and neck target delineation using a novel PET automatic segmentation algorithm.

PURPOSE: To evaluate the feasibility and impact of using a novel advanced PET auto-segmentation method in Head and Neck (H&N) radiotherapy treatment (RT) planning. METHODS: ATLAAS, Automatic decision Tree-based Learning Algorithm for Advanced Segmentation, previously developed and validated on pre-clinical data, was applied to 18F-FDG-PET/CT scans of 20 H&N patients undergoing Intensity Modulated Radiation Therapy. Primary Gross Tumour Volumes (GTVs) manually delineated on CT/MRI scans (GTVpCT/MRI), together with ATLAAS-generated contours (GTVpATLAAS) were used to derive the RT planning GTV (GTVpfinal). ATLAAS outlines were compared to CT/MRI and final GTVs qualitatively and quantitatively using a conformity metric. RESULTS: The ATLAAS contours were found to be reliable and useful. The volume of GTVpATLAAS was smaller than GTVpCT/MRI in 70% of the cases, with an average conformity index of 0.70. The information provided by ATLAAS was used to grow the GTVpCT/MRI in 10 cases (up to 10.6mL) and to shrink the GTVpCT/MRI in 7 cases (up to 12.3mL). ATLAAS provided complementary information to CT/MRI and GTVpATLAAS contributed to up to 33% of the final GTV volume across the patient cohort. CONCLUSIONS: ATLAAS can deliver operator independent PET segmentation to augment clinical outlining using CT and MRI and could have utility in future clinical studies.

Role of (chemo)-radiotherapy in resectable gastric cancer.

The prognosis of patients with locally advanced gastric cancer remains poor, despite radical surgical resection. Adjuvant therapy has been shown to improve survival and, in Western countries, is delivered either postoperatively (chemoradiotherapy) or perioperatively (chemotherapy). Debate continues as to which of these represents the optimal strategy. High-dose gastric irradiation comes at the expense of significant toxicity, and increasing efforts have focused on attempts to reduce toxicity and normal tissue doses. The development of advancing radiotherapy technologies now allows improved target delineation and coverage. However, gastric irradiation remains technically challenging and requires an understanding of postoperative surgical anatomy, patterns of failure and lymph node drainage, as well as an appreciation of the uncertainties around organ motion and filling. Ongoing trials are examining the optimal strategy in which to incorporate (chemo)-radiotherapy, as well as the addition of targeted therapies, in gastric cancer. This overview discusses the current role and evidence for (chemo)-radiotherapy, as well as the technical challenges encountered in the radiotherapeutic management of resectable gastric cancer.

Definitive chemoradiotherapy for oesophageal cancer -- a promising start on an exciting journey.

Despite many advances in the management of oesophageal cancer, survival rates remain poor. Currently there is no clear consensus on the optimum management modality for localised disease. Surgery alone or combined with neoadjuvant chemotherapy or chemoradiotherapy and definitive chemoradiotherapy are all treatment options used for treating selected patient groups throughout the world. This overview discusses the evidence for definitive chemoradiotherapy, its role for certain patient groups and compared with other treatment options and how it has evolved with emerging technologies over recent decades. It highlights some key areas of research for future trials, including more precise treatment delivery, treatment intensification and a possible randomised controlled trial comparing radiation and surgical-based treatment.