Fourth edition of the Radiotherapy dose fractionation guidance launched

RCR – 5th January 2024

We’re pleased to announce the launch of the fourth edition of theRadiotherapy dose fractionation guidance.

Originally published in 2006, this comprehensive document is widely recognised as one of the most important clinical oncology publications ever produced by the RCR. The third edition was one of the most popular downloaded publications in the last year.

Compiled by a team of highly experienced clinical oncologists, the fourth edition incorporates changes based on evidence published since the last update in 2019. It provides a concise summary of evidence-based radiotherapy fractionation schedules for all anatomical sites, to ensure its continuing role as a key reference document for all practicing clinical oncologists.

This fourth edition supersedes the previous third edition, which has now been withdrawn.

Read the Guidance – Radiotherapy Dose Fractionation Fourth Edition, January 2024

International Advances in Radiotherapy

APPG for Radiotherapy – July 2023

On 14th June 2023, the APPG for Radiotherapy (APPG-RT) heard from representatives of the global
radiotherapy industry to better understand how advances in Radiotherapy are being implemented in
other countries, and how similar approaches could fundamentally improve outcomes for cancer
patients in the UK.

Read the Report – International Advances in Radiotherapy

Stereotactic body radiotherapy versus conventional external beam radiotherapy in patients with painful spinal metastases: an open-label, multicentre, randomised, controlled, phase 2/3 trial

Sahgal, A. et al | 2021| Stereotactic body radiotherapy versus conventional external beam radiotherapy in patients with painful spinal metastases: an open-label, multicentre, randomised, controlled, phase 2/3 trial | The Lancet Oncology | DOI:https://doi.org/10.1016/S1470-2045(21)00196-0

Summary

Background

Conventional external beam radiotherapy is the standard palliative treatment for spinal metastases; however, complete response rates for pain are as low as 10–20%. Stereotactic body radiotherapy delivers high-dose, ablative radiotherapy. We aimed to compare complete response rates for pain after stereotactic body radiotherapy or conventional external beam radiotherapy in patients with painful spinal metastasis.

Methods

This open-label, multicentre, randomised, controlled, phase 2/3 trial was done at 13 hospitals in Canada and five hospitals in Australia. Patients were eligible if they were aged 18 years and older, and had painful (defined as ≥2 points with the Brief Pain Inventory) MRI-confirmed spinal metastasis, no more than three consecutive vertebral segments to be included in the treatment volume, an Eastern Cooperative Oncology Group performance status of 0–2, a Spinal Instability Neoplasia Score of less than 12, and no neurologically symptomatic spinal cord or cauda equina compression. Patients were randomly assigned (1:1) with a web-based, computer-generated allocation sequence to receive either stereotactic body radiotherapy at a dose of 24 Gy in two daily fractions or conventional external beam radiotherapy at a dose of 20 Gy in five daily fractions using standard techniques. Treatment assignment was done centrally by use of a minimisation method to achieve balance for the stratification factors of radiosensitivity, the presence or absence of mass-type tumour (extraosseous or epidural disease extension, or both) on imaging, and centre. The primary endpoint was the proportion of patients with a complete response for pain at 3 months after radiotherapy. The primary endpoint was analysed in the intention-to-treat population and all safety and quality assurance analyses were done in the as-treated population (ie, all patients who received at least one fraction of radiotherapy). The trial is registered with ClinicalTrials.gov, NCT02512965.

Findings

Between Jan 4, 2016, and Sept 27, 2019, 229 patients were enrolled and randomly assigned to receive conventional external beam radiotherapy (n equal to 115) or stereotactic body radiotherapy (n equal to 114). All 229 patients were included in the intention-to-treat analysis. The median follow-up was 6·7 months (IQR 6·3–6·9). At 3 months, 40 (35 per cent) of 114 patients in the stereotactic body radiotherapy group, and 16 (14 per cent ) of 115 patients in the conventional external beam radiotherapy group had a complete response for pain (risk ratio 1·33, 95 per cent CI 1·14–1·55; p equal to 0·0002). This significant difference was maintained in multivariable-adjusted analyses (odds ratio 3·47, 95 per cent CI 1·77–6·80; p equal to 0·0003). The most common grade 3–4 adverse event was grade 3 pain (five [4 per cent] of 115 patients in the conventional external beam radiotherapy group vs five (5 per cent) of 110 patients in the stereotactic body radiotherapy group). No treatment-related deaths were observed.

Interpretation

Stereotactic body radiotherapy at a dose of 24 Gy in two daily fractions was superior to conventional external beam radiotherapy at a dose of 20 Gy in five daily fractions in improving the complete response rate for pain. These results suggest that use of conformal, image-guided, stereotactically dose-escalated radiotherapy is appropriate in the palliative setting for symptom control for selected patients with painful spinal metastases, and an increased awareness of the need for specialised and multidisciplinary involvement in the delivery of end-of-life care is needed.

Request a copy of this article from the Library & Knowledge Service

COVID-19 rapid guideline: delivery of radiotherapy

NICE | March 2020| COVID-19 rapid guideline: delivery of radiotherapy

The purpose of this guideline is to maximise the safety of patients who need radiotherapy and make the best use of NHS resources, while protecting staff from infection. It will also enable services to match the capacity for radiotherapy to patient needs if services become limited because of the COVID-19 pandemic.

NICE has also produced a COVID-19 rapid guideline on delivery of systemic anticancer treatments.

This guideline is for:

• health and care practitioners
• health and care staff involved in planning and delivering services
• commissioners

Full details from NICE

COVID-19 rapid guideline: delivery of radiotherapy NICE guideline

NICE |  March 2020 | COVID-19 rapid guideline: delivery of radiotherapy [NG162]

The purpose of this guideline is to maximise the safety of patients who need radiotherapy and make the best use of NHS resources, while protecting staff from infection. It will also enable services to match the capacity for radiotherapy to patient needs if services become limited because of the COVID-19 pandemic.

This guidance was first published on 28 March 2020.

NICE has also produced a COVID-19 rapid guideline on delivery of systemic anticancer treatments.

This guideline is for:

• health and care practitioners
• health and care staff involved in planning and delivering services
• commissioners

The recommendations bring together

• existing national and international guidance and policies
• advice from specialists working in the NHS from across the UK. These include people with expertise and experience of treating patients for the specific health conditions covered by the guidance during the current COVID-19 pandemic.

Full details from NICE

Manchester research: One dose of radiotherapy as effective as five doses for cancer in the spine

University of Manchester| December  2019 | One dose of radiotherapy as effective as five doses for cancer in the spine 

A study conducted by a team of researchers from the Universities of Manchester and University College London aimed to test whether administering just one dose (single-fraction) of radiotherapy could be used instead of five doses (multi-fraction) which requires several hospital visits. The findings of the SCORAD randomised clinical trial, now published in JAMA, indicate that one dose of radiotherapy should be used instead of five doses for most patients with spinal canal compression, this finding is supported by all of the other statistical criteria and multiple patient outcomes.

The lead trial investigator, Professor Peter Hoskin (University of Manchester, Mount Vernon Cancer Centre (NHS), said: “In the UK, NICE guidelines do not currently stipulate a standard treatment regimen, though most patients with spinal canal compression or other metastatic bone disease are given several fractions.

“We believe our findings, which show equal clinical effectiveness for single-dose radiotherapy, provide strong evidence for NICE guidelines, and those in other countries, to be changed to stipulate a one-dose one-visit approach, reducing unnecessary discomfort for end of life cancer patients without compromising efficacy” (Source: University of Manchester).

Key points 

Question  Is treatment with a single dose of radiotherapy noninferior to multifraction radiotherapy delivered over 5 days among patients with metastatic cancer who have spinal canal compression?

Findings  In a clinical trial of 686 patients, the percentage who were ambulatory at 8 weeks was 69.3% in the single-fraction group vs 72.7% in the multifraction radiotherapy group. The lower CI limit for the risk difference (−11.5%) did not meet the predefined noninferiority margin of −11.0%.

Meaning  Treatment with single-fraction radiotherapy did not meet the criterion for noninferiority compared with multifraction radiotherapy for ambulatory response rate at 8 weeks, but consideration should be given to the extent to which the lower bound of the CI overlapped with the noninferiority margin.

See also:

University of Manchester One dose of radiotherapy as effective as five doses for cancer in the spine

University College London One dose of radiotherapy as effective as five doses for cancer in the spine

Full reference:

Hoskin, P.J., et al.|2019| Effect of Single-Fraction vs Multifraction Radiotherapy on Ambulatory Status Among Patients With Spinal Canal Compression From Metastatic Cancer: The SCORAD Randomized Clinical Trial | JAMA|322| 21| P. 2084–2094 |doi:https://doi.org/10.1001/jama.2019.17913

The full article is available from JAMA

Abstract

Importance  Malignant spinal canal compression, a major complication of metastatic cancer, is managed with radiotherapy to maintain mobility and relieve pain, although there is no standard radiotherapy regimen.

Objective  To evaluate whether single-fraction radiotherapy is noninferior to 5 fractions of radiotherapy.

Design, Setting, and Participants  Multicenter noninferiority randomized clinical trial conducted in 42 UK and 5 Australian radiotherapy centers. Eligible patients (n = 686) had metastatic cancer with spinal cord or cauda equina compression, life expectancy greater than 8 weeks, and no previous radiotherapy to the same area. Patients were recruited between February 2008 and April 2016, with final follow-up in September 2017.

Interventions  Patients were randomized to receive external beam single-fraction 8-Gy radiotherapy (n = 345) or 20 Gy of radiotherapy in 5 fractions over 5 consecutive days (n = 341).

Main Outcomes and Measures  The primary end point was ambulatory status at week 8, based on a 4-point scale and classified as grade 1 (ambulatory without the use of aids and grade 5 of 5 muscle power) or grade 2 (ambulatory using aids or grade 4 of 5 muscle power). The noninferiority margin for the difference in ambulatory status was −11%. Secondary end points included ambulatory status at weeks 1, 4, and 12 and overall survival.

Results  Among 686 randomized patients (median [interquartile range] age, 70 [64-77] years; 503 (73%) men; 44% had prostate cancer, 19% had lung cancer, and 12% had breast cancer), 342 (49.8%) were analyzed for the primary end point (255 patients died before the 8-week assessment). Ambulatory status grade 1 or 2 at week 8 was achieved by 115 of 166 (69.3%) patients in the single-fraction group vs 128 of 176 (72.7%) in the multifraction group. The difference in ambulatory status grade 1 or 2 in the single-fraction vs multifraction group was −0.4% at week 1, −0.7%; P value for noninferiority = .01) at week 4, and 4.1%; P value for noninferiority = .002) at week 12. Overall survival rates at 12 weeks were 50% in the single-fraction group vs 55% in the multifraction group. Of the 11 other secondary end points that were analyzed, the between-group differences were not statistically significant or did not meet noninferiority criterion.

Conclusions and Relevance  Among patients with malignant metastatic solid tumors and spinal canal compression, a single radiotherapy dose, compared with a multifraction dose delivered over 5 days, did not meet the criterion for noninferiority for the primary outcome (ambulatory at 8 weeks). However, the extent to which the lower bound of the CI overlapped with the noninferiority margin should be considered when interpreting the clinical importance of this finding.

Trial Registration  ISRCTN Identifiers: ISRCTN97555949 and ISRCTN97108008

The full paper is available from JAMA 

 

Single-Fraction Stereotactic vs Conventional Multifraction Radiotherapy for Pain Relief in Patients With Predominantly Nonspine Bone Metastases

Nguyen Q, Chun SG, Chow E, et al.| 2019|  Single-Fraction Stereotactic vs Conventional Multifraction Radiotherapy for Pain Relief in Patients With Predominantly Nonspine Bone Metastases: A Randomized Phase 2 Trial| JAMA Oncology  doi:10.1001/jamaoncol.2019.0192

Research published in the JAMA Oncology concludes that delivering high-dose, single-fraction (SBRT) seems to be an effective treatment option for patients with painful bone metastases.

Question  Does single-fraction stereotactic body radiotherapy (SBRT) for bone metastases lead to better pain response rates than standard multifraction radiotherapy (MFRT)?

Findings  In this prospective randomized phase 2 noninferiority trial, 160 patients with mostly nonspine bone lesions were randomly assigned to receive single-fraction SBRT (12 Gy for less than or equal to 4-cm lesions or 16 Gy for more than 4-cm lesions) or MFRT to 30 Gy in 10 fractions. Single-fraction radiation led to more patients experiencing complete or partial pain response at 2 weeks, 3 months, and 9 months compared with standard MFRT.

Meaning  Pain response rates were higher for high-dose, single-fraction SBRT, which should be considered for patients with bone metastases and long estimated survival times.

The full text of the article is available from the Library

In the news:

OnMedica  OTP Oncology – May 2019

 

New device will protect prostate cancer patients during radiation treatment

An innovation that can reduce the side-effects of radiotherapy for prostate cancer patients by over 70 per cent will be rolled out across the NHS, as part of the Long Term Plan to put cutting-edge treatments at the heart of people’s care.

Thanks to a deal struck by the NHS with manufacturer Boston Scientific, hospitals in England will now be encouraged to use its hydrogel device for all patients who could benefit, making radiotherapy a safer and less painful treatment option for many men.

The hydrogel acts as a spacer, reducing the amount of radiation that can pass through the prostate and damage the rectum during treatment, by temporarily positioning it away from the high dose radiation used in treatment.

The gel, made mostly of water, is injected before treatment starts and then remains in place during radiation therapy, before being naturally absorbed by the body after about 6 months.

In studies, its use has been shown to relatively reduce life-changing side effects, such as rectal pain, bleeding and diarrhoea, by over 70%, meaning significant improvements in quality of life for those battling prostate cancer.

Full story at NHS England

Radiotherapy benefits some men whose prostate cancer has spread to their bones

NIHR | January 2019 | Radiotherapy benefits some men whose prostate cancer has spread to their bones

An NIHR Signal highlights a trial part-funded by NIHR, published in October 2018, which compared the effects of standard care with or without radiotherapy to the prostate on overall survival for over 2000 men.  The standard treatment for men with metastatic prostate cancer is anti-androgen hormone therapy, and this is sometimes combined with chemotherapy. Radiotherapy of the prostate itself is only usually used for symptom relief.

The trial found that radiotherapy improved three-year survival rate from 73 to 81% in men with a limited number of metastases confined to the spine and pelvis. In this group, it also prevented any disease progression over three years in half of them compared to a third on standard care.

STAMPEDE was a randomised controlled trial  that took place in more than 100 hospitals in Switzerland and the UK. Over 2,000 men with newly diagnosed prostate cancer with metastases, confirmed on a bone scan, were recruited to the study.

Participants were randomised to either standard care (lifelong anti-androgen hormone therapy, with or without chemotherapy using docetaxel) or standard care plus radiotherapy to the prostate.

This study adds further evidence that radiotherapy could benefit men with newly diagnosed prostate cancer with local metastases.

The trial used CT and bone scans to define low and high metastatic burden. PET scans, which can detect smaller cancer deposits, are becoming widely available and may allocate people differently.

Treating the primary once the cancer has metastasised has conventionally thought to be futile. This has been challenged by finding that in low metastatic burden prostate cancer, radiotherapy to the primary significantly improves survival and should become standard of care.

This study raises the issue whether this would apply to other cancers and interesting biological questions as to the mechanism. Is it an effect of debulking the primary?  Is it immunological?  Is it due to reducing secondary spread of aggressive clones?

It seems we have underestimated in prostate cancer, the impact of local control in the setting of metastatic disease

Professor Robert Huddart, Reader and Honorary Consultant, Royal Marsden NHS Foundation Trust 

(Source: NIHR)

NIHR Radiotherapy benefits some men whose prostate cancer has spread to their bones

 

 Parker, C.  et al | 2018| Radiotherapy to the primary tumour for newly diagnosed, metastatic prostate cancer (STAMPEDE): a randomised controlled phase 3 trial|  The Lancet| 

 

Background

Based on previous findings, we hypothesised that radiotherapy to the prostate would improve overall survival in men with metastatic prostate cancer, and that the benefit would be greatest in patients with a low metastatic burden. We aimed to compare standard of care for metastatic prostate cancer, with and without radiotherapy.
Methods

We did a randomised controlled phase 3 trial at 117 hospitals in Switzerland and the UK. Eligible patients had newly diagnosed metastatic prostate cancer. We randomly allocated patients open-label in a 1:1 ratio to standard of care (control group) or standard of care and radiotherapy (radiotherapy group). Randomisation was stratified by hospital, age at randomisation, nodal involvement, WHO performance status, planned androgen deprivation therapy, planned docetaxel use (from December, 2015), and regular aspirin or non-steroidal anti-inflammatory drug use. Standard of care was lifelong androgen deprivation therapy, with up-front docetaxel permitted from December, 2015. Men allocated radiotherapy received either a daily (55 Gy in 20 fractions over 4 weeks) or weekly (36 Gy in six fractions over 6 weeks) schedule that was nominated before randomisation. The primary outcome was overall survival, measured as the number of deaths; this analysis had 90% power with a one-sided α of 2·5% for a hazard ratio (HR) of 0·75. Secondary outcomes were failure-free survival, progression-free survival, metastatic progression-free survival, prostate cancer-specific survival, and symptomatic local event-free survival. Analyses used Cox proportional hazards and flexible parametric models, adjusted for stratification factors. The primary outcome analysis was by intention to treat. Two prespecified subgroup analyses tested the effects of prostate radiotherapy by baseline metastatic burden and radiotherapy schedule.

Findings

Between Jan 22, 2013, and Sept 2, 2016, 2061 men underwent randomisation, 1029 were allocated the control and 1032 radiotherapy. Allocated groups were balanced, with a median age of 68 years (IQR 63–73) and median amount of prostate-specific antigen of 97 ng/mL (33–315). 367 (18%) patients received early docetaxel. 1082 (52%) participants nominated the daily radiotherapy schedule before randomisation and 979 (48%) the weekly schedule. 819 (40%) men had a low metastatic burden, 1120 (54%) had a high metastatic burden, and the metastatic burden was unknown for 122 (6%). Radiotherapy improved failure-free survival but not overall survival. Radiotherapy was well tolerated, with 48 (5%) adverse events (Radiation Therapy Oncology Group grade 3–4) reported during radiotherapy and 37 (4%) after radiotherapy. The proportion reporting at least one severe adverse event (Common Terminology Criteria for Adverse Events grade 3 or worse) was similar by treatment group in the safety population (398 [38%] with control and 380 [39%] with radiotherapy).

Interpretation

Radiotherapy to the prostate did not improve overall survival for unselected patients with newly diagnosed metastatic prostate cancer.

Use genetic data to predict the best time of day to give radiotherapy to breast cancer patients, say researchers

University of Leicester | November 2018 | Use genetic data to predict the best time of day to give radiotherapy to breast cancer patients, say Researchers

Scientists from the University of Leicester followed two independent cohorts of patients with breast cancer being treated with radiotherapy (P equal to 879); where the researchers found that patients with variations of two genes were more likely to experience side effects if they received radiotherapy in the morning. 

The researchers explain that this is due to their circadian rhythms, with radiotherapy treatment in the morning causing worse acute toxicity for these patients.  They suggest that in future treatment it may be possible to reduce toxicity associated with breast cancer radiotherapy by identifying gene variants that affect circadian rhythm and tailoring treatment for appropriate morning or afternoon radiotherapy.

Professor Paul Symonds, a consultant oncologist at Leicester’s Hospitals and professor of clinical oncology at the University of Leicester said: “Our study found that some patients with a particular genetic profile are more at risk of side effects if given radiotherapy in the morning. This happens because the skin of these particular patients divides earlier in the day than others and dividing cells are more easily damaged by X-rays. This could allow an easy way to personalise treatment just by recommending what time of day a patient should be treated.”

The study was part-funded by the Breast Cancer Now charity and supported by funding from the European Union Seventh Framework Programme for research, technological development and demonstration (Source: University of Leicester).

Read the full article from the University of Leicester

Read and download the article Genetic Variants Predict Optimal Timing of Radiotherapy to Reduce Side-effects in Breast Cancer Patients from Clinical Oncology

Johnson, K., Chang-Claude, J., Critchley, A. M., Kyriacou, C., Lavers, S., Rattay, T., … & Talbot, C. J. (2018). Genetic variants predict optimal timing of radiotherapy to reduce side-effects in breast cancer patients. Clinical Oncology. https://doi.org/10.1016/j.clon.2018.10.001

Abstract

Aims

Radiotherapy is an important treatment for many types of cancer, but a minority of patients suffer long-term side-effects of treatment. Multiple lines of evidence suggest a role for circadian rhythm in the development of radiotherapy late side-effects.

Materials and methods

We carried out a study to examine the effect of radiotherapy timing in two breast cancer patient cohorts. The retrospective LeND cohort comprised 535 patients scored for late effects using the Late Effects of Normal Tissue-Subjective Objective Management Analytical (LENT-SOMA) scale. Acute effects were assessed prospectively in 343 patients from the REQUITE study using the CTCAE v4 scales. Genotyping was carried out for candidate circadian rhythm variants.

Results

In the LeND cohort, patients who had radiotherapy in the morning had a significantly increased incidence of late toxicity in univariate (P equal to 0.03) and multivariate analysis (P equal to 0.01). Acute effects in the REQUITE group were also significantly increased in univariate analysis after morning treatment (P equal to 0.03) but not on multivariate analysis.

Conclusion

Our results suggest that it may be possible to reduce toxicity associated with breast cancer radiotherapy by identifying gene variants that affect circadian rhythm and scheduling for appropriate morning or afternoon radiotherapy.

In the news:

The Telegraph Radiotherapy should be given at different times of day to reduce side effects, Leicester Uni study suggests