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 MetastasesA 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.

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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

Evidence-based Peer Review for Radiation Therapy

Updated Review of the Literature with a Focus on Tumour Subsite and Treatment Modality | Clinical Oncology

Technological advances in radiation therapy permit steep dose gradients from the target to spare normal tissue, but increase the risk of geographic miss. Suboptimal target delineation adversely affects clinical outcomes. Prospective peer review is a method for quality assurance of oncologists’ radiotherapy plans. Published surveys suggest it is widely implemented. However, it may not be feasible to review every case before commencement of radiation therapy in all departments. The rate of plan changes following peer review of cases without a specific subsite or modality is typically around 10%. Stereotactic body radiation therapy, head and neck, gynaecological, gastrointestinal, haematological and lung cases are associated with higher rates of change of around 25%. These cases could thus be prioritised for peer review. Other factors may limit peer review efficacy including organisational culture, time constraints and the physical environment in which sessions are held. Recommendations for peer review endorsed by the American Society for Radiation Oncology were made available in 2013, but a number of relevant studies have been published since. Here we review and update the literature, and provide an updated suggestion for the implementation of peer review to serve as an adjunct to published guidelines. This may help practitioners evaluate their current processes and maximise the utility and effectiveness of peer review sessions.

Full reference: Huo, M. et al. (2017) Evidence-based Peer Review for Radiation Therapy – Updated Review of the Literature with a Focus on Tumour Subsite and Treatment Modality. Clinical Oncology. DOI: 10.1016/j.clon.2017.04.038

Movies could replace anaesthetic for child radiotherapy

Children with cancer could be spared dozens of doses of general anaesthesia by projecting a video directly on to the inside of a radiotherapy machine during treatment | OnMedica

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The new research was presented this week at the ESTRO 36 conference (European Society for Radiotherapy & Oncology), taking place in Vienna, Austria.

Catia Aguas, a radiation therapist and dosimetrist at the Cliniques Universitaires Saint Luc, Brussels, Belgium, told the conference that using video instead of general anaesthesia is less traumatic for children and their families, as well as making each treatment quicker and more cost effective.

The study included 12 children aged between one and a half and six years old who were treated with radiotherapy using a Tomotherapy® treatment unit at the university hospital. Six were treated before a video projector was installed in 2014 and six were treated after.

Before the video was available, general anaesthesia was needed for 83% of children’s treatments. Once the projector was installed, anaesthesia was only needed in 33% of treatments.

Read the full commentary here

Individualised mindfulness-based stress reduction for head and neck cancer patients undergoing radiotherapy

Pollard, A. et al. (2017) European Journal of Cancer Care. 26(2)

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Image source: mindfulness – Flickr // CC BY 2.0

People with head and neck cancer (HNC) experience elevated symptom toxicity and co-morbidity as a result of treatment, which is associated with poorer psychosocial and quality-of-life (QoL) outcomes.

This Phase I study examined whether an individualised mindfulness-based stress reduction (IMBSR) programme could be successfully used with HNC patients undergoing curative treatment.

After controlling for pre-intervention mindfulness, there was an association between higher post-intervention mindfulness and lower psychological distress and higher total, social and emotional QoL. This study offers important preliminary evidence than an IMBSR intervention can be administered to HNC patients during active cancer treatment. A randomised controlled trial is warranted to confirm these findings.

Read the full abstract here