Radiotherapy

Radiotherapy to the primary tumour for newly diagnosed, metastatic prostate cancer (STAMPEDE): a randomised controlled phase 3 trial (2018)

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Type of publication:
Randomised controlled trial

Author(s):
Parker, Christopher C; James, Nicholas D; Brawley, Christopher D; Clarke, Noel W; Hoyle, Alex P; Ali, Adnan; Ritchie, Alastair W S; Attard, Gerhardt; Chowdhury, Simon; Cross, William; Dearnaley, David P; Gillessen, Silke; Gilson, Clare; Jones, Robert J; Langley, Ruth E; Malik, Zafar I; Mason, Malcolm D; Matheson, David; Millman, Robin; Russell, J Martin; Thalmann, George N; Amos, Claire L; Alonzi, Roberto; Bahl, Amit; Birtle, Alison; Din, Omar; Douis, Hassan; Eswar, Chinnamani; Gale, Joanna; Gannon, Melissa R; Jonnada, Sai; Khaksar, Sara; Lester, Jason F; O'Sullivan, Joe M; Parikh, Omi A; Pedley, Ian D; Pudney, Delia M; Sheehan, Denise J; *Srihari, Narayanan Nair; Tran, Anna T H; Parmar, Mahesh K B; Sydes, Matthew R; Systemic Therapy for Advanced or Metastatic Prostate cancer: Evaluation of Drug Efficacy (STAMPEDE) investigators

Citation:
Lancet, Volume 392, Issue 10162, 1–7 December 2018, Pages 2353-2366

Abstract:
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. This trial is registered with ClinicalTrials.gov, number CT00268476. 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 (HR 0·76, 95% CI 0·68-0·84; p<0·0001) but not overall survival (0·92, 0·80-1·06; p=0·266). 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. FUNDING Cancer Research UK, UK Medical Research Council, Swiss Group for Clinical Cancer Research, Astellas, Clovis Oncology, Janssen, Novartis, Pfizer, and Sanofi-Aventis.

Link to full-text [NHS OpenAthens account required]

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Results of a multicentre randomised controlled trial of cochlear-sparing intensity-modulated radiotherapy versus conventional radiotherapy in patients with parotid cancer (COSTAR; CRUK/08/004) (2018)

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Type of publication:
Journal article

Author(s):
Nutting , Morden JP, Beasley M, Bhide S, Cook A, De Winton E, Emson M, Evans M, Fresco L, Gollins S, Gujral D, Harrington K, Joseph M, Lemon C, Luxon L, van den Blink Q, Mendes R, Miah A, Newbold K, Prestwich R, Robinson M, Sanghera P, Simpson J, Sivaramalingam M, *Srihari NN, Sydenham M, Wells E, Witts S, Hall E; COSTAR Investigators.

Citation:
European Journal of Cancer; Nov 2018; vol. 103 ; p. 249-258

Abstract:
Purpose: About 40-60% of patients treated with post-operative radiotherapy for parotid cancer experience
ipsilateral sensorineural hearing loss. Intensity-modulated radiotherapy (IMRT) can reduce radiation dose to the cochlea. COSTAR, a phase III trial, investigated the role of cochlear-sparing IMRT (CS-IMRT) in reducing hearing loss. Methods: Patients (pT1-4 N0-3 M0) were randomly assigned (1:1) to 3-dimensional conformal radiotherapy (3DCRT) or CS-IMRT by minimisation, balancing for centre and radiation dose of 60Gy or 65Gy in 30 daily fractions. The primary end-point was proportion of patients with sensorineural hearing loss in the ipsilateral cochlea of >=10 dB bone conduction at 4000 Hz 12 months after radiotherapy compared using Fisher's exact test. Secondary end-points included hearing loss at 6 and 24 months, balance assessment, acute and late toxicity, patient-reported quality of life, time to recurrence and survival. Results: From Aug 2008 to Feb 2013, 110 patients (54 3DCRT; 56 CS-IMRT) were enrolled from 22 UK centres. Median doses to the ipsilateral cochlea were 3DCRT: 56.2Gy and CS-IMRT: 35.7Gy (p < 0.0001). 67/110 (61%) patients were evaluable for the primary end-point; main reasons for non-evaluability were non-attendance at follow-up or incomplete audiology assessment. At 12 months, 14/36 (39%) 3DCRT and 11/31 (36%) CS-IMRT patients had >=10 dB loss (p = 0.81). No statistically significant differences were observed in hearing loss at 6 or 24 months or in other secondary end-points including patient-reported hearing outcomes. Conclusion: CS-IMRT reduced the radiation dose below the accepted tolerance of the cochlea, but this did not lead to a reduction in the proportion of patients with clinically relevant hearing loss.

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Sparing the superficial lobe of the parotid during radical radiotherapy for oropharyngeal carcinoma (2018)

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Type of publication:
Conference abstract

Author(s):
*Pettit L.; *Welsh A.G.; *Williams M.T.; *Puzey C.H.

Citation:
Radiotherapy and Oncology; Apr 2018; vol. 127

Abstract:
Purpose or Objective: Parotid sparing IMRT has been shown to reduce incidence of xerostomia, leading to
recovery of salivary function and subsequently improve quality of life. It is usual to contour the whole parotid gland (WPG) which is considered a parallel organ. It can be challenging to meet dose constraints of the WPG even with VMAT. The general consensus in the U.K. has been to use a simple planning constraint of mean < 24 Gy to the WPG. However, this is not always achievable, especially with large tumours. Previous work suggests if only part of the parotid was spared this may be enough for preservation of saliva function. Material and Methods A retrospective dosimetric analysis of ten previous unselected patients who had received bilateral radical radiotherapy 65 Gy in 30 fractions for squamous cell carcinoma of the oropharynx that were identified from ARIA. Demographics were recorded on an excel spreadsheet. The deep lobe (DL) and superficial lobe (SL) of the ipsilateral (IL) and contralateral (CL) parotid gland were contoured on each CT planning slice. Mean dose to the deep lobe (DL) and superficial lobe (SL) was calculated from the original plan with the volume of the WPG. V40 and D50 were recorded. All treatment was replanned using a SL tolerance of V40 < 33% and D50 < 50% without compromise to the PTV's or change to other OAR. The DL of the parotid was not considered an organ at risk (OAR) for the re-plan. Results 10 patients were identified. 8 male, 2 female. All had squamous cell carcinoma of the oropharynx, 7 had tonsilar primaries, 2 base of tongue and 1 posterior pharyngeal wall. 7 were positive for p16. 9 also received concurrent platinum based chemotherapy. As expected the mean volume of the IL and CL parotid were similar (32.8 cc IL (7.8 cc DL, 24.7 cc SL, 31.9 cc CL (7.6 cc DL, 23.7 cc SL). On average, the DL accounted for 24.8% of the IL parotid and 25.1% of the CL parotid. Average IL SL mean dose was significantly reduced from 36.1 Gy to 33.9 Gy, average CL SL mean dose reduced from 28.3 Gy to 25.5 Gy (p = 0.02 t-test). Conclusion Our retrospective study confirmed that tolerances to the superficial lobe only are relatively easy and practical to meet. Previous work suggests that D50 may be a more reliable predictor of recovery of parotid function than mean dose to whole gland. Following this retrospective study our department will change dose constraints to superficial lobe V40 < 33% and D50 < 50% and no longer consider the deep lobe an OAR. Prospective data will investigate preservation of salivary function using D50/V40. (Figure Presented).

Partial breast radiotherapy after breast conservation: 5 year outcomes from the IMPORT LOW (CRUK/06/003) phase III trial (2017)

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Type of publication:
Conference abstract

Author(s):
Coles C.; Griffin C.; Bhattacharya I.; Emson M.; Haviland J.; Hopwood P.; Kaggwa R.; Bliss J.; Kirby A.; Donovan E.; *Agrawal R.; Alhasso A.; Brunt A.M.; Ciurlionis L.; Chan H.; Harnett A.; Sawyer E.; Sybdikus I.; Tsang Y.; Wheatley D.; Wilcox M.; Yarnold J.; Jefford M.

Citation:
Radiotherapy and Oncology; May 2017; vol. 123

Abstract:
Background: Local cancer relapse rates after breast conservation surgery followed by radiotherapy have fallen sharply in many countries with risk influenced by patient age and clinico-pathological factors. In women at lower than average risk of local relapse, partial breast radiotherapy restricted to the vicinity of the original tumour is hypothesised to improve the balance of beneficial versus adverse effects compared with whole breast radiotherapy. Methods: The IMPORT LOW trial (ISRCTN12852634) recruited women aged >=50 years after breast conserving surgery for invasive ductal adenocarcinoma pT<=3cm, pN0- 3, G1-3 and >=2mm resection margins. Using 15 daily treatments, patients were randomly allocated (1:1:1) to 40 Gy whole breast radiotherapy (control), 36 Gy whole breast plus 40 Gy to partial breast (reduced dose) or 40 Gy partial breast only (partial breast). Primary endpoint was ipsilateral local relapse rate (80% power to exclude a +2.5% noninferiority margin at 5 years for each test group). Findings: Between May 2007 and October 2010, 2018 women were recruited (control n=675, reduced dose: n=674, partial breast: n=669). With a 72.2 month median followup (IQR 61.7-83.2), 5-year local relapse rates were 1.1% (95%CI 0.5-2.3), 0.2% (0.02-1.2) and 0.5% (0.2-1.4) in control, reduced dose and partial breast groups. Absolute differences in local relapse rate compared with the control group were -0.73% (-0.99, 0.22) for the reduced dose and -0.38% (-0.84, 0.90) for the partial breast groups, demonstrating non-inferiority for both test groups. Photographs, patients and clinicians reported similar or lower levels of adverse effects after reduced dose or partial breast radiotherapy compared with whole breast radiotherapy (see Table 1). (Table presented) Interpretation: At 5 years, partial breast and reduced
dose radiotherapy showed local relapse rates non-inferior to that observed following whole breast radiotherapy and produced equivalent or milder late normal tissue side effects. This simple radiotherapy technique is implementable in radiotherapy centres worldwide.

The impact of body mass index on organs at risk in breast axillarynodal radiotherapy (2016)

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Type of publication:
Conference abstract

Author(s):
*Pettit L., *Welsh A., *Puzey-Kibble C., *Williams M., *Santos J., *Wardle G., *Khanduri S.

Citation:
Radiotherapy and Oncology, April 2016, vol./is. 119/(S558)

Abstract:
Purpose or Objective: There has been recent move within the U.K. to contour the nodal CTV for patients receiving adjuvant radiotherapy for breast cancer. Axillary radiotherapy (ART) following a positive sentinel lymph node biopsy is becoming more common for certain groups of patients. Organs at risk (OAR) should be delineated and considered during the planning process. Body mass index (BMI) has been shown to impact upon spinal cord and brachial plexus doses in irradiation of the supraclavicular fossa. The impact upon the OAR in the axilla has not yet been well documented. Material and Methods: Patients undergoing ART between 01/04/15-01/10/15 were identified. Non – contrast radiotherapy planning CT scans were taken. External beam radiotherapy was planned with extended tangents using a field in field approach with an additional low weighted anterior oblique field if deemed appropriate for adequate dose coverage. Dose delivered was 40.05 Gy in 15 fractions. BMI was calculated by: weight(kg)/height (m)2. CTV's were contoured in accordance with the RTOG contouring atlas. OAR including ipsilateral lung, humeral head and brachial plexus were delineated. Results: Fifteen patients were identified. Six patients had a BMI between 20-25, 3 between 25-30, 5 between 30-40 and 1 BMI>40. Mean ipsilateral lung V12 was 10.44% (range 2.3%- 14.33%). Mean V12 did not vary with BMI (BMI 20-25;mean V12=9.33%, BMI 25-30; mean V12=8.52%, BMI 30-40;mean V12=9.51%, BMI>40 mean V12=6.38%, p=0.55 Chi-Squared). The mean humeral head maximum dose was 35.2 Gy (range 1.2-41.5 Gy). Mean humeral head maximum dose did not vary with BMI (BMI 20-25; mean=34.2Gy, BMI 25-30;mean=27.8Gy, BMI 30-40; mean=40.3Gy, BMI>40; mean=38.2Gy, p=0.49 ttest). The ipsilateral brachial plexus D2 mean was15.6Gy (range 1.2-37.4 Gy). Mean ipsilateral brachial plexus D2 dose did not vary with BMI(p=0.21 t-test). Conclusion: BMI did not significantly impact upon OAR dosage although this series is limited by a small sample size. Ipsilateral lung and brachial plexus were comfortably within departmental tolerance. A planning risk volume of 10 mm around the humeral head has now been adopted within the department. It is recognised that intravenous contrast provides better quality images for delineating OAR in particular for the brachial plexus. However, this impacts upon resources in terms of radiographer scanning time. Adequate time needs to be allocated in consultant and physics teams job plans to enable high quality delineation and subsequent radiotherapy plans to be produced.

Link to more details or full-text: https://user-swndwmf.cld.bz/ESTRO-35/ESTRO-35-Abstract-book3/584

External beam radiotherapy in differentiated thyroid carcinoma: A systematic review. (2016)

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Type of publication:
Systematic Review

Author(s):
*Fussey JM, Crunkhorn R, Tedla M, Weickert MO, Mehanna H.

Citation:
Head Neck. Volume38, IssueS1, April 2016, Pages E2297-E2305

Abstract:
External beam radiotherapy (EBRT) is not a first line treatment in differentiated thyroid carcinoma (DTC), but is recommended as an adjuvant treatment in certain cases. The evidence for EBRT in DTC is limited. A comprehensive literature search was performed. Data on patient demographics, disease stage, treatment characteristics, and outcomes were collected from included articles after quality appraisal. Sixteen articles met the inclusion criteria, with a pooled population of 5114. Only 1 study was prospective and there were no randomized controlled trials. Most of the evidence suggests that EBRT improves locoregional control in patients at high risk of locoregional recurrence. This was corroborated by analysis of pooled patient data. Available evidence suggests an improvement in locoregional control when EBRT is used in patients over the age of 45 at high risk for locoregional recurrence. However, there is a need for long-term prospective multicenter research on the subject.