Dataset Information

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).

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.

SUBMITTER: Nutting CM

PROVIDER: S-EPMC6202674 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Publications

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).

Nutting Christopher M CM Morden James P JP Beasley Matthew M Bhide Shreerang S Cook Audrey A De Winton Emma E Emson Marie M Evans Mererid M Fresco Lydia L Gollins Simon S Gujral Dorothy D Harrington Kevin K Joseph Mano M Lemon Catherine C Luxon Linda L van den Blink Qurrat Q Mendes Ruheena R Miah Aisha A Newbold Kate K Prestwich Robin R Robinson Martin M Sanghera Paul P Simpson Joanna J Sivaramalingam Muthiah M Srihari Narayanan Nair NN Sydenham Mark M Wells Emma E Witts Stephanie S Hall Emma E

European journal of cancer (Oxford, England : 1990) 20181001

<h4>Purpose</h4>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.<h4>Methods</h4>Patients (pT1-4 N0-3 M0) were randomly assigned (1:1) to 3-dimensional conformal radiotherapy (3DCRT) or CS-IMRT by minimisation, balancing f ...[more]

PMID: 30286418

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Project description:BackgroundXerostomia is the most common late side-effect of radiotherapy to the head and neck. Compared with conventional radiotherapy, intensity-modulated radiotherapy (IMRT) can reduce irradiation of the parotid glands. We assessed the hypothesis that parotid-sparing IMRT reduces the incidence of severe xerostomia.MethodsWe undertook a randomised controlled trial between Jan 21, 2003, and Dec 7, 2007, that compared conventional radiotherapy (control) with parotid-sparing IMRT. We randomly assigned patients with histologically confirmed pharyngeal squamous-cell carcinoma (T1-4, N0-3, M0) at six UK radiotherapy centres between the two radiotherapy techniques (1:1 ratio). A dose of 60 or 65 Gy was prescribed in 30 daily fractions given Monday to Friday. Treatment was not masked. Randomisation was by computer-generated permuted blocks and was stratified by centre and tumour site. Our primary endpoint was the proportion of patients with grade 2 or worse xerostomia at 12 months, as assessed by the Late Effects of Normal Tissue (LENT SOMA) scale. Analyses were done on an intention-to-treat basis, with all patients who had assessments included. Long-term follow-up of patients is ongoing. This study is registered with the International Standard Randomised Controlled Trial register, number ISRCTN48243537.Findings47 patients were assigned to each treatment arm. Median follow-up was 44·0 months (IQR 30·0-59·7). Six patients from each group died before 12 months and seven patients from the conventional radiotherapy and two from the IMRT group were not assessed at 12 months. At 12 months xerostomia side-effects were reported in 73 of 82 alive patients; grade 2 or worse xerostomia at 12 months was significantly lower in the IMRT group than in the conventional radiotherapy group (25 [74%; 95% CI 56-87] of 34 patients given conventional radiotherapy vs 15 [38%; 23-55] of 39 given IMRT, p=0·0027). The only recorded acute adverse event of grade 2 or worse that differed significantly between the treatment groups was fatigue, which was more prevalent in the IMRT group (18 [41%; 99% CI 23-61] of 44 patients given conventional radiotherapy vs 35 [74%; 55-89] of 47 given IMRT, p=0·0015). At 24 months, grade 2 or worse xerostomia was significantly less common with IMRT than with conventional radiotherapy (20 [83%; 95% CI 63-95] of 24 patients given conventional radiotherapy vs nine [29%; 14-48] of 31 given IMRT; p<0·0001). At 12 and 24 months, significant benefits were seen in recovery of saliva secretion with IMRT compared with conventional radiotherapy, as were clinically significant improvements in dry-mouth-specific and global quality of life scores. At 24 months, no significant differences were seen between randomised groups in non-xerostomia late toxicities, locoregional control, or overall survival.InterpretationSparing the parotid glands with IMRT significantly reduces the incidence of xerostomia and leads to recovery of saliva secretion and improvements in associated quality of life, and thus strongly supports a role for IMRT in squamous-cell carcinoma of the head and neck.FundingCancer Research UK (CRUK/03/005).

Project description:Coplanar extended-field intensity-modulated radiation therapy (EF-IMRT) targeting the whole-pelvic and para-aortic lymph nodes in patients with advanced cervical cancer results in impaired creatinine clearance. An improvement in renal function cannot be expected unless low-dose (approximately 10 Gy) kidney exposure is reduced. The dosimetric method should be considered during EF-IMRT planning to further reduce low-dose exposure to the kidneys. To assess the usefulness of non-coplanar EF-IMRT with kidney-avoiding beams to spare the kidneys during cervical carcinoma treatment in dosimetric analysis between non-coplanar and coplanar EF-IMRT, we compared the doses of the target organ and organs at risk, including the kidney, in 10 consecutive patients. To estimate the influence of EFRT on renal dysfunction, creatinine clearance values after treatment were also examined in 18 consecutive patients. Of these 18 patients, 10 patients who were included in the dosimetric analysis underwent extended field radiation therapy (EFRT) with concurrent chemotherapy, and eight patients underwent whole-pelvis radiation therapy with concurrent chemotherapy to treat cervical carcinoma between April 2012 and March 2015 at our institution. In the dosimetric analysis, non-coplanar EF-IMRT was effective at reducing low-dose (approximately 10 Gy) exposure to the kidneys, thus maintaining target coverage and sparing other organs at risk, such as the small bowel, rectum, and bladder, compared with coplanar EF-IMRT. Renal function in all 10 patients who underwent EFRT, including coplanar EF-IMRT (with kidney irradiation), was low after treatment, and differed significantly from that of the eight patients who underwent WPRT (no kidney irradiation) 6 months after the first day of treatment (P = 0.005). In conclusion, non-coplanar EF-IMRT should be considered in patients with advanced cervical cancer, particularly in patients with a long life expectancy or with pre-existing renal dysfunction.

Project description:PURPOSE:To concurrently quantify the radiation-induced changes and temporal evolutions of parotid volume and parotid apparent diffusion coefficient (ADC) in nasopharyngeal carcinoma (NPC) patients treated by intensity-modulated radiotherapy by using magnetic resonance imaging (MRI). MATERIALS AND METHODS:A total of 11 NPC patients (9 men and 2 women; 48.7 ± 11.7 years, 22 parotid glands) were enrolled. Radiation dose, parotid sparing volume, severity of xerostomia, and radiation-to-MR interval (RMI) was recorded. MRI studies were acquired four times, including one before and three after radiotherapy. The parotid volume and the parotid ADC were measured. Statistical analysis was performed using SPSS and MedCalc. Bonferroni correction was applied for multiple comparisons. A P value less than 0.05 was considered as statistically significant. RESULTS:The parotid volume was 26.2 ± 8.0 cm(3) before radiotherapy. The parotid ADC was 0.8 ± 0.15 × 10(-3) mm(2)/sec before radiotherapy. The parotid glands received a radiation dose of 28.7 ± 4.1 Gy and a PSV of 44.1 ± 12.6%. The parotid volume was significantly smaller at MR stage 1 and stage 2 as compared to pre-RT stage (P < .005). The volume reduction ratio was 31.2 ± 13.0%, 26.1 ± 13.5%, and 17.1 ± 16.6% at stage 1, 2, and 3, respectively. The parotid ADC was significantly higher at all post-RT stages as compared to pre-RT stage reciprocally (P < .005 at stage 1 and 2, P < .05 at stage 3). The ADC increase ratio was 35.7 ± 17.4%, 27.0 ± 12.8%, and 20.2 ± 16.6% at stage 1, 2, and 3, respectively. The parotid ADC was negatively correlated to the parotid volume (R = -0.509; P < .001). The parotid ADC was positively associated with the radiation dose significantly (R(2) = 0.212; P = .0001) and was negatively associated with RMI significantly (R(2) = 0.203; P = .00096) significantly. Multiple regression analysis further showed that the post-RT parotid ADC was related to the radiation dose and RMI significantly (R(2) = 0.3580; P < .0001). At MR stage 3, the parotid volume was negatively associated with the dry mouth grade significantly (R(2) = 0.473; P < .0001), while the parotid ADC was positively associated with the dry mouth grade significantly (R(2) = 0.288; P = .015). CONCLUSION:Our pilot study successfully demonstrates the concurrent changes and temporal evolution of parotid volume and parotid ADC quantitatively in NPC patients treated by IMRT. Our results suggest that the reduction of parotid volume and increase of parotid ADC are dominated by the effect of acinar loss rather than edema at early to intermediate phases and the following recovery of parotid volume and ADC toward the baseline values might reflect the acinar regeneration of parotid glands.

Dataset Information

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).

Purpose

Methods

Results

Conclusion

Publications

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).

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