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Background: Patients with intermediate and high-risk oropharyngeal cancer (OPC) have poorer response to standard treatment and poorer overall survival compared to low-risk OPC. CompARE is designed to test alternative approaches to intensified treatment for these patients to improve survival., Methods: CompARE is a pragmatic phase III, open-label, multicenter randomised controlled trial with an adaptive multi-arm, multi-stage design and an integrated QuinteT Recruitment Intervention. Eligible OPC patients include those with human papillomavirus (HPV) negative, T1-T4, N1-N3 or T3-4, N0, or HPV positive N3, T4, or current smokers (or ≥ 10 pack years previous smoking history) with T1-T4, N2b-N3. CompARE was originally designed with four arms (one control [arm 1] and three experimental: arm 2-induction chemotherapy followed by arm 1; arm 3-dose-escalated radiotherapy plus concomitant cisplatin; and arm 4-resection of primary followed by arm 1). The three original experimental arms have been closed to recruitment and a further experimental arm opened (arm 5-induction durvalumab followed by arm 1 and then adjuvant durvalumab). Currently recruiting are arm 1 (control): standard treatment of 3-weekly cisplatin 100 mg/m 2 or weekly 40 mg/m 2 with intensity-modulated radiotherapy using 70 Gy in 35 fractions ± neck dissection determined by clinical and radiological assessment 3 months post-treatment, and arm 5 (intervention): one cycle of induction durvalumab 1500 mg followed by standard treatment then durvalumab 1500 mg every 4 weeks for a total of 6 months. The definitive and interim primary outcome measures are overall survival time and event-free survival (EFS) time, respectively. Secondary outcome measures include quality of life, toxicity, swallowing outcomes, feeding tube incidence, surgical complication rates, and cost-effectiveness. The design anticipates that after approximately 7 years, 84 required events will have occurred to enable analysis of the definitive primary outcome measure for this comparison. Planned interim futility analyses using EFS will also be performed., Discussion: CompARE is designed to be efficient and cost-effective in response to new data, emerging new treatments or difficulties, with the aim of bringing new treatment options for these patients., Trial Registration: ISRCTN ISRCTN41478539 . Registered on 29 April 2015., (© 2024. The Author(s).)

Background: Prior reports have raised concerns that a prophylactic gastrostomy may be detrimental to long-term swallow function. This study evaluates patient-reported swallow function following chemoradiotherapy for oropharyngeal carcinoma in relation to the use of a prophylactic gastrostomy or nasogastric (NG) tube as required. Material and methods: The MD Anderson Dysphagia Inventory (MDADI) was posted to 204 disease-free patients at least 2 years following chemoradiotherapy for oropharyngeal carcinoma between 2010 and 2014. Results: Overall, 181/204 (89%) patients returned questionnaire at a median of 34 months post-treatment. 97/181 (54%) and 84/181 (46%) were managed with an approach of a prophylactic gastrostomy or NG tube as required, respectively. A prophylactic gastrostomy was associated with higher rates of enteral feeding (92% vs. 58%, p  < .001), lower median percentage weight loss (7.0% vs. 9.4%, p  < .001), increased duration of enteral feed (median 3.3 vs. 1.1 months, p  < .001). There was no significant difference in patient-reported swallow function measured by MDADI summary scores and subscales for patients managed with an approach of prophylactic gastrostomy or NG as required. Duration of enteral feed correlated negatively with composite MDADI scores. A subgroup of 116/181 (64%) patients were documented as having been offered a choice of enteral feeding approach and therefore can be considered to represent clinical equipoise; there were no significant differences in MDADI scores according to route. Conclusions: Despite concern regarding the use of a prophylactic gastrostomy in prior studies, the approaches of using a prophylactic gastrostomy or an NG tube as required to support patients during/after chemoradiotherapy for oropharyngeal carcinoma were associated with similar long-term swallow outcomes.

Background: The incidence of human papillomavirus (HPV)-positive oropharyngeal cancer, a disease affecting younger patients, is rapidly increasing. Cetuximab, an epidermal growth factor receptor inhibitor, has been proposed for treatment de-escalation in this setting to reduce the toxicity of standard cisplatin treatment, but no randomised evidence exists for the efficacy of this strategy., Methods: We did an open-label randomised controlled phase 3 trial at 32 head and neck treatment centres in Ireland, the Netherlands, and the UK, in patients aged 18 years or older with HPV-positive low-risk oropharyngeal cancer (non-smokers or lifetime smokers with a smoking history of <10 pack-years). Eligible patients were randomly assigned (1:1) to receive, in addition to radiotherapy (70 Gy in 35 fractions), either intravenous cisplatin (100 mg/m 2 on days 1, 22, and 43 of radiotherapy) or intravenous cetuximab (400 mg/m 2 loading dose followed by seven weekly infusions of 250 mg/m 2 ). The primary outcome was overall severe (grade 3-5) toxicity events at 24 months from the end of treatment. The primary outcome was assessed by intention-to-treat and per-protocol analyses. This trial is registered with the ISRCTN registry, number ISRCTN33522080., Findings: Between Nov 12, 2012, and Oct 1, 2016, 334 patients were recruited (166 in the cisplatin group and 168 in the cetuximab group). Overall (acute and late) severe (grade 3-5) toxicity did not differ significantly between treatment groups at 24 months (mean number of events per patient 4·8 [95% CI 4·2-5·4] with cisplatin vs 4·8 [4·2-5·4] with cetuximab; p=0·98). At 24 months, overall all-grade toxicity did not differ significantly either (mean number of events per patient 29·2 [95% CI 27·3-31·0] with cisplatin vs 30·1 [28·3-31·9] with cetuximab; p=0·49). However, there was a significant difference between cisplatin and cetuximab in 2-year overall survival (97·5% vs 89·4%, hazard ratio 5·0 [95% CI 1·7-14·7]; p=0·001) and 2-year recurrence (6·0% vs 16·1%, 3·4 [1·6-7·2]; p=0·0007)., Interpretation: Compared with the standard cisplatin regimen, cetuximab showed no benefit in terms of reduced toxicity, but instead showed significant detriment in terms of tumour control. Cisplatin and radiotherapy should be used as the standard of care for HPV-positive low-risk patients who are able to tolerate cisplatin., Funding: Cancer Research UK., (Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background and Purpose: Limited data are available to inform on long term swallowing outcomes following concurrent chemoradiotherapy for oropharyngeal carcinoma. The aims of this study are to determine long term patient-reported swallowing outcomes across two large UK centres in routine clinical practice and identify associated factors., Material and Methods: All patients treated for oropharyngeal squamous cell carcinoma with concurrent chemoradiotherapy, and irradiation of the bilateral neck, between 2011 and 2013 were identified. Those requiring therapeutic enteral feeding prior to treatment, or having subsequent disease relapse, were excluded from the study. Patients were sent postal invitations to complete the MD Anderson Dysphagia Inventory (MDADI), at least two years following completion of treatment., Results: Completed MDADI were received from 201/242 eligible patients (83%) at a median of 3.4 years (range 2-5) post treatment. Median composite MDADI score was 68.4. 64 (32%) had composite MDADI <60 classed as 'poor' function, 76 (38%) scores ≥60-<80 classed as adequate function, and 61 (31%) had scores ≥80 classed as optimal function. Patients with normal and abnormal pre-treatment diet had median composite MDADI scores of 70.5 versus 47.4 respectively. Patients who did not require enteral feeding during treatment and those who did had median composite MDADI scores of 76.3 versus 65.3 respectively. On multivariate analysis poorer performance status, abnormal pre-treatment diet, and use of enteral feeding during radiotherapy were all significantly associated with lower composite, global and subscale MDADI scores., Conclusions: Patient reported swallowing dysfunction remains common in the long term post-chemoradiotherapy. Impaired pre-treatment diet and use of enteral feeding during treatment are key factors associated with poorer swallowing outcomes., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objectives: The purpose of this matched pair analysis is to assess patient-reported long term swallow function following chemoradiotherapy for locally advanced oropharyngeal cancer in relation to the use of a prophylactic gastrostomy or reactive nasogastric (NG) tube., Materials and Methods: The MD Anderson Dysphagia Inventory (MDADI) was posted to 68 consecutive patients with stage III/IV oropharyngeal squamous cell carcinoma who had completed parotid sparing intensity modulated radiotherapy with concurrent chemotherapy between 2010 and 2012, had not required therapeutic enteral feeding prior to treatment, minimum 2years follow up post treatment, and who were disease free. 59/68 replies were received, and a matched pair analysis (matching for T and N stage) was performed for 52 patients, 26 managed with a prophylactic gastrostomy and 26 with an approach of an NG tube as needed., Results: There were no significant differences in patient demographics, pre-treatment diet and treatment factors between the two groups. Patient-reported swallowing function measured using the MDADI was superior for patients managed with an NG tube as required compared with a prophylactic gastrostomy: overall composite score 68.1 versus 59.4 (p=0.04), global score 67.7 versus 60 (p=0.04), emotional subscale 73.5 versus 60.4 (p<0.01), functional subscale 75.4 versus 61.7 (p<0.01), and physical subscale 59.6 versus 57.1 (p=0.38)., Conclusions: Compared with an approach of an NG tube as required, the use of a prophylactic gastrostomy was associated with inferior long term patient-reported long term swallow outcomes., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: This study aimed to quantify the variation in oropharyngeal squamous cell carcinoma gross tumour volume (GTV) delineation between CT, MR and FDG PET-CT imaging., Methods: A prospective, single centre, pilot study was undertaken where 11 patients with locally advanced oropharyngeal cancers (2 tonsil, 9 base of tongue primaries) underwent pre-treatment, contrast enhanced, FDG PET-CT and MR imaging, all performed in a radiotherapy treatment mask. CT, MR and CT-MR GTVs were contoured by 5 clinicians (2 radiologists and 3 radiation oncologists). A semi-automated segmentation algorithm was used to contour PET GTVs. Volume and positional analyses were undertaken, accounting for inter-observer variation, using linear mixed effects models and contour comparison metrics respectively., Results: Significant differences in mean GTV volume were found between CT (11.9 cm(3)) and CT-MR (14.1 cm(3)), p < 0.006, CT-MR and PET (9.5 cm(3)), p < 0.0009, and MR (12.7 cm(3)) and PET, p < 0.016. Substantial differences in GTV position were found between all modalities with the exception of CT-MR and MR GTVs. A mean of 64 %, 74 % and 77 % of the PET GTVs were included within the CT, MR and CT-MR GTVs respectively. A mean of 57 % of the MR GTVs were included within the CT GTV; conversely a mean of 63 % of the CT GTVs were included within the MR GTV. CT inter-observer variability was found to be significantly higher in terms of position and/or volume than both MR and CT-MR (p < 0.05). Significant differences in GTV volume were found between GTV volumes delineated by radiologists (9.7 cm(3)) and oncologists (14.6 cm(3)) for all modalities (p = 0.001)., Conclusions: The use of different imaging modalities produced significantly different GTVs, with no single imaging technique encompassing all potential GTV regions. The use of MR reduced inter-observer variability. These data suggest delineation based on multimodality imaging has the potential to improve accuracy of GTV definition., Trial Registration: ISRCTN Registry: ISRCTN34165059 . Registered 2nd February 2015.

To determine the outcomes of patients managed with different routes of enteral feeding during chemoradiotherapy for oropharynx cancer. The hospital and dietetic records of consecutive patients with oropharynx squamous cell carcinoma treated between January 2007 and June 2009 with concurrent chemoradiotherapy were reviewed retrospectively. One hundred and four patients were analysed. Seventy-one received a prophylactic gastrostomy, 21 were managed with a strategy of NG tube as required and 12 received a therapeutic gastrostomy. Patients with a prophylactic gastrostomy commenced enteral feeding a median of 24 days after commencing radiotherapy, compared with a median of 41 days (p<0.001) for the NG as required group. Comparing prophylactic gastrostomy, NG as required and therapeutic gastrostomy, median number of unplanned inpatient days were 6, 14 and 7, respectively (p<0.01 for prophylactic gastrostomy vs. NG as required). Mean percentage weight loss at the end of treatment (6.1% vs. 7.1% vs. 5.2%, respectively) and at 6 months post-radiotherapy (11.7%, 14.3% and 8.9%) were similar in all groups (p=0.23). There was no significant difference in type of diet post-radiotherapy between prophylactic gastrostomy and NG as required groups (p=0.22). Median duration of enteral feeding was 181, 64 and 644 days, respectively (p<0.01 for prophylactic gastrostomy vs. NG as required). Use of a prophylactic gastrostomy (p<0.01) and higher T stage (p<0.01) were associated with increased duration of enteral feeding on a multivariate analysis. These data reinforce concerns regarding the detrimental impact of prophylactic gastrostomy placement upon long-term enteral feed dependence., (Copyright © 2011 Elsevier Ltd. All rights reserved.)