Comparative cohort study of volumetric modulated arc therapy for squamous cell cancer of unknown primary in the head and neck-Involved neck only versus mucosal irradiation.

OBJECTIVES: Target volumes for irradiation remain ill-defined for squamous cell cancer of unknown primary in the head and neck (SCCUP). The aim of this study was to compare involved neck only (INO) radiotherapy (RT) with irradiating involved neck plus potential mucosal primary sites and contralateral neck (MUC) in patients diagnosed and treated with modern diagnostics and techniques. DESIGN: This is a retrospective cohort study. Patients with a diagnosis of SCCUP with unilateral neck disease were included. RESULTS: Thirty patients were identified. All underwent FDG PET-CT. 47% of patients had HPV-positive SCC. 20 patients received RT to INO, 10 patients to MUC, all with volumetric modulated arc therapy (VMAT). A significantly lower dose for each organ at risk was delivered in INO-treated patients, with mean dose to contralateral parotid gland 57% less. The proportion of patients with late grade 2 or worse xerostomia was higher in MUC patients. The incidence of grade 2-3 mucositis (89% vs 45%) and grade 3 or worse dysphagia (50% vs 10%) was higher in MUC patients. Median follow-up was 31 months. No mucosal primaries emerged. Progression-free survival at 2 years was 74.7% for INO patients, 70% in the MUC group. Overall survival at 2 years was 79.7% in the INO group and 70% in the MUC patients. CONCLUSION: INO radiotherapy for patients with SCCUP of the head and neck is a safe treatment strategy resulting in clinically significant lower RT doses to OARS. Acute and late toxicities are reduced without detriment to patient survival.

How did the COVID-19 pandemic change patient experience during radiation therapy for head and neck cancer: A single centre survey.

INTRODUCTION/BACKGROUND: Patients receiving treatment for head and neck cancer (HNC) with curative intent, will potentially undergo primary or adjuvant radiation therapy (RT). These patients require supportive management from an extended multi-disciplinary team, to manage the severe toxicities and distress that a course of treatment can bring. A survey was designed to determine if there were changes in the experience of HNC patients attending for radical RT, from the beginning to the end of their treatment course. During the conduct of the survey the COVID-19 pandemic began. As a result cancer services were adapted to keep patients receiving treatment protected from the virus, while continuing to treat their malignant disease. This enabled a comparison of HNC patient experiences pre-pandemic (PP) and during the pandemic (DP). The study aimed to assess the impact of changes in treatment logistics, implemented as a result of the COVID-19 pandemic, on the patient experience, analysing and comparing how well patients understood the information provided to them, their level of distress and anxiety during treatment, and their overall satisfaction with the experience. METHODS: Eligible patients were receiving radical RT for HNC of any sub-site or histological type. Identical, anonymous surveys were distributed to patients at week 1 and the final week of RT. The initial PP questionnaire (distributed December 2019 to 11th March 2020) contained 22 questions with space for free text. The questionnaire was amended DP to include 6 additional COVID-19 related questions (distributed June to November 2020). RESULTS: One hundred and eighty two surveys were returned; 95 (52%) PP and 87 (48%) DP. Patients were moderately distressed from wearing the immobilisation mask towards the end of treatment DP with a statistically significant difference in the final week, median (IQR) values of 1 (0-4) PP and 2 (1-6) DP, p=0.024. Patients reported increased distress by attending daily for treatment by the final week of RT DP, with a PP and DP median of 1 (0-3) and 2 (1-4) respectively, p=0.039. Patients reporting increased levels of distress about attending for RT also reported high levels of anxiety about COVID-19 (r=0.40, p=0.005). COVID-19 anxiety score displayed a weak inverse association with overall treatment satisfaction score (r=-0.28, p=0.008). CONCLUSION: Despite the adapted COVID-19 working practices implemented and the challenges a course of head and neck RT entails, patients reported a positive experience attending for treatment, both PP and DP.

Consensus statement for metastatic surveillance of uveal melanoma in Scotland.

Ophthalmic treatments are successful in managing uveal melanomas achieving good local control. However, a large number still metastasise, primarily to the liver, resulting in mortality. There is no consensus across the world on the mode, frequency, duration or utility of regular liver surveillance for metastasis and there are no published protocols. The Scottish Ocular Oncology Service (SOOS) constituted a Scottish Consensus Statement Group (SCSG) which included ocular oncologists, medical oncologists, radiologists and a uveal melanoma patient as a lay member. This group carried out an extensive review of literature followed by discussions to arrive at a consensus regarding surveillance planning for posterior uveal melanoma patients in Scotland. The Consensus Statement would provide a framework to guide each patient's surveillance plan and provide all patients with clarity and transparency on the issue. The SCSG was unable to find adequate evidence on which to base the strategy. The consensus statement recommends a risk-stratified approach to surveillance for these patients dividing them into low to medium-risk and high-risk groups defining the mode and duration of surveillance for each. It supplements the UK-wide Uveal Melanoma National Guidelines and allows a more uniform consensus-based approach to surveillance in Scotland. It has been adopted nationally by all health care providers in Scotland as a guideline and is available to patients on a publicly accessible website.

Holistic needs assessment in outpatient cancer care: a randomised controlled trial.

DESIGN: Analyst blinded, parallel, multi-centre, randomised controlled trial (RCT). PARTICIPANTS: People with confirmed diagnoses of cancer (head and neck, skin or colorectal) attending follow-up consultation 3 months post-treatment between 2015 and 2020. INTERVENTION: Holistic needs assessment (HNA) or care as usual during consultation. OBJECTIVE: To establish whether incorporating HNA into consultations would increase patient participation, shared decision making and postconsultation self-efficacy. OUTCOME MEASURES: Patient participation in the consultations examined was measured using (a) dialogue ratio (DR) and (b) the proportion of consultation initiated by patient. Shared decision making was measured with CollaboRATE and self-efficacy with Lorig Scale. Consultations were audio recorded and timed. RANDOMISATION: Block randomisation. BLINDING: Audio recording analyst was blinded to study group. RESULTS: 147 patients were randomised: 74 control versus 73 intervention. OUTCOME: No statistically significant differences were found between groups for DR, patient initiative, self-efficacy or shared decision making. Consultations were on average 1 min 46 s longer in the HNA group (respectively, 17 m 25 s vs 15 min 39 s). CONCLUSION: HNA did not change the amount of conversation initiated by the patient or the level of dialogue within the consultation. HNA did not change patient sense of collaboration or feelings of self-efficacy afterwards. HNA group raised more concerns and proportionally more emotional concerns, although their consultations took longer than treatment as usual. IMPLICATIONS FOR PRACTICE: This is the first RCT to test HNA in medically led outpatient settings. Results showed no difference in the way the consultations were structured or received. There is wider evidence to support the roll out of HNA as part of a proactive, multidisciplinary process, but this study did not support medical colleagues facilitating it. TRIAL REGISTRATION NUMBER: NCT02274701.

Randomized Phase 3 Trial of the Hypoxia Modifier Nimorazole Added to Radiation Therapy With Benefit Assessed in Hypoxic Head and Neck Cancers Determined Using a Gene Signature (NIMRAD).

PURPOSE: Tumor hypoxia is an adverse prognostic factor in head and neck squamous cell carcinoma (HNSCC). We assessed whether patients with hypoxic HNSCC benefited from the addition of nimorazole to definitive intensity modulated radiation therapy (IMRT). METHODS AND MATERIALS: NIMRAD was a phase 3, multicenter, placebo-controlled, double-anonymized trial of patients with HNSCC unsuitable for concurrent platinum chemotherapy or cetuximab with definitive IMRT (NCT01950689). Patients were randomized 1:1 to receive IMRT (65 Gy in 30 fractions over 6 weeks) plus nimorazole (1.2 g/m2 daily, before IMRT) or placebo. The primary endpoint was freedom from locoregional progression (FFLRP) in patients with hypoxic tumors, defined as greater than or equal to the median tumor hypoxia score of the first 50 patients analyzed (≥0.079), using a validated 26-gene signature. The planned sample size was 340 patients, allowing for signature generation in 85% and an assumed hazard ratio (HR) of 0.50 for nimorazole effectiveness in the hypoxic group and requiring 66 locoregional failures to have 80% power in a 2-tail log-rank test at the 5% significance level. RESULTS: Three hundred thirty-eight patients were randomized by 19 centers in the United Kingdom from May 2014 to May 2019, with a median follow-up of 3.1 years (95% CI, 2.9-3.4). Hypoxia scores were available for 286 (85%). The median patient age was 73 years (range, 44-88; IQR, 70-76). There were 36 (25.9%) locoregional failures in the hypoxic group, in which nimorazole + IMRT did not improve FFLRP (adjusted HR, 0.72; 95% CI, 0.36-1.44; P = .35) or overall survival (adjusted HR, 0.96; 95% CI, 0.53-1.72; P = .88) compared with placebo + IMRT. Similarly, nimorazole + IMRT did not improve FFLRP or overall survival in the whole population. In total (N = 338), 73% of patients allocated nimorazole adhered to the drug for ≥50% of IMRT fractions. Nimorazole + IMRT caused more acute nausea compared with placebo + IMRT (Common Terminology Criteria for Adverse Events version 4.0 G1+2: 56.6% vs 42.4%, G3: 10.1% vs 5.3%, respectively; P < .05). CONCLUSIONS: Addition of the hypoxia modifier nimorazole to IMRT for locally advanced HNSCC in older and less fit patients did not improve locoregional control or survival.

Patterns of recurrence amongst patients undergoing resection of oral squamous cell carcinoma with curative intent.

This study was aimed to identify key clinicopathological variables that predict recurrence in those undergoing curative resection of oral squamous cell carcinoma (OSCC) with emphasis on initial treatment failure patterns. Between February 2006 to May 2020, clinicopathological data on 833 patients who underwent curative resection of OSCC were gathered. Outcomes of interest included local, regional, distant, and overall recurrence. Univariate analysis was performed to identify significant clinicopathological variables for each recurrence type, and a multivariate regression analysis was utilised to generate predictive models. A total of 187 patients (22.4%) developed recurrent disease; 79 local, 63 regional, and 46 distant. For local recurrence: tumour depth of invasion (DOI) >5--10 mm, tumour DOI >10 mm and modified Glasgow Prognostic Score (mGPS) 2 were independently predictive (c-index 0.708). For regional recurrence: primary OSCC of hard palate/maxilla, pN1, pN3b, and non-cohesive invasive front were independently predictive (c-index 0.738). For distant recurrence: pN1 pN2a, pN2b, pN2c, pN3b, and tumour DOI >10 mm were independently predictive (c-index 0.809). For recurrence at any site; pN1, pN2a, pN2b, pN2c, pN3b, tumour DOI >5-10 mm, tumour DOI >10 mm, mGPS 2, and involved surgical margins were independently predictive (c-index 0.750). Recurrence events after curative treatment for OSCC are relatively predictable on the basis of available clinicopathological characteristics. It seems likely that trials of adjuvant systemic therapy in high-risk OSCC will continue to be designed with emerging therapeutic agents. Trials should focus on those of highest risk of relapse and this study adds clarity to the selection of the correct target population.

Outcomes of cataract surgery in patients previously treated with orbital radiotherapy.

PURPOSE: To quantify the risks for cataract surgery in patients who have previously undergone external beam radiotherapy (EBRT). SETTING: Tertiary ophthalmology and oncology hospital. DESIGN: Retrospective case series. METHODS: Patients treated with orbital EBRT at the Beatson West of Scotland Cancer Centre between 2001 and 2019 were identified, and clinical records were reviewed to identify those who had subsequently undergone cataract surgery. Preoperative and postoperative case records, and operation records, were reviewed to identify demographic data and data regarding complications and surgical outcomes. RESULTS: 46 eyes (of 33 patients) were included. The indications for EBRT included thyroid eye disease, lymphoma, choroidal metastases, and other orbital malignancies. Mean corrected preoperative Snellen visual acuity was 20/100 (range 20/30 to 20/2000) improving to 20/25 (20/12 to 20/160, 1-way analysis of variance P < .01). Mean visual gain was 0.5 logMAR (-0.9 to 1.9). There was 1 case of posterior capsule (PC) rupture with vitreous loss (2%). Dense PC plaque was noted intraoperatively in 19.5% (n = 9). 13% (n = 6) required Nd:YAG laser posterior capsulotomy. There were 6 cases (13%) of cystoid macular edema (CME). CONCLUSIONS: Visual outcomes after cataract surgery in this cohort of patients were similar to those obtained in a nationwide cohort. EBRT seemed to be associated with an increased incidence of intraoperative PC plaque, postoperative CME (which in most cases settled with treatment), and need for posterior capsulotomy.

Long term survival in patients with human papillomavirus-positive oropharyngeal cancer and equivocal response on 12-week PET-CT is not compromised by the omission of neck dissection.

BACKGROUND AND AIM: The aim of this study was to evaluate the long-term safety of the omission of immediate neck dissections (IND) in patients with human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC) achieving a less than complete nodal response on 12-week FDG PET-CT. MATERIAL AND METHODS: Patients with HPV-positive, node-positive HNSCC that were treated with radical (chemo) radiotherapy (RT) between January 2013 and September 2019 were identified. PET-CT responses were classified as complete (CR), incomplete (ICR) or equivocal (EQR) nodal responses. Clinical outcomes were obtained. RESULTS: 347 patients were identified. Median follow-up was 43.9 (IQR, 30.8-61.2) months. 62.8% (218/347) achieved a CR, 23.4% (81/347) EQR and 13.8% (48/347) ICR nodal response. 70 of 81 (86.4%) patients with an EQR and 25 of 48 (52.1%) with an ICR had no residual disease during follow up (a pathologically negative ND if surgery undertaken or no subsequent neck or distant relapse clinically/radiologically). Median survival of the EQR and CR groups were not reached, and despite the omission of IND in 95% of the EQR group there was no statistically significant differences in overall survival (OS) between the groups, p = 1.0. Median survival of ICR was not reached. However, OS for ICR group was significantly worse than that of CR, and EQR, both p < 0.001. CONCLUSION: The omission of IND in those achieving an EQR nodal response does not compromise long-term survival. This supports the safety of extended surveillance in patients with HPV-positive disease and an EQR on 12-week FDG PET-CT.