The Effects of Human Papillomavirus Status and Treatment on the Positive Predictive Value of Post-radiotherapy 18F-Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography in Advanced Head and Neck Squamous Cell Carcinoma.

AIMS: The high negative predictive value of post-chemoradiation (CRT) positron emission tomography-computed tomography (PET-CT) is well established in head and neck squamous cell cancers (HNSCC). The positive predictive value (PPV) remains under scrutiny, with increasing evidence that it is affected by several factors. The aim of this study was to assess the PPV of post-treatment PET-CT for residual nodal disease when stratified by treatment modality and tumour human papillomavirus (HPV) status. MATERIALS AND METHODS: This was a retrospective cohort study in a tertiary oncology centre carried out between January 2013 and December 2019. Patients were radically treated with radiotherapy only/CRT for node-positive HNSCC. PET-CT nodal responses were categorised as complete, equivocal (EQR) or incomplete (ICR), and outcomes extracted from electronic records. RESULTS: In total, 480 patients were evaluated, all had a minimum potential follow-up of 2 years, with a median of 39.2 months. The PPV of 12-week PET-CT was significantly different between HPV-positive (22.5%) and HPV-unrelated (52.7%) disease, P < 0.001. It was also significantly different between the CRT (24.8%) and radiotherapy-only (51.1%) groups, P = 0.001. The PPV of an EQR was significantly less than an ICR, irrespective of HPV status and primary treatment modality. In HPV-positive disease, the PPV of an EQR was 9.0% for the CRT group compared with 21.4% for radiotherapy only, P = 0.278. The PPV in those who achieved an ICR was 34.2% in the CRT group, significantly lower than 70.0% in the radiotherapy-only group, P = 0.03. CONCLUSION: The PPV of 12-week PET-CT is significantly lower for HPV-positive compared with HPV-unrelated HNSCC. It is poorer in patients with HPV-positive disease treated with CRT compared with radiotherapy alone.

Positron Emission Tomography-Computed Tomography Surveillance after (Chemo)Radiotherapy in Advanced Head and Neck Squamous Cell Cancer: Beyond the PET-NECK Protocol.

AIMS: To evaluate the implementation of 18-fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) surveillance after (chemo)radiotherapy, to compare outcomes for those who achieved a complete (CR), equivocal (EQR) and incomplete (ICR) nodal response on 12-week PET-CT according to their human papillomavirus (HPV) status, and to assess the safety of ongoing surveillance beyond 12 weeks in the HPV-positive EQR group. MATERIALS AND METHODS: All patients with node-positive head and neck squamous cell carcinoma (HNSCC) treated with (chemo)radiotherapy between January 2013 and September 2017 were identified. PET-CT responses were classified as CR, ICR or EQR. Patient outcomes were obtained from electronic records. RESULTS: In total, 236 patients with a minimum of 2 years of follow-up were identified. The mean age was 59 years; 79.3% had N2 disease; 77.1% of patients had oropharyngeal cancer and 10.1% had squamous cell carcinoma of unknown primary, of whom 82.0% (169) were HPV positive; 78.0% received chemoradiotherapy. The median time from the end of radiotherapy to PET-CT was 91 days. Of the HPV-related HNSCC, 60.4% achieved CR, 29.0% EQR and 10.6% ICR. With a median follow-up of 41.7 months, there was no difference in survival between patients with HPV-related HNSCC achieving CR and EQR (median overall survival not reached for both, P = 0.67) despite the omission of immediate neck dissection in 98.0% of the EQR group. CONCLUSION: Patients with HPV-positive HNSCC who have achieved EQR have comparable survival outcomes to those who achieved a CR despite the omission of immediate neck dissections; this shows the safety of ongoing surveillance beyond 12 weeks in this group of patients.

Reduced Fractionation in Lung Cancer Patients Treated with Curative-intent Radiotherapy during the COVID-19 Pandemic.

Patients treated with curative-intent lung radiotherapy are in the group at highest risk of severe complications and death from COVID-19. There is therefore an urgent need to reduce the risks associated with multiple hospital visits and their anti-cancer treatment. One recommendation is to consider alternative dose-fractionation schedules or radiotherapy techniques. This would also increase radiotherapy service capacity for operable patients with stage I-III lung cancer, who might be unable to have surgery during the pandemic. Here we identify reduced-fractionation for curative-intent radiotherapy regimes in lung cancer, from a literature search carried out between 20/03/2020 and 30/03/2020 as well as published and unpublished audits of hypofractionated regimes from UK centres. Evidence, practical considerations and limitations are discussed for early-stage NSCLC, stage III NSCLC, early-stage and locally advanced SCLC. We recommend discussion of this guidance document with other specialist lung MDT members to disseminate the potential changes to radiotherapy practices that could be made to reduce pressure on other departments such as thoracic surgery. It is also a crucial part of the consent process to ensure that the risks and benefits of undergoing cancer treatment during the COVID-19 pandemic and the uncertainties surrounding toxicity from reduced fractionation have been adequately discussed with patients. Furthermore, centres should document all deviations from standard protocols, and we urge all colleagues, where possible, to join national/international data collection initiatives (such as COVID-RT Lung) aimed at recording the impact of the COVID-19 pandemic on lung cancer treatment and outcomes.

Toxicity and Efficacy of Stereotactic Ablative Body Radiotherapy for Moderately Central Non-small Cell Lung Cancers Using 50 Gy in Five Fractions.

AIMS: Stereotactic ablative body radiotherapy doses for peripheral lung lesions caused high toxicity when used for central non-small cell lung cancer (NSCLC). To determine a safe stereotactic ablative body radiotherapy dose for central tumours, the phase I/II Radiation Therapy Oncology Group RTOG 0813 trial used 50 Gy/five fractions as a baseline. From 2013, 50 Gy/five fractions was adopted at the Beatson West of Scotland Cancer Centre for inoperable early stage central NSCLC. We report our prospectively collected toxicity and efficacy data. MATERIALS AND METHODS: Patient and treatment characteristics were obtained from electronic medical records. Tumours were classed as moderately central or ultra-central tumours using published definitions. Toxicity was assessed in a centralised follow-up clinic at 2 weeks, 6 weeks, 3 months, 6 months, 1 year and 2 years after treatment. RESULTS: Fifty patients (31 women, 19 men, median age 75.1 years) were identified with T1-2N0M0 moderately central NSCLC; one patient had both an ultra-central and a moderately central tumour. Eighty-four per cent were medically unfit for surgery. Forty per cent had biopsy-proven NSCLC and 60% were diagnosed radiologically using 18-fluorodeoxyglucose positron emission tomography/computed tomography imaging. Fifty-six per cent of patients were Eastern Cooperative Oncology Group (ECOG) performance status 2 or worse. All patients received 50 Gy/five fractions on alternate days on schedule. Two patients died within 90 days of treatment, one from a chest infection, the other cause of death was unknown. There was one episode of early grade 3 oesophagitis and one grade 3 late dyspnoea. There was no grade 4 toxicity. Over a median follow-up of 25.2 months (range 1-70 months), there were 34 deaths: 18 unrelated to cancer and 16 due to cancer recurrence. The median overall survival was 27.0 months (95% confidence interval 20.6-35.9) and cancer-specific survival was 39.8 months (95% confidence interval 28.6, not reached). CONCLUSION: This study has shown that 50 Gy/five fractions is a safe dose and fractionation for early stage inoperable moderately central NSCLC, with outcomes comparable with other series, even with patients with a poor performance status.

Radiotherapy-induced xerostomia: a randomised, double-blind, controlled trial of Visco-ease™ oral spray compared with placebo in patients with cancer of the head and neck.

Radiotherapy-induced xerostomia (RIX) is a common and untreatable side effect of radiotherapy to the head and neck. Visco-ease™ mouth spray (Lamellar Biomedical Ltd), a new product that is made from lamellar body mimetics, reduces the viscosity of saliva ex vivo. The purpose of this study was to evaluate its safety and effectiveness in the treatment of RIX in 43 patients with cancer of the head and neck. They were randomised into the Visco-ease™ or placebo groups, and asked to complete the Groningen radiotherapy-induced xerostomia (GRIX) questionnaire each week. The primary endpoint was a change in GRIX score from baseline to end of treatment. There was no difference in scores between the two groups, and none of the patients had device-related serious adverse events. Visco-ease™ oral spray was safe and tolerable but no better than placebo in reducing RIX in this group of patients.

Re-irradiation for Locally Recurrent Lung Cancer: Evidence, Risks and Benefits.

In spite of recent improvements in both the technical delivery of radiotherapy and systemic therapy in the treatment of non-small cell lung cancer, local recurrence rates after radiotherapy remain a significant challenge. In the setting of local relapse after radiotherapy, treatments such as surgical resection or radiofrequency ablation are often not appropriate owing to disease and patient factors. Re-irradiation may be a potential treatment option. This overview considers the published evidence and potential treatment strategies.

Pancreatic cancer genomics: where can the science take us?

The incidence of pancreatic ductal adenocarcinoma (PDAC) is steadily increasing and the annual death-to-incidence ratio approaches one. This is a figure that has not changed for several decades. Surgery remains the only chance of cure; however, only less than 20% of patients are amenable to operative resection. Despite successful surgical resection, the majority of the patients still succumb to recurrent metastatic disease. Therefore, there is an urgent need to develop novel therapeutic strategies and to better select patients for current therapies. In this review, we will discuss current management by highlighting the landmark clinical trials that have shaped current care. We will then discuss the challenges of therapeutic development using the current randomized-controlled trial paradigm when confronted with the molecular heterogeneity of PDAC. Finally, we will discuss strategies that may help to shape the management of PDAC in the near future.