The use of pembrolizumab monotherapy for the management of head and neck squamous cell carcinoma (HNSCC) in the UK.

Pembrolizumab has received approval in the UK as first-line monotherapy for recurrent and/or metastatic HNSCC (R/M HNSCC) following the results of the KEYNOTE-048 trial, which demonstrated a longer overall survival (OS) in comparison to the EXTREME chemotherapy regimen in patients with a combined positive score (CPS) ≥1. In this article, we provide retrospective real-world data on the role of pembrolizumab monotherapy as first-line systemic therapy for HNSCC across 18 centers in the UK from March 20, 2020 to May 31, 2021. 211 patients were included, and in the efficacy analysis, the objective response rate (ORR) was 24.7%, the median progression-free survival (PFS) was 4.8 months (95% confidence interval [CI]: 3.6-6.1), and the median OS was 10.8 months (95% CI 9.0-12.5). Pembrolizumab monotherapy was well tolerated, with 18 patients having to stop treatment owing to immune-related adverse events (irAEs). 53 patients proceeded to second-line treatment with a median PFS2 of 10.2 months (95% CI: 8.8-11.5). Moreover, patients with documented irAEs had a statistically significant longer median PFS (11.3 vs. 3.3 months; log-rank p value = <.001) and median OS (18.8 vs. 8.9 months; log-rank p value <.001). The efficacy and safety of pembrolizumab first-line monotherapy for HNSCC has been validated using real-world data.

A multi-centre survey reveals variations in the standard treatments and treatment modifications for head and neck cancer patients during Covid-19 pandemic.

BACKGROUND: The onset of the COVID-19 pandemic necessitated rapid changes to the practice of head and neck oncology in UK. There was a delay between the onset of the pandemic and the release of guidelines from cancer societies and networks, leading to a variable response of individual centres. This survey was conducted to assess the pre-Covid-19 pandemic standard of practice for head and neck oncology patients and the treatment modifications introduced during the first wave of the pandemic in UK. METHODOLOGY: The UK National Cancer Research Institute (NCRI) Head and Neck Clinical Studies Group initiated a multi-centre survey using questionnaire to investigate the effect on feeding tube practice, radiotherapy (RT) fractionation and volumes, use of chemotherapy in the neo-adjuvant, concurrent and palliative setting, the use of immunotherapy in the palliative setting, access to radiology and histopathology services, and availability of surgical procedures. RESULTS: 30 centres were approached across UK; 23 (76.7%) centres responded and were included in the survey. There were differences in the standard practices in feeding tube policy, RT dose and fractionation as well as concurrent chemotherapy use. 21 (91%) participating centres had at least one treatment modification. 15 (65%) centres initiated a change in radical RT; changing to either a hypofractionation or acceleration schedule. For post-operative RT 10 centres (43.5%) changed to a hypofractionation schedule. 12 (52.2%) centres stopped neo-adjuvant chemotherapy for all patients; 13 (56.5%) centres followed selective omission of chemotherapy in concurrent chemo-radiotherapy patients, 17 (73.9%) centres changed first-line chemotherapy treatment to pembrolizumab (following NHS England's interim guidance) and 8 (34.8%) centres stopped the treatment early or offered delays for patients that have been already on systemic treatment. The majority of centres did not have significant changes associated with surgery, radiology, histopathology and dental screening. CONCLUSION: There are variations in the standard of practice and treatment modifications for head and neck cancer patients during Covid-19 pandemic. A timely initiative is required to form a consensus on head and neck cancer management in the UK and other countries.

Transoral laser microsurgery and radiotherapy for oropharyngeal squamous cell carcinoma: Equitable survival and enhanced function compared with contemporary standards of care.

INTRODUCTION: We describe the 5-year oncological and functional outcomes of transoral laser microsurgery, neck dissection (TLM + ND) and adjuvant radiotherapy (PORT) used to treat patients with oropharyngeal carcinoma. The effectiveness of external carotid artery (ECA) ligation in reducing post-operative bleeding, and fibrin glue following ND in reducing wound drainage and length of hospital stay is reported. MATERIALS AND METHODS: This retrospective case review of consecutive patients undergoing TLM between 2006 and 2017 used the Kaplan-Meier Estimator and Log-Rank Test for univariate, time-to-event analyses, and Cox-Proportionate Hazard modelling for multivariate analysis. RESULTS: 264 consecutive patients were included. Mean follow-up was 49.4 months. 219 (82.9%) patients received PORT. Five-year overall survival (OS), disease-free survival (DFS), and disease-specific survival (DSS) rates were 74.9%, 73.7%, and 86.2%, respectively. Five-year locoregional control was 89.4%. 65.5% of cases were Human papillomavirus associated (HPV+), for whom OS, DFS and DSS was 85.6%, 84.7% and 92.7%, respectively, and demonstrated significantly higher OS (hazard ratio (HR) 0.28, CI 0.16-0.49, p < 0.0001), DFS (HR 0.28, CI 0.17-0.47, p < 0.0001) and DSS (HR 0.2, CI 0.09-0.44, <0.001). Post-operative oropharyngeal bleeding occurred in 23 patients (8.7%), of which 5 were major/severe, in patients without ECA ligation. Fibrin glue significantly reduced neck drain output (p < 0.001), and length of hospital stay (p < 0.001). One-year gastrostomy dependence rate was 2.3%. CONCLUSIONS: TLM + ND + PORT results in favourable 5-year survival and locoregional control rates, and low feeding tube dependency rates. ECA ligation and fibrin glue appear to reduce major post-operative haemorrhage, wound drainage and length of hospital stay.

Developments in Stereotactic Body Radiotherapy.

Stereotactic body radiotherapy is the technique of accurately delivering high doses of radiotherapy to small volume targets in a single or small number of sessions. The high biological effective dose of this treatment is reflected in the high rates of local control achieved across multiple tumour sites. Toxicity of the treatment can be significant and ongoing prospective trials will help define the utility of this treatment as an alternative to surgery in treating primary tumours and oligometastatic disease. Longer follow-up and survival data from prospective trials will be essential in determining the value of this resource-intensive treatment. The opportunity to combine this treatment with systemic therapies and its potential synergy with immunotherapy opens up interesting avenues for research in the future.

Dynamic CT angiography for cyberknife radiosurgery planning of intracranial arteriovenous malformations: a technical/feasibility report.

BACKGROUND: Successful radiosurgery for arteriovenous malformations (AVMs) requires accurate nidus delineation in the 3D treatment planning system (TPS). The catheter biplane digital subtraction angiogram (DSA) has traditionally been the gold standard for evaluation of the AVM nidus, but its 2D nature limits its value for contouring and it cannot be imported into the Cyberknife TPS. We describe a technique for acquisition and integration of 3D dynamic CT angiograms (dCTA) into the Cyberknife TPS for intracranial AVMs and review the feasibility of using this technique in the first patient cohort. PATIENTS AND METHODS: Dynamic continuous whole brain CT images were acquired in a Toshiba 320 volume CT scanner with data reconstruction every 0.5 sec. This multi-time-point acquisition enabled us to choose the CT data-set with the clearest nidus without significant enhancement of surrounding blood vessels. This was imported to the Cyberknife TPS and co-registered with planning CT and T2 MRI (2D DSA adjacent for reference). The feasibility of using dCTA was evaluated in the first thirteen patients with outcome evaluation from patient records. RESULTS: dCTA data was accurately co-registered in the Cyberknife TPS and appeared to assist in nidus contouring for all patients. Imaging modalities were complementary. 85% of patients had complete (6/13) or continuing partial nidus obliteration (5/13) at 37 months median follow-up. CONCLUSIONS: dCTA is a promising imaging technique that can be successfully imported into the Cyberknife TPS and appears to assist in radiosurgery nidus definition. Further study to validate its role is warranted.

Volumetric modulated arc therapy in prostate cancer patients with metallic hip prostheses in a UK centre.

AIM: This study aimed to investigate whether IMRT using VMAT is a viable and safe solution in dose escalated RT in these patients. BACKGROUND: An increasing number of prostate cancer patients are elderly and have hip prostheses. These implants pose challenges in radiotherapy treatment planning. Although intensity modulated radiotherapy (IMRT) is commonly used, there is a lack of clinical studies documenting its efficacy and toxicities in this subgroup of patients. MATERIALS AND METHODS: The data from 23 patients with hip prostheses and non-metastatic prostate cancer treated with VMAT (volumetric modulated arc therapy) between 2009 and 2011, were retrospectively analyzed. Baseline characteristics, treatment details and outcome data were collected on all patients. The median follow up was 40.9 months. MRI-CT image fusion was performed and the treatment plans were created using RapidArc™ (RA) techniques utilizing 1 or 2 arcs and 10 MV photon beams. RESULTS: 96% of patients were treated with a dose of 72 Gy/32 fractions over 44 days. 21/23 plans met the PTV targets. The mean homogeneity index was 1.07. 20/23 plans met all OAR constraints (rectum, bladder). Two plans deviated from rectal constraints, four from bladder constraints; all were classed as minor deviations. One patient experienced late grade 3 genitourinary toxicity. Three other patients experienced late grade 2 or lower gastrointestinal toxicity. One patient had biochemical failure and one had a non-prostate cancer related death. CONCLUSIONS: VMAT provides an elegant solution to deliver dose escalated RT in patients with unilateral and bilateral hip replacements with minimal acute and late toxicities.

Creation of 3-dimensional prostate cancer maps: methodology and clinical and research implications.

CONTEXT: The creation of 3-dimensional prostate cancer maps could assist with surgical intervention, radiotherapy treatment planning and for correlative pathology-imaging research. OBJECTIVES: To develop methodology for creating detailed, 3-dimensional, prostate cancer maps (3DPCM) of tumor location, extra prostatic extension sites, and positive margins and to assess the adequacy of current clinical target volumes for postoperative radiotherapy to the prostate using 3DPCM coregistered with preoperative magnetic resonance imaging. DESIGN: Parallel slices of prostatectomy specimens were created with ProCUT, and 2-dimensional cancer maps were generated as line diagrams after microscopic examination of each slice. The 2-dimensional cancer maps were aligned and stacked to create a 3DPCM, which was coregistered with the preoperative magnetic resonance imaging scan. The map was exported to the radiotherapy planning system and was used to determine the areas at greater risk, which were then compared against the current Radiation Therapy Oncology Group guidelines for contouring postoperative clinical target volumes to assess the adequacy of coverage. RESULTS: Twenty-eight patients with a mean age of 66 years (range, 52-73) underwent radical prostatectomy and postoperative radiotherapy. Seventeen patients (61%) received adjuvant radiotherapy for pT3 disease and/or positive margins, and the rest underwent salvage radiotherapy. Thirty-nine percent (11 of 28) of the patients had Gleason scores of 8 or 9. The contours based on the Radiation Therapy Oncology Group guidelines for postoperative radiotherapy resulted in inadequate coverage of extraprostatic extensions in 79% (22 of 28) and positive margins in 64% (18 of 28) of the cases. CONCLUSIONS: We have developed a methodology for creation of 3DPCM. Modification of the radiotherapy contours, based on the 3DPCM coregistered with pretreatment magnetic resonance imaging, covers the areas at high risk of recurrence. The 3DPCM could become an important clinical and research tool for urologists, pathologists, radiologists, and oncologists.