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.

Xerostomia quality of life and resource requirements following parotid sparing adaptive radiotherapy in head and neck cancers: Results of a prospective cohort study (Study ID CTRI/2017/11/010683).

BACKGROUND AND PURPOSE: Parotid sparing adaptive radiotherapy (PSART) is resource intensive to implement. Selection criteria for using ART and its impact on quality of life (QoL) is poorly reported. This has been addressed in our study. MATERIALS AND METHODS: Patients planned for curative radiotherapy for Head Neck Cancers were recruited following informed consent in a prospective cohort study. PSART was planned if the mean dose to index parotid(s) increased by 2% from the baseline approved plan. To assess the resource requirements of PSART manpower and time required for treatment planning both for initial as well as PSART was documented. Patient reported QoL using QualiXeQLS and EORTC QLQ C30 and HN35 were obtained pre radiotherapy, and at 3 and 9 months post radiotherapy. RESULTS: Of the ninety patients accrued, 87 were evaluable. 45 (51%) received PSART based on the prespecified criteria. The average time spent in contouring (276 min versus 133 min) and treatment planning (293 min versus 108 min) were almost doubled when PSART was implemented. XeQoL scores at 3 months were significantly worse in those receiving PSART (mean 2.3 vs 1.2, p 0.002). Despite this, xerostomia related QoL recovered to near baseline scores by 9 months after receiving PSART. CONCLUSION: Implementation of PSART is resource intensive. The proposed cutoff for implementing PSART identifies a higher risk population that have worse xerostomia related quality of life. This study lays the foundation for a randomized trial to determine the efficacy of PSART on xerostomia related QoL.

Volumetric and dosimetric impact of post-surgical MRI-guided radiotherapy for glioblastoma: A pilot study.

Objectives: Glioblastoma (GBM) radiotherapy (RT) target delineation requires MRI, ideally concurrent with CT simulation (pre-RT MRI). Due to limited MRI availability, <72 h post-surgery MRI is commonly used instead. Whilst previous investigations assessed volumetric differences between post-surgical and pre-RT delineations, dosimetric impact remains unknown. We quantify volumetric and dosimetric impact of using post-surgical MRI for GBM target delineation. Methods: Gross tumour volumes (GTVs) for five GBM patients receiving chemo-RT with post-surgical and pre-RT MRIs were delineated by three independent observers. Planning target volumes (PTVs) and RT plans were generated for each GTV. Volumetric and dosimetric differences were assessed through: absolute volumes, volume-distance histograms and dose-volume histogram statistics. Results: Post-surgical MRI delineations had significantly (p < 0.05) larger GTV and PTV volumes (median 16.7 and 64.4 cm3, respectively). Post-surgical RT plans, applied to pre-RT delineations, had significantly decreased (p < 0.01) median PTV doses (ΔD99% = -8.1 Gy and ΔD95% = -2.0 Gy). Median organ-at-risk (OAR) dose increases (brainstem ΔD5% =+0.8, normal brain mean dose =+2.9 and normal brain ΔD10% = 5.3 Gy) were observed. Conclusion: Post-surgical MRI delineation significantly impacted RT planning, with larger normal-appearing tissue volumes irradiated and increased OAR doses, despite a reduced coverage of the pre-RT defined target. Advances in knowledge: We believe this is the first investigation assessing the dosimetric impact of using post-surgical MRI for GBM target delineation. It highlights the potential of significantly degraded RT plans, showing the clinical need for dedicated MRI for GBM RT.

Centralised RECIST Assessment and Clinical Outcomes with Lenvatinib Monotherapy in Recurrent and Metastatic Adenoid Cystic Carcinoma.

Adenoid cystic carcinoma (ACC) is a rare cancer of secretory glands. Recurrent or metastatic (R/M) ACC is generally considered resistant to cytotoxic chemotherapy. Recent phase II studies have reported improved objective response rates (ORR) with the use of the multi-kinase inhibitor lenvatinib. We sought to evaluate real-world experience of R/M ACC patients treated with lenvatinib monotherapy within the UK National Health Service (NHS) to determine the response rates by Response Evaluation Criteria of Solid Tumour (RECIST) and clinical outcomes. Twenty-three R/M ACC patients from eleven cancer centres were included. All treatment assessments for clinical decision making related to drug therapy were undertaken at the local oncology centre. Central radiology review was performed by an independent clinical trial radiologist and blinded to the clinical decision making. In contrast to previously reported ORR of 12-15%, complete or partial response was not observed in any patients. Eleven patients (52.4%) had stable disease and 5 patients (23.8%) had progression of disease as the best overall response. The median time on treatment was 4 months and the median survival from discontinuation was 1 month. The median PFS and OS from treatment initiation were 4.5 months and 12 months respectively. Multicentre collaborative studies such as this are required to evaluate rare cancers with no recommended standard of care therapy and variable disease courses.

Setting up a lung stereotactic body radiotherapy service in a tertiary center in Eastern India: The process, quality assurance, and early experience.

CONTEXT: Stereotactic body radiotherapy (SBRT) is increasingly being used for early-stage lung cancer and lung oligometastases. AIMS: To report our experience of setting up lung SBRT and early clinical outcomes. SETTINGS AND DESIGN: This was a retrospective, interventional, cohort study. SUBJECTS AND METHODS: Patients were identified from multidisciplinary tumor board meetings. They underwent four-dimensional computed tomography-based planning. The ROSEL trial protocol, the Radiation Therapy Oncology Group (RTOG) 0236, and the UK-Stereotactic Ablative Body Radiotherapy Consortium guidelines were used for target volume and organs-at-risks (OARs) delineation, dosimetry, and plan quality assessment. Each SBRT plan underwent patient-specific quality assurance (QA). Daily online image guidance using KVCT or MVCT was done to ensure accurate treatment delivery. STATISTICAL ANALYSIS USED: Microsoft Excel 2010 was used for data analysis. RESULTS: Fifteen patients were treated to one or more lung tumors. One patient received helical tomotherapy in view of bilateral lung oligometastases at similar axial levels. All the remaining patients received volumetric modulated arc therapy (VMAT)-based treatment. The prescription dose varied from 40 to 60 Gy in 5-8 fractions with alternate-day treatment. The mean and median lung V20 was 5.24% and 5.16%, respectively (range, 1.66%-9.10%). The mean and median conformity indexes were 1.02 and 1.06, respectively (range, 0.70-1.18). After a median follow-up of 17 months, the locoregional control rate was 93.3%. CONCLUSIONS: SBRT was implemented using careful evaluation of OAR dose constraints, dosimetric accuracy and plan quality, patient-specific QA, and online image guidance for accurate treatment delivery. It was safe and effective for early-stage nonsmall cell lung cancer and lung metastases. Prospective data were collected to audit our outcomes.

Multiple subcutaneous metastases as the solitary presenting site of colorectal cancer.

Skin metastases, as a presenting symptom of gastrointestinal malignancies, are very rare and signify aggressive disease. They usually occur after a long period of diagnosis and along with other visceral metastases. We present the case of an 18-year-old male with diffuse subcutaneous metastases as a presenting feature and as the only site of distant metastases due to rectosigmoid adenocarcinoma. They clinically mimic benign skin lesions and the patient might not present to an oncologist. The diagnosis has to be established by skin biopsy, which will show tumor cell infiltration of the epidermis, dermis, and/or subcutaneous fat. There is no established local treatment for diffuse lesions. Systemic chemotherapy indicated for metastatic colon carcinoma was employed with not much favorable response. Irinotecan based chemotherapy also resulted in posterior reversible encephalopathy syndrome in this patient. Overall, the disease carries a poor prognosis and with no effective treatment available the survival is less than a year.

Radical radiotherapy or chemoradiotherapy for inoperable, locally advanced, non-small cell lung cancer: Analysis of patient profile, treatment approaches, and outcomes for 213 patients at a tertiary cancer center.

INTRODUCTION: Radical radiotherapy (RT) with curative intent, with or without chemotherapy, is the standard treatment for inoperable, locally advanced nonsmall cell lung cancer (NSCLC). MATERIALS AND METHODS: We retrospectively reviewed the data for all 288 patients who presented with inoperable, locally advanced NSCLC at our institution, between May 2011 and December 2016. RESULTS: RT alone or sequential chemoradiotherapy (SCRT) or concurrent chemoradiotherapy (CCRT) was used for 213 patients. Median age was 64 years (range: 27-88 years). Stage-III was the biggest stage group with 189 (88.7%) patients. Most patients with performance status (PS) 0 or 1 received CCRT, whereas most patients with PS 2 received RT alone (P < 0.001). CCRT, SCRT, and RT alone were used for 120 (56.3%), 24 (11.3%), and 69 (32.4%) patients, respectively. A third of all patients (32.4%) required either volumetric-modulated arc radiotherapy (VMAT) or tomotherapy. Median follow-up was 16 months. The median progression-free survival and median overall survival (OS) were 11 and 20 months, respectively. One-year OS and 2-year OS were 67.9% and 40.7%, respectively. Patients treated using CCRT lived significantly longer with a median survival of 28 months, compared with 13 months using SCRT and RT alone (P < 0.001). On multivariate analysis, OS was significantly affected by age, stage group, treatment approach, and response to treatment. CONCLUSION: RT including CCRT is feasible, safe, and well tolerated in our patient population and results in survival benefits comparable with published literature. CCRT should be considered for all patients with inoperable, locally advanced NSCLC, who are fit and have good PS.

Resource requirements and reduction in cardiac mortality from deep inspiration breath hold (DIBH) radiation therapy for left sided breast cancer patients: A prospective service development analysis.

INTRODUCTION: Use of deep inspiration breath hold (DIBH) radiation therapy may reduce long-term cardiac mortality. The resource and time commitments associated with DIBH are impediments to its widespread adoption. We report the dosimetric benefits, workforce requirements, and potential reduction in cardiac mortality when DIBH is used for left-sided breast cancers. METHODS AND MATERIALS: Data regarding the time consumed for planning and treating 50 patients with left-sided breast cancer with DIBH and 20 patients treated with free breathing (FB) radiation therapy were compiled prospectively for all personnel (regarding person-hours [PH]). A second plan was generated for all DIBH patients in the FB planning scan, which was then compared with the DIBH plan. Mortality reduction from use of DIBH was calculated using the years of life lost resulting from ischemic heart disease for Indians and the postulated reduction in risk of major cardiac events resulting from reduced cardiac dose. RESULTS: The median reduction in mean heart dose between the DIBH and FB plans was 166.7 cGy (interquartile range, 62.7-257.4). An extra 6.76 PH were required when implementing DIBH as compared with FB treatments. Approximately 3.57 PH were necessary per Gy of reduction in mean heart dose. The excess years of life lost from ischemic heart disease if DIBH was not done in was 0.95 per 100 patients, which translates into a saving of 12.8 hours of life saved per PH of work required for implementing DIBH. DIBH was cost effective with cost for implementation of DIBH for all left-sided breast cancers at 2.3 times the annual per capita gross domestic product. CONCLUSION: Although routine implementation of DIBH requires significant resource commitments, it seems to be worthwhile regarding the projected reductions in cardiac mortality.

Clinico-Epidemiologic Patterns of Laryngeal Cancer: 5-year Results from a Regional Cancer Centre in Northeastern India.

PURPOSE: To determine the risk factors, clinical symptoms and patterns of spread in laryngeal cancer. MATERIALS AND METHODS: A cross sectional study was carried out in the Regional Cancer Centre, Imphal, Manipur, India. One hundred and sixteen patients with laryngeal cancer were retrospectively reviewed for epidemiological data and descriptive statistics were reported for various variables. RESULTS: Median age at presentation was 65 years and 32.8% were undernourished at presentation. The male to female ratio was 5.4:1. Heavy smoking and tobacco chewing was associated in 91.4% and 33.6% of patients respectively. Tracheostomy was required in 21.5% leading to diagnosis of laryngeal cancer. Almost all were squamous cell carcinoma with neuroendocrine and verrucous carcinoma accounting for less than 2%. Supraglottic, glottic and trans-glottic tumors were 56.9%, 36.3% and 6.9% respectively. Nodal metastases were seen in 81.8% of supraglottic cancers and 31.6% of glottic cancers with supraglottic involvement. Level II neck nodes were the commonest site followed by level III. Distant metastases (only liver) were apparent in 1.7% at presentation. Including these liver metastases, unresectable cases were limited to 6% of the patients. CONCLUSIONS: Tobacco use is implicated in almost all of the cases and the sex ratio has also decreased due to increased female smokers. The supraglottis remains the commonest site and incidence of nodal metastases is higher than in other countries. There is also a higher requirement for tracheostomy at presentation in this region.