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.

The impact of Oncotype DX testing on adjuvant chemotherapy decision making in 1-3 node positive breast cancer.

BACKGROUND: Oncotype DX testing has reduced the use of adjuvant chemotherapy in node-negative early breast cancer but less is known about its impact in node positive patients. AIM: This study aimed to investigate the impact of Oncotype DX gene assay testing on the decision to offer adjuvant chemotherapy in oestrogen positive, human epidermal growth factor receptor 2 negative, 1-3 lymph node positive patients. METHODS: Retrospective review of all node positive patients who underwent Oncotype DX testing at a single centre. Clinicopathological data, as well as estimated survival benefit data (from the PREDICT tool), was evaluated by a multidisciplinary group of surgeons and oncologists. Treatment decisions based on clinicopathological data were compared to recurrence scores (RS). A cut off RS > 30 was used to offer adjuvant chemotherapy. RESULTS: The 69 patients were identified, of which 9 (13%) had an RS > 30 and assigned a high-genomic risk of recurrence. The 32 patients (46.4%) were offered adjuvant chemotherapy. Overall based on the use of the RS, the decision to offer adjuvant chemotherapy changed in 36% of patients, and ultimately 24 patients (34.7%) would have been spared chemotherapy. CONCLUSION: Using clinicopathological data alone to make decisions regarding adjuvant chemotherapy in node positive breast cancer leads to overtreatment. Additional information on tumour biology as assessed by the Oncotype DX RS helps to select those patients who will benefit from adjuvant chemotherapy and spare patients from unnecessary chemotherapy.

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.

Ipsilateral neck radiotherapy in N2b well-lateralized tonsil cancer - Approach with caution.

BACKGROUND: Treatment of the uninvolved neck in well-lateralized tonsillar squamous cell carcinoma is controversial. We became concerned after a number of contralateral neck recurrences (CNRs) in patients receiving ipsilateral radiotherapy (RT). METHODS: This is a single center retrospective series including patients with well-lateralized tonsillar cancer treated with ipsilateral neck RT between 2004 and 2011. RESULTS: We identified 53 patients treated with ipsilateral neck RT during the study period. The rate of CNR was 7.5% (4 of 53). All four patients had p16-positive, T1, N2b, M0 tumors. The subgroup of patients with N2b disease (28 of 53) had a CNR of 14.3%. We subsequently switched to treat patients with N2b with bilateral neck RT. We analyzed the outcomes of 23 patients with N2b treated with bilateral neck intensity-modulated RT (IMRT) and observed no CNRs. CONCLUSIONS: We observed a higher than expected rate of CNR in the N2b population. Bilateral neck IMRT for these patients represents a safe alternative.

Treatment of choice for patients with EGFR mutation-positive non-small cell lung carcinoma presenting with choroidal metastases: radiotherapy or TKIs?

INTRODUCTION: It is not uncommon for patients with non-small cell lung cancer (NSCLC) to develop choroidal metastases (CM). External beam radiotherapy (EBRT) has traditionally been considered the treatment of choice for CM as it offers high response rates and quick relief of symptoms. However, new targeted treatments can offer an effective, alternative treatment strategy for patients harbouring specific genetic abnormalities. CASE STUDY: We present the case of a patient presenting with a symptomatic metastasis to the choroid from an epidermal growth factor receptor (EGFR) mutation-positive NSCLC and exhibiting an excellent clinical and radiological response to the tyrosine kinase inhibitor (TKI) gefitinib. DISCUSSION: A review of the literature reveals 6 more reported cases of patients with NSCLC successfully treated with an EGFR-TKI (gefitinib or erlotinib). There are no prospective or retrospective studies comparing EBRT with EGFR-TKIs for the treatment of CM in patients with EGFR mutation-positive NSCLC. All available data suggest that in EGFR mutation-positive NSCLC patients, EGFR-TKIs can offer response rates, time to response, and duration of response equivalent to that seen with EBRT. In addition, EGFR-TKIs can promise a more favourable ophthalmic toxicity profile compared with EBRT. CONCLUSION: We conclude that initial treatment with an EGFR-TKI is a reasonable option for patients presenting with EGFR mutation-positive NSCLC and a CM. EBRT can be reserved for those who either do not respond to treatment with an EGFR-TKI or have recurrence after initial therapy.