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Take a look at a selection of our recent media coverage:
25th November 2022
Pembrolizumab and radiotherapy failed to improve tumour control and survival compared to a standard of care regime with cetuximab and radiotherapy in patients with locally advanced squamous cell carcinoma of the head and neck according to a phase II randomised study by French researchers.
Most head and neck cancers are derived from the mucosal epithelium in the oral cavity, pharynx and larynx and are known collectively as head and neck squamous cell carcinoma. Head and neck cancer is the seventh most common cancer worldwide and accounts for over 800,000 new cases annually.
Pembrolizumab is a monoclonal antibody directed against programmed cell death protein 1 (PD-1) and it has been shown that in combination with platinum and 5-fluorouracil, the drug is an appropriate first-line treatment for recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). In addition, pembrolizumab monotherapy is also an appropriate first-line treatment for PD-L1-positive recurrent or metastatic HNSCC. However, while effective as monotherapy, the drug has also been found to significantly increase both the response and outcome in patients with metastatic non-small-cell lung cancer, when combined with radiotherapy. Many patients with HNSCC have locally advanced disease and are commonly managed with cetuximab plus radiotherapy which significantly improves overall survival at 5 years compared with radiotherapy alone, hence confirming the regime as an important treatment option in this group of patients. Nevertheless, the regime is associated with acute and late toxicities, including myelosuppression, severe nausea/vomiting, irreversible renal failure, hearing loss, and neurotoxicity, prompting the need for effective alternatives.
Based on the effectiveness of pembrolizumab and radiation therapy in patients with non-small cell lung cancer, in the present study, the French team tested this combination against cetuximab-radiotherapy in patients with non-operated stage III-IVa-b SCC of oral cavity, oropharynx, hypopharynx and larynx. Patients received once-daily radiotherapy with weekly cetuximab or 200mg Q3W pembrolizumab during RT and the primary endpoint was the loco-regional control (LRC) rate 15 months after radiotherapy.
Pembrolizumab and head and neck squamous cell carcinoma outcomes
A total of 133 patients with a median age was 65 years, 92% of whom were smokers, were randomised to either arm (67 to pembrolizumab) and followed for a median of 25 months.
The 15-month LRC rate was 59% with cetuximab and 60% with pembrolizumab, representing a non-significant difference (Odds ratio, OR = 1.05, 95% CI 0.43 – 2.59, p = 0.91). In addition, there were no significant difference between arms for progression-free survival (Hazard ratio, HR = 0.85, 95% CI 0.55 – 1.32, p = 0.47) or for overall survival (HR = 0.83, 95% CI 0.49 – 1.40, p = 0.49).
Despite the lack of difference in cancer outcomes, toxicity was lower with pembrolizumab than with cetuximab, with 74% vs 92% patients having at least one grade ≥ 3 adverse event (p=0.006) and which were mainly mucositis, radio-dermatitis and rash.
The authors concluded that compared to cetuximab with radiotherapy, pembrolizumab and concomitant radiotherapy, did not improve the tumour control and survival but appeared less toxic in unfit patients with locally, advanced, squamous cell carcinoma of the head and neck.
Toa Y et al. Pembrolizumab versus cetuximab, concurrent with radiotherapy in patients with locally advanced squamous cell carcinoma of head and neck unfit for cisplatin (GORTEC 2015-01 PembroRad): a multicenter, randomized, phase 2 trial. Ann Oncol 2022
14th January 2022
Ultrasonography (US) is better than clinical examination for the detection of lymph node (LN) metastases in patients with squamous cell carcinoma (SCC) but is associated with higher rate of false positives. This was the conclusion of a study by a team from the Department of Dermatology, Erasmus Medical Center Cancer Institute, Rotterdam, the Netherlands.
Squamous cell carcinoma represents a malignant proliferation of the cutaneous epithelium and accounts for 20% to 50% of skin cancers. Fortunately however, the incidence of metastases with the cancer is low, with one UK study observing that after 36 months, 1.1% of cases in women and 2.5% in men become metastatic. Although a 2020 interdisciplinary European consensus guideline noted that imaging methods, for example, US are more sensitive than clinical examination, it added that ‘there are limited data on the use of US for nodal metastasis‘ for SCC.
Where clinical examination reveals suspicious findings, clinicians may request US although the added value of this imaging modality remains uncertain. For the present analysis, the Dutch researchers therefore examined the diagnostic accuracy of clinical examination and baseline US for the detection of LN metastases in patients with high risk cutaneous SCC of the head and neck. They also explored the accuracy of baseline US where baseline clinical examination did not suspect metastases.
The team retrospectively reviewed all consecutive, high risk patients at their centre. Where lymphadenopathy was detected upon examination or with one or more suspicious lymph nodes detected on US, a biopsy was undertaken and nodal metastasis was confirmed by cytology. The diagnostic accuracy of clinical examination and US was calculated based on sensitivity, specificity and positive predictive value (PPV).
During a 3-year period, 233 patients with a median age of 79.1 years (75.5% male) with 246 high-risk SCCs were included in the analysis.
Among the 246 tumours, 20 (8.1%) had suspicious lymphadenopathy upon clinical examination and 11 confirmed as LN metastatic after cytology. Suspicious lymph nodes were found on US in 28.5% (70/246) of cases and in 20 of these, metastasis was confirmed by cytology.
Using these data, the authors calculated the sensitivity of clinical examination to be 50% (95% CI 28 – 72%), with a specificity of 96% (95% CI 93 – 98%) and a PPV of 55%. In contrast, US had a sensitivity of 91% (95% CI 71 – 99%), a specificity of 78% (95% CI 72 – 83%) and a PPV of 29%.
In patients with a negative result upon clinical examination, 9 of 11 metastases were detected by US with a sensitivity of 82% although there were 45 false positives, making the PPV only 17%. Based on these findings, the authors suggested that while US examination was very sensitive, this needs to be seen in the context of a higher number of false positives.
The concluded that while US was a more sensitive screening tool to detect LN metastasis, the high false positive rate would in practice lead to a higher rate of unnecessary US and cytology procedures. They suggested that future studies should focus on identifying specific populations of those with SCCs who would benefit the most from baseline US to detect metastatic disease.
Tokez S et al. Assessment of the Diagnostic Accuracy of Baseline Clinical Examination and Ultrasonographic Imaging for the Detection of Lymph Node Metastasis in Patients With High-Risk Cutaneous Squamous Cell Carcinoma of the Head and Neck JAMA Dermatol 2021
20th September 2021
A squamous cell carcinoma on the head or neck is the sixth most common cancer globally, with around 890,000 new cases and 450,000 deaths in 2018. The main form of treatment is curative radiotherapy and in patients with locoregionally advanced cancers, prior scanning with fluorodeoxyglucose positron emission tomography and computed tomography (PET-CT) has been shown to have good diagnostic performance for the detection of regional nodal metastasis. However, where there is a delay between radiotherapy and the initial PET-CT scan, does this impact on radiotherapy planning and might it be necessary to perform a second scan prior to radiotherapy? This was the question posed by researchers from the Department of Radiation Oncology, Inselspital, Bern University Hospital, Bern, Switzerland. The team performed a retrospective analysis of patients with advanced head or neck squamous cell carcinoma and who had received two PET-CT scans prior to radiotherapy, to determine whether the second scan led to any modifications to radiotherapy treatment. The team looked for changes in the primary tumour, lymphatic spread and the presence of distant metastases between the two scans. They categorised any changes as minor if there were modifications to the RT plans such as dose changes and major where treatment moved from curative to palliative or the addition of induction chemotherapy, a switch to surgery or any additional diagnostic work-up that led to postponement or cancellation of treatment.
There were 32 newly diagnosed patients with locoregionally advanced squamous cell cancer with a median age of 64 years (34% female). The median interval between the initial scan for staging assessment and the second scan was 42.5 days. Just over half (53%) of patients had a grade 2 and 41% a grade 3 tumour. Fortunately, a major treatment change occurred in only 1 patient although nodal upstaging occurred in 10% (3/29) of patients. Minor treatment changes were required in 52% (16/31) of patients with new lymph node metastases detected in all 16 patients and in 6 cases, there was evidence of progression of the primary tumour size.
In discussing their findings, the authors noted that despite an initial PET-CT scan to assess tumour staging, a second scan identified the need for minor changes in just over half of all patients. Based on these findings, they called for the potential benefits of a second scan to be further investigated and validated. They also noted that the practice of undertaking a second scan of patients where the delay was more than four weeks has become the established practice at their hospital.
Elicin O et al. Impact of pre-treatment second look 18FDG-PET/CT on stage and treatment changes in head and neck cancer. Clin Trans Radiat Oncol 2021