High somatostatin receptor expression and efficacy of somatostatin analogues in patients with metastatic Merkel cell carcinoma.

BACKGROUND: Merkel cell carcinoma (MCC) is an aggressive, high-grade, cutaneous neuroendocrine tumour (NET). Agents blocking programmed death 1/programmed death ligand 1 have efficacy in metastatic MCC (mMCC), but half of patients do not derive durable benefit. Somatostatin analogues (SSAs) are commonly used to treat low- and moderate-grade NETs that express somatostatin receptors (SSTRs). OBJECTIVES: To assess SSTR expression and the efficacy of SSAs in mMCC, a high-grade NET. Methods In this retrospective study of 40 patients with mMCC, SSTR expression was assessed radiologically by somatostatin receptor scintigraphy (SRS; n = 39) and/or immunohistochemically when feasible (n = 9). Nineteen patients (18 had SRS uptake in MCC tumours) were treated with SSA. Disease control was defined as progression-free survival (PFS) of ≥ 120 days after initiation of SSA. RESULTS: Thirty-three of 39 patients (85%) had some degree (low 52%, moderate 23%, high 10%) of SRS uptake. Of 19 patients treated with SSA, seven had a response-evaluable target lesion; three of these seven patients (43%) experienced disease control, with a median PFS of 237 days (range 152-358). Twelve of 19 patients did not have a response-evaluable lesion due to antecedent radiation; five of these 12 (42%) experienced disease control (median PFS of 429 days, range 143-1757). The degree of SSTR expression (determined by SRS and/or immunohistochemistry) did not correlate significantly with the efficacy endpoints. CONCLUSIONS: In contrast to other high-grade NETs, mMCC tumours appear frequently to express SSTRs. SSAs can lead to clinically meaningful disease control with minimal side-effects. Targeting of SSTRs using SSA or other novel approaches should be explored further for mMCC.

ERCC1 is a prognostic biomarker in locally advanced head and neck cancer: results from a randomised, phase II trial.

BACKGROUND: Cisplatin-radiotherapy is a preferred standard for locally advanced, head and neck squamous cell carcinoma (HNSCC). However, the cisplatin-attributable survival benefit is small and toxicity substantial. A biomarker of cisplatin resistance could guide treatment selection and spare morbidity. The ERCC1-XPF nuclease is critical to DNA repair pathways resolving cisplatin-induced lesions. METHODS: In a phase II trial, patients with untreated Stage III-IVb HNSCC were randomised to cisplatin-radiotherapy with/without erlotinib. Archived primary tumours were available from 90 of 204 patients for this planned substudy. Semi-quantitative ERCC1 protein expression (H-score) was determined using the FL297, 4F9, and 8F1 antibodies. The primary analysis evaluated the relationship between continuous ERCC1 protein expression and progression-free survival (PFS). Secondary analyses included two pre-specified ERCC1 cutpoints and performance in HPV-associated disease. RESULTS: Higher ERCC1 expression was associated with inferior PFS, as measured by the specific antibodies FL297 (HR=2.5, 95% CI=1.1-5.9, P=0.03) and 4F9 (HR=3.0, 95% CI=1.2-7.8, P=0.02). Patients with increased vs decreased/normal ERCC1 expression experienced inferior PFS (HR=4.8 for FL297, P=0.003; HR=5.5 for 4F9, P=0.007). This threshold remained prognostic in HPV-associated disease. CONCLUSION: ERCC1-XPF protein expression by the specific FL297 and 4F9 antibodies is prognostic in patients undergoing definitive cisplatin-radiotherapy for HNSCC, irrespective of HPV status.

Do Radiologists Report the TNM Staging in Radiology Reports for Head and Neck Cancers? A National Survey Study.

BACKGROUND AND PURPOSE: CT and MR imaging are widely used for the staging of head and neck cancer. Currently, there are no data regarding whether the primary tumor, nodes, metastasis (TNM) staging is routinely incorporated into radiology reports. We conducted a national survey to determine whether radiologists routinely address staging, in particular regarding T (primary tumor) and N (nodal). MATERIALS AND METHODS: The survey was sent to 782 members of the American Society of Head and Neck Radiology. The survey asked whether they assign TN staging in reports. If they do assign TN staging, what are the reasons for doing so, and if not, what are the barriers or reasons for not including it in the radiology report? The method of measuring the size of the primary tumor and pathologic lymph nodes was also queried. RESULTS: A total of 229 responses were returned (29.3% response rate). Approximately half (49%; 95% confidence interval, 43.55-54.5%) of the responders thought that incorporating TN staging is important. However, only 24.5% (95% confidence interval, 19.8%-29.2%) stated that they routinely assigned TN staging in their radiology reports. The most common barriers were being afraid of being inaccurate (59%) and being unable to remember the staging classifications (58.2%); 76.9% indicated that they measure a primary tumor in 3D. CONCLUSIONS: Staging head and neck cancer based on imaging presents unique challenges. Nearly half of the responding radiologists think it is important to incorporate TN staging in radiology reports, though only a quarter of them routinely do so in practice.