Short-term culture of tumour slices reveals the heterogeneous sensitivity of human head and neck squamous cell carcinoma to targeted therapies.

BACKGROUND: Despite recent progress, investigating the impact of targeted therapies on Head and Neck Squamous Cell Carcinoma (HNSCC) remains a challenge. We investigated whether short-term culture of tumour fragments would permit the evaluation of tumour sensitivity to targeted therapies at the individual level. METHODS: We cultivated tumour slices prepared from 18 HNSCC tumour samples obtained during surgical resection. The samples were treated for 48 h with a panel of 8 targeted therapies directed against selected oncogenic transduction pathways. We analysed the cell proliferation index (CPI) of tumour cells using Ki67 labelling and the activation status of the RAF-MEK-ERK cascade through ERK phosphorylation analysis. RESULTS: Fourteen tumours were successfully analysed after short-term culture of tumour samples, revealing a striking individual heterogeneity of HNSCC in terms of tumour cell sensitivity to targeted therapies. Using 50% inhibition of CPI as threshold, sorafenib was shown to be active in 5/14 tumours. Cetuximab, the only approved targeted drug against HNSCC, was active in only 2/14 tumours. A more than 50% inhibition was observed with at least one drug out of the eight tested in 10/14 tumours. Cluster analysis was carried out in order to examine the effect of the drugs on cell proliferation and the RAF-MEK-ERK cascade. CONCLUSIONS: In vitro culture of tumour fragments allows for the evaluation of the effects of targeted therapies on freshly resected human tumours, and might be of value as a possible guide for the design of clinical trials and for the personalization of the medical treatment of HNSCC.

Therapeutic Management of Pyriform Sinus Cancer.

Objective To analyze the survival rate of a nonselected pyriform sinus cancer population. Study Design Case series with chart review. Setting University hospital. Subjects and Methods A total of 122 patients were included in this study covering the 2002-2008 period. All patients had squamous cell carcinoma originating from the pyriform sinus. Survival and prognostic factors were analyzed. Results The 3- and 5-year overall survival rates were 39.7% and 2.4%, respectively. The 3- and 5-year survival rates without recurrence were 34% and 27%, respectively. The median survival rates by UICC stage were as follows: stage 1 and 2 patients, 60 months; stage 3, 40 months; stage 4, 19 months. Stage 4 patients had a lower median survival rate than other stages ( P = .039). The 5-year survival rate was 46% for patients having T3-T4 operable cancers treated by surgery vs 45% for patients treated by laryngeal conservation protocol (not significant). The 5-year survival rate for patients having nonoperable T4 cancers was 17.2%. The 3- and 5-year overall survival rates of N0 patients was significantly higher than N1 patients ( P = .042). N2 and N3 patients had 100% 5-year mortality. Conclusion This study showed that overall survival and therapeutic management depend on the initial stage of pyriform sinus cancer, notably on the N status. In particular, nonoperable T4 pyriform sinus cancer and N2 and N3 patients had a very poor prognosis. A laryngeal conservation protocol seemed as effective as surgical management in terms of survival.

Personalization of the medical treatment of solid tumours using patient-derived tumour explants (Review).

Improving the pre-clinical characterization of therapeutic approaches and developing new biological assays that will enable treatment personalization for individual patients are promising developments in oncology. Here we describe a new approach consisting of culturing human tumour explants. This approach involves the preparation of slices from freshly-obtained, surgically-resected material that can be maintained ex vivo for several days. Recent studies have provided proof of principle that this approach can be easily implemented in order to explore the mode of action of various anticancer drugs and the responses of 'real' tumours at the individual patient level. We present the practical aspects and highlight the versatility of this approach, which allows for the analysis of the susceptibility of any individual tumour to multiple anticancer drugs in parallel. We discuss its potential as a companion assay in the design of optimal clinical trials and as a guide for the prescription of medical treatment. We discuss which future clinical and biological studies are needed to validate the information gathered from cultured tumour explants, and to integrate this information with that gathered from other assays in order to optimize the medical treatment of cancer.

Evaluation of individual sensitivity of head and neck squamous cell carcinoma to cetuximab by short-term culture of tumor slices.

BACKGROUND: Cetuximab is a targeted therapy with demonstrated efficacy in the management of head and neck squamous cell carcinoma (HNSCC). However, no laboratory assay is available to predict its efficacy in an individual patient. METHODS: Short-term cultures of tumor slices were performed on 9 tumor samples obtained after surgical resection in patients. Cancer cell proliferation was evaluated by immunohistochemistry and the impact of cetuximab on cell proliferation was examined. RESULTS: Tumor architecture and the heterogeneous composition of HNSCC were preserved for at least 48 hours during short-term culture of tumor slices. HNSCC cells demonstrated a heterogeneous individual response to cetuximab. CONCLUSION: Short-term culture of tumor slices is a strategy to estimate the clinical activity of cetuximab in individual patients with HNSCC. Further studies are required to correlate the results obtained with the clinical response of individual patients to cetuximab. © 2015 Wiley Periodicals, Inc. Head Neck 38: E911-E915, 2016.