Circulating tumor cell analysis in locally advanced and metastatic squamous cell carcinoma of the head and neck.

BACKGROUND: Circulating tumors cells (CTCs) are considered an early step towards metastasis and have been linked to poor prognosis in several types of cancer. CTCs in squamous cell carcinoma of the head and neck (SCCHN) have an unclear role. METHODS: In this prospective study, patients with locally advanced or metastatic SCCHN had CTC counts assessed before starting systemic treatment using the CellSearch System. Select cases also had sequential CTC evaluation. Presence of CTCs was correlated with patient characteristics and outcomes. RESULTS: Forty-eight patients enrolled, and 36 had evaluable clinical data and baseline CTC counts. Twenty-five patients had locally advanced disease (LAD) and 11 had metastatic disease. ≥1 CTCs were detected in six patients with LAD (24%) and four with metastatic disease (36%). On univariate analysis, smoking was associated with CTCs. CONCLUSION: CTCs are not associated with prognosis in patients with LAD and metastatic disease; however, they are present in this patient population, and ≥1 CTCs is associated with a history of smoking. LEVEL OF EVIDENCE: 1b; individual prospective cohort study.

Chemotherapy after immune checkpoint blockade in patients with recurrent, metastatic squamous cell carcinoma of the head and neck.

OBJECTIVES: Given that immune checkpoint inhibitors (ICIs) are now preferred agents in first-line treatment of recurrent/metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN), we retrospectively studied outcomes on post-ICI therapies. MATERIALS AND METHODS: We collected data from the medical records of 60 patients with R/M SCCHN who received ICIs followed by at least one further line of cytotoxic or biologic therapy at our institution from 2014 to 2019. We also compared outcomes with those of historical trials in the ICI-naïve, second-line or greater setting. RESULTS: Patients who received platinum-based regimens as their post-ICI therapies experienced improved overall response (ORR) (50% versus 10%, p < 0.01) and improved overall survival (OS) (15.1 months versus 7.3 months, HR 0.46, p = 0.04) compared to the rest of the cohort. Patients receiving platinum re-challenge were more likely to respond than all other patients in the cohort (OR 8.37, p = 0.01). The ORR for patients on 5-fluorouracil (5-FU)-containing regimens (63%) was also higher than other patients in the cohort (p = 0.03). Immunotherapy-based regimens compared favorably to historical data of first exposure to ICIs (disease control rate 54% versus 36%). Singlet regimens were associated with shorter OS than other regimens (HR = 2.38, p = 0.01). CONCLUSIONS: Platinum- and 5-FU-based doublet or triplet regimens may be superior options in the post-ICI setting. Immunotherapy re-challenge following ICI therapy may also be a reasonable option.

Chromosome 3q arm gain linked to immunotherapy response in advanced cutaneous squamous cell carcinoma.

AIMS: The activity that the immune checkpoint inhibitor (ICI) cemiplimab has recently demonstrated has led to a paradigm shift in the management of patients with advanced cutaneous squamous cell carcinoma (cSCC). To identify predictive biomarkers of response to ICIs in advanced cSCC, we studied 33 patients who received ICI therapy at the Dana-Farber/Harvard Cancer Center (DF/HCC) and analysed sequencing data for a subset of these patients. METHODS: We collected clinical data using electronic health records and genomic data using the institutional OncoPanel platform of the DF/HCC. We compared tumour genomics with data from previously sequenced cSCC cohorts. RESULTS: We observed high tumour mutational burden regardless of smoking status and response to ICI and longer median overall survival among those patients who achieved an ICI response. We compared the genetic data from our cohort with data from other cohorts that included fewer patients with distant metastatic disease. Although our cohort had a similar genetic landscape to those of comparator cohorts, mutations in PIK3C2B were more common in our study. In our cohort, copy number alterations (CNAs) in the 3q chromosomal arm appeared to predict response to ICI therapy. CONCLUSION: CNAs in the 21-27 bands of chromosome arm 3q, a region that includes PIK3CA, ETV5 and BCL6, may represent predictors of response to ICI and may be candidates for drug targeting in combination or sequence with ICI agents.

Everolimus in Anaplastic Thyroid Cancer: A Case Series.

Background: Anaplastic thyroid cancer (ATC) is a very aggressive disease and accounts for over 50% of thyroid-cancer related deaths. mTOR inhibition has shown anti-tumor activity in ATC. We report our experience treating patients with ATC with everolimus off-protocol. Methods: Patients with confirmed ATC and treated with everolimus at DFCI were identified and reviewed retrospectively. NexGen sequencing was performed, and radiologic responses were correlated with mutational profile. Results: Five patients were treated from 2013 to 2016. Three patients had a response, which included one patient who achieved a partial response for 27.9 months, and two patients who had stable disease for 3.7 and 5.9 months, respectively. Genomic analysis was available in two patients and revealed that the partial responder had mutations involving the PI3K/mTOR pathway. Conclusion: Everolimus has anti-tumor activity in ATC, and responses may correlate with mutations involving the PI3K/mTOR pathway. Further studies are warranted.