Datasets for gene expression profiles of head and neck squamous cell carcinoma and lung cancer treated or not by PD1/PD-L1 inhibitors.

Identification of tumors harboring an overall active immune phenotype may help for selecting patients with advanced head and neck squamous cell carcinomas (HNSCC) and non-small cell lung cancer (NSCLC) who may benefit from immunotherapies. In this context, we generated targeted gene expression profiles in three and two independent cohorts of patients with HNSCC or NSCLC respectively, treated or not by PD-1/PD-L1 inhibitors. Notably, we generated two datasets including 102 and 82 patients with HNSCC or NSCLC treated with PD-1/PD-L1 inhibitors. Clinical information, including detailed survival raw data, is available for each patient, allowing to test association between gene expression data and patient survival (overall and progression-free survival). Moreover, we also generated gene expression datasets of 27 paired HNSCC samples from diagnostic biopsies and versus surgically resected specimens as well as 33 paired HNSCC samples at initial diagnosis (untreated) and at recurrence. Those datasets may allow to test the stability of a given biomarker across paired samples.

Immunologically active phenotype by gene expression profiling is associated with clinical benefit from PD-1/PD-L1 inhibitors in real-world head and neck and lung cancer patients.

INTRODUCTION: Identification of tumours harbouring an overall active immune phenotype may help for selecting patients with advanced head and neck squamous cell carcinomas (HNSCC) and non-small cell lung cancer (NSCLC) who may benefit from immunotherapies. Our objective was to develop a reliable and stable scoring system to identify those immunologically active tumours. METHODS: Using gene expression profiles of 421 HNSCC, we developed a score to identify immunologically active tumours. Validation of the 'HOT' score was done in 40 HNSCC and 992 NSCLC. Stability of the 'HOT' score was tested in paired HNSCC samples from diagnostic biopsies versus surgically resected specimens, untreated versus recurrent samples, and pre-versus post-cetuximab samples in a total of 76 patients. The association between the 'HOT' score with overall survival (OS) and progression-free survival (PFS) was tested in 184 patients with HNSCC or NSCLC treated with PD-1/PD-L1 inhibitors. RESULTS: A 27-gene expression based 'HOT' score was correlated with: (i) PD-L1 and IDO1 expression, (ii) TCD8 infiltrate and (iii) activation of the IFN-γ pathway. The HOT score concordance when comparing diagnostic biopsies and surgically resected specimens was higher than in untreated samples versus recurrent or pre-versus post-cetuximab samples. In 102 and 82 patients with HNSCC or NSCLC treated with PD-1/PD-L1 inhibitors, the HOT score was associated with an improved OS and PFS in multivariate analysis. CONCLUSION: The 'HOT' score is a simple and robust approach to identify real-world patients with HNSCC and NSCLC immunologically active tumours who may benefit from PD-1/PD-L1 inhibitors.

Lack of efficacy of neoadjuvant chemotherapy in adult patients with maxillo-facial high-grade osteosarcomas: A French experience in two reference centers.

INTRODUCTION: Neoadjuvant chemotherapy (neo-CT) for osteosarcomas is the standard of care. Management of maxillo-facial osteosarcomas (MFOS) is challenging. In this rare disease, we collected a large cohort of patients with the aim to report the histological and radiological local response rates to neo-CT. PATIENTS AND METHODS: All consecutive adult patients treated between 2001 and 2016 in two French sarcoma referral centers (Pitié-Salpêtrière Hospital, APHP, RESAP France and Gustave Roussy Institute France), for a histologically proved MFOS were included. Clinical, histological and radiological data were independently reviewed. Tumor response to neo-CT was assessed clinically, radiologically with independent review using RECIST v1.1 criterion and pathologically (percentage of necrosis). Multivariate analysis was done for outcomes, tumor response and disease-free survival (DFS). RESULTS: A total of 35 high grade MFOS were collected. The clinical tumor response was 4% (1/24 receiving neo-CT), the radiological response was 0% (0/18 with available data) and the pathological response was 5% (1/20 with available data). Three patients (12.5%) initially resectable became unresectable due to clinical and radiological progression during neo-CT. Tumor size and R0 (clear margins) surgical resections were significantly associated with DFS. CONCLUSION: MFOS is a rare disease. This large retrospective cohort of MFOS indicates the lack of benefit and potentially deleterious effects of neo-CT. We suggest privileging primary surgery in initially localized resectable MFOS. The benefit of adjuvant chemotherapy should be prospectively studied.

18F-Fluorocholine PET/CT and Parathyroid 4D Computed Tomography for Primary Hyperparathyroidism: The Challenge of Reoperative Patients.

BACKGROUND: To evaluate FCH-PET/CT and parathyroid 4D-CT so as to guide surgery in patients with primary hyperparathyroidism (pHPT) and prior neck surgery. METHODS: Medical records of all patients referred for a FCH-PET/CT in our institution were systematically reviewed. Only patients with pHPT, a history of neck surgery (for pHPT or another reason) and an indication of reoperation were included. All patients had parathyroid ultrasound (US) and Tc-99m-sestaMIBI scintigraphy, and furthermore, some patients had 4D-CT. Gold standard was defined by pathological findings and/or US-guided fine-needle aspiration with PTH level measurement in the washing liquid. RESULTS: Twenty-nine patients were included in this retrospective study. FCH-PET/CT identified 34 abnormal foci including 19 ectopic localizations. 4D-CT, performed in 20 patients, detected 11 abnormal glands at first reading and 6 more under FCH-PET/CT guidance. US and Tc-99m-sestaMIBI found concordant foci in 8/29 patients. Gold standard was obtained for 32 abnormal FCH-PET/CT foci in 27 patients. On a per-lesion analysis, sensitivity, specificity, positive and negative predictive values were, respectively, 96%, 13%, 77% and 50% for FCH-PET/CT, 75%, 40%, 80% and 33% for 4D-CT. On a per-patient analysis, sensitivity was 85% for FCH-PET/CT and 63% for 4D-CT. FCH-PET/CT results made it possible to successfully remove an abnormal gland in 21 patients, including 12 with a negative or discordant US/Tc-99m-sestaMIBI scintigraphy result, with a global cure rate of 73%. CONCLUSION: FCH-PET/CT is a promising tool in the challenging population of reoperative patients with pHPT. Parathyroid 4D-CT appears as a confirmatory imaging modality.

Alpha-interferon secreting blastic plasmacytoid dendritic cells neoplasm: a case report with histological, molecular genetics and long-term tumor cells culture studies.

We report a new case of blastic plasmacytoid dendritic cell neoplasm (BPDCN) with extensive immunophenoptyping, genotyping (karyotype, array-comparative genomic hybridization, and fluorescent in situ hybridization), and long-term tumor cells culture. BPDCN is a very rare and aggressive disease clinically characterized by a skin revealing localization more or less rapidly disseminating to the bone marrow and other organs with or without and leukemia. The disease was initially phenotypically characterized by the expression of both CD4 and CD56 antigens, whereas lymphoid and myeloid lineage antigens were negative. A phenotypic link with alpha-interferon (IFN-I)-producing plasmacytoid dendritic cells was demonstrated. The data collected in this case report provide additional biological and genotypical data on tumor cells of BPDCN. This study confirms the capability of tumor cells to secrete IFN-I, demonstrated by biological IFN-I activity of cultured cells and immunohistochemical expression of Mx-1 protein. Although a common genetic profile involving chromosomes 5, 6, 9, 12, 13, and 15 has been identified, no specific genetic marker has been demonstrated that is specific to BPDCN. The demonstration of ETV6 gene deletion in this case deserves further investigations as a putative BPDCN marker.