Systemic therapies for salivary gland carcinoma (excluding adenoid cystic carcinoma): REFCOR recommendations by the formal consensus method.

OBJECTIVE: To determine the therapeutic indications for systemic medical treatment in the management of salivary gland carcinoma (excluding adenoid cystic carcinoma) according to the clinical situation. MATERIALS AND METHODS: The French Network of Rare Head and Neck Tumors (REFCOR) formed a steering group who drafted a narrative review of the literature published on Medline and proposed recommendations. The level of adherence to the recommendations was then assessed by a rating group, according to the formal consensus method. RESULTS: Salivary gland carcinoma is rare and there is currently insufficient evidence to indicate chemotherapy at the localized stage. At the metastatic stage, initial management can be based on a phase of monitoring for indolent disease. Some histological subtypes (salivary duct carcinoma and adenocarcinoma) are more aggressive and require systemic treatment from the outset. To guide systemic treatment, it is recommended to perform immunohistochemistry and molecular biology analyses (overexpression of HER2 and androgen receptors, NTRK fusion, next-generation sequencing). CONCLUSION: Salivary gland carcinoma is a rare tumor for which there are currently few effective medical treatments. It is therefore recommended to include patients in clinical trials.

Systemic therapies for salivary gland cancer: Adenoid cystic carcinoma. REFCOR recommendations by the formal consensus method.

OBJECTIVE: To determine the therapeutic indications for systemic medical treatment in the management of adenoid cystic carcinoma (ACC) according to the clinical situation. MATERIALS AND METHODS: The French Network of Rare Head and Neck Tumors (REFCOR) formed a steering group, which drafted a narrative review of the literature published on Medline and proposed recommendations. The level of adherence to the recommendations was then assessed by a rating group, according to the formal consensus method. RESULTS: ACCs are rare tumors and there is currently insufficient evidence to indicate chemotherapy at the localized stage. At the metastatic stage, progression is often slow. In case of oligometastatic ACC, local treatment should be discussed. The most often indolent nature of polymetastatic ACC can allow management by active surveillance. Molecular screening is recommended, for abnormalities potentially accessible to targeted therapy. CONCLUSION: ACCs are rare tumors for which there are currently few effective medical treatments. It is therefore recommended to include patients in clinical trials.

Radiotherapy for salivary gland cancer: REFCOR recommendations by the formal consensus method.

OBJECTIVE: To determine the indications for radiotherapy in salivary gland cancer and to specify the modalities and target radiation volumes. MATERIAL AND METHODS: The French Network of Rare Head and Neck Tumors (REFCOR) formed a steering group which drafted a narrative review of the literature published on Medline and proposed recommendations. The level of adherence to the recommendations was then assessed by a rating group, according to the formal consensus method. RESULTS: Postoperatively, radiotherapy to the primary tumor site±to the lymph nodes is indicated if one or more of the following adverse histoprognostic factors are present (risk>10% of locoregional recurrence): T3-T4 category, lymph node invasion, extraglandular invasion, close or positive surgical margins, high tumor grade, perineural invasion, vascular emboli, and/or bone invasion. Intensity-modulated radiation therapy (IMRT) is the gold standard. For unresectable cancers or inoperable patients, carbon ion hadrontherapy may be considered. CONCLUSION: Radiotherapy in salivary gland cancer is indicated in postoperative situations in case of adverse histoprognostic factors and for inoperable tumors.

Oncologic outcomes, prognostic factor analysis and therapeutic algorithm evaluation of head and neck mucosal melanomas in France.

BACKGROUND: Head and neck mucosal melanoma (HNMM) is aggressive and rare, with a poor prognosis because of its high metastatic potential. The two main subtypes are sinonasal (sinonasal mucosal melanoma [SNMM]) and oral cavity (oral cavity mucosal melanoma [OCMM]). Consensual therapeutic guidelines considering the primary tumour site and tumour-node-metastasis (TNM) stage are not well established. MATERIAL & METHODS: Patients with HNMM from the prospective national French Rare Head and Neck Cancer Expert Network database between 2000 and 2017 were included. Clinical characteristics, treatment modalities, outcomes and prognostic factors were analysed. RESULTS: In total, 314 patients were included. The 5-year overall survival (OS) and progression-free survival (PFS) rates were 49.4% and 24.7%, respectively, in the surgery group; no long-term survivors were observed when surgery was not feasible. Moreover, even after surgery, a high recurrence rate was reported with a median PFS of 22 months. In multivariate analysis, Union for International Cancer Control (UICC) stage and tumour site correlated with PFS and OS. Postoperative radiotherapy (PORT) improved the PFS but not OS in patients with small (T3) SNMM and OCMM tumours. Nodal involvement was more frequent in patients with OCMM (p < 10-4), although, as in SNMM, it was not a significant prognostic predictor. CONCLUSION: Even early HNMM was associated with poor oncologic outcomes due to distant metastases despite surgical resection with clear margins. Lymph node metastases had no impact on the prognosis, suggesting treatment de-escalation in cervical node management. PORT might be useful for local control.

[Therapeutic targeted approaches on androgen receptors in prostate cancer]. / Traitements ciblant la voie du récepteur aux androgènes dans le cancer de la prostate.

The treatment of metastatic prostate cancer since the 1940s is based on the consideration of oncogenic addiction to its androgen receptor (AR). The significant improvement in survival outcomes over the past decade depends not only on the development of effective cytotoxic chemotherapy but also new molecules targeting the AR or decreasing testosterone levels, even in case of castration-resistant cancer. In this review, we summarize the structure and function of the RA, the mechanisms of androgen suppression, the concept of resistance to castration, historical targeted treatment on the AR and those recently marketed as abiraterone acetate and enzalutamide.

[Neuroendocrine carcinoma of the digestive tract: a literature review]. / Carcinome neuro-endocrine du tractus digestif : revue de la littérature.

Neuroendocrine carcinoma is a rare and agressive malignant tumor, mainly developing at the expense of the respiratory and of the digestive tract. Among the digestive tract, appendix, small bowel, and pancreas are the preferential sites of involvement, other locations have been more rarely reported. Neuroendocrine digestive tumors may present with various symptoms in relationship with their localization and a complex pathophysiology. Diagnosis is often made at an advanced stage, explaining partly the bad prognosis of these tumors. The optimal management of digestive neuroendocrine tumors is rendered difficult by their rarity and by a low number of randomized trials. We review the literature regarding epidemiologic and prognostic features of these rare tumors, their diagnostic and therapeutic care. Potential complications are also discussed.

Multimodal treatment and long-term outcome of patients with esthesioneuroblastoma.

PURPOSE/OBJECTIVES: To analyze the clinical features, treatment modalities and outcome of patients treated for a localized esthesioneuroblastoma (ENB). MATERIALS AND METHODS: Forty-three consecutive patients with biopsy proven ENB treated at two referral cancer centers between 1998 and 2010 were retrospectively reviewed. RESULTS: Overall, 5 patients had stage A disease, 13 stage B, 16 stage C and 9 stage D according to the modified Kadish classification. Neo-adjuvant chemotherapy was performed in 23 patients leading to a 74 % response rate. Thirty-one patients were treated by surgery. Thirty-nine patients (90.6%) underwent radiation therapy. Twelve patients received bilateral cervical lymph node irradiation (LNI). After a median follow-up of 77 months, the 5-year overall and progression free survival were 65% and 57%. Twelve patients (28%) had a locoregional relapse leading to 10 ENB-related deaths. The major prognostic factor was the modified Kadish stage with a 3-year survival for stage A-B, C and D of 100%, 48% and 22% respectively (p < 0.0001). Two (9%) isolated cervical lymph node relapses occurred among staged B and C patients treated without elective LNI and none after elective or adjuvant LNI. CONCLUSION: The high risk of locoregional failure in ENB justifies the use of multimodal therapy. Induction chemotherapy leads to a high response rate. Elective LNI might prevent regional failure in locally advanced disease.

Disseminated and circulating tumor cells in gastrointestinal oncology.

Circulating (CTCs) and disseminated tumor cells (DTCs) are two different steps in the metastatic process. Several recent techniques have allowed detection of these cells in patients, and have generated many results using different isolation techniques in small cohorts. Herein, we review the detection results and their clinical consequence in esophageal, gastric, pancreatic, colorectal, and liver carcinomas, and discuss their possible applications as new biomarkers.

Granulocytic sarcoma in a nonleukemic patient: place of radiotherapy and systemic therapies.

Granulocytic sarcoma is a rare extramedullary tumour, which most often occurs in the course of an acute or chronic leukaemia or myeloproliferative disorders. Rarely it is found before peripheral blood or bone marrow evidence of leukemia is present. We report an unusual case of acute paraplegia at first presentation of a spinal epidural granulocytic sarcoma without any haematological disorder. Therapeutic strategies are discussed in the light of the literature.

[Second-line therapy in patients with malignant pleural mesothelioma. A French retrospective study (2005-2006)]. / Traitement de seconde ligne dans le mésothéliome pleural malin. Étude rétrospective française (2005-2006).

BACKGROUND: The role of second-line chemotherapy (SLC) has still not been established in malignant pleural mesothelioma (MPM) but SLC is increasingly used because many patients are still fit at the time of the progression of the disease. METHODS: In this retrospective study, the authors reviewed their experience with SLC in pemetrexed-pretreated patients with MPM at two French thoracic oncology units (institut Gustave-Roussy, Villejuif, and hôpital d'Instruction des Armées Percy, Clamart). RESULTS: Between January 2005 and December 2006, 84 consecutive patients with progressing MPM after pemetrexed chemotherapy were enrolled. Forty-four patients received an SLC. There were 30 men and 14 women. The median age was 58 years (range: 34 to 76 years). Most patients had a performance status (PS) less than or equal to 1 (82%) and an epithelial histological subtype (91 %). The median time to progression (TTP) after first-line chemotherapy was 6.1 months. The SLC was a pemetrexed therapy in 21 patients and a new regime in 20 patients (gemcitabine alone or with oxaliplatin). The other three patients were enrolled in a phase I study. According to the Recist criteria, a partial response was observed in four patients and the disease was stabilised in six patients after SLC. The median TTP after SLC was 3.8 months. The median survival was 12.2 months (range: 2 to 72 months). Four of these 44 patients then received third-line (4.8 %) and two received fourth-line therapy (2.4 %). CONCLUSIONS: This experience indicates the feasibility of administering SLC in patients with MPM who are healthy at the time of the progression of the disease. The optimal treatment has not been defined to date and prospective trials are needed.