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.

Thoracic bite trauma in dogs and cats: a retrospective study of 65 cases.

OBJECTIVES: To report a case series of thoracic bite trauma in dogs and cats and to evaluate risk factors for mortality. METHODS: A retrospective study concerning thoracic bite wounds in dogs and cats was performed. Lesions were categorized by depth of penetration: no wound, superficial, deep or penetrating. Thoracic radiographic reports were reviewed. Lesion management was classified as non-surgical, wound exploration, or explorative thoracotomy. RESULTS: Sixty-five cases were collected. Twenty-two percent of patients with normal respiratory patterns showed thoracic radiographic lesions. Respiratory distress was not correlated with mortality. Twenty-eight patients were presented with superficial wounds and 13 with deep wounds. Eight patients exhibited penetrating wounds. Radiographic lesions were observed in 77% of dogs and 100% of cats. Explorative thoracotomy was performed in 28% of patients, and surgical wound exploration in 17.2%. With the exception of skin wounds, thoracic wall discontinuity was the most frequent lesion. Thoracotomy was associated with increased length of hospitalisation but was not correlated with mortality. The mortality rate was 15.4%. No studied factor correlated with mortality, and the long-term outcomes were excellent. CLINICAL SIGNIFICANCE: A penetrating injury, more than three radiographic lesions, or both together seemed to be indicative of the need for a thoracotomy. In the absence of these criteria, systematic bite wound explorative surgery is recommended, with extension to thoracotomy if thoracic body wall disruption is observed.

[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.

Impact of primary tumour resection on survival of patients with colorectal cancer and synchronous metastases treated by chemotherapy: results from the multicenter, randomised trial Fédération Francophone de Cancérologie Digestive 9601.

OBJECTIVE: To assess the impact of primary tumour resection on overall survival (OS) of patients diagnosed with stage IV colorectal cancer (CRC). DESIGN: Among the 294 patients with non-resectable colorectal metastases enrolled in the Fédération Francophone de Cancérologie Digestive (FFCD) 9601 phase III trial, which compared different first-line single-agent chemotherapy regimens, 216 patients (73%) presented with synchronous metastases at study entry and constituted the present study population. Potential baseline prognostic variables including prior primary tumour resection were assessed by univariate and multivariate Cox analyses. Progression-free survival (PFS) and OS curves were compared with the logrank test. RESULTS: Among the 216 patients with stage IV CRC (median follow-up, 33 months), 156 patients (72%) had undergone resection of their primary tumour prior to study entry. The resection and non-resection groups did not differ for baseline characteristics except for primary tumour location (rectum, 14% versus 35%; p=0.0006). In multivariate analysis, resection of the primary was the strongest independent prognostic factor for PFS (hazard ratio (HR), 0.5; 95% confidence interval [CI], 0.4-0.8; p=0.0002) and OS (HR, 0.4; CI, 0.3-0.6; p<0.0001). Both median PFS (5.1 [4.6-5.6] versus 2.9 [2.2-4.1] months; p=0.001) and OS (16.3 [13.7-19.2] versus 9.6 [7.4-12.5]; p<0.0001) were significantly higher in the resection group. These differences in patient survival were maintained after exclusion of patients with rectal primary (n=43). CONCLUSION: Resection of the primary tumour may be associated with longer PFS and OS in patients with stage IV CRC starting first-line, single-agent chemotherapy.

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.

Differences in biomarkers of type II collagen in atrophic and hypertrophic osteoarthritis of the hip: implications for the differing pathobiologies.

BACKGROUND: Cartilage destruction in osteoarthritis (OA) involves the excessive degradation and increased synthesis of cartilage matrix macromolecules including type II collagen (CII) and proteoglycans. The lack of osteophytes (atrophic form of OA) has been shown to be a disease severity factor in hip OA. Since osteophyte formation involves endochondral ossification and a cartilage intermediate, atrophic OA may also exhibit differences in cartilage turnover compared to hypertrophic OA. Cartilage serum biomarkers may offer an opportunity to identify such differences in patients. AIM: To determine whether serum levels of cartilage biomarkers can distinguish between the presence and absence of osteophyte formation in patients with atrophic and hypertrophic hip OA. PATIENTS AND METHODS: Fifty-six patients (mean age/standard deviation (SD): 62/11; mean body mass index (BMI)/SD: 27/11) with symptomatic hip OA (American College of Rheumatology criteria; mean Lequesne index/SD: 8.3/4) were classified as having an atrophic or hypertrophic form of OA, according to the absence or presence, respectively, of any osteophyte on a standard radiograph of the pelvis. Minimum joint space width (minJSW) and angles of dysplasia [centre-edge (CE) and head-neck-shaft (HNS)] were determined by computerized measurements. The following serum markers were used which are commercial kits from Ibex Diagnostics (Montreal, QC): proteoglycan aggrecans turnover: CS 846; CII synthesis: C-propeptide (CPII), cleavage by collagenase of type II (C2C) and type I and II (C1,2C) collagens. STATISTICS: Patients with atrophic and hypertrophic OA were compared for each variable and step to step logistic regression was used to determine the effect of variables on the belonging to each group. Correlations were examined using linear regression or Spearman test. RESULTS: CPII serum levels were significantly lower in the atrophic OA patients (77.3 vs 117.4 ng/mL). There were no significant differences between groups for C2C, C1,2C and CS 846 . CPII and C2C concentrations were highly correlated in hypertrophic OA (P=0.002) but not in atrophic OA (P=0.8). CONCLUSION: Atrophic hip OA is characterized by reduced synthetic activity involving type II collagen synthesis. This could account in part for the absence of osteophyte formation. The highly significant correlation between CPII and C2C in hypertrophic but not in atrophic OA suggests that the physiological coupling between CII formation and degradation may be lost in atrophic OA. These differences may therefore help explain the absence of osteophyte in atrophic OA and its association with more rapid disease progression.

[Treatment of diaphragmatic ruptures by laparoscopic approach in the lateral position]. / Traitement des ruptures de la coupole diaphragmatique par coelioscopie en décubitus latéral.

STUDY AIM: The aim of this retrospective study was to assess the feasibility of the treatment of recent diaphragmatic ruptures through laparoscopic approach in lateral position in patients with stable hemodynamic condition. PATIENTS AND METHOD: From 1994 to 1999, seven patients, 16 to 68 years old, were operated on for diaphragmatic rupture after a 6 hours to 15 days delay. Diaphragmatic rupture was located on the left side in 6 patients, on the right side in 1. Diagnosis was confirmed by CT-scan with reconstructions; there was no associated visceral injury. Patients were operated on by laparoscopic approach in lateral position, herniated viscera reintegrated by moderate pulling and diaphragmatic rupture repaired with non resorbable continuous suture. RESULTS: Stomach was the usual herniated viscera (n = 6); hemothorax was less than 300 cL; diaphragmatic rupture was 8 to 12 cm long. Duration of surgery was no more than 120 minutes. The seven patients after a two months to two years delay had normal chest X-rays. CONCLUSION: The laparoscopic approach in lateral position provides good visibility of the diaphragmatic lesions, easy reduction of herniated organs, complete thorax exploration and cleaning, and easy diaphragmatic repair. This technique is only feasible in patients with stable hemodynamic conditions and does not provide a complete abdominal exploration.

[Role of the pathologist in the treatment of osteosarcoma]. / Rôle du pathologiste dans le traitement des ostéosarcomes.

We describe the pathological method for the study of osteosarcoma surgical specimens treated by chemotherapy according to Rosen and Huvos. The aims of this method are to assess the extent and the histological viability of each tumor after chemotherapy. The borderline between good and bad response is about 5% viable tumor cells. This histological response determines postoperative chemotherapy.

[Fibrolipomatous hamartoma of the peripheral nerves. Anatomico-clinical study of 5 cases, including 2 with ultrastructural study]. / Hamartome lipofibromateux des nerfs périphériques. Etude anatomo-clinique de 5 cas dont 2 avec étude ultrastructurale.

Five cases of fibrolipomatous hamartoma are described. The median nerve was involved in four cases, the medial plantar nerve in one case. In the two cases with involvement of the median nerve in the wrist, the diagnosis was macroscopically suspected on the typical fusiform, segmentary enlargement of the nerve by fibrolipomatous tissue. Histologically, the epineurium was expanded by fibrolipomatous tissue and the scattered nerve bundles were dissociated by perineurial and endoneurial fibrosis. At ultrastructural examination the nerve bundles were constituted of "onion bulblike formations" with one or two central nerve fibers and peripheral perineurial cells. Eighty-eight cases of fibrolipomatous hamartoma were published in the medical literature, thirty-six with macrodactyly. This rare and probably congenital affection frequently involve the median nerve (78%).