Pembrolizumab versus cetuximab concurrent with radiotherapy in patients with locally advanced squamous cell carcinoma of head and neck unfit for cisplatin (GORTEC 2015-01 PembroRad): a multicenter, randomized, phase II trial.

BACKGROUND: To evaluate potential synergistic effect of pembrolizumab with radiotherapy (RT) compared with a standard-of-care (SOC) cetuximab-RT in patients with locally advanced-squamous cell carcinoma of head and neck (LA-SCCHN). PATIENTS AND METHODS: Patients with nonoperated stage III-IV SCC of oral cavity, oropharynx, hypopharynx, and larynx and unfit for receiving high-dose cisplatin were enrolled. Patients received once-daily RT up to 69.96 Gy in 33 fractions with weekly cetuximab (cetuximab-RT arm) or 200 mg Q3W pembrolizumab during RT (pembrolizumab-RT arm). The primary endpoint was locoregional control (LRC) rate 15 months after RT. To detect a difference between arms of 60%-80% in 15-month LRC, inclusion of 66 patients per arm was required to achieve a power of at least 0.85 at two-sided significance level of 0.20. RESULTS: Between May 2016 and October 2017, 133 patients were randomized to cetuximab-RT (n = 66) and pembrolizumab-RT (n = 67). Two patients (one in each arm) were not included in the analysis (a consent withdrawal and a progression before treatment start). The median age was 65 years (interquartile range 60-70 years), 92% were smokers, 60% were oropharynx (46% of oropharynx with p16+) and 75% were stage IV. Median follow-up was 25 months in both arms. The 15-month LRC rate was 59% with cetuximab-RT and 60% with pembrolizumab-RT ]odds ratio 1.05, 95% confidence interval (CI) 0.43-2.59; P = 0.91]. There was no significant difference between arms for progression-free survival (hazard ratio 0.85, 95% CI 0.55-1.32; P = 0.47) and for overall survival (hazard ratio 0.83, 95% CI 0.49-1.40; P = 0.49). Toxicity was lower in the pembrolizumab-RT arm than in the cetuximab-RT arm: 74% versus 92% patients with at least one grade ≥3 adverse events (P = 0.006), mainly due to mucositis, radiodermatitis, and rash. CONCLUSION: Compared with the SOC cetuximab-RT, pembrolizumab concomitant with RT did not improve the tumor control and survival but appeared less toxic in unfit patients with LA-SCCHN.

Need for risk-adapted therapy for malignant ovarian germ cell tumors: A large multicenter analysis of germ cell tumors' patients from French TMRG network.

BACKGROUND: Malignant ovarian germ cell tumors are rare tumors, affecting young women with a generally favorable prognosis. The French reference network for Rare Malignant Gynecological Tumors (TMRG) aims to improve their management. The purpose of this study is to report clinicopathological features and long-term outcomes, to explore prognostic parameters and to help in considering adjuvant strategy for stage I patients. PATIENTS AND METHODS: Data from patients with MOGCT registered among 13 of the largest centers of the TMRG network were analyzed. We report clinicopathological features, estimated 5-year event-free survival (5y-EFS) and 5-year overall survival (5y-OS) of MOGCT patients. RESULTS: We collected data from 147 patients including 101 (68.7%) FIGO stage I patients. Histology identifies 40 dysgerminomas, 52 immature teratomas, 32 yolk sac tumors, 2 choriocarcinomas and 21 mixed tumors. Surgery was performed in 140 (95.2%) patients and 106 (72.1%) received first line chemotherapy. Twenty-two stage I patients did not receive chemotherapy. Relapse occurred in 24 patients: 13 were exclusively treated with upfront surgery and 11 received surgery and chemotherapy. 5y-EFS was 82% and 5y-OS was 92.4%. Stage I patients who underwent surgery alone had an estimated 5y-EFS of 54.6% and patients receiving adjuvant chemotherapy 94.4% (P < .001). However, no impact on estimated 5y-OS was observed: 96.3% versus 97.8% respectively (P = .62). FIGO stage, complete primary surgery and post-operative alpha fetoprotein level significantly correlated with survival. CONCLUSION: Adjuvant chemotherapy does not seem to improve survival in stage I patients. Active surveillance can be proposed for selected patients with a complete surgical staging.

Phase II study of the PI3K inhibitor BKM120 in patients with advanced or recurrent endometrial carcinoma: a stratified type I-type II study from the GINECO group.

Backround:Patients with metastatic endometrial carcinoma have a poor prognosis and PIK3CA mutations and amplifications are common in these cancers. This study evaluated the efficacy and safety of the pure PI3K inhibitor BKM120 in advanced or recurrent endometrial carcinoma. METHODS: This phase II, multicentre, single-arm, double strata (histological low grade (LG) or high grade (HG)) open-label study enrolled patients with histologically confirmed advanced or recurrent endometrial carcinoma who had received not more than one prior chemotherapy regimen. Patients received initially BKM120 100 mg tablets once daily. Primary end points were proportion of patients free of progression at 2 months (HG strata) or at 3 months (LG strata), objective response rate (ORR), and safety. RESULTS: A total of 40 patients were enrolled, of whom 16 patients had received BKM120 at 100 mg. Because of high toxicities (cutaneous rash (54%), depressive events (47%), and anxiety (40%), the IDMC has proposed to stop recruitment at 100 mg and to continue the clinical trial with a lower dose of 60 mg per day. In addition, 24 patients (median age 67 years old) were newly enrolled (14 in the LG strata and 10 in the HG strata). Rate of nonprogression at 2 months in the HG strata was 70% and at 3 months was 60% in the LG strata. Median progression-free survival (PFS) for all patients is 4.5 months (CI 95% 2.8-6.1), and the median PFS for LG strata is 8.3 months compared with 3.8 months for the HG strata. No response was reported. At 60 mg per day, the most commonly reported treatment-related adverse events (AEs) were hyperglycaemia (58%), cognitive (31%), digestive (28%), hepatic liver functions (26%), and rash (23%). The most commonly reported treatment-related grade ⩾3 AEs were HTA (17%), hyperglycaemia (17%), and increased alanine aminotransferase (24%). Five patients (21%) stopped BKM120 for toxicity. CONCLUSIONS: The BKM120 was associated with an unfavourable safety profile and minimal antitumour activity in monotherapy in advanced or recurrent endometrial carcinoma. The clinical trial was stopped before end of recruitment for toxicity.

A proof of concept trial of the anti-EGFR antibody mixture Sym004 in patients with squamous cell carcinoma of the head and neck.

PURPOSE: The purpose of the trial was to assess the efficacy and tolerability of Sym004, a novel 1:1 mixture of two chimeric monoclonal antibodies (992 and 1024) targeting non-overlapping epitopes of the anti-epidermal growth factor receptor (EGFR), in patients with squamous cell carcinoma of the head and neck (SCCHN). METHODS: Incurable, recurrent and/or metastatic SCCHN patients with acquired resistance to anti-EGFR monoclonal antibody-containing treatment received weekly infusions of 12 mg/kg Sym004 until disease progression or unacceptable toxicity. RESULTS: Among the 26 patients treated with Sym004, the proportion of patients alive without disease progression at 6 months was 12 % (95 % CI 1-39 %). The median duration of progression-free survival was 82 days (95 % CI 41-140 days). Of 19 patients evaluable for response, eight showed a decrease in the sum of the largest diameter in their target lesions (median 11 %; range 7-27 %). The best overall response was stable disease in 13 patients (50 %). Paired biopsies showed a significant down-regulation of EGFR in both skin and tumors following exposure to Sym004. All patients had EGFR-related adverse events, including grade 3 skin toxicities and grade ≥3 hypomagnesemia reported in 13 (50 %) and 10 (38 %) of 26 patients, respectively. One event fulfilling the protocol-defined criteria for infusion-related reactions (grade 2) was reported. No anti-drug antibodies were detected. CONCLUSIONS: The marked EGFR down-regulation shown in target tissues supports the proposed mechanism of action of Sym004. This trial revealed modest anti-tumor activity of Sym004 in extensively pretreated advanced SCCHN patients.

Cisplatin alone or combined with gemcitabine in carcinomas of unknown primary: results of the randomised GEFCAPI 02 trial.

PURPOSE: To compare the overall survival rates of good-prognosis carcinomas of an unknown primary site (CUPS) patients treated with cisplatin alone (C) or in combination with gemcitabine (CG). PATIENTS AND METHODS: Good prognosis was defined according to the GEFCAPI (Groupe d'Etude Français des Carcinomes de site Primitif Inconnu) classification by PS (Performance Status) ≤ 1 and LDH (Lactate Deshydrogenase) within the normal range. Patients were randomly assigned to receive C or CG. Patients in the C arm received cisplatin 100 mg/m(2) repeated every 3 weeks. In the CG arm, chemotherapy consisted of gemcitabine 1250 mg/m(2) on days 1 and 8 and cisplatin 100 mg/m(2) IV on day 1, repeated every 3 weeks. The original plan was to accrue 192 patients in order to detect a 20% difference in overall survival. RESULTS: Fifty-two patients were enrolled (arm A: 25; arm B: 27). The trial was stopped early due to insufficient accrual. The median overall survival (OS) rate was 11 months [95% confidence interval: 9-20] and 8 months [95%CI: 6-12], in the CG arm and in the C arm, respectively. The 1-year survival rate was 46% [95%CI: 28-64] in the combination arm and 35% [95%CI: 19-56] in the C arm (log rank test: p=0.73). The median progression-free survival (PFS) rate was 5 [95%CI: 3-11] and 3 [95%CI: 1-8] months in the CG and in the C arm, respectively. The 1-year PFS rate was 29% [95%CI: 15-48] in the combination arm and 15% [95%CI: 5-35] in the C arm (log rank test: p=0.27). No toxic deaths occurred. Grade 3-4 neutropenia (63% versus 12%) and grade 3-4 thrombocytopenia (37% versus 4%) were more frequent in the CG arm than in the C arm. CONCLUSION: A non-significantly better outcome was observed with CG as compared to C in patients with CUP and a non-unfavourable prognosis. The toxicity profile of the combined arm was represented by haematologic toxicity with thrombocytopenia and leuconeutropenia. International collaboration is required to conduct phase III trials in patients with CUP.

Ovarian cancer in elderly patients: carboplatin and pegylated liposomal doxorubicin versus carboplatin and paclitaxel in late relapse: a Gynecologic Cancer Intergroup (GCIG) CALYPSO sub-study.

BACKGROUND: CALYPSO (CAeLYx in Platinum Sensitive Ovarian) patients compared carboplatin-pegylated liposomal doxorubicin (C-PLD) with carboplatin-paclitaxel (C-P) in patients with late-relapsing recurrent ovarian cancer (ROC). We analyzed outcomes in patients ≥70 years. PATIENTS AND METHODS: Nine hundred and seventy-six patients with taxane-pretreated ROC relapsing >6 months after first- or second-line platinum-based therapy were randomly assigned to 4-weekly C area under the curve (AUC) 5 plus PLD 30 mg/m(2) or 3-weekly C AUC 5 plus P 175 mg/m(2) for six or more cycles. RESULTS: One hundred and fifty-seven (16%) patients ≥70 years (median: 74 years, C-PLD; 73 years, C-P; range 70-82 years) were included (n = 71, C-PLD; n = 86, C-P). In comparing elderly and younger, elderly patients experienced fewer grade ≥2 allergic reactions (P = 0.005) but more grade ≥2 sensory neuropathy (P = 0.007). Myelosuppression did not differ with age. Elderly patients completed planned treatment as frequently as younger (79%, C-PLD; 82%, C-P). In comparing arms within elderly patients, C-P was associated with more grade ≥2 alopecia, sensory neuropathy, arthralgia/myalgia (P < 0.001 for all), severe leukopenia plus febrile neutropenia; C-PLD was associated with more grade ≥2 hand-foot syndrome (P = 0.005). Median progression-free survival was 11.6 months (C-PLD) and 10.3 months (C-P; P = 0.44). CONCLUSIONS: Patients ≥70 years experienced more neuropathy, with a higher incidence in the C-P arm. Similar to all study patients, C-PLD provided a better therapeutic index with less toxicity than C-P in elderly women with platinum-sensitive ROC.

Management of patients with head and neck tumours presenting at diagnosis with a synchronous second cancer at another anatomic site.

AIMS: To understand management strategies and outcomes of patients diagnosed with a head and neck tumour and a synchronous second cancer developed at another anatomic site. MATERIALS AND METHODS: Retrospective analysis of all patients diagnosed with a head and neck carcinoma and a synchronous cancer and engaged in curative-intent treatments. To evaluate therapeutic strategies, each patient's treatment process was divided into sequential therapeutic modalities and corresponding targets (head and neck and/or synchronous tumour) were identified. Patient outcome was analysed with an intent-to-treat approach. RESULTS: Forty-three patients were entered into the study (mean age=57.4 years). Synchronous tumours concerned the lung (57.8%), oesophagus (31.1%) or other sites (11.1%). Treatments were complex, including one to four consecutive modalities, with a mean duration of 4.6 months. When both tumours were advanced, treatments were frequently initiated with dual-spectrum chemotherapy (66.7%). In other situations, a locoregional treatment was often (81.1%) proposed immediately. When both tumours were in early stages, this initial locoregional treatment could be extended to target both tumours together (30.0%). For patients whose tumours differed in severity, this locoregional treatment targeted only one tumour (85%); priority was given to the most advanced one (76.5%). Nine patients had definitive treatment interruption. Associated risk factors were a low body mass index (P=0.03) and advanced-stage tumours (P=0.01). Thirty-one patients died (72.1%) with a median time to death of 7.7 months. The median follow-up for survivors was 46.2 months. Three-year overall survival was 33.9%. Low body mass index (P=0.001), advanced-stage synchronous tumours (P=0.03) and oesophageal primaries (P=0.03) altered the overall survival. Three-year locoregional and metastatic progression-free survival was 40.8 and 62.5%, respectively. Low body mass index (P=0.01) and advanced-stage synchronous tumours (P=0.01) increased the risk of disease failure. CONCLUSIONS: Head and neck tumours diagnosed with a synchronous cancer are a complex challenge. Despite a severe prognosis, patients who are not underweight, presenting with lower-stage tumours (especially the synchronous tumour) and without oesophageal involvement could most benefit from aggressive treatments.

CT assessment of woodworkers' nasal adenocarcinomas confirms the origin in the olfactory cleft.

BACKGROUND AND PURPOSE: Endoscopic endonasal surgery let us observe that woodworkers' nasal adenocarcinomas originate in the olfactory cleft. Our aim was the identification of CT imaging features that corroborate the olfactory cleft as the site of origin for woodworkers' adenocarcinoma. MATERIALS AND METHODS: We designed a retrospective study to compare CT scans of 27 unilateral olfactory cleft adenocarcinomas with 30 cases of nasosinusal polyposis (NSP) and 33 healthy sinus controls. Enlargement of the olfactory cleft, lateralization of the ethmoidal turbinate wall, and contralateral bulging of the nasal septum were measured on coronal scans passing through crista galli and posterior half of both ocular globes. Comparisons have been performed by using analysis of variance and the Bonferroni procedure. RESULTS: The nasal septum was significantly bulging across the midline in adenocarcinoma (4.6 +/- 3 mm; range, -0.1-13.7 mm) compared with NSP (0.7 +/- 1 mm; range, -2.1-2.3 mm) or healthy sinus controls (0.5 +/- 1 mm; range, -1.2-2 mm) (P < .001). The olfactory cleft was significantly wider in adenocarcinoma (15.1 +/- 4.5 mm; range, 8.6-25.7 mm) than in NSP (3.6 +/- 0.4 mm; range, 2.8-4.6 mm) or healthy sinus controls (3.3 +/- 0.7 mm; range, 1.4-4.6 mm). The ethmoidal labyrinth width was significantly smaller on the pathologic side in adenocarcinoma (7.2 +/- 2.7 mm; range, 3.2-14.2 mm) than in the control groups (P < .001). Whereas the angle between the conchal lamina and vertical midline was close to zero degrees in NSP (0.03 +/- 2.25 degrees ; range, -5 degrees -3 degrees ) and healthy sinus controls (0.45 +/- 2.13 degrees , range, -5 degrees -5 degrees ), it reached 39.76 +/- 13.83 degrees (P < .001) in adenocarcinoma. CONCLUSIONS: Radiologists should suspect nasal adenocarcinoma on sinus CT scans showing a unilateral expanding opacity of the olfactory cavity.

[Curative salvage treatment of mediastinal and pleuropulmonar metastatis from anal canal cancer]. / Chimioradiothérapie de rattrapage pour métastases médiastinales et pleuropulmonaires d'un cancer du canal anal.

This case report presents a 57 years-old woman treated for a squamous cell carcinoma of the anal canal by radiochemotherapy and brachytherapy. The particularity of this case lays on the fact that she presented a mediastinal and pleural metastatic evolution three years later, which was also treated by radiochemotherapy, leading to a complete remission of 50 months. This observation is interesting for its curative treatment in metastatic cancer of the anal canal. It also illustrates the radiosensibility of anal canal cancers, including metastatic situations, and raises the contribution of PET-scanner to evaluate the response to treatment and detect a recurrence.

Endoscopic surgery reveals that woodworkers' adenocarcinomas originate in the olfactory cleft.

The olfactory cleft is a narrow chamber located under the cribriform plate and between the turbinate wall of the ethmoidal labyrinth and the corresponding nasal septum. Nasal adenocarcinomas are mostly described as originating in the ethmoid sinus and operated via external approaches. We designed a prospective study on twenty consecutive woodworkers' adenocarcinomas without intracranial extension to determine the precise site of origin of the tumour. All patients were operated under endoscopic endonasal control according to a methodical surgical procedure as follows: 1) debulking of the tumour and identification of the middle turbinate or conchal lamina, 2) exenteration of the ethmoidal labyrinth according to the nasalisation procedure, and 3) exenteration of the olfactory cleft. Endoscopic endonasal surgery showed that woodworkers' adenocarcinomas constantly originated in the olfactory cleft, appearing as polyp-like neoplasms with well-defined bodies. Over a long period of time, they do not invade, but just displace and push out the surrounding structures, i.e. the nasal septum and the turbinate wall. More than the volume of the tumour, the precise location of the pedicle and especially its connection to the cribriform plate could be of major prognosis value.

Carcinoma of an unknown primary: are EGF receptor, Her-2/neu, and c-Kit tyrosine kinases potential targets for therapy?

Carcinomas of an unknown primary site (CUP) are heterogeneous tumours with a median survival of only 8 months. Tyrosine kinase inhibitors are promising new drugs. The aim of this study was to determine the expression of EGF-receptor, Her-2/neu, and c-Kit tyrosine kinases in CUP. Paraffin-embedded specimens were obtained from 54 patients with a CUP who were included in the GEFCAPI 01 randomised phase II trial. Immunohistochemistry was performed using the Dako autostainer with antibodies directed against HER-2/neu protein, EGFR protein, and c-Kit protein (CD117). EGFR expression was found in 36 out of 54 samples (66%). In contrast, Her-2/neu overexpression and c-Kit positivity were only detected in 4 and 10% of patients, respectively. No significant association was found between the expression of the tyrosine kinase receptors and prognosis. EGFR expression was significantly associated with response to cisplatin-based chemotherapy: the response rates were 50 and 22% in patients with EGFR-positive tumours and EGFR-negative tumours, respectively (P<0.05). This study shows that EGFR is frequently expressed in CUP. This finding may prompt clinical trials investigating EGFR inhibitors in this setting. In contrast, c-Kit expression and Her-2/neu overexpression occur infrequently in CUP. EGFR expression was correlated to tumour chemosensitivity.

[Long-term results and prognostic factors of squamous cell carcinoma of the anal canal treated by irradiation]. / Résultats à long terme et facteurs pronostiques des carcinomes épidermoïdes du canal anal traités par irradiation.

PURPOSE: To analyze the prognostic factors of loco regional control (LRC), specific survival (SS) and sphincter conservation (SC) of patients treated by curative and conservative irradiation for an epidermoid cancer of anal canal in our institution. PATIENTS AND METHODS: From 1976 to 2005, 286 patients (pts) were treated by exclusive radiotherapy (180 pts) or chemo-radiotherapy (106 pts) followed by a brachytherapy boost (233 pts) or external beam radiotherapy boost (24 pts). Forty-three pts were stage I, 154 stage II, 31 stage IIIA and 53 stage IIIB. RESULTS: The mean follow-up was 65 months (range: 1.3-250 months). The 5-years-overall survival and SS rates were 66.4% and 78.1% respectively. In multivariate analysis, tumor size (>or=40 mm) [RR=2.1], node involvement (RR=2.4), and poor response (<75%) to first course irradiation [RR=1.9], local relapse (RR=4.5) and distant metastases were factors of poor prognosis for SS. Five-years-LRC were 71.5% (88% for stage I, 69% for stage II, 77%, for stage IIIA and 60% for stage IIIB). Prognosis factors of LCR were tumor size (RR=2.5), response to first course of irradiation (RR=2.9). SC was 71% at 5 years. Prognosis factors of SC were tumor size (RR=1.9) and response to first course of irradiation (RR=2.4). CONCLUSION: The results of this series are similar to those of the literature. As well as initial tumor extension, response to first course of irradiation was found as prognostic factor on LCR, SS, SC. Our results are similar to other series and brachytherapy seems not to be deleterious. Its impact to local control remains to be evaluated.

Patient preference for either the EORTC QLQ-C30 or the FACIT Quality Of Life (QOL) measures: a study performed in patients suffering from carcinoma of an unknown primary site (CUP).

The objective of this study was to examine and compare two core measures of Quality Of Life (QOL) used in cancer clinical trials: the European Organisation for Research and Treatment of Cancer QOL Core Questionnaire 30 (EORTC QLQ-30) and the Functional Assessment of Chronic Illness Therapy (FACIT), in order to identify which one patients have the strongest preference for using. 68 patients suffering from Carcinomas of an Unknown Primary site (CUP) were recruited in a multicentric study; all of them completed both questionnaires, administered in a randomised manner. The criteria were the percentage of preferences, and four indicators of acceptability. The results indicated that an equal proportion of patients preferred the QLQ-C30 (19%) and FACIT (19%). 54% of patients felt both questionnaires were acceptable. All the indicators of acceptability favoured the QLQ-C30. Analysis of open-ended questions shed light on the difficulties encountered by the patients. As no significant preference was observed for one of the questionnaires, the QLQ-C30 was chosen on the basis of its significantly better acceptability criteria.

[Measure of quality of life in patients with metastatic colorectal cancer: techniques and main results]. / Mesure de la qualité de vie des patients atteints de cancer colorectal métastatique: techniques et principaux résultats.

PURPOSE: Until the 1990s, the patient's duration of life was the main measure for determining the value of palliative chemotherapy for colorectal cancer. Quality of life recently appeared as a main end point. The aim of this article is to provide an overview of the instruments used to measure quality of life in patients with metastatic colorectal cancer, to review the published data and to analyse the bias and methodological problems. CURRENT KNOWLEDGE AND KEY POINTS: QoL is a multidimensional subjective concept, which can be measured using psychometric instruments. Quality of life measurement has a descriptive and prognostic value. Results from quality of life assessment in randomized trials have given useful information and help patients and physicians to choose between treatment options. More than half of the patients with palliative chemotherapy had at least stabilization of quality of life. Response to chemotherapy and side-effects influence quality of life. Quality of life assessment clearly requires methodological improvement. Missing data are a particularly difficult problem, which should be improved by a better organization. FUTURE PROSPECTS AND PROJECTS: Psychometric properties of EORTC QLQ-CR38 et FACT-C should be checked in French language. An international consensus on methods of measurement of quality of life in oncology is warranted to enhance compliance, to better interpret quality of life results et to optimize publications of precise quality of life data.

[Management of mucositis following radiotherapy for head and neck cancers]. / Prise en charge des mucites après radiothérapie des cancers des voies aérodigestives supérieures.

Acute mucositis is common after radiotherapy for head and neck cancers. During the past 3 decades, there was a gradual evolution in the treatment modalities for locally advanced carcinomas (concomitant radio-chemotherapy, accelerated radiotherapy). These new strategies are accompanied by an increase in early mucosal reactions. At the present time, there is no widely accepted prophylaxis or effective treatment. Many traditional remedies or new agents seem ineffective (Sucralfate, Chlorhexidine, GM-CSF, Silver nitrate, Prostaglandin, anti-oxidants, Benzydamine hydrochloride), while others seem promising (Povidone-iodine, nonabsorbable antibiotic lozenges and antifungals, local GM-CSF, Glutamide, Low-energy laser, corticosteroïds). Radioprotectors are controversial and should be only used in experimental protocols and not in routine practice. However, some recommendations can be proposed: general prevention and global care before cancer therapy should be systematic (oral hygiene, dental and periodontal treatment, advice to avoid the use of tobacco and alcohol); frequent oral rinsing with a bland mouthwash (Povidone-iodine or others) should be used at the start of treatment because there are significant modifications of the oral microflora increased by a disturbed salivary flow; these mouthwashes could be associated with nonabsorbable antibiotic lozenges or antifungal topicals (bicarbonates, Amphotéricine B); Systematic percutaneous fluoroscopic gastrostomy should be decided before any aggressive treatments (concomitant radio-chemotherapy, accelerated radiotherapy); pain should be controlled; finally, the radiation technique should be optimized (mucosal-sparing block, conformal radiotherapy and intensity-modulated radiation therapy).

[Non-surgical treatments of esophageal cancers]. / Traitements non chirurgicaux des cancers de l'oesophage.

INTRODUCTION: Despite improvements in surgical techniques and perioperative mortality, only slight improvements in the 5-year survival of patients with esophageal cancer have been observed in the last 20 years. Many patients with apparently localized cancer will have recurrences or metastatic disease despite surgery with curative resection. Consequently, multimodal therapies, including chemotherapy and radiotherapy, were introduced. This review outlines and critically analyzes current non-surgical treatments, including palliative care. CURRENT KNOWLEDGE AND KEY POINTS: Esophageal cancers appear to be chemosensitive but the median duration of response is short and toxicity consistent, especially in metastatic disease. Consequently, palliative chemotherapy should be offered preferably within a clinical trial. Chemotherapy as the only adjuvant treatment cannot be recommended outside clinical trials. Radiotherapy alone as a curative treatment has been proven to be inferior to chemoradiotherapy in inoperable tumors. Some data support the use of preoperative chemoradiotherapy, but randomized trials are conflicting. A pathological complete response has been identified as a favorable prognostic factor for survival. Self-expanding esophageal metal stents are a simple and effective palliative treatment of malignant dysphagia and can be considered as the reference treatment in patients with obstruction of the lower esophagus or with fistula. FUTURE PROSPECTS AND PROJECTS: Taxanes should be evaluated in randomized studies using chemotherapy or chemo-radiotherapy. Progress in radiotherapy, such as accelerated fractionation, greater radiation dose, and the addition of brachytherapy, will increase locoregional control and probably survival. The role of secondary surgery in patients responding to chemoradiotherapy still needs to be answered.

[Long-term treatment of Lambert-Eaton syndrome by 3, 4 diaminopyridine]. / Traitement au long cours du syndrome de Lambert-Eaton par la 3,4 diaminopyridine.

A patient with a 5 year history of slow-progressive Lambert-Eaton Myasthenic Syndrome (LEMS) was treated for a period of 12 months with 3,4-diaminopyridine (3,4-DAP). The therapy led to an objective increase in muscle power. During the treatment period, there was no increase in muscle weakness, but attempts at withdrawal of the drug confirmed a progression. The mouth dryness disappeared and autonomic regulation disturbances were improved. All of the laboratory parameters remained unchanged. A neoplasia was excluded by extensive endoscopic and radiological investigations. Side-effects included initial perioral paresthesia and, later, paresthesia down the skin and along the ulnar edge of the forearm. 3,4-DAP seems to be an effective and acceptable long-term symptomatic therapy in LEMS.

[Magnetic resonance imaging in lupic chorea]. / Imagerie par résonance magnétique dans une chorée lupique.

A case of disseminated lupus erythematosus with chorea is reported. CT was normal. Magnetic resonance imaging showed multiple focal lesions on T2-weighted sequences, predominating in the periventricular white matter. This MRI pattern did not change in a second MRI investigation, 7 months later. The contribution of MRI to our understanding of the neurolupus pathophysiology is discussed.