Association between binge drug use and suicide attempt among people who inject drugs.

BACKGROUND: People who inject drugs (PWID) have an elevated risk of suicide attempt. Although different substances are associated with suicide attempt, the overall risk posed by binge behavior, a high-risk pattern of drug use, remains unclear. The objective of this study is to assess the association between binge drug use and suicide attempt in a prospective cohort of PWID in Montreal, Canada. METHODS: Participants answered a biannual interviewer-administered questionnaire compiling information on sociodemographics, pattern of substance use (cocaine, amphetamine, opioids, sedative-hypnotics, alcohol, and cannabis), and psychosocial stressors and related markers. The relationship between suicide attempt and binge behavior was modeled using generalized estimating equations (GEEs), controlling for type and pattern of substance use, sociodemographic characteristics, and significant mental health markers. RESULTS: Among 1240 participants (mean age ± SD: 38.2 ± 9.8) at baseline, 222 (17.9%) reported binge during the past 6-months. PWID reporting binge were significantly younger (P < .001), less educated (P = .012), less likely male (P = .047), and had shorter history of injection (P < .001). In addition, they were younger at first injection (P = .014), reported higher rates of prostitution and psychological disorders (P = .003), and were more likely to use other drugs except cannabis and alcohol. Binge was independently associated with attempted suicide in the GEE multivariate model (adjusted odds ratio [aOR 95% CI] = 1.91 [1.38-2.65], P < .001). CONCLUSIONS: Among PWID at high risk of suicide attempt, those who binge represent a particularly vulnerable subgroup. Although the exact mechanisms underlying this finding remain unresolved, several hypothesis pertaining to the neurobiological and psychosocial consequences of binge, as well as common personality traits, warrant further investigations.

Selection of ultimately ill cancer patients able to fulfill a questionnaire: Identification of inherent biases.

AIM: Physical or psychological well-being is an essential component of quality care assessment in palliative unit. This assessment is mainly based on self-assessment (questionnaires or interviews). The aim of this study is to compare the clinical characteristics of patients able to fulfill a questionnaire and those not able to do that. METHODS: The clinical characteristics of 166 cancer patients admitted in palliative care unit from December 2006 to February 2008 have been collected. Characteristics of patients able to fulfill a questionnaire (80, 48.2%) have been compared to other patients (86, 51.8%). Moreover, functional independence measure (FIM) had been evaluated by nurses. RESULTS: Median age (60 versus 62) and sex ratio (40/40 versus 42/44) are similar in both groups. Lung primaries are significantly less frequent in patients able to fulfill the questionnaire (4% versus 17%, P=0.005). Patients able to fulfill the questionnaire had had better performance status (Karnofsky Index≤30%: 54% versus 21%, P<0.0001). The total score of FIM (56.0 versus 91.5, P<0.00001) and the median overall survivals (2.3 weeks versus 6.6 weeks, P=0.0001) were significantly lower in the group of patients non able to fulfill the questionnaire. CONCLUSIONS: Patients able to fulfill a questionnaire represent only 48.2% of all consecutive admitted patients. These patients are not representative of all patients since they had better performance status, they are less dependent and they display significant better survival. We have to think about new methods to avoid the biases generated by the use of patient-reported outcomes.

Occult invasive cervical cancer found after inadvertent simple hysterectomy: is the ideal management: systematic parametrectomy with or without radiotherapy or radiotherapy only?

BACKGROUND: After the diagnosis of occult cervical cancer during simple hysterectomy, is the best treatment option for the patient surgery with or without radiotherapy or radiation therapy only? Our study aims to answer this question. MATERIALS AND METHODS: We retrospectively analyzed 29 patients with occult cervical cancer found after inadvertent simple hysterectomy and who were referred to our cancer center between 2000 and 2010. All of the patients were discussed by the tumor board. Thirteen patients underwent surgery (radical parametrectomy and pelvic lymphadenectomy) using the minimally invasive approach (surgical group), and 16 patients underwent pelvic lymphadenectomy and radiation therapy or concurrent chemoradiation (radiation group). RESULTS: Age, BMI, and the tumor diameter were not statistically different between the surgical and radiation group: 44 and 49 (± 11) years (p = .23), 24.6 (± 6.2) and 26.7 (± 5) (p = 0.33), and 22 (± 13) and 31 (± 11) mm (p = .09), respectively. The 5-year overall and disease-free survivals for the surgical and radiation groups were: 100 and 77 % (p = .04), and 86 and 37 % (p = .02), respectively. These results were statistically significant. CONCLUSIONS: In the case of occult cervical cancer found after simple hysterectomy, radical parametrectomy with pelvic lymphadenectomy using minimally invasive surgery seems to be more efficient than radiation therapy or concurrent chemoradiation, with acceptable minimal morbidity being observed.

Single-port access laparoscopic surgery in gynecologic oncology: outcomes and feasibility.

OBJECTIVES: Single-port access laparoscopic surgery (SPALS) is supposed to simplify and improve the outcomes of current multiport laparoscopic procedures. This retrospective study was performed to assess the actual outcomes of SPALS in 2 simple gynecological oncology procedures, namely, diagnostic laparoscopy and bilateral adnexectomy. METHODS: We conducted a retrospective monocentric study. Case files of only those women who underwent bilateral adnexectomies and diagnostic and/or staging laparoscopy were studied with respect to the operative room time, intraoperative and postoperative complications, postoperative pain, and lengths of hospital stays. The main objective was to assess the feasibility and utility of SPALS surgery in gynecology. The secondary objective was to compare this group with a cohort of patients with multiport conventional laparoscopic surgery (MPCLS) performed during the same period. RESULTS: From December 2009 to March 2013, there were 134 patients who underwent these 2 procedures. Eighty adnexectomies were performed, 41 by SPALS and 39 by MPCLS. Fifty-four diagnostic laparoscopies were performed, with 27 patients in each group. In the group of adnexectomies, operative time was significantly lower in SPALS compared with MPCLS (36 vs 59 minutes, P < 10) and also compared with the postoperative stay (1 vs 2.2 nights, P < 10). By contrast, no significant difference was observed between the 2 methods of access in all the parameters studied in the group of diagnostic laparoscopies. CONCLUSIONS: Our experience demonstrates that SPALS is feasible and safe for simple gynecological procedures. This approach may result in a smooth postoperative course and shorter hospital stay and can thus be promoted to a day care procedure.

Low level of baseline circulating VEGF-A is associated with better outcome in patients with vascular sarcomas receiving sorafenib: an ancillary study from a phase II trial.

We have carried out a stratified phase II study of sorafenib (So) in patients with advanced angiosarcoma (n = 32) and epithelioid hemangioendothelioma (n = 13). This report concerns the correlative analysis of the predictive values of circulating pro/anti-angiogenetic biomarkers. Using the ELISA method (R&D Systems), circulating biomarkers (VEGF-A, in picograms per milliliter), thrombospondin-1 (TSP1, in micrograms per milliliter), stem cell factor (SCF, in picograms per milliliter), placental growth factor (PlGF, in picograms per milliliter), VEGF-C (in picograms per milliliter), and E-selectin (in nanograms per milliliter) were measured before So treatment and after 7 days. VEGF-A (mean value 475 vs. 541, p = 0.002), TSP1 (16 vs. 24, p = 0.0002), and PlGF (20.9 vs. 40.7, p = 0.0001) significantly increased during the treatment. Treatment did not affect the levels of SCF, VEGF-C, and E-selectin. Only two biomarkers were associated with better outcome as follows: VEGF-A and PlGF. Best objective response and non-progression at 180 days were associated with low level of VEGF-A at baseline (p = 0.04 and 0.03, respectively). There was a correlation between the circulating level of VEGF-A and time to progression (TTP) (r = -0.47, p = 0.001). Best objective response and non-progression at 180 days were not associated with baseline level of PIGF, but there was a correlation between the circulating level of PIGF at baseline and TTP. Low level of VEGF-A at baseline (<500) was significantly associated with better outcome.

Sorafenib in patients with progressive epithelioid hemangioendothelioma: a phase 2 study by the French Sarcoma Group (GSF/GETO).

BACKGROUND: There is no standard treatment for progressive epithelioid hemangioendothelioma (EHE). To investigate the significant vascularization of EHE, the activity/toxicity of sorafenib in patients with progressive EHE was explored. METHODS: In this multicenter, 1-stage, phase 2 trial of sorafenib (800 mg daily), the primary endpoint, which was chosen by default, was the 9-month progression-free rate. All patients had documented progressive disease at the time of study entry. RESULTS: Fifteen patients were enrolled between June 2009 and February 2011. The median age was 57 years (range, 31-76 years), and the ratio of men to women was 9:6. The performance status was zero in 10 patients and 1 in 5 patients. Twelve patients had metastases, mainly in the lung (12 patients), liver (5 patients), and bone (3 patients). Five patients had received prior chemotherapy (doxorubicin in 5 patients and taxane in 3 patients). The median sorafenib treatment duration was 124 days (range, from 27 to >271 days). Seven patients required dose reductions or transient treatment discontinuation. The 9-month progression-free rate was 30.7% (4 of 13 patients). The 2-month, 4-month, and 6-month progression-free rate was 84.6% (11 of 13 patients), 46.4% (6 of 13 patients), and 38.4% (5 of 13 patients), respectively. Two partial responses were observed that lasted 2 months and 9 months. CONCLUSIONS: Further clinical trials exploring sorafenib as treatment of progressive EHE are needed.

Expression of Egfl7 correlates with low-grade invasive lesions in human breast cancer.

Egfl7 (VE-statin) is specifically expressed by endothelial cells of normal tissues but its expression is deregulated in human cancers. Analysis of expression of Egfl7 protein and transcripts in 211 human breast cancer samples shows that Egfl7 is strongly expressed by breast tumor cells. Egfl7 expression is significantly higher in invasive ductal than in invasive lobular carcinoma. Expression of Egfl7 transcripts is also higher in lower SBR grade lesions and in lesions which are not associated with lymph node invasion. Within the invasive ductal carcinoma sub-population, expression of Egfl7 transcripts is correlated with the SBR score and with the ER+ status. High transcript and Egfl7 protein levels significantly correlate with the absence of axillary lymph node invasion. In lymph nodes, the levels of Egfl7 are correlated with the histological type of the primary lesions; they are higher in ductal than in lobular carcinoma. Egfl7 expression is thus associated with better prognosis factors and with the absence of lymph node invasion in human breast cancer lesions.

Febrile neutropenia incidence and hematological toxicity with the FEC100-docetaxel regimen in the treatment of early-stage breast cancer.

BACKGROUND: Chemotherapy for the treatment of early-stage breast cancer (ESBC) patients improves survival outcomes. However, its most common acute toxicity is myelosuppression, which can reduce the delivered dose and compromise the survival benefit. Because FEC100-docetaxel (FEC100-D) is a common protocol for ESBC, we evaluated its febrile neutropenia (FN) incidence and the role of its hematological toxicity on the individual relative dose-intensity (RDI). PATIENTS AND METHODS: It is a French single-center, observational, retrospective study. Patients received adjuvant/neoadjuvant FEC100-D treatment, without primary prophylaxis by granulocyte colony-stimulating factors (G-CSF). The neutrophil count the day before the planned chemotherapy cycle had to be over 1,500.mm(-3) for the treatment to be administered. Data collected included: date and dose of chemotherapy cycles, FN and high grade of hematological toxicity occurrence for each course, G-CSF prescription. RESULTS: One thousand, seven hundred and fifty-seven cycles in 284 patients were delivered. FN was observed in 4.9% (n = 14) of the patients, without hospitalizations or deaths after. Grade 3-4 neutropenia occurred in 5.8% of the cycles, during the first cycle in 40% of cases. Seventeen percent of our patients received less than 85% of RDI. CONCLUSION: The hematotoxicity of this treatment is acceptable. The risk of FN is low. No G-CSF primary prophylaxis is needed without additional risk factor.

Serum creatine kinase increase in patients treated with tyrosine kinase inhibitors for solid tumors.

Regarding the frequency of muscular complains with the use of tyrosine kinase inhibitors (TKIs), we hypothesize that creatine kinase (CK) elevation may be more frequent than usually reported. We conducted a prospective study on patients treated with TKIs for solid tumors, to assess the incidence of CK increase on treatment. Most of the patients (105/155) had a gastrointestinal stromal tumor. Treatments were carried out with the following drugs: imatinib (87 cases); sunitinib (21 cases); HER antagonists (14 cases), other TKIs (15 cases); and imatinib-based combinations (2 cases). Myalgias were found in 50/155 patients (32%). Fifty-four patients (35%; 95%CI, 27-42%) had elevated CK. According to NCI-CTC grading, there was 49/54 (31%) grade 1 and 5/54 (3%) grade 2 (2.5 to 5 times ULN). CK elevation was more frequent with imatinib than with other TKIs (39 cases, 45% vs. 14 cases, 21%, respectively; chi-squared test: P=0.003), and CK was more likely to be abnormal in patients treated with any TKI for more than 6 months. We found increased CK in about one-third of patients under TKIs for solid tumors, including 3% of patients with CK as high as 2.5-5 times ULN.

Sorafenib for patients with advanced angiosarcoma: a phase II Trial from the French Sarcoma Group (GSF/GETO).

BACKGROUND: Angiosarcomas account for <2% of all soft tissue sarcomas. This subtype is one of the most aggressive forms of soft tissue sarcoma. The prognosis for angiosarcoma patients in the advanced phase remains poor with current cytotoxic agents (progression-free survival [PFS] time of ∼4 months and overall survival [OS] time of ∼8 months). We investigated the antitumor activity of sorafenib in patients with metastatic or advanced angiosarcomas in a phase II trial. METHODS: We conducted a stratified phase II trial. The primary endpoint was the progression-free rate (PFR) at 9 months according to the Response Evaluation Criteria in Solid Tumors. A two-stage design (optimal Simon design) was used. Patients received sorafenib (400 mg twice daily) for 9 months until unacceptable toxicity or tumor progression. Central pathological and radiological reviews were performed. Data on stratum A (superficial angiosarcoma) and stratum B (visceral angiosarcoma) are currently available. This trial is registered with ClinicalTrials.gov (identifier, NCT00874874). FINDINGS: Strata A and B recruited 26 and 15 patients, respectively. The median age was 63 years (range, 31-82 years), with 17 male and 24 female patients. Fourteen cases arose in irradiated fields. Thirty patients (73.0%) had been pretreated with conventional chemotherapy. No unexpected toxicity occurred. The PFR at 9 months was 3.8% in stratum A and 0.0% in stratum B. The median PFS times were 1.8 months and 3.8 months, respectively, whereas the median OS times were 12.0 months and 9.0 months, respectively. No responses were observed in chemotherapy-naïve patients, whereas a 40% tumor control rate and 23% response rate were observed in the pretreated population. In this cohort, no activating mutation of the KDR gene (exons 15, 16, 24) was detected. INTERPRETATION: Sorafenib showed limited antitumor activity in pretreated patients only, for both visceral and superficial angiosarcoma, but tumor control was of short duration.

Vacuum-assisted closure therapy in the management of patients undergoing vulvectomy.

OBJECTIVES: To investigate whether systematic postoperative VAC therapy could improve vulvectomy healing. STUDY DESIGN: We reviewed medical data from 54 women who underwent in the period of March 2006 to December 2009 radical vulvectomy or wide local vulvectomy with defect volume >40cm(3). Patients were divided into two groups according to immediate postoperative care. Patients treated with systematic vacuum-assisted closure (VAC) therapy immediately after surgery were included in the "VAC group" while patients receiving conventional care (CC) were included in the "CC group". RESULTS: The characteristics of the VAC group (n=30) and CC group (n=24) were similar and there were no significant differences in operative data, histological results or oncologic follow-up. The median length of use of VAC was 11 days after surgery (6-38). The length of hospital stay for patients in the VAC group and CC group was 17.8 (±8.7) and 18.4 days (±9.9) (p=0.8) respectively. The lengths of complete healing were 44.4 (±18.4) vs. 60.2 (±28.7) days (p=0.0175) respectively. CONCLUSIONS: In our study we proved that using VAC dressing immediately after vulvectomy (at least 6cm×7cm) for 11 days reduces the total length of cicatrization by approximately 16 days.

Predictive value of neoadjuvant chemotherapy failure in breast cancer using FDG-PET after the first course.

The aim of this study was to prospectively evaluate the predictive value of (18)F-fluorodeoxyglucose-positron emission tomography (FDG-PET) to detect the absence of pathological response to preoperative chemotherapy in patients (pts) with breast cancer. 63 consecutive pts with non-metastatic, non-inflammatory breast cancer, eligible for neoadjuvant chemotherapy (3 FEC 100 followed by 3 Docetaxel) were enrolled. FDG-PET was performed just before the first as well as before the second course. Metabolic activity (tumour FDG uptake) was measured by standardised uptake value (SUV(max)). Pts were classified as non-responders (NR) when the decrease of SUV(max) in the primary tumour was less than 15% at the time of the second PET (EORTC 1999 criteria). The metabolic response in FDG-PET was correlated with WHO criteria (clinical evaluation and ultrasound and/or mammography) evaluated after three cycles, pathological complete response (pCR) after surgery (according to Sataloff classification) and 4-year relapse-free survival (RFS). The mean SUV(max) decrease according to histological response was -52 ± 21% in case of pCR (Sataloff A) and 25 ± 34% in other cases (Sataloff B + C + D). Out of the 16 pts with no PET response (SUV decrease less than 15%), only one had a clinical response after the third cycle, and no pCR was observed. The 4-year RFS rate was significantly longer for metabolic responders than for NR (respectively, 85 vs. 44%; P = 0.01). This prospective study shows that a decrease in the SUV of less than 15% after the first chemotherapy course is a very potent predictor for failure of neoadjuvant chemotherapy, especially of pCR. It is interesting to note that this was shown despite the fact that the chemotherapy regimen was changed after the third course.

Functional and sensitive outcomes after tongue reconstruction: about a series of 30 patients.

Few studies reported both functional and sensitive long-term evaluations after tongue reconstruction. The aim of this study was to assess functional outcomes and sensitive recovery after tongue reconstruction with fasciocutaneous free flap (FCFF) or musculocutaneous pedicled flap (MCPF) without nerve anastomosis. We enrolled 30 patients having no recurrence from a consecutive series of 79 tongue reconstructions as part of a cancer treatment. All patients were submitted to functional and sensitive tests. The functional study included intelligibility, tongue motility, food, and swallowing scores. Flap sensibility was evaluated too. Male-to-female sex ratio was 6.5 with a mean age of 52 years old. The lesions were mainly advanced (T3-T4 73%). Mobile tongue and base of tongue resection was carried out in 43% of cases, and resection was limited to the oral tongue for 53%. Twenty-one FCFF and nine MCPF were performed. The mean follow-up was 2 years and 11 months. Swallowing (slightly impaired 63%), food (normal 40%), and intelligibility (excellent 77%) assessments were satisfactory. Spontaneous sensory recovery was regularly observed (mean response 62%). The two groups FCFF and MCPF were similar regarding population and tumors characteristics. Functional results were higher in case of FCFF (food score p=0.05; intelligibility p=0.04). No difference was observed on sensitive recovery. This study emphasizes good functional results either for swallowing or intelligibility, with higher scores for the FCFF, strengthening the opinion that FCFF is the best choice for tongue reconstruction whenever possible.

[Screening pelvic tumours for hereditary risk of ovarian neoplasms, a cancer center experience]. / Inefficacité du dépistage des cancers tubo-ovariens dans les situations de risque héréditaire de cancer de l'ovaire ; l'expérience du Centre Oscar-Lambret.

As part of a study in the North of France for screening pelvic tumours with plasma proteomic analysis, we included 82 women with hereditary risk of ovarian cancer. We report here the consequences of organized screening with usual tests. CA 125 sampling and a transvaginal pelvic ultrasound by a radiologist were systematically conducted every 6 months. Seventy-two patients were eventually evaluable. Two incident cases of peritoneal carcinomatosis (FIGO IIIB, malignant epithelial serous high-grade tumors) were discovered in two asymptomatic women with a deleterous BRCA1 mutation (2.7%). We did not observe any other primary cancer cases but an ovarian metastasis of a breast cancer. Forty women went off the study: 32 had a prophylactic bilateral salpingo-oophorectomy. Consistent with the literature, biannual screening tests combining CA125 and pelvis ultrasound is ineffective for early detection of a pelvic tumor of tubal or ovarian origin. Testing for BRCA1 or BRCA2 deleterious mutations is then crucial for suspected family syndromes of breast and ovarian cancer. For women carrying a deleterous mutation on BRCA1/2 a salpingo-oophorectomy is the only way, only the time of this surgery is debatable.

Proposal for size justification of expanded cohort at phase-2-recommended dose.

PURPOSE: Most current dose-seeking phase 1 trials include an expanded cohort at phase-2-recommended dose (P2RD) to better characterize the drug safety or to obtain a better estimate of secondary endpoints. Nevertheless, the sample size of this expanded cohort has generally not been justified. MATERIALS AND METHODS: We reviewed 330 phase 1 trials (1998-2008). We estimated the rate of patients experiencing dose-limiting toxicity (DLT) at P2RD. Next, we estimated the probability of observing 1, 2 or 3 DLT in different fictive cohorts (from 8 to 22 patients). RESULTS: In the literature, the rate of patients experiencing DLT at P2RD was 367/2433, or 15.0%. We drew a table estimating the probability of observing 1, 2 or 3 DLTs in the different fictive cohorts. For example, in a cohort of 16 patients, the probabilities of observing 1, 2 or 3 DLTs are about 92.6%, 91.3 and 91.1% respectively. CONCLUSION: This simple tool could provide a justification for the sample size of an expanded cohort when DLT remains the metric for dose-seeking.

Head and neck cancer in young people: a series of 52 SCCs of the oral tongue in patients aged 35 years or less.

CONCLUSION: Prognosis was very poor as soon as a local failure developed. Up-front treatment should be optimized to control this rare disease. We propose producing and reporting recommendations via a concerted oncologic physician referral network. OBJECTIVES: Squamous cell carcinoma (SCC) in young people is rare and the literature is confusing. This study was carried out to assess the demographics, clinical features, and treatment outcome in a cohort of patients aged 35 years or less with SCC of the oral tongue (SCCOT). PATIENTS AND METHODS: This was a multicenter retrospective study. Fifty-two patients treated between 1990 and 2000 were identified. Descriptive statistics were analyzed to assess demographic and tumor variables. RESULTS: The WHO performance status was excellent for all patients. Thirty-seven were classified as T1-T2 and 38 were N0. All of them except one were treated with curative intent. Treatment failures were observed in 25 patients (48%). Four patients could be successfully salvaged after SCCOT recurrence or progression. The disease-free survival (DFS) was 52% at 5 years. The 5-year overall survival (OS) rate was 64%. Factors that affected the OS were invasion of the floor (p=0.009), cross over of the midline (p=0.02), positive lymph nodes (p=0.02), and the lack of disease control (p=0.0001).

Phase II trial of weekly paclitaxel for unresectable angiosarcoma: the ANGIOTAX Study.

PURPOSE: The objective of this phase II trial was to assess the efficacy and toxicity of weekly paclitaxel for patients with metastatic or unresectable angiosarcoma. PATIENTS AND METHODS: Thirty patients were entered onto the study from April 2005 through October 2006. Paclitaxel was administered intravenously as a 60-minute infusion at a dose of 80 mg/m(2) on days 1, 8, and 15 of a 4-week cycle. The primary end point was the nonprogression rate after two cycles. RESULTS: The progression-free survival rates after 2 and 4 months were 74% and 45%, respectively. With a median follow-up of 8 months, the median time to progression was 4 months and the median overall survival was 8 months. The progression-free survival rate was similar in patients pretreated with chemotherapy and in chemotherapy-naïve patients (77% v 71%). Three patients with locally advanced breast angiosarcoma presented partial response, which enabled a secondary curative-intent surgery with complete histologic response in two cases. One toxic death occurred as a result of a thrombocytopenia episode. Six patients presented with grade 3 toxicities and one patient presented with a grade 4 toxicity. Anemia and fatigue were the most frequently reported toxicities. CONCLUSION: Weekly paclitaxel at the dose schedule used in the current study was well tolerated and demonstrated clinical benefit.

O-Mel-Inib: a Cancéro-pôle Nord-Ouest multicenter phase II trial of high-dose imatinib mesylate in metastatic uveal melanoma.

BACKGROUND: Nowadays, there is no consensual and effective treatment in metastatic uveal melanoma (MUM). Numerous preclinical data (for example, 75% of MUM express c-kit) suggest that imatinib mesylate (IM) may be a potential treatment of UMM. METHODS: The primary objective of this phase II trial was to determine the non-progression rate at 3 months for patients receiving IM at dose of 400 mg twice per day orally. The study was based on a Simon's optimal design, which allows entry a total of 29 patients, if at least two non-progressions among ten first patients were observed. RESULT: Thirteen patients including ten assessable patients were enrolled in 12 months. No objective response and only one stable disease with duration of 5 months were noted. Five and one out of 13 enrolled patients experienced grade 3 and grade 4 toxicities, respectively. The most common severe adverse events were abdominal pain. The overall survival was 10.8 months. CONCLUSIONS: Despite promising preclinical data, IM is an inactive single agent in MUM. This phase II clinical trial has been stopped at the first step.

[Methodological approaches of clinical studies with targeted therapies]. / Particularités méthodologiques des études cliniques appliquées à l'évaluation des thérapeutiques ciblées.

The development of molecular targeted therapies requires some specific methodological approaches. Dose-limiting toxicities are rare in phase I studies the maximal tolerated dose is rarely established. On the contrary, the biological active dose is often determined as the dose inducing biological effect on the target without significant clinical toxicity. Several designs of phase II are described (selection phase II, randomized phase II, stratified phase II...). All of them are indicated in specific situations. The discontinuation treatment studies and the validation of biomarkers (as surrogate endpoints or as classifiers) are the two main particularities of phase III studies designed for the assessment of molecular targeted therapies.

Survival prognostic factors for lateral bucco-pharyngeal junction squamous cell carcinoma.

Squamous cell carcinomas (SCC) localized at the lateral buccopharyngeal junction are frequent occurrences in our experience. This anatomical site gives the tumor ample space to spread in different directions, making tumor management all the more difficult. We focused our study on this localization to underline their specificities and evaluate our practices. In the Department of Head and Neck Oncology at the Centre Oscar Lambret, 57 patients with lateral bucco-pharyngeal junction SCC were treated from 1995 to 2000. Epidemiological data were extracted from the medical chart. Description of the tumor was based on clinical and imaging data. Treatment modalities frequently combined surgery, radiotherapy and chemotherapy. Protocol was adapted with the health status and the aggressiveness of the disease. Follow-up and survival rates are outlined below. Fifty men and seven women with a mean age of 57 years constitute the patient population. Forty-nine out of 57 presented a history of smoking, and 44 out of 46 presented a history of alcoholism. Patient overall clinical status, social and family background were also discussed. Thirty-one of fifty-seven tumors were categorized as T1 or T2. Forty-five out of fifty-seven presented limited lymph-node involvement. Tumor extension, growth pathology and degree of differentiation were described. Twenty-eight out of fifty-seven had undergone primary surgery. Primary radiotherapy with or without chemotherapy was delivered to the others. The modality of the different treatments and their results were specified. The 3-year disease-free survival rate was 52.7% and the 3-year overall survival rate was 48.2%. The mean survival rate was 3 years. Univariate analysis was performed on all occasions. Gender (P=0.008), surgery first versus non-surgical treatment first (P=0.03), spread beyond the midline (P=0.03), and small tumors T1 T2 versus T3 T4 (P=0.003) were predictive factors of overall survival. A Multivariate analysis showed that the type of treatment (surgery first versus no primary surgery P=0.006), and the T (T1, T2 versus T3, T4 P=0.005) were the two predictive factors of the overall survival. Because of the small size of the population studied, the retrospective nature of the study and the scarcity of the publications on the subject, results must be carefully interpreted. For example, surgery must be proposed whenever deemed possible. It is in an independent factor in our series. All the statuses linked to the population type, tumor extension and tumor differentiation are also discussed.