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.

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.

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.

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.

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.

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.

Assessment of baseline clinical predictive factors of response to cetuximab-irinotecan in patients with irinotecan-refractory metastatic colorectal cancer.

OBJECTIVE: To identify easily available predictive factors of response to cetuximab-irinotecan in patients with irinotecan-refractory metastatic colorectal cancer. METHODS: Retrospective analysis of patients treated with cetuximab (400 mg/m(2) in week 1, 250 mg/m(2) in subsequent weeks) plus irinotecan (180 mg/m(2) every 2 weeks). We assessed demographic data, prior response to chemotherapy, number of metastatic sites, disease and metastatic disease durations, irinotecan-free interval and tumoral immunohistochemical epidermal growth factor receptor status. RESULTS: We analyzed 311 patients. Objective response rate under cetuximab-irinotecan was 26%. In univariate analysis, prior response to irinotecan, presence of only 1 metastatic site, disease duration, metastatic disease duration and irinotecan-free interval equal or above median (24, 18 and 1.8 months, respectively) were predictive of response to cetuximab-irinotecan. Multivariate analysis confirmed independent predictive value of prior response to irinotecan, number of metastatic sites and disease duration. CONCLUSION: Prior response to irinotecan, number of metastatic sites and disease duration may contribute to better select patients suitable for cetuximab-irinotecan therapy.

External beam radiation therapy followed by high-dose-rate brachytherapy for inoperable superficial esophageal carcinoma.

PURPOSE: The aim of this study was to retrospectively evaluate the feasibility, efficacy, and tolerance of external beam radiotherapy followed by high-dose-rate brachytherapy in inoperable patients with superficial esophageal cancer. PATIENTS AND METHODS: From November 1992 to May 1999, 66 patients with superficial esophageal cancer were treated with exclusive radiotherapy. The median age was 60 years (range, 41-85). Fifty-three percent of them were ineligible for surgery owing to synchronous or previously treated head-and-neck cancer. Most of the patients (n = 49) were evaluated with endoscopic ultrasonography (EUS) or computed tomography (CT). The mean doses of external beam radiotherapy and high-dose rate brachytherapy were 57.1 Gy (+/-4.83) and 8.82 Gy (+/-3.98), respectively. The most frequently used regimen was 60 Gy followed by 7 Gy at 5 mm depth in two applications. RESULTS: Among patients evaluated with EUS or CT, the complete response rate was 98%. The 3-, 5-, and 7-year survival rates were 57.9%, 35.6%, and 26.6%, respectively. Median overall survival was 3.8 years. The 5-year relapse-free survival and cause-specific survival were 54.6% and 76.9%. The 5-year overall, relapse-free, and cause-specific survival of the whole population of 66 patients was 33%, 53%, and 77%, respectively. Local failure occurred in 15 of 66 patients; 6 were treated with brachytherapy. Severe late toxicity (mostly esophageal stenosis) rated according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer scale occurred in 6 of 66 patients (9%). CONCLUSION: This well tolerated regimen may be a therapeutic alternative for inoperable patients with superficial esophageal cancer. Only a randomized study could be able to check the potential benefit of brachytherapy after external beam radiation in superficial esophageal cancer.

Mitochondrial proliferation during apoptosis induced by anticancer agents: effects of doxorubicin and mitoxantrone on cancer and cardiac cells.

Doxorubicin is one of the most largely prescribed antitumor drug for the treatment of breast, liver and colon cancers as well as leukemia, but the cardiotoxicity of this anthracycline derivative limits its clinical use. Although doxorubicin is toxic to both cancer and cardiac cells, there are evidences suggesting that the mechanism of cell death is different for the two cell types. To investigate further this issue, we have compared the proapoptotic effects of doxorubicin and the functionally related anthracenedione compound mitoxantrone, which is also used in the clinic for the treatment of cancer. After evaluating the toxicity of the two drugs to mammary adenocarcinoma MTLn3 cells and H9C2 cardiomyocytes, we dissected the drug-induced apoptotic machinery by measuring the effects on the cell cycle progression, DNA condensation and fragmentation, production of endogenous peroxides and caspase activation. Both doxorubicin and mitoxantrone are potent inducers of apoptosis in H9C2 cardiomyocytes and MTLn3 breast cancer cells, but there are significant differences between the two cell types in terms of kinetics and order of the events. In particular, flow cytometry measurements of drug-induced changes in mitochondrial transmembrane potential and mitochondrial mass with different fluorescent probes suggested that the two drugs induced a progressive increase in mitochondrial mass in the cancer cells but not in the cardiac cells. The hypothesis was validated by means of electron microscopy, which revealed a significant increase in the number of mitochondria in drug-treated MTLn3 but not in H9C2 cells. The mitochondrial proliferation precedes the nuclear apoptosis in doxorubicin-treated MTLn3 cells. The changes in the architecture and number of mitochondria are linked to the drug-induced perturbation of the cell cycle progression and apoptosis. The proliferation of mitochondria could explain the higher toxicity of doxorubicin to cancer cells compared to cardiac cells and this suggests novel therapeutic opportunities to better control the cardiotoxicity of anthracyclines.

Exclusive low-dose-rate brachytherapy in 279 patients with T2N0 mobile tongue carcinoma.

PURPOSE: To evaluate the therapeutic results obtained with (192)Ir low-dose-rate interstitial brachytherapy in T2N0 mobile tongue carcinoma. PATIENTS AND METHODS: Between December 1979 and January 1998, 279 patients with T2N0 mobile tongue carcinoma were treated by exclusive low-dose-rate brachytherapy, with or without neck dissection. (192)Ir brachytherapy was performed according to the "Paris system" with a median total dose of 60 Gy (median dose rate, 0.5 Gy/h). RESULTS: Overall survival was 74.3% and 46.6% at 2 and 5 years. Local control was 79.1% at 2 years and regional control, respectively, 75.9% and 69.5% at 2 and 5 years (Kaplan-Meier method). Systematic dissection revealed 44.6% occult node metastases, and histologic lymph node involvement was identified as the main significant factor for survival. Complication rate was 16.5% (Grade 3, 2.9%). Half of the patients presented previous and/or successive malignant tumor (ear-nose-throat, esophagus, or bronchus). CONCLUSION: Exclusive low-dose-rate brachytherapy is an effective treatment for T2 tongue carcinoma. Regional control and survival are excellent in patients undergoing systematic neck dissection, which is mandatory in our experience because of a high rate of occult lymph node metastases.

Multivariate analysis of risk factors for wound infection in head and neck squamous cell carcinoma surgery with opening of mucosa. Study of 260 surgical procedures.

The goal of this prospective study was to determine risk factors for wound infections (WI) for patients with head and neck cancer who had undergone surgical procedures with opening of upper aerodigestive tract mucosa in multimodal therapeutic approaches. Two hundred and sixty consecutive surgical procedures were studied at Oscar Lambret Cancer Center over a 36-month period. Twenty-five variables were recorded for each patient. Statistical evaluation used chi2 test analysis (categorical data) and Mann-Whitney test (continuous variables). Multivariate analysis was performed with logistic regression model. The overall rate of WI was 45% (117/260). Univariate analysis indicated that five variables were significantly related to the likelihood of WI: male sex (p = 0.03), previous chemotherapy (p = 0.009), duration of previous hospital stay (p = 0.013), hypopharyngeal location (p = 0.003), post-laryngectomy tracheostoma (p < 0.001). Multivariate analysis identified only one major risk factor for WI: post-laryngectomy tracheostoma (Odd Ratio 1.9 [95% CI 1.3-3]; 33% versus 64%; p = 0.001). Despite antibiotic prophylaxis, WI occurrence is high. This study identified one major risk factor, post-laryngectomy tracheostomy. Long-term curative antibiotherapy must be evaluated in cancer head and neck surgery requiring post-laryngectomy tracheostoma.

Prognosis of hypercalcemia in aerodigestive tract cancers: study of 136 recent cases.

Recent data issuing the prognostic impact of hypercalcemia on outcome of aerodigestive tract cancers are spare. To assess the prognosis and the survival of head and neck cancer patients with hypercalcemia, we reviewed 136 recent successive cases, including also oesophageal and lung cancers. Data were collected from a retrospective database (July 2002-January 2004). Hypercalcemia was defined by calcemia level above 2.55 mmol/l. Univariate analysis for prognosis was performed with Mann-Whitney test (continuous variables) and Odd Ratio with 95% confidence interval (categorical variables). The primary locations were : oropharynx and oral cavity (79, 58%), hypopharynx (13, 9.5%), larynx (10, 7.3%), oesophagus (17, 12.5%) and lung (17, 12.5%). There were 23 females and 123 males, with a median age of 53 (18-86). The incidence of bone metastasis was low: 20/136, 14.5%. At cancer diagnosis, 32 hypercalcemia were observed. With a median follow-up of 88 days (2-553), we observed 98 deaths (overall mortality=72%). The median overall survival was 35 days (2-553+). The pejorative prognostic factors were: male gender (OR=2.64 CI 95% 1.07-6.82), age inferior to 50 (OR=2.67 CI 95% 1.23-5.8), presence of distant metastasis (OR=4.45 CI 95% 1.8-11.01), elevation of alkaline phosphatases (OR=7 CI 95% 2.73-17.9) and need of hospitalization for intravenous hydratation (OR=5.11 CI 95% 1.99-13.17). We observed 39 recurrences of hypercalcemia. The predictive factors for recurrence of hypercalcemia were: age superior to 50 (OR=4.61 CI 95% 2.02-10.52), male gender (OR=38.22 CI 95% 12.2-89), calcemia level superior to 2.7 mmol/l (OR=3.08 CI 95% 1.42-6.64) and absence of diphosphonates (bisphosphonates: OR=2.16 CI 95% 1.01-4.63). Despite use of diphosphonates (infusions of pamidronate), hypercalcemia is associated with very poor prognosis. Tumour location and level of calcemia had no prognostic value.

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.

MRI definition of target volumes using fuzzy logic method for three-dimensional conformal radiation therapy.

PURPOSE: Three-dimensional (3D) volume determination is one of the most important problems in conformal radiation therapy. Techniques of volume determination from tomographic medical imaging are usually based on two-dimensional (2D) contour definition with the result dependent on the segmentation method used, as well as on the user's manual procedure. The goal of this work is to describe and evaluate a new method that reduces the inaccuracies generally observed in the 2D contour definition and 3D volume reconstruction process. METHODS AND MATERIALS: This new method has been developed by integrating the fuzziness in the 3D volume definition. It first defines semiautomatically a minimal 2D contour on each slice that definitely contains the volume and a maximal 2D contour that definitely does not contain the volume. The fuzziness region in between is processed using possibility functions in possibility theory. A volume of voxels, including the membership degree to the target volume, is then created on each slice axis, taking into account the slice position and slice profile. A resulting fuzzy volume is obtained after data fusion between multiorientation slices. Different studies have been designed to evaluate and compare this new method of target volume reconstruction and a classical reconstruction method. First, target definition accuracy and robustness were studied on phantom targets. Second, intra- and interobserver variations were studied on radiosurgery clinical cases. RESULTS: The absolute volume errors are less than or equal to 1.5% for phantom volumes calculated by the fuzzy logic method, whereas the values obtained with the classical method are much larger than the actual volumes (absolute volume errors up to 72%). With increasing MRI slice thickness (1 mm to 8 mm), the phantom volumes calculated by the classical method are increasing exponentially with a maximum absolute error up to 300%. In contrast, the absolute volume errors are less than 12% for phantom volumes calculated by the fuzzy logic method. On radiosurgery clinical cases, target volumes defined by the fuzzy logic method are about half of the size of volumes defined by the classical method. Also, intra- and interobserver variations slightly decrease with the fuzzy logic method, resulting in the definition of a better common volume fraction. CONCLUSION: Our fuzzy logic method shows accurate, robust, and reproducible results on phantoms and clinical targets imaged on MRI.

Radiotherapy alone for primary Merkel cell carcinoma.

BACKGROUND: Merkel cell carcinoma is a rare and potentially aggressive cancer of the skin. Cumulative data from small retrospective series have supported treatment by wide excision and adjuvant radiotherapy. However, wide excision may be difficult to perform in patients with tumors of the head and neck or in older populations with comorbidities that may be incompatible with general anesthesia. OBSERVATIONS: Nine patients (group 1) with stage I (without lymph node involvement) Merkel cell carcinoma primary tumors were treated in our center by radiotherapy alone. The rate of recurrence was compared between this group and 17 additional patients (group 2) with stage I Merkel cell carcinoma who received conventional treatment (surgery followed by radiotherapy). RESULTS: The median follow-up was 3.0 years (range, 8 months to 7 years) for group 1 and 4.6 years (range, 5 months to 11 years) for group 2. During this period, we observed 1 relapse and 1 progression of disease in group 2. No statistical difference was found in overall and disease-free survival between the 2 groups of patients. CONCLUSION: This study demonstrates the possibility of treating inoperable Merkel cell carcinoma by radiotherapy alone, with outcomes similar to those of classic treatment.

[A prospective evaluation of antibiotic prophylaxis efficacy for breast cancer surgery following previous chemotherapy]. / Evaluation prospective du bénéfice d'une antibioprophylaxie dans la chirurgie carcinologique mammaire après chimiothérapie.

Use of antibiotic prophylaxis (AP) in clean breast cancer surgery is still controversial. We assessed the efficacy of preoperative AP in a prospective study of 171 clean breast cancer procedures following previous anticancer chemotherapy. From June 1998 to July 2001, we analyzed 171 procedures. In 133 cases. AB with cefuroxime was performed. Wound infection rate was 3 out of 171 procedures (WI rate of 2/131 with AP compared with 1/37 without AP, p = 1.0). This study suggests that AP is not systematically required in breast cancer surgery following previous anticancer chemotherapy.

[Induction chemotherapy and larynx preservation: is such practice useful?]. / Chimiothérapie d'induction et préservation laryngée qu'en est-il en pratique?

BACKGROUND: Surgery followed by irradiation is considered to be the standard treatment but require frequently a total laryngectomy. Chemotherapy followed by irradiation is available in larynx and hypopharynx squamous cell carcinoma (SCC) treatment. Are results obtained in daily induction chemotherapy usefulness identical to results obtained in larynx preservation studies? PATIENTS AND METHOD: We conducted a retrospective study on patients treated at centre Oscar-Lambret, Lille, from 1986 to 1995, by chemotherapy followed by definitive radiotherapy or by surgery and radiotherapy for laryngeal or hypopharyngeal cancer treatment. All patients were naive of previous head and neck SCC and a surgical treatment, requiring total laryngectomy, should be proposed with curative intent. Induction chemotherapy associated cisplatin (100 mg/m2) on day 1 and 5-fluorouracil (5FU)(1,000 mg/m2) on days 1-4 or 1-5. Irradiation was performed for responders (complete or partial > 50%). If case of non-responder, patients underwent surgical treatment followed by irradiation. We compared results obtained with patients enrolled in clinical trial and with patients whom benefited from this protocol out of trial. RESULTS: Hundred-eight patients were evaluable for purposes of this study. Fifty-two patients were included in clinical trial (group 1) while 56 patients (group 2) were not. There was no statistical difference as regard neither to sex nor to node (palpable or not palpable) and metastasis status between the groups. We found a higher frequency of laryngeal tumour in group 2 (31 vs 17; p =.03). We observed more stage III and less stage IV in group 1. For chemotherapy-related toxic reactions, the exclusive statistical difference observed was haematological toxicity grade III and IV after the second cycle (0 pt in group 1 vs 8 pts in group 2; p =.02). After initial treatment, complete response was achieved without statistical difference between the groups (88.2% vs 78%; p =.27). A surgical procedure was performed in 46 cases without difference according to the reference group and functional larynx preservation was 55.8% (29/52) in group 1 and 53.6% (30/56) in group 2. Whatever the group, causes of death were similarly distributed. Cancer was the first cause of death in both groups. The overall survival of the population (108 patients) was 81.5% at one year, 49.6% at 3 years and 35.3% at 5 years with a median survival of 3 years. There was no statistical difference between both groups. Some parameters influenced the overall survival like T (p =.04), response to chemotherapy (p=.006), extra capsular spread (p = 0.03) and response after completion treatment. CONCLUSION: Induction chemotherapy is available for larynx preservation but cannot be considered as a standard treatment. Nevertheless, results should be reproduced in daily practice with experimented teams as found with non included patient's results. The long-term side effects of such protocols should be evaluated. Recent publication, on increase postoperative infection after chemotherapy, should be evaluated in clinical trial. If confirmed, cost effectiveness of such complication must be integrated in larynx preservation protocols. Larynx preservation remains an interesting point of view for patients but stay an optional procedure and not a reference.

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.

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.