Quality of life in cancer patients undergoing anticoagulant treatment with LMWH for venous thromboembolism: the QUAVITEC study on behalf of the Groupe Francophone Thrombose et Cancer (GFTC).

BACKGROUND: Clinical guidelines recommend at least 3-months low molecular weight heparin (LMWH) treatment for established venous thromboembolism (VTE) in cancer patients. However, no study has analyzed the impact of 3-6 months of LMWH therapy on quality-of-life (QoL) in cancer patients. RESULTS: Among 400 cancer patients included at M0, 88.8% received long-term LMWH. Using a random-effects linear regression model with time as covariate, QoL scores in the MOS SF-36 (Global HRQoL, 1.3-fold per month [95% confidence interval (CI) 0.81-1.79], p < 0.0001) and EORTC QLQ-C30 (global health status/qol, 2.25-fold per month [95% CI 1.63-2.88]; p < 0.0001) questionnaires significantly improved over the 6-month study period in patients treated with LMWH, while VEINES-QOL scores did not change. In the MOS SF-36 and EORTC QLQ-C30, the following factors were associated with change in QoL: symptomatic VTE, cancer dissemination and histological type. Factors pertaining to reduced mobility were also identified as significant predictors of QoL outcomes, including being bedridden in the MOS SF-36 and ECOG score ≥ 2 in the EORTC QLQ-C30. Presence of acute infection and not undergoing anti-angiogenic therapy were additional factors associated with QoL improvement in the EORTC QLQ-C30. METHODS: QUAVITEC, a prospective, longitudinal, multicenter study, recruited all consecutive eligible adult cancer patients with objectively confirmed VTE between February 2011 and 2012. Patients were asked to answer three QoL questionnaires at anticoagulant treatment initiation (M0) and at 3 (M3) and 6 (M6)-month follow-ups. CONCLUSION: QUAVITEC is the first study to show that QoL was improved in cancer patients receiving long-term LMWH treatment for established VTE.

Safety and efficacy of temsirolimus as second line treatment for patients with recurrent bladder cancer.

BACKGROUND: Bladder cancer is the 7th cause of death from cancer in men and 10th in women. Metastatic patients have a poor prognosis with a median overall survival of 14 months. Until recently, vinflunine was the only second-line chemotherapy available for patients who relapse. Deregulation of the PI3K/AKT/mTOR pathway was observed in more than 40% of bladder tumors and suggested the use of mTOR as a target for the treatment of urothelial cancers. METHODS: This trial assessed the efficacy of temsirolimus in a homogenous cohort of patients with recurrent or metastatic bladder cancer following first-line chemotherapy. Efficacy was measured in terms of non-progression at two months according to the RECIST v1.1 criteria. Based on a two-stage optimal Simon's design, 15 non-progressions out of 51 evaluable patients were required to claim efficacy. Patients were treated at a weekly dose of 25 mg IV until progression, unacceptable toxicities or withdrawal. RESULTS: Among the 54 patients enrolled in the study between November 2009 and July 2014, 45 were assessable for the primary efficacy endpoint. A total of 22 (48.9%) non-progressions were observed at 2 months with 3 partial responses and 19 stable diseases. Remarkably, 4 patients were treated for more than 30 weeks. Fifty patients experienced at least a related grade1/2 (94%) and twenty-eight patients (52.8%) a related grade 3/4 adverse event. Eleven patients had to stop treatment for toxicity. This led to recruitment being halted by an independent data monitoring committee with regard to the risk-benefit balance and the fact that the primary objective was already met. CONCLUSIONS: While the positivity of this trial indicates a potential benefit of temsirolimus for a subset of bladder cancer patients who are refractory to first line platinum-based chemotherapy, the risk of adverse events associated with the use of this mTOR inhibitor would need to be considered when such an option is envisaged in this frail population of patients. It also remains to identify patients who will benefit the most from this targeted therapy. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01827943 (trial registration date: October 29, 2012); Retrospectively registered.

[Prognosis prediction of febrile neutropenia by MASCC score: A retrospective study]. / Prédiction de la gravité des neutropénies fébriles par le score de MASCC : une étude de cohorte rétrospective.

INTRODUCTION: The score of the MASCC, by means of clinical criteria, estimates the risk of serious complications in patients with neutropenic fever induced by chemotherapy. METHODS: We retrospectively studied a cohort of patients hospitalized for a neutropenic fever and analyzed complications according to the criteria defined by the MASCC. RESULTS: Eighty-one neutropenic fevers in 71 patients were identified. Microbiological documentation was obtained in 33% of cases only. Fifty-eight patients (72%) presented with a MASCC score≥21 and were considered as low risk of complications. In the total population, 10 patients died during their hospitalizations for neutropenic fever, 7 in the high-risk group versus 3 in the low risk group, including 2 patients suffering from significant comorbidities not taken into account by MASCC score. Within the low risk group, presence of a metastatic disease and existence of 2 or more comorbidities were associated with a longer duration of hospitalization. CONCLUSION: This analysis suggests that the criteria of the MASCC are not always enough to thoroughly identify which patients were at risk of complications or could be treated through outpatient management. By better taking into account the comorbidities and tumoral stage, a better selection of the patients who are likely to receive an ambulatory treatment could be made. To date, hospitalization remains frequently necessary in neutropenic fevers, at least in its initial steps, and the place of the general practitioner remains to be better defined.

Chemotherapy Regimen in Nonagenarian Cancer Patients: A Bi-Institutional Experience.

BACKGROUND: The elderly population in Western countries is growing and constitutes a public health issue. Concomitantly, age-related diseases such as cancer increase. There are few data on the efficacy, tolerability and toxicity of specific anticancer therapy in the very elderly patients; therefore, their management is not standardized. METHODS: In this bi-institutional study, we reviewed medical records of patients who received or continued specific anticancer therapy beyond the age of 90 years. Geriatric assessment was not reported for our patients. Twelve patients were enrolled. Their general health condition was good, and half of them were living in elderly institutions. Ten patients had a solid tumor and 2 were treated for hematological malignancies. Most were diagnosed with a locally advanced or metastatic disease, and the goal of treatment was curative for only 1 patient. Six patients received chemotherapy as first-line treatment, 4 patients received targeted therapy and 2 received concomitant chemoradiation. Four patients received a second-line treatment. RESULTS: Despite a significant reduction in treatment posology in half of the patients, 8 acute grade 3/4 toxicities were reported and 2 patients died of treatment-related septic shock. Median duration of first-line treatment was 3.2 months, and progression-free survival ranged from 18 to 311 days. Overall survival ranged from 18 days to 11 years. CONCLUSION: Aging is a heterogeneous process, and management of elderly patients is a multidisciplinary approach. Geriatric assessment helps to identify older patients with a higher risk of morbidity/mortality and allows to assess the risks and benefits of specific anticancer therapy. The choice of treatment should be based primarily on the expected symptomatic benefit, and treatment should not compromise the quality of life.

[Role of general practitioners in cancer screening: A survey in the French armed forces]. / Place du médecin militaire dans le dépistage du cancer : évaluation des pratiques professionnelles.

INTRODUCTION: The French Military Health Service organizes medical survey of 340,000 military men. The aim of the present study was to evaluate the practices of solid cancer screening of general practitioners in military medical units and to compare the results with the recommendations of the French National Institute of Cancer. METHODS: We conducted a prospective, observational study among general practitioners in Army Medical Unit by sending them a self-assessment questionnaire. Physicians should report on their practices for screening cancers with official screening recommendations. Compliance rates with the recommendations were reviewed. Screening practices for other cancers (prostate cancer, melanoma, thyroid cancer, lung cancer, testicular cancer) were assessed. RESULTS: A total of 133 questionnaires were analyzed. Despite a strong involvement of army general health practitioners, guidelines adherence rates (examination frequency, ages of screening beginning and ending) were of 4% for cervical cancer, 7% for breast cancer, and 37% for colorectal cancer. Those rates are comparable to those reported with civilian general practitioners. For cancers without screening recommendation, practitioners felt highly concerned, especially for the most common cancers among the military population. One third of physicians stated that they had diagnosed a testicular cancer through routine screening. CONCLUSION: Military general health practitioners feel themselves concerned by solid cancer screening, and more particularly for cancers that are the most prevalent in young adults. However, current guidelines are neither known nor applied in routine.

Clinical benefits of non-taxane chemotherapies in unselected patients with symptomatic metastatic castration-resistant prostate cancer after docetaxel: the GETUG-P02 study.

OBJECTIVE: To evaluate the overall benefits of non-taxane chemotherapies in a non-selected population including unfit patients presenting with symptoms and pain. PATIENTS AND METHODS: This randomized phase II study reports data from 92 patients (52% >70 years old; 40% with a performance score of 2) previously treated with taxane-based chemotherapy, collected from 15 centres in France. Patients received i.v. mitoxantrone (MTX), oral vinorelbine, or oral etoposide, together with oral prednisone. Palliative benefit (pain response without progression of the disease), biological and tumoural responses, and toxicity profile as well as geriatric assessment (in elderly population) were analysed on an intention-to-treat basis. RESULTS: The palliative response rate was 17% for the whole population, and reached 29% when considering the MTX arm. Pain control was achieved in 40% of the patients. The median overall survival was 10.4 months, and was longer in palliative responders. Few grade 3-4 toxicities were observed. The subgroup analysis of elderly patients showed similar results regarding the number and dose intensity of treatments, efficacy and safety. CONCLUSION: In a population including frail and/or elderly patients, who are poorly represented in most clinical studies, non-taxane chemotherapy may remain a relevant option for metastatic prostate cancer having relapsed after a docetaxel-based regimen. Although new treatment options are now approved, the decision-making process should take into account their expected benefit/risk ratio based on the patient status.

[Towards an integrated approach to cardiovascular toxicities related to the treatments of breast cancer]. / Vers une approche intégrée des toxicités cardiovasculaires liées aux traitements du cancer du sein.

There is an increasing number of therapeutic options in breast cancer management. While prognosis improves, the cardiac toxicity related to treatments remains a significant issue. This toxicity has several clinical presentations and can be explained by complex and diverse molecular mechanisms. Systemic treatments (anthracyclines, inhibitors of HER2 signaling pathway, hormone therapy, antiangiogenic agents) and radiotherapy have their own cardiac toxicity. However, the toxicities associated with these treatments may potentiate together and the existence of pre-existing cardiovascular risk factors should be taken into account. The assessment of cardiac hazard evolves toward a multifactorial approach. Several possibilities exist to minimize the incidence of cardiac complications. Those include pharmacological and technological innovations, but also a more accurate selection of patients and a growing involvement of practitioners in the field of cardiac toxicity, which is prerequisite for an early management of cardiac events.

Feasibility of radiation therapy in patients 90years of age and older: a French multicentre analysis.

BACKGROUND: There are only scarce data on the management of patients aged 90years or older with cancer, and more particularly on the place of radiation therapy (RT). We report the first large study on patients (pts) aged 90years or older receiving RT. METHODS AND MATERIALS: Records from RT departments from five institutions were reviewed to identify pts 90years of age and older who underwent RT for various malignant tumours treated between 2003 and 2012. Tumours' characteristics were examined, as well as treatment specificities and treatment intent. RESULTS: 308 pts receiving 318 RT courses were identified, mean age was 93.2years (standard deviation 2.8). Treatment was given with curative and palliative intent in 44% and 56%, respectively. Factors associated with a curative treatment were performance status (PS), place of life, previous surgery and tumour stage. Median total prescribed dose was 36Gy (4-76Gy). Hypofractionation and split course were used in 88% and 7.3%, respectively. Most toxicities were mild to moderate. RT could not be completed in 23 pts (7.5%). No long-term toxicity was reported. Median overall survival was 22.9months (95CI: 15.5-42.7months). Cancer was the cause of death in 8.7% and 46% of pts treated with curative and palliative intent, respectively. CONCLUSION: This study shows that RT is feasible for patients aged 90years or more. PS, place of life and tumour stage were factors of the therapeutic decision. There is no reason to withdraw pts with good general health condition from potentially curative RT, provided that careful attention is paid to factors of toxicity and to geriatric vulnerabilities.

Combination of paclitaxel and bevacizumab in heavily pre-treated non-small-cell lung cancer (NSCLC) patients: a case series study on 15 patients.

BACKGROUND: The combination of paclitaxel and bevacizumab was EMA-approved as first-line therapy in metastatic breast cancer. Moreover, in vitro studies showed a potential antiangiogenic synergistic effect of paclitaxel and bevacizumab. METHODS: Between November 2008 and March 2010, this case series study included 15 patients with metastatic non squamous-cell lung carcinoma (NSCLC). Those were bevacizumab eligible and received the same regimen used in metastatic breast cancer with weekly paclitaxel (80 mg/m(2), days 1, 8 and 15) and bevacizumab (10 mg/kg at days 1 and 15) after at least one prior line of chemotherapy. Efficacy was evaluated by CT-scan and PET-FDG every two months. Circulating endothelial progenitor cells (CEP) and circulating endothelial cells (CEC) levels were explored in a subset of patients. RESULTS: Median age 56 (36-75), female: 47%, never smokers: 27%, adenocarcinoma: 100%, PS 0-1: 87% and PS 3: 13%. All patients were treated with a first-line platinum-based doublet with or without bevacizumab and 70% of them with erlotinib in the second-line. No major toxicity was observed. Partial response (PR) rate was 44% (31-63%) using RECIST criteria on CT-scan, and 65% (29-88%) with PET FDG. PS improved in 33% of the cases. Median progression free survival was 4.6 months. An increase of CEC and CEP was observed in patients with NSCLC treated with paclitaxel and bevacizumab. CONCLUSION: In this retrospective series, our results suggest efficacy signal in pre-treated metastatic NSCLC and warrant further assessment in a randomized clinical trial.

First assessment of whole-brain radiation therapy combined with pemetrexed-based chemotherapy in non-small-cell lung carcinoma: data on safety and efficacy.

The folate antimetabolite pemetrexed was approved for the treatment of patients with metastatic nonsquamous non-small-cell lung carcinoma. Its activity on brain metastases makes pemetrexed attractive in combination with whole-brain radiation therapy (WBRT), but it could also potentially increase toxicity. We examined the medical records of 43 consecutive patients with brain metastases from non-small-cell lung carcinoma. Patients received pemetrexed-based chemotherapy at a dose of 500 mg/m. The median total number of pemetrexed-based chemotherapy cycles was 4 (range: 1-28). During the course of chemotherapy, patients received WBRT delivering 30 Gy in 10 fractions (n=34) or 20 Gy in five fractions (n=9). The median follow-up time was 30.5 weeks (range: 1-79 weeks). Intracranial progression was a cause of death in nine patients (20.9%). Clinical benefit of WBRT was reported in 30 patients (69.8%). The best radiological response was a complete response in eight patients (18.6%), a partial response in 16 patients (37.2%), stable disease in 11 patients (25.6%), and progression in four patients (9.3%). A stable intracranial disease until the last follow-up was observed in 26 patients (60.5%). The median estimated overall survival was 31 weeks (95% CI: 24-37 weeks). Most WBRT-related toxicities were low and 21 patients (48.9%) had no reported acute neurological toxicity. One patient developed unexplained encephalopathy 5 weeks after WBRT completion in the context of progressive diffuse brain metastases. The combination of pemetrexed with WBRT led to considerable clinical improvement and tumor responses in most patients. Overall neurological toxicity was rather low. A clinical trial is essential for better analysis of the potential synergistic effects of a drug with radiation and evaluation of neurological toxicity.

[Cancer stem cells, cornerstone of radioresistance and perspectives for radiosensitization: glioblastoma as an example]. / Facteurs de radiorésistance des cellules souches cancéreuses et perspectives de radiosensibilisation : l'exemple du glioblastome.

Cancer stem cells are a subject of increasing interest in oncology. In particular, several data suggest that cancer stem cells are involved in the mechanisms of tumor radioresistance, and may explain the therapeutic failures after radiotherapy. Because of its poor prognosis and high recurrence rate after irradiation, glioblastoma model is often studied in the search for new radiosensitizers. There are several preclinical data suggesting that cancer stem cells could be a potential therapeutic target for improving the biological effectiveness of radiation therapy. Through the example of glioblastoma, we review the main signaling pathways involved in the mechanisms of radiation resistance of cancer stem cells and for which pharmacological targeting could potentially enhance tumor radiosensitivity.

Primary intracranial extraskeletal myxoid chondrosarcoma.

Extraskeletal myxoid chondrosarcomas (EMC) are extremely rare and are usually located in the deep soft tissues of the lower extremities. Less than 10 cases of intracranial EMC have been reported in the literature, making their management and early diagnosis difficult. We present a new case of intracranial EMC occurring in a 70-year-old woman presenting with a right frontal mass initially assumed to be a brain metastasis from breast adenocarcinoma. The optimal management of these tumours is also discussed. Analysis from the literature suggests that complete resection should be recommended, whenever feasible. Although the high risk for relapse after surgery encourages postoperative treatments, relative resistance to both radio-therapy and chemotherapy characterizes EMC. Future perspectives might include multimodal treatments with highly conformal radiotherapy modalities for dose escalation strategies or use of new molecules. Knowledge of these unusual malignant tumours will be the first step for improving patients' outcome.

Knowledge and screening of testicular cancer in the French Armed Forces: a prospective study.

We performed a prospective study in the French Armed Forces regarding testicular cancer. Our primary objective was to assess whether willingness to have a testicular examination by medical doctor could be improved by a self-administered questionnaire through invitation to self-reflection. A total of 415 soldiers were enrolled. The study used a test-posttest design in that soldiers estimated their willingness to have a testicular palpation before and after responding to a self-administered questionnaire. The willingness to have testicular palpation significantly increased after responding to the questionnaire (p < 0.000001). Acceptance of testicular palpation after responding the questionnaire did not change in 82.25%, increased in 15%, and decreased in 2.75%. Analysis of responses to the questionnaire showed that 26.75% of soldiers (n = 107) had previously received general information on testicular cancer and 85.8% (n = 343) declared that they would be delighted if they were proposed a short educational course on testicular cancer. As a conclusion, this study demonstrates that the willingness to have a testicular examination by medical doctor could be easily improved, since there is a strong demand on medical education regarding testicular cancer.

External beam radiotherapy in the management of spinal metastases: review of current strategies and perspectives for highly conformal irradiation modalities.

Bone metastases are frequent in advanced metastatic solid tumors. These secondary lesions are responsible for significant impairment of quality of life of patients with onset of pain, which is frequently resistant to standard analgesics. The therapeutic challenge for a patient with spinal metastasis is to maintain a quality of life as good as possible, commensurate with its life expectancy. Radiotherapy can provide efficient pain relief, but it should be integrated into a multidisciplinary approach. In the case of epidural spinal cord compression, it should be performed whenever possible after surgery. New highly conformal irradiation modalities have emerged for treatment of spinal metastases with therapeutic perspectives. Stereotactic radiosurgery could be provided for patients with single lesions or oligometastatic disease, a good general condition, absence of cord compression, and a life expectancy greater than 6 months. It is particularly promising for the treatment of classically radioresistant tumors or relapsing disease. Intensity-modulated radiotherapy, including Helical Tomotherapy, is a new perspective for treatment of multiple metastases. However, if these new techniques can provide efficient pain sedation, hindsight is currently low to judge their therapeutic benefit and these techniques are hardly available in most centers. Here, we offer a quick review of current strategies and new modalities of radiotherapy to put into perspective the place of these techniques in therapy of spinal metastases.

Prostate needle biopsy examination by means of virtual microscopy.

This study aimed at determining whether virtual microscopy improves the accuracy in the pathological examination of prostate needle biopsies regarding maximum tumor length, percentage of positive cores, and Gleason grading. We assessed a series of 816 prostate needle biopsy cores in 68 consecutive patients with prostate adenocarcinoma. Biopsy specimens were reviewed using conventional examination. Then, slides were converted to whole slide imaging (Olympus BX51). Tumor was measured, and Gleason score was assigned using the OlyVia software. Optically evaluated pathological features were compared with digital findings to determine whether one of these two methods for the assignment of a preoperative Gleason score is appropriate for predicting the definitive Gleason score of radical prostatectomy. When comparing optical and digital measurements, maximum tumor length in biopsy cores and percent prostate needle biopsy with cancer showed no significant difference. The mean variation in the measurement of tumor length was 2.65mm per biopsy. Among 240 biopsy cores involved with cancer, the concordance rate for Gleason score assignment was 75.8% (κ=0.49, good agreement). When considering the higher Gleason score assignment as the score for the entire case (ISUP 2005), the concordance rate was 69.1% (κ=0.46, good agreement). When comparing the biopsy scores with the definitive score of radical prostatectomy, the concordance rate was significantly increased from 54.4% for conventional examination (κ=0.23, marginal agreement) to 66.2% for virtual slide examination (κ=0.42, good agreement). Virtual microscopy does not compromise, but might improve, the accuracy of grading in prostate needle biopsies. This requires further assessment.