Acute neurovascular events in cancer patients receiving anti-vascular endothelial growth factor agents: Clinical experience in Paris University Hospitals.

BACKGROUND: Despite the increasing and broadening use of agents targeting the vascular endothelial growth factor (VEGF) pathway, little is known on their acute neurovascular toxicities. METHODS: This retrospective, multi-centre study examined the characteristics of patients with solid tumours who experienced an ischaemic or haemorrhagic stroke, a transient ischaemic accident (TIA) or a posterior reversible encephalopathy syndrome (PRES) while under anti-VEGF and until 8 weeks after termination of treatment and evaluated their management in our institutions from 2004 to 2014. Patients with newly diagnosed or progressive cerebral metastases at the time of the acute neurovascular event were excluded. RESULTS: Thirty-four patients (55.9% men) were identified, and experienced either ischaemic stroke (n = 18), PRES (n = 9), TIA (n = 6) or haemorrhagic stroke (n = 1). At initiation of anti-VEGF agents, 64.7% of patients had previous cardiovascular risk factors, and 52.9% had hypertension. Eight patients (23.5%) had received cerebral radiotherapy, five of which concomitantly to anti-VEGF treatment. Six (17%) patients died in the 8 weeks following the acute neurovascular event, and only 55.9% recovered their initial neurological status. Overall, 1-year and 2-year survival rates after the acute neurovascular event were 67.9% and 50%, respectively. When anti-VEGF agents were reintroduced (n = 6), severe vascular toxicity recurred in two patients. CONCLUSIONS: Neurovascular events under VEGF treatments are potentially severe, and the management of comorbid conditions has to be improved. A prospective collection of data and standardised management of such events is therefore being structured in our institutions.

[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.

Quick, non-invasive and quantitative assessment of small fiber neuropathy in patients receiving chemotherapy.

Chemotherapy-induced peripheral neurotoxicity (CIPN) is a common, potentially severe and dose-limiting adverse effect; however, it is poorly investigated at an early stage due to the lack of a simple assessment tool. As sweat glands are innervated by small autonomic C-fibers, sudomotor function testing has been suggested for early screening of peripheral neuropathy. This study aimed to evaluate Sudoscan, a non-invasive and quantitative method to assess sudomotor function, in the detection and follow-up of CIPN. Eighty-eight patients receiving at least two infusions of Oxaliplatin only (45.4%), Paclitaxel only (14.8%), another drug only (28.4%) or two drugs (11.4%) were enrolled in the study. At each chemotherapy infusion the accumulated dose of chemotherapy was calculated and the Total Neuropathy Score clinical version (TNSc) was carried out. Small fiber neuropathy was assessed using Sudoscan (a 3-min test). The device measures the Electrochemical Skin Conductance (ESC) of the hands and feet expressed in microSiemens (µS). For patients receiving Oxaliplatin mean hands ESC changed from 73 ± 2 to 63 ± 2 and feet ESC from 77 ± 2 to 66 ± 3 µS (p < 0.001) while TNSc changed from 2.9 ± 0.5 to 4.3 ± 0.4. Similar results were observed in patients receiving Paclitaxel or another neurotoxic chemotherapy. During the follow-up, ESC values of both hands and feet with a corresponding TNSc < 2 were 70 ± 2 and 73 ± 2 µS respectively while they were 59 ± 1.4 and 64 ± 1.5 µS with a corresponding TNSc ≥ 6 (p < 0.0001 and p = 0.0003 respectively). This preliminary study suggests that small fiber neuropathy could be screened and followed using Sudoscan in patients receiving chemotherapy.

Safety of spinal radiotherapy in metastatic cancer patients receiving bevacizumab therapy: a bi-institutional case series.

We retrospectively assessed the outcome of patients receiving emergency spinal radiation therapy (RT) concurrently with bevacizumab. Clinical records of 18 consecutive patients receiving emergency spinal RT for symptomatic vertebral metastases during the course of bevacizumab-based therapy were examined. Patients were receiving biweekly bevacizumab combined with paclitaxel (n=17) or with docetaxel/carboplatin (n=1) or as a single agent (n=1) for advanced metastatic carcinoma. RT was delivered at doses of 30 Gy in 10 fractions (n=8), 20 Gy in five fractions (n=9) or 18 Gy in nine fractions (n=1). In 10 patients (56%), irradiation field encompassed the thoracic vertebrae. The median time interval between the bevacizumab infusion and the RT course was 1.5 days (0-8 days). The median follow-up was 8.3 months (2 days-42 months). A clinical benefit of RT was reported in 13 patients (72%), including four patients with complete pain relief. Two of the three patients with neurological impairment at the time of RT experienced a partial improvement in their symptoms. No pain recrudescence was reported within the irradiated field after RT completion. All toxicities were mild to moderate, with no acute toxicity reported in 13 patients (72%). No RT disruption was necessary because of acute toxicity. No delayed toxicity was reported within RT fields among 11 patients with at least 6 months of follow-up. Spinal RT during the course of bevacizumab-based therapy was not associated with the occurrence of unexpected adverse effects. This suggests that emergency RT should not be contraindicated in these patients, provided that doses and treatment volumes are defined carefully.

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.

Effectiveness and safe use of modified FOLFOX-6 for metastatic gastric cancer with signet ring cell components complicated by disseminated intravascular coagulation and diffuse bone marrow carcinomatosis.

We report the case of a 62-year-old woman with a metastatic gastric cancer complicated by diffuse bone marrow carcinomatosis, disseminated intravascular coagulation (DIC) and microangiopathic hemolytic anemia (MHA) treated by modified FOLFOX-6 as front-line chemotherapy regimen. This chemotherapy showed clinical, morphological and biological efficiency and safety in this rare and severe hematological complication at initial diagnosis. Furthermore, this is the first case of diffuse bone carcinomatosis from a gastric cancer to be monitored by positron emission tomography integrated computed tomography (PET-CT) scan using 18-fluorodeoxyglucose (18-FDG).

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.

Pancreatic metastasis from prostate cancer.

The pancreas is an unusual location for metastases from other primary cancers. Rarely, pancreatic metastases from kidney or colorectal cancers have been reported. However, a variety of other cancers may also spread to the pancreas. We report an exceptional case of pancreatic metastasis from prostate cancer. Differences in management between primary and secondary pancreatic tumors make recognition of metastases to the pancreas an objective of first importance. Knowledge of unusual locations for metastatic spread will reduce diagnostic delay and lead to a timely delivery of an appropriate treatment.

Reapprasial of the role of endocrine therapy in meningioma management.

Recurrent meningiomas constitute an uncommon but significant problem after standard therapy failure. Speculation that meningiomas may be subject to endocrine influence was supported by both immunohistochemical analyses and epidemiological data. Therefore, alternative strategies such as endocrine therapy have been suggested. Although evidence of consistent findings for the role of specific hormonal exposures is mounting, there are numerous discrepancies about the mitogenic effect of hormonal manipulation on meningioma cells. A better understanding of the molecular mechanisms involved in meningioma pathogenesis may not only lead to the identification of novel diagnostic and prognostic markers but may also facilitate the development of new pathogenesis-based targeted strategies. This review of literature aims to summarize the present state of the art of endocrine therapy in the management of meningiomas, in order to establish whether hormonotherapy could be included in the therapeutic strategy for unresectable and/or progressive tumours in previously irradiated meningioma patients.

[Craniopharyngiomas: role of radiotherapy]. / Craniopharyngiomes: place de la radiothérapie.

Craniopharyngiomas are benign tumors of the parasellar region, characterised by high relapsing rate. Aggressive attempt at total removal does result in prolonged progression-free survival in most patients. But for tumors that clearly involve the hypothalamus, complications associated with radical surgery have prompted to adopt a combined strategy of conservative surgery and radiation therapy to residual tumor with an as high rate of cure. This strategy seems to offer the best long-term control rates with acceptable morbidity. But optimal management of craniopharyngiomas remains controversial. Although it is generally recommended that radiotherapy is given following sub-total excision of a craniopharyngioma, it remains unclear as to whether all patients with residual tumour should receive immediate or differed at relapse radiotherapy.

[Testicular metastasis of prostatic adenocarcinoma: a case report]. / Métastase testiculaire d'un adénocarcinome prostatique: à propos d'un cas.

Metastasis of prostate adenocarcinoma to testis is an extremely rare occurrence. Orchiectomy is necessary to confirm histopathological diagnosis. Metastatic carcinoma of the prostate to the testis is a commonly accepted as a sign of disseminated disease. Systemic treatment are therefore required. We report a case of a 62-year-old patient who presented a prostatic carcinoma with a testicular metastasis.