Delay in starting radiotherapy due to neoadjuvant therapy does not worsen survival in unresected glioblastoma patients

Purpose

We retrospectively examined the potential effect on overall survival (OS) of delaying radiotherapy to administer neoadjuvant therapy in unresected glioblastoma patients.

Patients and methods

We compared OS in 119 patients receiving neoadjuvant therapy followed by standard treatment (NA group) and 96 patients receiving standard treatment without neoadjuvant therapy (NoNA group). The MaxStat package of R identified the optimal cut-off point for waiting time to radiotherapy.

Results

OS was similar in the NA and NoNA groups. Median waiting time to radiotherapy after surgery was 13 weeks for the NA group and 4.2 weeks for the NoNA group. The longest OS was attained by patients who started radiotherapy after 12 weeks and the shortest by patients who started radiotherapy within 4 weeks (12.3 vs 6.6 months) (P?=?0.05). OS was 6.6 months for patients who started radiotherapy before the optimal cutoff of 6.43 weeks and 19.1 months for those who started after this time (P?=?0.005). Patients who completed radiotherapy had longer OS than those who did not, in all 215 patients and in the NA and NoNA groups (P?=?0.000). In several multivariate analyses, completing radiotherapy was a universally favorable prognostic factor, while neoadjuvant therapy was never identified as a negative prognostic factor.

Conclusion

In our series of unresected patients receiving neoadjuvant treatment, in spite of the delay in starting radiotherapy, OS was not inferior to that of a similar group of patients with no delay in starting radiotherapy.

     

Whole-genome duplication increases tumor cell sensitivity to MPS1 inhibition

Several lines of evidence indicate that whole-genome duplication resulting in tetraploidy facilitates carcinogenesis by providing an intermediate and metastable state more prone to generate oncogenic aneuploidy. Here, we report a novel strategy to preferentially kill tetraploid cells based on the abrogation of the spindle assembly checkpoint (SAC) via the targeting of TTK protein kinase (better known as monopolar spindle 1, MPS1). The pharmacological inhibition as well as the knockdown of MPS1 kills more efficiently tetraploid cells than their diploid counterparts. By using time-lapse videomicroscopy, we show that tetraploid cells do not survive the aborted mitosis due to SAC abrogation upon MPS1 depletion. On the contrary diploid cells are able to survive up to at least two more cell cycles upon the same treatment. This effect might reflect the enhanced difficulty of cells with whole-genome doubling to tolerate a further increase in ploidy and/or an elevated level of chromosome instability in the absence of SAC functions. We further show that MPS1-inhibited tetraploid cells promote mitotic catastrophe executed by the intrinsic pathway of apoptosis, as indicated by the loss of mitochondrial potential, the release of the pro-apoptotic cytochrome c from mitochondria, and the activation of caspases. Altogether, our results suggest that MPS1 inhibition could be used as a therapeutic strategy for targeting tetraploid cancer cells.     

Retransplantation of the liver for recurrent hepatitis B virus infection: the Paul Brousse experience.

Recurrent hepatitis B virus (HBV) infection of the liver graft is characterized by a severe outcome and high level of HBV replication. For many investigators, retransplantation appears contraindicated because of constant recurrence and a high mortality. We report our experience in this setting. Between January 1985 and December 1995, 10 patients who underwent retransplantation for HBV graft reinfection were studied. According to the antiviral treatment administered after HBV recurrence on the first liver graft and the protocol of antiviral prophylaxis after retransplantation, two groups were defined: group 1 underwent retransplantation before January 1992 (n = 5), and group 2 underwent retransplantation after January 1992 (n = 5). At the time of reinfection, serum HBV DNA was positive in all patients, hepatitis Be antigen (HBeAg) was positive in 6 patients. Antiviral therapy was administered to 7 patients (group 1, adenine arabinoside mono phosphate [ara-Amp; n = 3]; group 2, ara-Amp [n = 5], ganciclovir [n = 4]). After retransplantation, long-term antibody to HB surface antigen (anti-HBs) immunoglobulins were administered to achieve an anti-HBs titer greater than 100 IU/L in group 1 and to achieve an anti-HBs titer greater than 500 IU/L associated with prophylactic intravenous ganciclovir administration (5 mg/kg three times weekly) for 2 years in group 2. In group 1, all patients died, either perioperatively or secondary to HBV recurrence (1 year survival, 0%). In group 2, 1 patient died 50 months after retransplantation of HBV cirrhosis on the second graft, and 4 patients remained HBsAg negative at a mean of 41 months (range, 24 to 68 months) after retransplantation. The prognosis of retransplantation for HBV recurrence was dramatically improved by the administration of antiviral therapy before retransplantation and the maintenance of a high anti-HBs level combined with antiviral therapy after retransplantation.     

SEOM guideline for the treatment of malignant glioma

High-grade gliomas are an infrequent disease diagnosed usually in the fifth or sixth decade. Careful histopathological diagnosis is essential because tumour grade and type condition the treatment. Magnetic resonance with gadolinium is considered the standard radiologic exploration and should be followed by tissue sampling. Treatment of these patients should be decided in a multidisciplinary committee. Surgery, radiotherapy and chemotherapy are the basis of patients' treatment, with the best results obtained when the three of them can be used.     

Traitements antifongiques des candidémies chez les patients non neutropéniques : évaluation des pratiques en réanimation

Objective

The authors had for objective to assess systemic antifungal treatment for candidemia in non-neutropenic patients, in intensive care units (ICU), and compare the results with French 2004 recommendations.

Study design

A retrospective multicenter study (nine ICU in two teaching hospitals) was made.

Patients and method

Thirty-eight non-neutropenic patients with at least one positive blood culture for Candida who had received systemic antifungal treatment were included between May 2004 and September 2007.

Results

Thirty-nine cases of candidemia were analyzed. The median age was 54.5 (21–80), the median SAPS II score at admission was 44 (20–79), the median duration of stay in ICU was 22.5 days (2–82), and the death rate was 45%. Candida albicans was identified in 69% of the cases. Eight percent of Candida sp. isolates were resistant or susceptible dose-dependent (S-DD) to fluconazole. Before identification, fluconazole, caspofungin, voriconazole, and amphotericin B were used in 74%, 15%, 5%, and 5% of cases respectively. After identification and antifungal susceptibility determination, fluconazole was used in 68% of cases, caspofungin in 24% of cases, any formulation of amphotericin B in 6% of cases, voriconazole in 3% of cases. The French recommendations were applied in 71% of cases before identification and in 68% of cases after identification and antifungal susceptibility determination.

Conclusion

The main causes of non-compliance to recommendations were the use of fluconazole in patients previously exposed to azole agents, the use of caspofungin in hemodynamically unstable patients, and the absence of therapeutic desescalade.     

Ocular bartonellosis in an HIV-HVC coinfected patient

Bartonella henselae is the etiologic agent of the cat scratch disease and in immunocompromised patients, of bacillary angiomatosis and peliosis hepatis. Less often, ocular complications associated with B. henselae infection have been reported in immunocompetent patients and five times in HIV-infected patients. We report the case of a 42-year-old woman, coinfected by HIV-HCV, presenting with cirrhosis, who owned a cat and was hospitalized for bilateral loss of visual acuity. Ophthalmologic examination revealed bilateral papillitis with hyalitis. Nuclear magnetic resonance revealed a retrobulbar neuritis. Confirmation was given by blood tests positive for B. henselae and the exclusion of other causes of neuroretinitis with biological data. Doxycycline cured the disease rapidly.