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International audience; BACKGROUND: Risk factors for breast cancer relapse are well-known, such as large tumour size or lymph node involvement. The aim of our study was to analyse the influence of bone mineral density, fractures and bisphosphonate or vitamin D prescription on 10 years' breast cancer outcome.PATIENTS AND METHODS: This is a longitudinal and prospective cohort of 450 postmenopausal women with local oestrogen receptor (ER)+ breast cancer. For every patient, we analysed tumour characteristics, bone status at the beginning of aromatase inhibitor treatment and 10 years' cancer outcome with Cox model.RESULTS: Mean follow-up was 10.3±3.0 years. Seventy nine women died, and 75 had a relapse; 30.7% had a history of fracture, 16.9% had a T-score≤-2.5and 11.3% had vitamin D deficiency. Bisphosphonates were prescribed to 35.3% women for osteoporosis for a mean duration of 5±1.7 years. Tumour size (hazard ratio [HR]=1.32, P≤0.01) and the number of lymph nodes involved (HR=1.07, P=0.03) were significantly associated with relapse. Bisphosphonate treatment was significantly associated with a decreased risk of relapse (HR=0.51, P=0.03). Age at cancer diagnosis (HR=1.07, P≤0.01) and vitamin D deficiency (HR=1.85, P=0.04) were significantly associated with an increased risk of death, whereas bisphosphonate treatment was associated with a decreased risk of death (HR=0.46, P=0.01).CONCLUSION: Osteoporosis treatment, including vitamin D and bisphosphonates, is associated with a 50% reduction of relapse and death in women treated with aromatase inhibitors for ER+ breast cancer.

The management of corticosteroids refractory chronic graft versus host disease (cGVHD) remains controversial. Retrospective analysis of patients treated at the Integrated Center of Oncology by total nodal irradiation (TNI) was performed to evaluate its therapy potency. TNI delivers a dose of 1 Gy in a single session. The delimitation of the fields is clinical (upper limit: external auditory meatus; lower limit: mid-femur). No pre-therapeutic dosimetry scanner was necessary. Evaluation of the efficacy was by clinical measures at 6 months after the treatment. Twelve patients were treated by TNI between January 2010 and December 2013. TNI was used in second-line treatment or beyond. The median time between allograft and TNI was 31.2 months, and the median time between the first manifestations of cGVHD and TNI was about 24.2 months. Of the 12 patients, nine had a clinical response at 6 months (75%), including five complete clinical responses (41.6%). Five patients could benefit from a reduction of corticosteroid doses. Three patients had hematologic toxicity. TNI could be considered as an option for the treatment of a cutaneous and/or soft tissues corticosteroids refractory cGVHD. However, prospective randomized and double-blind trials remain essential to answer the questions about TNI safety and effectiveness.

Purpose To determine event free and overall survival, and long-term cognitive sequelae of children with standard-risk medulloblastoma (SRM) treated with hyperfractionated radiotherapy, conformal reduced boost volume without chemotherapy, and online quality assurance. Patients and Methods Forty-eight patients (age 5 to 18 years) were included in the Medulloblastoma-Société Française d'Oncologie Pédiatrique (MSFOP 98) protocol (December 1998 to October 2001). Patients received hyperfractionated radiotherapy (HFRT; 36 Gy, 1 Gy/fraction twice per day) to the craniospinal axis followed by a boost to the tumor bed (1.5-cm margin) to a dose of 68 Gy. Records of craniospinal irradiation were reviewed before treatment started. Neuropsychologic evaluations were done according to the protocol (1, 3, 5, and 7 years after irradiation). Cognitive outcomes were followed longitudinally with full-scale intelligence quotient (FSIQ) obtained with age-adapted Wechsler scales. Results After a median follow-up of 77.7 months, 6-year overall survival (OS) and event-free survival (EFS) rates for the cohort were 78% (95% CI, 66% to 90%) and 75%, respectively (95% CI, 62% to 87%). Thanks to quality control, 14 major deviations were detected. Annual full scale IQ decline was 2 points over a 6-year period. Predicted change in FSIQ points per year was 2.15 (95% CI, −1.24 to 3.51) with an intercept (ie, predicted FSIQ) of 93.57 at baseline. Conclusion HFRT protocol with conformal reduced boost and online quality control allows excellent long-term OS and EFS in the absence of chemotherapy. In addition, FSIQ drops seem to be less pronounced than previously reported with standard irradiation regimens.

Between December 1998 and October 2001, patients19 years old were treated for standard-risk medulloblastoma according to the Medulloblastome-Société Française d'Oncologie Pédiatrique 1998 (M-SFOP 98) protocol. Patients received hyperfractionated radiotherapy (36 Gy in 36 fractions) to the craniospinal axis, a boost with conformal therapy restricted to the tumor bed (to a total dose of 68 Gy in 68 fractions), and no chemotherapy. Records of craniospinal irradiation were reviewed before treatment start.A total of 48 patients were considered assessable. With a median follow-up of 45.7 months, the overall survival and progression-free survival rate at 3 years was 89% and 81%, respectively. Fourteen major deviations were detected and eight were corrected. No relapses occurred in the frontal region and none occurred in the posterior fossa outside the boost volume. Nine patients were available for volume calculation without reduction of the volume irradiated. We observed a reduction in the subtentorial volume irradiated to60 Gy, but a slight increase in the volume irradiated to 40 Gy. No decrease in intelligence was observed in the 22 children tested during the first 2 years.This hyperfractionated radiotherapy protocol with a reduced boost volume and without chemotherapy was not associated with early relapses in children. Moreover, intellectual function seemed to be preserved. These results are promising.

To determine (i) the efficiency of radiosensitizing 5-FU-loaded microspheres and (ii) the impact of microparticle formulation on response to treatment.C6 tumor-bearing rats were stereotactically implanted with microspheres and/or allocated to: control groups (untreated) or treatment (only radiotherapy; fast-release 5-FU microspheres + radiotherapy; slow-release 5-FU microspheres + radiotherapy). The next day, fractionated radiotherapy, limited to the hemibrain, was initiated in all treated animals. The irradiation cycle included 36 Gy, given in 9 sessions for 3 consecutive weeks. Tumor development was assessed by T2-weighted MRI.5-FU microspheres associated with radiotherapy caused a 47% complete remission rate (9/19) as opposed to the 8% rate (1/12) when radiotherapy alone or 0% in control animals. Drug delivery for 3 weeks produced better survival results (57%) compared to one-week sustained release (41%). MR images showed exponentially increasing tumor volumes during the first half of the radiotherapy cycle, followed by a decrease, and the disappearance of the tumor if survival exceeded 120 days.5-FU controlled delivery is a promising strategy for radiosensitizing gliomas. Drug delivery system formulation is unambiguously implicated in both the response to treatment and the limitation of toxic side effects.