Summary Background Increasing the dose intensity of cytotoxic therapy by shortening the intervals between cycles, or by giving individual drugs sequentially at full dose rather than in lower-dose concurrent treatment schedules, might enhance efficacy. Methods To clarify the relative benefits and risks of dose-intense and standard-schedule chemotherapy in early breast cancer, we did an individual patient-level meta-analysis of trials comparing 2-weekly versus standard 3-weekly schedules, and of trials comparing sequential versus concurrent administration of anthracycline and taxane chemotherapy. The primary outcomes were recurrence and breast cancer mortality. Standard intention-to-treat log-rank analyses, stratified by age, nodal status, and trial, yielded dose-intense versus standard-schedule first-event rate ratios (RRs). Findings Individual patient data were provided for 26 of 33 relevant trials identified, comprising 37 298 (93%) of 40 070 women randomised. Most women were aged younger than 70 years and had node-positive disease. Total cytotoxic drug usage was broadly comparable in the two treatment arms; colony-stimulating factor was generally used in the more dose-intense arm. Combining data from all 26 trials, fewer breast cancer recurrences were seen with dose-intense than with standard-schedule chemotherapy (10-year recurrence risk 28·0% vs 31·4%; RR 0·86, 95% CI 0·82–0·89; p<0·0001). 10-year breast cancer mortality was similarly reduced (18·9% vs 21·3%; RR 0·87, 95% CI 0·83–0·92; p<0·0001), as was all-cause mortality (22·1% vs 24·8%; RR 0·87, 95% CI 0·83–0·91; p<0·0001). Death without recurrence was, if anything, lower with dose-intense than with standard-schedule chemotherapy (10-year risk 4·1% vs 4·6%; RR 0·88, 95% CI 0·78–0·99; p=0·034). Recurrence reductions were similar in the seven trials (n=10 004) that compared 2-weekly chemotherapy with the same chemotherapy given 3-weekly (10-year risk 24·0% vs 28·3%; RR 0·83, 95% CI 0·76–0·91; p<0·0001), in the six trials (n=11 028) of sequential versus concurrent anthracycline plus taxane chemotherapy (28·1% vs 31·3%; RR 0·87, 95% CI 0·80–0·94; p=0·0006), and in the six trials (n=6532) testing both shorter intervals and sequential administration (30·4% vs 35·0%; RR 0·82, 95% CI 0·74–0·90; p<0·0001). The proportional reductions in recurrence with dose-intense chemotherapy were similar and highly significant (p<0·0001) in oestrogen receptor (ER)-positive and ER-negative disease and did not differ significantly by other patient or tumour characteristics. Interpretation Increasing the dose intensity of adjuvant chemotherapy by shortening the interval between treatment cycles, or by giving individual drugs sequentially rather than giving the same drugs concurrentl...

Objectives. The aim of this prospective phase II study is to evaluate the treatment of early-stage breast cancer (T1 N0) with intraoperative electron radiation therapy (IOERT) in terms of local control, early complications, and cosmesis. Patients and Methods. From February 2010 to February 2012, 200 patients underwent partial IOERT of the breast. Inclusion criteria were unifocal invasive ductal carcinoma, age ≥40 years, histological tumour size ≤20 mm, and no lymph node involvement. A 21 Gy dose was prescribed over the 90% isodose line in the tumour bed. Median follow-up is 23.3 months (7–37). Results. Acute toxicity was not frequent (Grade 1: 4.5%, Grade 2: 1%). The cosmetic result was considered to be very good or good in 92.5%. One ipsi lateral out-quadrant recurrence at 18 months was observed. The crude and actuarial local recurrence rates after median follow-up were 0.5% and 0.9%, respectively. Conclusion. The preoperative diagnostic work-up must be comprehensive and the selection process must be rigorous for this therapeutic approach reserved for small ductal unifocal cancers. After a 23.3-month median follow-up time, the clinical results of IOERT for selected patients are encouraging for the locoregional recurrence and the toxicity rates. The satisfaction of our patients in terms of quality of life was extremely high.

Apoptosis is an essential physiological process in embryonic development. In the developing eye of vertebrates, three periods of developmental apoptosis can be distinguished: early, intermediate and later. Within the apoptosis pathway, caspases play a crucial role. It has also been shown that HSP110 may have a potential role in apoptosis.The aim of this research was to study the expression of HSP110, caspase-3 and -9 in physiological, retinoic-or irradiation-induced apoptosis during early eye development. Seven pregnant C57Bl/6J mice received 80 mg kg − 1 of all-trans retinoic acid mixed with sesame oil. Seven pregnant NMRI mice received 2 Gy irradiation at the same gestational day. Control mice of both strains (seven mice of each) were not submitted to any treatment. Embryos were harvested at 3, 6, 12 and 24 h after exposition, fixed, dehydrated and embedded. Coronal sections (5 µ m) were made. Slide staining occurred alternatively using anti-caspase-3, anti-caspase-9 and anti-HSP110 immunohistochemistry. HSP110 and caspase-3 expression presented similar topographic and chronological patterns, whereas expression of HSP110 was more precocious in retinoic acid-treated embryos. After retinoic exposure, caspase-3-and HSP110-positive cells were increased in the region of the optic vesicle. By contrast, after irradiation, caspase-3-and HSP110-positive cells were noticeably increased in the optic vesicle, peri-optical mesoderm but less in lens placode. HSP110 was expressed before caspase-3. By contrast, caspase-9 was expressed by a very small number of cells in the optic vesicle either under physiological or under teratogenic conditions. Thus, it seems that activation of caspase-9 is dispensable in early eye developmental apoptosis.

This paper studies the feasibility of using Monte Carlo (MC) for treatment planning of intraoperative electron radiation therapy (IOERT) procedure to get 3D dose by using patient's CT images. Methods: The IOERT treatment planning was performed using the following successive steps:I) The Mobetron 1000® machine was modelled with the EGSnrc MC codes. II) The MC model was validated with measurements of percentage depth doses and profiles for three energies (12, 9, 6) MeV. III) CT images were imported as DICOM files. IV) Contouring of the planning target volume (PTV) and the organs at risk was done by the radiation oncologist. V) The medical physicist with the radiation oncologist, had chosen the same parameters of IOERT procedures like energy, applicator (type, size) and using or not bolus. VI) Finally, dose calculation and analysis of 3D maps was carried out. Results: The tuning process of the MC model provides good results, as the maximum value of the root mean square deviation (RMSD) was less than 3% between the MC simulated PDDs and the measured PDDs. The contouring and dose analysis review were easy to conduct for the classical treatment planning system. The radiation oncologist had many tools for dose analysis such as DVH and color wash for all the slides. Summation of the 3D dose of IOERT with other radiotherapy plans is possible and helpful for total dose estimation. Archiving and documentation is as good as treatment planning system (TPS). Conclusions: The method displayed in this paper provides a step forward for IOERT Dosimetry and allows to obtain accurate dosimetry of treated volumes.

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