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Purpose To evaluate the feasibility and toxicity of a single-fraction 8-Gy stereotactic boost after whole-breast irradiation in early breast cancer. The primary aim of this phase 2 study was to evaluate cutaneous breast toxicity using National Cancer Institute Common Terminology Criteria for Adverse Events (version 4) 3 months after the boost. Secondary objectives were local control, survival, and patient-reported quality of life using the European Organisation for Research and Treatment of Cancer QLQ-C30 and breast-specific European Organisation for Research and Treatment of Cancer QLQ-BR 23 questionnaires. Methods and Materials Patients with invasive ductal or lobular pT1-2 breast cancer treated with lumpectomy with clear margins and pN0 were included. Patients requiring chemotherapy were excluded. Results Twenty-eight eligible patients received the planned boost, and 26 had hormonal therapy. The procedure was technically successful without procedural complications. A median of 3 fiducials were tracked, and 115 beams were used. There were 22 acute grade 1 breast skin toxicities, including fibrosis, pain, erythema, or pigmentation. There were 2 acute grade 2 erythemas. Median skin boost dose was inversely correlated with acute skin toxicity (P = .028). QLQ-C30 scores revealed acute dyspnea and arm symptoms without correlation to the boost dose. Breast symptom QLQ-BR23 scores did not deteriorate, although upset with hair loss and systemic side effects of hormonal therapy were observed. After a median follow-up of 38 months, 1 patient had in-boost-field relapse, and there were 5 late grade 1 and 1 grade 2 skin toxicities. Conclusions Single-fraction stereotactic boost after conventional whole-breast irradiation in early breast cancer is feasible with minor toxicities. Quality of life and specific breast items showed excellent patient acceptance.

Les traitements utilisant des rayons X de basse energie continuent a etre realises mais en faible nombre. Le praticien se trouve en general pres du patient pour maintenir l’appareil et expose donc ses yeux. Avec la modification envisagee de la limite maximale d’exposition du cristallin, des mesures ont ete jugees necessaires pour mieux en connaitre l’exposition. Pour cela une simulation des traitements a ete realisee. Pour la dose d’un traitement superficiel de 42 Gy, l’exposition du cristallin derriere des verres radio attenuateurs se situe entre 130 et 43 μ Sv pour des distances entre 40 et 60 cm. Pour l’intra cavitaire les valeurs obtenues sont vingt fois plus faibles. L’attenuation par les verres est superieure a 90 %. Le port des lunettes avec verres radio attenuateurs permet de minimiser la dose au cristallin de facon significative. L’application de la nouvelle limite maximale n’aura pas d’impact sur le nombre de traitements.

Objective To evaluate clinical outcome after accelerated partial breast irradiation (APBI) in the elderly after high-dose-rate interstitial multi-catheter brachytherapy (HIBT). Methods and materials Between 2005 and 2013, 70 patients underwent APBI using HIBT. Catheter implant was performed intra or post-operatively (referred patients) after lumpectomy and axillary sentinel lymph node dissection. Once the pathological results confirmed the indication of APBI, planification CT-scan was performed to deliver 34 Gy/10f/5d or 32 Gy/8f/4d. Dose-volume adaptation was manually achieved (graphical optimization). Dosimetric results and clinical outcome were retrospectively analyzed. Physician cosmetic evaluation was reported. Results With a median follow-up of 60.9 months [4.6 – 90.1], median age was 80.7 years [62 – 93.1]. Regarding APBI ASTRO criteria, 61.4%, 18.6% and 20% were classified as suitable, cautionary and non-suitable respectively. Axillary sentinel lymph node dissection was performed in 94.3%; 8 pts (11.5%) presented an axillary involvement. A median dose of 34 Gy [32 – 35] in 8 to 10 fractions was delivered. Median CTV was 75.2 cc [16.9 – 210], median D90 EQD2 was 43.3 Gy [35 – 72.6] and median DHI was 0.54 [0.19 – 0.74]. One patient experienced ipsilateral recurrence (5-year local free recurrence rate: 97.6%. Five-year specific and overall survival rates were 97.9% and 93.2% respectively. Thirty-four patients (48%) presented 47 late complications classified grade 1 (80.8%) and grade 2 (19.2%) with no grade ≥ 3. Cosmetic results were considered excellent/good for 67 pts (95.7%). Conclusion APBI using HIBT and respecting strict rules of implantation and planification, represents a smart alternative between no post-operative irradiation and whole breast irradiation delivered over 6 consecutive weeks.

Metastatic lymph nodes of EMT6 tumors growing in athymic nude mice were used at different sizes and their radiosensitivity was tested with the in vitro colony method. Following the administration of 1250 rad, the surviving fraction in air-breathing animals was found to be dependent on the size of these metastases, expressed either in weight or in cell yield per lymph node. The increasing radioresistance with increase in size was probably due to the presence of higher hypoxic fraction in big nodes (0.43 in nodes weighing more than 320 mg vs 0.10 in nodes less than 80 mg). The surviving fraction after irradiation in acutely hypoxic conditions (asphyxiated animals) or in fully oxygenated ones (in vitro) was not size dependent. Great variations were observed in the radiosensitivity of small metastatic nodes, whereas bigger metastases had a more homogeneous response. The effect of the radiosensitizer misonidazole at a dose of 0.3 mg/g was assessed on lymph node metastases of different sizes. In the presence of the drug, the survival level of big and small metastases differed by a factor of 2.2, as opposed to 4.3 in untreated metastases. This suggests that the radiosensitization is less pronounced in metastases containing a smaller hypoxicmore » fraction.« less

The mean inactivation dose (D) is calculated for published in vitro survival curves obtained from cell lines of both normal and neoplastic human tissues. Cells belonging to different histological categories (melanomas, carcinomas, etc.) are shown to be characterized by distinct values of D which are related to the clinical radiosensitivity of tumors from these categories. Compared to other ways of representing in vitro radiosensitivity, e.g., by the multitarget parameters D0 and n, the parameter D has several specific advantages: (i) D is representative for the whole cell population rather than for a fraction of it; (ii) it minimizes the fluctuations of the survival curves of a given cell line investigated by different authors; (iii) there is low variability of D within each histological category; (iv) significant differences in radiosensitivity between the categories emerge when using D. D appears to be a useful concept for specifying intrinsic radiosensitivity of human cell lines.

The in vivo and in vitro radiosensitivity of EMT6 tumor cells growing subcutaneously and metastasizing to the regional lymph nodes has been studied in congenitally athymic nude mice. The fraction of hypoxic cells was determined using an in vitro colony method to assay cell survival after irradiation of both air-breathing and nitrogen-asphyxiated animals. In air-breathing animals, lymph node metastases contained a significantly higher fraction of hypoxic cells than subcutaneous tumors of the same size (61 and 36% respectively). Survival curves did not differ under hypoxic conditions (nitrogen-asphyxiated animals). Likewise, survival curves of cells extracted from tumors at both sites and irradiated in vitro were identical.