Feasibility and Safety of the "One-Week Breast Radiation Therapy" Program.

AIMS: FAST-Forward and UK-FAST-trials have demonstrated the safety and efficacy of five-fraction breast adjuvant radiation therapy (RT) and have become the standard of care for selected early breast cancer patients. In response to the additional burden caused by the COVID-19 pandemic, we implemented "One-Week Breast RT," an innovative program delivering five-fraction whole breast RT in a complete 5-day workflow. The primary objective of this study was to demonstrate the feasibility and safety of our program. The secondary objective was to evaluate cosmetic results. MATERIAL AND METHODS: A total of 120 patients treated from February 2021 to March 2022, received whole breast RT without lymph node irradiation nor boost, with 26 Gy in five fractions over one week. Inverse planning with restricted optimization parameters offers systematic deep inspiration breath-hold aimed to provide treatment plans compliant with FAST-Forward recommendations. Toxicity and cosmetic evaluations were prospectively registered prior (pre-RT), at the end (end-RT), and 6 months after RT (6 months) based on Common Terminology Criteria for Adverse Events v. 4.03 and Harvard scale. RESULTS: With a median age of 70 years (interquartile range (IQR): 66-74) and a median follow-up of 6 months (IQR: 6.01-6.25), most patients (93.3%) completed their RT in one week from baseline to the end of the treatment consultation. The most common acute toxicities (at end-RT) were skin-related: radio-dermatitis (72%), induration (35%), hyperpigmentation (8%), and breast edema (16%). The rate of radio-dermatitis decreased from end-RT to 6 months (71.7% vs 5.4%, P< 0.001). No patient experienced grade ≥3 toxicity. At 6 months, cosmetic results were generally good or excellent (94.1%). CONCLUSION: This study confirms the feasibility and acute safety of the "One-Week Breast RT" in real life. Favorable toxicity profiles and good cosmetic outcomes are in line with FAST-Forward results. A prospective national cohort, aimed at decreasing treatment burden, maintaining safety, efficacy, and improving RT workflow efficiency with longer follow-up is ongoing.

[Extreme hypofractionation: New indications for breast cancer radiotherapy]. / Hypofractionnement extrême en pratique : les nouvelles indications dans les cancers du sein.

Due to the continuously increasing number of newly diagnosed breast cancer and limited health resources hypofractionated radiotherapy is a major topic. Recent results from randomized clinical trials assessing extreme hypofractionated radiotherapy for whole or partial breast radiotherapy are practice changing. Here we report toxicity and oncological outcomes from major recent trials of extreme hypofractionated breast irradiation and present an ongoing prospective implementation program. For whole breast irradiation, with a 10 years follow up, the UK-FAST trial demonstrated no significant difference in toxicity between a once weekly 5 fractions (5,7Gy/fr) regimen and a conventional 50Gy/25fr regimen. With a 5 years follow up, the FAST-Forward trial showed non inferiority on local control for a 5 fractions over 1 week (5,2Gy/fr) regimen versus standard 40Gy/15fr over 3 weeks with safe toxicity profile. For accelerated partial breast irradiation, in low-risk breast cancers patients, several phase III randomized trials confirmed that extreme hypofractionation is a valid option. With our "One Week Breast Radiotherapy" program, we propose the implementation of a one-week full workflow preparing and delivering 5 fractions over 1 week (26Gy) in selected patients with prospective follow-up. Several extreme hypofractionated breast radiotherapy regimens are validated and can be routinely discussed with patients in a share decision-making process following patient selection criteria and dosimetric constraints.

[Margin determination from clinical to planning target volume for lung cancer treated with conformal or intensity-modulated irradiation]. / Détermination des marges du volume cible anatomoclinique au volume cible prévisionnel des cancers bronchiques en radiothérapie conformationnelle tridimensionnelle ou avec modulation d'intensité.

Technological progress in radiotherapy enables more precision for treatment planning and delivery. The margin determination between the clinical target volume and the planning target volumes stem from the estimation of geometric uncertainties of the tumour localization into the radiation beam. The inner motion complexity of lung tumours has led to the use of 4D computed tomography and nurtures specific dosimetric concerns. Few strategies consisting in integrating tumour motion allow margin reduction regarding inner movements. The patient immobilization and onboard imagery improvement decrease the setup uncertainties. Each step between the initial planning imagery and treatment delivery has to be analysed as systematic or random errors to calculate the optimal planning margin.

Reduction of restenosis after angioplasty in an atheromatous rabbit model by suicide gene therapy.

BACKGROUND: Gene delivery of the thymidine kinase (tk) gene combined with ganciclovir (GCV) limits intimal hyperplasia after abrasion of normal arteries. However, the low efficiency of adenoviral-mediated gene transfer to atherosclerotic arteries has raised concerns about the applicability of this strategy to the prevention of restenosis. METHODS AND RESULTS: A replication-defective adenoviral vector expressing tk (Ad-RSVtk) demonstrated selective toxicity toward GCV-treated arterial smooth muscle cells, with oligonucleolytic cleavage suggesting apoptosis. In vivo, after demonstration of tk expression after Ad-RSVtk delivery, the combination of Ad-RSVtk followed by GCV was tested in a rabbit model of angioplasty of atheromatous iliac arteries. Angioplasty (8 atm, 20 minutes) was performed by use of a hydrogel balloon coated with Ad-RSVtk (4x10(9) plaque forming units). GCV was infused (25 mg.kg(-1) I.V. BID) from days 2 through 7 after angioplasty in 8 of 12 rabbits. Four weeks later, morphometric analysis demonstrated a reduced intima-to-media ratio in the group receiving combination therapy compared with Ad-RSVtk alone (3.0+/-1.2 versus 5.2+/-0.5, P<.018). GCV per se had no effect on intimal hyperplasia after arterial injury. CONCLUSIONS: In vitro, Ad-RSVtk demonstrates selective toxicity toward GCV-treated arterial smooth muscle cells involving apoptosis. In vivo, GCV conditions reduction of neointimal formation after percutaneous delivery of Ad-RSVtk during angioplasty of atheromatous arteries.

Opposite in vitro and in vivo regulation of hepatic apolipoprotein A-I gene expression by retinoic acid. Absence of effects on apolipoprotein A-II gene expression.

We studied the pharmacological potential of retinoids to modulate apolipoprotein (apo) A-I and apoA-II gene expression and production in vitro in the human cell line HepG2 as well as in primary cultures of adult rat hepatocytes and in vivo in the rat. In HepG2 cells, addition of all-trans retinoic acid (RA) doubled apoA-I mRNA within 24 hours and protein secreted in the culture medium after 48 hours. The induction of apoA-I mRNA by RA was completely blocked by actinomycin D, suggesting that RA acts at the transcriptional level in HepG2 cells. In primary cultures of rat hepatocytes, addition of RA increased apoA-I mRNA in a dose- and time-dependent manner as well as the secretion of apoA-I protein. Similar changes in apoA-I mRNA were observed with 9-cis RA. However, in vivo, hepatic apoA-I mRNA levels decreased after a single administration of RA at 10 mg/kg and remained low after prolonged treatment or at a higher dose, and serum apoA-I concentrations did not change. Furthermore, RA treatment did not substantially affect apoA-II mRNA levels or protein secretion either in vitro or in vivo. As a control, RA receptor-beta mRNA levels increased after RA both in vitro and in vivo. In conclusion, RA treatment selectively induces apoA-I and not apoA-II expression in vitro but not in vivo. These results therefore show additional regulatory effects of RA on apoA-I gene expression in vivo and raise questions about the usefulness of RA in the treatment of atherosclerosis.