Vitamine D et cancer du sein : physiopathologie,implications biologiques et cliniques

There is a recent increase in interest of vitamin D and breast cancer, facing the number of publications on the subject. This increase have several reasons, on the one hand, vitamin D deficiency is more and more prevalent and, on the other hand, there are new data that highlights the extra-bone effects of vitamin D, especially in breast cancer, the vitamin D is involved in the breast cancer risk factor, the prognosis, and the interaction with breast cancer treatments. This combination between vitamin D deficiency and breast cancer is extremely usual, and combined with all cancer clinical parameters: the incidence, the tumour biology, the clinical presentation, the prognosis, and the antineoplastic treatment tolerance. This vitamin D deficiency is increased after adjuvant cancer treatments. And yet, this problem increases bone metabolism disruptions in breast cancer patients, inducing osteoporotic risk at long time, even though this population is curable. This problem is therefore serious in the adjuvant breast cancer treatment. Unfortunately, in this population, the current recommendations are clearly insufficient, and the current randomized clinical trial results would contribute to define the best way to correct the vitamin D deficiency, quickly and secure.     

Radiation recall syndrome in a patient with breast cancer,after introduction of everolimus

The addition of everolimus to exemestane is recommended in patients with HR+ advanced breast cancer with disease recurrence or progression following prior non-steroidal aromatase inhibitors. We report a case of radiation recall syndrome in a breast cancer patient, after introduction of everolimus. A woman with a right breast cancer underwent a mastectomy, then adjuvant chemotherapy, radiation therapy and hormonotherapy. In a phase III trial (UNIRAD protocol), she received everolimus 5 months after radiation therapy. Seven days after introduction, she was suffering from a radiation recall syndrome with exacerbation skin reactions. The exact pathophysiological mechanism of radiation recall syndrome is unknown. The combination of radiation therapy and mTor inhibitor, even sequentially, should be done with caution as several cases have already been reported.     

Evaluating cardiac substructure radiation exposure in breast rotational intensity modulated radiation therapy: Effects of cancer laterality,fractionation and deep inspiration breath-hold

PurposeRotational intensity-modulated radiation therapy currently has a growing role in breast cancer radiation therapy, since this radiation technique reduces cardiac radiation exposure while homogeneously covering target volumes. This study aims to evaluate radiation exposure of cardiac substructures across a broad spectrum of breast cancer cases differing by cancer laterality, fractionation regimen and addition of deep-inspiration breath hold.Materials and methodsCardiac substructures were delineated following guidelines endorsed by the European Society for Radiotherapy and Oncology (ESTRO) for forty-four breast cancer patients having undergone conserving surgery and adjuvant rotational intensity-modulated radiation therapy. Target volumes consisted of the whole breast with a boost, axillary and internal mammary nodes. Patients were treated using free-breathing technique for left-sided or right-sided, normofractionated or hypofractionated helical tomotherapy or volumetric modulated arc therapy, or using deep-inspiration breath hold for left-sided normofractionated volumetric modulated arc therapy. Mean and maximum doses to cardiac substructures were retrieved. Correlations were performed between mean- and maximum radiation doses to cardiac substructures.ResultsLeft-sided and right-sided irradiations were associated with different cardiac substructure exposure patterns despite comparable mean heart dose: 7.21 Gy for left-sided normofractionated regimen, 6.28 Gy for right-sided normofractionated regimen. Deep-inspiration breath hold reduced mean doses to almost all cardiac substructures for left-sided irradiation, but did not decrease maximum doses to coronary arteries. Correlations between mean- and maximum doses to cardiac substructures were usually moderate, but stronger for right-sided irradiation.ConclusionDespite comparable mean heart dose, cardiac substructure radiation exposure patterns with rotational intensity-modulated radiation therapy strongly depend on the breast side, which could trigger clinically different long-term cardiotoxicity events. Deep-inspiration breath hold improves cardiac substructure dosimetry. Mean- and maximum heart dose could probably not be used as surrogate markers for precise cardiac substructure evaluation. In a near future, clinical practice and cardiotoxicity studies could possibly gain by considering cardiac substructure in a more systematic manner, possibly relying on cardiac autosegmentation algorithms.     

Impact of external beam pelvic radiotherapy of endometrial carcinoma: A focus on chronic digestive toxicity

PurposeThe standard treatment for endometrial cancer is surgery, although depending on the risk factors, adjuvant radiation therapy may also be given. It is proposed for high-risk carcinomas for which an improvement in progression-free survival though not overall survival has been shown. However, despite the development of radiotherapy treatments with intensity modulation and image guidance, adjuvant radiation therapy remains toxic to the digestive system. We aimed to investigate the incidence of digestive toxicity and the presence of any predictive factors.Materials and methodsData were retrospectively collected from patients treated with adjuvant radiotherapy for endometrial carcinoma at the Institut de cancérologie de Lorraine and centre hospitalier Émile-Durkheim between January 2010 and October 2016 and analyzed to identify factors associated with chronic digestive toxicity.ResultsOne hundred and thirty-nine patients received a total dose of 50 Gy fractionated into 25 sessions, five per week for five weeks. The median follow-up after irradiation completion was 38 months. The incidence of gastrointestinal and rectal toxicity in all patients treated with pelvic irradiation for endometrial carcinoma was 11.1% (95% confidence interval [95%CI]: 5.4–19%) for grade 3–4 and 25.6% (95%CI: 17.0–34.9%) for grade 2–4. No factor was found to be significantly predictive of chronic digestive toxicity. At five years, the overall survival was 74.3%, (95%CI: 65.3–81.4%), progression-free survival was 69.6% (95%CI: 60.1–77.3%) and incidence of pelvic recurrence was 7.9% (95%CI: 3.8–13.9%).ConclusionOur results confirmed that pelvic radiotherapy can induce a relatively high rate of digestive toxicity but failed to identify relevant factors able to predict it.     

I125 irradiation stent for treatment of hepatocellular carcinoma with portal vein thrombosis: A meta-analysis

PurposeA meta-analysis aimed to systematically evaluate the safety and efficiency of I¹²⁵ irradiation stent placement for patients with hepatocellular carcinoma (HCC) combined with portal vein tumor thrombosis (PVTT).Materials and methodsThe Cochrane library, PubMed/Medline, EMBASE, CNKI, Wanfang Data and CQVIP were systematically screened out from the earliest to December 2019. The qualities of all included studies were assessed. The primary endpoints were the 6-month, 12-month stent cumulative patency rate and 6-month, 12-month, 24-month overall survival rate while the secondary endpoints were the objective response rate of PVTT, main portal venous pressure changes and treatment-related adverse events. Our meta-analysis was conducted using Stata 12.0 software.ResultsTotally seven studies with 1018 patients were included in the final analysis, in which 602 patients received TACE and I¹²⁵ irradiation stent placement, and 416 patients in control group underwent TACE and stent placement without endovascular brachytherapy (EVBT). Meta-analysis showed that the I¹²⁵ irradiation stent improved the cumulative stent patency rates in 6 months [OR = 1.65, 95% CI (1.32–2.05), P < 0.001] and 12 months [OR = 2.55, 95% CI (1.90–3.42), P < 0.001] and the survival rates in 6 months [OR = 1.77, 95% CI (1.41–2.22), P < 0.001], 12 months [OR = 3.14, 95% CI (2.24–4.40), P < 0.001] and 24 months [OR = 7.39, 95% CI (3.55–15.41), P < 0.001]. However, there was no difference in the objective response rate of PVTT [OR = 1.13, 95% CI (0.87–1.48), P = 0.365], main portal venous pressure and the occurrence adverse event [OR = 0.88, CI = 0.72–1.08, P = 0.212] between two groups.ConclusionI¹²⁵ irradiation stent seems to be more effective in treating hepatocellular carcinoma with portal vein tumor thrombosis. The usage of portal vein stent combined endovascular brachytherapy has the potential to act as an alternative therapy for HCC with PVTT. On account of the limitation of studies included, more studies with high-level evidence, such as RCTs, are requisite to support the above promising results.     

Comparison between the ICRU rectal point and modern volumetric parameters in brachytherapy for locally advanced cervical cancer

PurposeThe implementation of image-guided brachytherapy in cervical cancer raises the problem of adapting the experience acquired with 2D brachytherapy to this technique. The GEC-ESTRO (Groupe européen de curiethérapie – European Society for Radiotherapy and Oncology) has recommended reporting the dose delivered to the rectum in the maximally exposed 2 cm³ volume, but so far, the recommended dose constraints still rely on 2D data. The aim of this study was to evaluate the relationship between the doses evaluated at the ICRU rectal point and modern dosimetric parameters.Material and methodsFor each patient, dosimetric parameters were generated prospectively at the time of dosimetry and were reported. For analysis, they were converted in 2 Gy equivalent doses using an α/β ratio of 3 with a half-time of repair of 1.5 hours.ResultsThe dosimetric data from 229 consecutive patients treated for locally advanced cervical cancer was analyzed. The mean dose calculated at ICRU point (DICRU) was 55.75 Gy ± 4.15, while it was 59.27 Gy ± 6.16 in the maximally exposed 2 cm³ of the rectum (P = 0.0003). The D2 cm³ was higher than the DICRU in 78% of the cases. The mean difference between D2 cm³ and DICRU was 3.53 Gy ± 4.91. This difference represented 5.41% ± 7.40 of the total dose delivered to the rectum (EBRT and BT), and 15.49% ± 24.30 of the dose delivered when considering brachytherapy alone. The two parameters were significantly correlated (P = 0.000001), and related by the equation: D2 cm³ = 0.902 × DICRU + 0.984. The r² coefficient was 0.369.ConclusionIn this large cohort of patients, the DICRU significantly underestimates the D2 cm³. This difference probably results from the optimization process itself, which consists in increasing dwell times above the ICRU point in the cervix. Considering these findings, caution must be taken while implementing image-guided brachytherapy and dose escalation.