[Security of supply: Getting to know more about the organization of suppliers]. / Sécurité d'approvisionnement : mieux connaître l'organisation des fournisseurs.

OBJECTIVES: The worsening pharmaceutical products shortage required the central purchasing structure of AP-HP to include a new criterion on supply safety in the tenders' procedures. Each provider answering to the tender needs to complete a dedicated form. The aim is to review the collected information and assess its relevance. METHODS: This study is based on a retrospective analysis conducted on the last 2 tenders' procedures forms (one started in September 2019 and the other in February 2020). RESULTS: These 2 tenders' procedures were composed of 155 lots. The form response rate was 81,4%. The average rating on 20 was 10,9±3,8. The rates could be very variable depending on the lots. Regarding the 2020s tenders procedures, 57.8% of specialties were classified as drugs of major therapeutic interest. A shortage management plan exists for 24.0% of them. Providers indicated several sources of raw materials (36,1%) and several factories (35,5%). The average advanced stock was 4.1±3.8 months in France and 2.3±2.6 months in Europe. The information system implemented by suppliers scored an average of 15 out of 20. CONCLUSIONS: This study allowed us to know better the suppliers' organisation. The concerning points are the low stocks and the discrepancies in the suppliers' drugs of major therapeutic interest classification of a same product and the existence of a shortage management plan. This form will be maintained with more specific questions. An assessment will be done to determine the relevance of this form to prevent disruptions.

[Serious adverse events after microbial sealant application in paediatric patients]. / Évènements indésirables graves à l'occasion de l'emploi d'un dispositif filmogène en pédiatrie.

BACKGROUND: Integuseal(®) is a cyanoacrylate-based medical device (IIa class), used in surgery after skin preparation to reduce bacterial contamination. It is not officially contraindicated for children. OBJECTIVES: To describe a case series of skin lesions in pediatric patients after using Integuseal(®) in cardiac surgery. METHODS: Case series. RESULTS: Between September 2012 and February 2013, 153 pediatric patients were treated by Integuseal(®) to prepare for a cardiac surgery in our center: 5 patients (2%) had serious cutaneous reactions. The average age of patients having had lesions is 16months (the youngest patient being 1month old and the oldest being 5years and 8months old). ISSUES: The risk factor in the development of skin lesion seems to be particularly related to the patient's age and sternal location. Other medical literature reports instances of cyanoacrylate intolerance in a variety of other situations. CONCLUSION: Using Integuseal(®) on children does not appear to be safe.

A Nomogram to predict parotid gland overdose in head and neck IMRT.

PURPOSES: To generate a nomogram to predict parotid gland (PG) overdose and to quantify the dosimetric benefit of weekly replanning based on its findings, in the context of intensity-modulated radiotherapy (IMRT) for locally-advanced head and neck carcinoma (LAHNC). MATERIAL AND METHODS: Twenty LAHNC patients treated with radical IMRT underwent weekly computed tomography (CT) scans during IMRT. The cumulated PG dose was estimated by elastic registration. Early predictors of PG overdose (cumulated minus planned doses) were identified, enabling a nomogram to be generated from a linear regression model. Its performance was evaluated using a leave-one-out method. The benefit of weekly replanning was then estimated for the nomogram-identified PG overdose patients. RESULTS: Clinical target volume 70 (CTV70) and the mean PG dose calculated from the planning and first weekly CTs were early predictors of PG overdose, enabling a nomogram to be generated. A mean PG overdose of 2.5Gy was calculated for 16 patients, 14 identified by the nomogram. All patients with PG overdoses >1.5Gy were identified. Compared to the cumulated delivered dose, weekly replanning of these 14 targeted patients enabled a 3.3Gy decrease in the mean PG dose. CONCLUSION: Based on the planning and first week CTs, our nomogram allowed the identification of all patients with PG overdoses >2.5Gy to be identified, who then benefitted from a final 4Gy decrease in mean PG overdose by means of weekly replanning.

Stereotactic body re-irradiation therapy for locally recurrent prostate cancer after external-beam radiation therapy: Initial report.

PURPOSE: Management of prostate cancer relapses after external-beam radiation therapy is still undefined. Re-irradiation schedules have been explored in different tumour sites. In this report, we present our preliminary experience of re-irradiation using stereotactic body radiotherapy for localized prostate cancer failure. MATERIAL AND METHODS: Between March 2011 and October 2014, robotic stereotactic body radiation therapy was administered to patients previously treated with external-beam radiation therapy to a median dose of 71.1Gy (range, 45-76.5Gy) and with biochemical failure corresponding to a local in-field recurrence of prostate cancer. Ten patients had recurrences after postoperative external-beam radiotherapy. Patients underwent a pelvic MRI to confirm the recurrence and a total body staging using a ((18)F)-fluorocholine PET/CT. The prescription dose consisted of five fractions of 7.25Gy to a total dose of 36.25Gy. Efficacy was evaluated based on biochemical response and toxicity was evaluated according to CTCAE v.4.0 questionnaires and International Prostate Symptom Score. RESULTS: Twenty-one patients were treated and followed for a median time of 11.7 months (mean: 13.4 months; range: 2.5-46.5 months). Median time between the first external-beam radiation therapy of prostate cancer and the first day of CyberKnife(®) treatment was 111 months (range: 38-398 months). One-year biochemical recurrence-free survival rate was 83.3%, and only one in-field progression was reported. Two patients had a biochemical failure corresponding to metastatic progression without evidence of local recurrence. Treatment was well tolerated, with only one grade 2 acute genitourinary toxicity, no grade≥2 acute gastrointestinal or late toxicities were reported. CONCLUSION: Stereotactic body re-irradiation therapy using CyberKnife(®) after failed external-beam radiation therapy showed favourable results in terms of in-field local and biochemical control. Toxicity was low and acceptable. Further prospective studies are needed to confirm these results to select patient and to evaluate the introduction of androgen-deprivation therapy.

[Acute skin toxicity in breast intensity modulated radiotherapy using field in field technique]. / Toxicité aiguë cutanée de l'irradiation mammaire avec modulation d'intensité avec technique de champ dans le champ (optimisation avec pré-segmentation).

PURPOSE: The optimization with presegmentation irradiation technique (Dosisoft™), used in treatment of breast carcinomas, facilitates the treatment delivery and improves radioprotection. The objective of our study was to evaluate the potential impact of this innovative technique on the acute skin toxicity especially on the rate of moist desquamation during irradiation of the whole breast after conservative surgery. PATIENTS AND METHODS: The scores of acute skin toxicity observed at 50 Gy in 103 patients treated with the presegmentation technique were compared to those of 101 patients with similar breast size treated with a classic 3D technique. All patients received 50 Gy/2 Gy per fraction, 5 days a week using 4 MV photon beam. The boost on the tumoural bed was realized according to conventional technique. Using the NCI-CTCAE V4, the skin toxicity was recorded every week during the medical visit. Moreover, the following factors that could induce skin toxicity have been studied: breast size, body mass index, age, prior chemotherapy, concurrent administration of trastuzumab, hypertension, diabetes, smoking habits and statin uptake. RESULTS: The incidence of moist desquamation observed in all sites, has been decreased to only 9.8% in the presegmentation group versus 16.8% in the test group, the difference being not statistically significant OR=0.53 [0.23; 1.22] (P=0.13). In univariate analysis the presegmentation technique enabled a significant decrease of 4.4 Gy in mean, of the value of maximum dose (P=0.001). The other risk factors of skin toxicity are the increase of breast size (P<0.001), a high body mass index (P<0.001), hypertension (P=0.03) and concurrent administration of trastuzumab (P=0.07). In multivariate analysis, the two remaining significant factors are breast size (OR=1.004 [1.002; 1.006]) and trastuzumab administration (OR=4.95 [1.17; 20.79]). CONCLUSION: The comparison of the skin toxicity induced by the presegmentation or the reference technique shows a trend regarding the improvement of the skin tolerance when using the presegmentation technique, thus pleading in favour of its use considering its dosimetric interest and the improvement of radioprotection of the patient. The next step will consist to experiment the simultaneous boost on tumoural bed using this technique.

[Long-term outcome of neoadjuvant radiochemotherapy followed by surgery for esophageal cancer: a single institution retrospective study of 102 patients]. / Résultats à long terme de la chimioradiothérapie néoadjuvante des cancers de l'œsophage: étude rétrospective monocentrique sur 102 patients.

PURPOSE AND OBJECTIVES: To report survival and morbidity of a large homogeneous cohort of patients with a locally advanced esophageal or cardia carcinoma and put in evidence predictive factors of locoregional control and survival. PATIENTS AND METHODS: Hundred and two patients were treated at the university hospital of Tours between 1990 and 2010 and received neo-adjuvant chemoradiation therapy with external irradiation (40Gy-44Gy) and two courses of chemotherapy (5-fluoro-uracile and cisplatine). Esophagectomy associated with lymph node dissection was performed about ten weeks after the end of chemoradiation therapy. RESULTS: The median follow-up was 22.4 months [6-185 months]. The overall survival rates at 2 and 5years were 53% and 27%, respectively. The median overall survival was estimated at 27months. The overall 2-year survival between patients "responders" and patients "non-responders" was 67% vs 26%, respectively (P<0.0001). In case of histological response, there was a benefit in terms of overall survival (P<0.0001), locoregional control (P<0.0036) and disease-free survival (P<0.001). Overall survival at 2years was 64% for ypN0 group vs 32% for ypN1 group (P<0.0001). The median survival was estimated at 37months against 15months in the absence of lymph node involvement (P<0.0001). CONCLUSION: Our results in terms of survival, tolerance and morbidity and mortality were comparable to those in the literature. Complete histological response of lymph node was associated with an improvement of local control, disease-free survival and overall survival.

Robotic stereotactic body radiation therapy for tumors of the liver: radiation-induced liver disease, incidence and predictive factors.

PURPOSE: Robotic stereotactic body radiation therapy is a new option to treated unresecable liver tumours. The objectives were to assess the tolerance of this technique, to identify predictive factors for toxicity and evaluate the efficiency of this treatment. PATIENTS AND METHODS: From June 2010 to November 2012, robotic stereotactic body radiation therapy was proposed for 56 patients with unresecable hepatocellular carcinomas (23 patients) or hepatic metastases (41 patients). Two or less hepatic lesions, lesion size under 75 mm and WHO score under 3 were selection criteria. The prescribed dose was 45 Gy/3 fractions or 60 Gy/3 fractions. The primary end-point was toxicity, using the radiation-induced liver disease definition and to identify predictive factors. Secondary end-points were in-field local control and overall survival. RESULTS: The median follow-up was 12.5 months. The one-year local control rate and the one-year overall survival rate were 64% [CI95%: 48.2 to 76.5%] and 89% [CI95%: 76 to 95%], respectively. For patient treated with a total dose of 60 Gy, no one experienced recurrence. According to the definition we took, radiation-induced liver disease rate was 0 or 9%. A lesion size at least 35 mm was a predictive factor to liver toxicity (P=0.01). CONCLUSION: Using robotic stereotactic body radiation therapy, the incidence of radiation-induced liver disease is weak and spontaneously reversible. Prospective studies are required to put in evidence other predictive factors of radiation-induced liver disease and confirm the optimal dose treatment.

[Guidelines for the delineation of the lymph nodes areas in gynecological malignancies]. / Recommandations pour la délinéation des aires ganglionnaires dans les cancers gynécologiques.

Gynecological cancers are lymphophilic cancers, which require the systematic inclusion of nodal areas in the clinical target volume when irradiation is planned in the therapeutic strategy for these cancers. Radiotherapy with intensity modulation that achieves better saving of healthy tissue is more often used. However, the very steep dose gradients generated by this technique can lead to poorer coverage of target volumes if they are not defined very precisely by taking into account their anatomical location. This is particularly true for lymph node target volumes, so the purpose of this article is to present recommendations from a literature review focused on this issue, in terms of selection and delineation of lymph node in irradiation of cervix and endometrial cancers.

[Induction chemotherapy for locally advanced head and neck cancer]. / Cancers des voies aérodigestives supérieures : le retour de la chimiothérapie néoadjuvante ?

Chemotherapy is a part of the combined multimodality treatment for locally advanced head and neck cancers. Concomitant administration with radiation therapy is the standard treatment for these patients. The efficacy of the docetaxel-cisplatinum-5-fluoro-uracil (TPF) regimen compared to the platinum-5-fluoro-uracil (PF) regimen raised the question of whether this treatment could improve the therapeutic results for locally advanced tumours. For larynx preservation, induction chemotherapy using TPF, followed by radiation therapy for good responders is a valid option. However, clinical studies have to be performed to compare this approach to the concomitant radiation therapy-chemotherapy approach using functional endpoints. For locally advanced tumors, despite the superiority of the TPF regimen over the PF, there is no evidence in the literature to support the use of induction chemotherapy prior to concomitant radiation therapy-chemotherapy. Two recent studies (DECIDE, PARADIGM) failed to demonstrate any benefit, but both trials were stopped early because of slow enrollment. Other studies are on going, or with recently finished accrual, will help to shed light on the role of this treatment.

[Cervix cancer]. / Cancer du col utérin.

Cervix cancers declined in most developed countries in recent years, but remain, the third worldwide leading cause of cancer death in women. A precise staging, based on clinical exam, an abdominal and pelvic MRI, a possible PET-CT and a possible lymph node sampling is necessary to adapt the best therapeutic strategy. In France, the treatments of tumors of less than 4 cm without nodal involvement are often based on radiotherapy followed by surgery and, whereas tumors larger than 4 cm and involved nodes are treated with concurrent chemoradiotherapy. Based on an illustrated clinical case, indications, delineation, dosimetry and complications expected with radiotherapy are demonstrated.