[Treatment of patients with brain metastases from a melanoma]. / Prise en charge des patients atteints de métastases cérébrales de mélanome.

Whereas immune checkpoint inhibitors of serine/threonine protein kinase B-raf therapy dramatically changed metastatic outcomes of patients with melanoma, they remain at high risk of brain extension. Additional local treatment can be offered in this situation such as surgery and or stereotactic radiotherapy. In this review article, we describe the different options with published data and their optimal timing.

[Dermatologic toxicities of immune checkpoint inhibitors]. / Toxicités dermatologiques des inhibiteurs de checkpoint immunologiques.

The development of immune checkpoint inhibitors (monoclonal antibodies targeting PD-1/PD-L1 or CTLA-4) represents a significant advance in the treatment of multiple cancers. Given their particular mechanism of action, which involves triggering CD4+/CD8+ T-cell activation and proliferation, they are associated with a specific safety profile. Their adverse events are primarily immune-related, and can affect practically all organs. In this context, dermatological toxicity is the most common, though it mostly remains mild to moderate and does not require discontinuation of treatment. More than a third of patients are faced with cutaneous adverse events, usually in the form of a maculopapular rash, pruritus or vitiligo (only in patients treated for melanoma). Much more specific dermatologic disorders, however, may occur such as lichenoid reactions, induced psoriasis, sarcoidosis, auto-immune diseases (bullous pemphigoid, dermatomyositis, alopecia areata), acne-like rash, xerostomia, etc. Rigorous dermatological evaluation is thus mandatory in the case of atypical, persistent/recurrent or severe lesions. In this article, we review the incidence and spectrum of dermatologic adverse events reported with immune checkpoint inhibitors. Finally, a management algorithm is proposed.

[Preliminary results of whole breast helical tomotherapy with simultaneous integrated boost in the adjuvant treatment of breast cancer]. / Résultats préliminaires d'une tomothérapie hélicoïdale adjuvante avec boost intégré dans le cadre d'un traitement conservateur d'un cancer du sein.

PURPOSE: To evaluate the dosimetry and acute toxicity of helical tomotherapy for locoregional irradiation of patients after breast-conserving surgery. PATIENTS AND METHODS: Twenty breast cancer patients with breast-conserving surgery treated by helical tomotherapy have been studied. The median age was 49 (min: 25, max: 69). The whole breast, tumour bed and lymph nodes were prescribed 52.2 Gy, 63.8 Gy and 50.4 Gy, all in 29 fractions. The dose per fraction was 2.2 Gy to the boost, 1.8 Gy to the breast and 1.74 Gy to the lymph node volumes. The reproducibility was analysed by recording the daily shifts in x, y and z directions and roll rotation. All toxicities were described using the Common Terminology Criteria for Adverse Effects v3.0. RESULTS: Twenty-two tumours were irradiated. Six-eight percent were located in the inner quadrant. In 90 % of patients supraclavicular and internal mammary nodes were treated. The coverage of planning target volumes (PTV) was as follows: PTV boost: V107 = 0.3 % ± 0.5 SD, V95 = 98.4 % ± 1.9 SD; PTV breast: -V107 = 7.8 % ± 17.3 SD, V95 = 96.8 % ± 2.2 SD; PTV LN: V107 = 2.5 % ± 4.2 SD, V95 = 92.7 % ± 13.2 SD. The mean V20 of the homolateral lung was 18.9 % ± 3.5 SD. For left side lesion, the mean V30 of the heart was 0.9 % ± 0.8 SD. The mean V5 was: V5 homolateral lung: 73.1 % ± 11.8 ET, controlateral lung: 38.9 % ± 21, heart (left side breast): 57.3 % ± 21, controlateral breast: 15.5 % ± 9.6. Median shifts were as follow: x-axis -0.04 mm (IC 95: -0.4 +0.38), y-axis -0.37 mm ± 5.51 (IC 95: -0.88 +0.14), z-axis 2.90 mm ± 5.42 (IC 95:+2.4+3.4) and roll rotation 0.22 ± 1.10 (IC 95: -0.1+0.32). The treatment tolerance was acceptable with 1 definitive interruption couple of fractions before the end and 3 temporal interruptions for skin toxicity. No grade 3 or 4 toxicity. Ninety-five percent of patients experienced skin toxicity: 45 % grade 2. There were 3 cases of oesophagitis. The median follow-up of presented series is 9.7 months and all of the patients are free of disease without any residual early or late toxicity. CONCLUSIONS: Helical tomotherapy can achieve full target coverage while protected to the heart and ipsilateral lung. This treatment was well tolerated and reproducible. However, the low doses to normal tissue volumes need to be reduced in future studies.

[High dose for prostate irradiation with image guided radiotherapy: contribution of intensity modulation arctherapy]. / Haute dose dans la prostate par radiothérapie guidée par l'image: apport de l'arcthérapie avec modulation d'intensité du faisceau.

PURPOSE: To compare two Intensity Modulated Radiation Therapy (IMRT) techniques for prostate cancer: the Volumetric Modulated Arc Therapy (VMAT) and the "Step and Shoot" technique (S&S). MATERIALS AND METHODS: VMAT and S&S plans (RX 18MV) were created and compared (Wilcoxon test) for 10 patients. The dosimetric goal of both treatments was to deliver 46 Gy to the seminal vesicles and 80 Gy to the prostate, while respecting the dose constrains in the organs at risk of toxicity. For one patient, the two techniques were compared for dose painting and escalation in target volumes defined on MRI and registered thanks to intraprostatic fiducials. RESULTS: VMAT, compared to S&S, offered: an increase of the PTV2s (prostate) volume receiving 77 to 80 Gy and a decrease of V(82) and V(83); a decrease of V(4) to V(6), V(16) to V(23), and V(69) to V(73) for the rectal wall; a decrease of V(25) for the bladder wall; a decrease of V(21) to V(43) for the femoral heads; a decrease of V(26) to V(44) and V(72) to V(80) but an increase of V(1) to V(21) and V(49) to V(60) for the healthy tissues. The Conformal Index "COIN" was better with VMAT than S&S (0.60 to 0.66). The delivered MU were significantly reduced with VMAT (8% mean) as well as the delivery time (4 min to 1.5 min). VMAT allowed delivering theorically 90Gy in the peripheral zone and 100 Gy in the tumor. CONCLUSION: In case of prostate irradiation, VMAT shows improvement compared with S&S. In particular, organs at risk are better spared, the delivery time is shortened and the number of delivered UM is decreased.

[Image-guided radiotherapy: rational, modalities and results]. / Radiothérapie guidée par l'image : pourquoi, comment et résultats.

The objective of Image-Guided Radiotherapy (IGRT) is to take in account the inter- or/and intrafraction anatomic variations (organ motion and deformations) in order to improve treatment accuracy. The IGRT should therefore translate in a clinical benefit the recent advances in both tumor definition thanks to functional imaging, and dose distribution thanks to intensity modulated radiotherapy. The IGRT enables direct or indirect tumor visualization during radiation delivery. If the tumor position does not correspond with the theoretical location of target derived from planning system, the table is moved. In case of important uncertainties related to target deformation, a new planning can be discussed. IGRT is realized by different types of devices which can vary in principle and as well as in their implementation: from LINAC-integrated-kV (or MV)-Cone Beam CTs to helicoidal tomotherapy, Cyberknife and Novalis low-energy stereoscopic imaging system. These techniques led to a more rational choice of Planning Target Volume. Being recently introduced in practice, the clinical results of this technique are still limited. Nevertheless, until so far, IGRT has showed promising results with reports of minimal acute toxicity. This review describes IGRT for various tumor localizations. The dose delivered by on board imaging should be taken in account. A strong quality control is required for safety and proper prospective evaluation of the clinical benefit of IGRT.

Intoxicación aguda por inhalación de acrilato de etilo, Lima 2002 / Acute intoxication caused by ethyl acrylate inhalation, Lima 2002

Objetivos: Describir las características clínico-epidemiológicas de los casos de intoxicación aguda por inhalación de acrilato de etilo, ocasionado por el manejo clandestino de un envase con restos de ésta sustancia, en una urbanización del distrito Comas, en Lima, Perú en noviembre del año 2002. Materiales y métodos: Estudio transversal analítico realizado en residentes y población del centro educativo aledaño a la zona del accidente. Se realizó una encuesta a todas las personas expuestas, se consideró como caso la presencia de cefalea, irritación ocular, nauseas, dolor abdominal y prurito intenso en el cuerpo. Se caracterizó el accidente en tiempo, espacio y persona.En el centro educativo se exploraron factores de exposición que favorecieron la presencia de intoxicados. Los datos fueron ingresados en Epi Info v 6.0 y analizados en STATA v.8.0 Resultados: Se encuestó 456 residentes y 326 personas en la escuela. La tasa de ataque general fue 21,9 por ciento, 46,9 por ciento en la escuela y 4,2 por ciento en viviendas. Los síntomas predominantes fueron cefalea 56 por ciento, irritación ocular 47 por ciento, dolor abdominal 42 por ciento. El 23 por ciento requirió hospitalización. El permanecer en pisos superiores de la escuela fue un factor de riesgo OR 4,54 (IC95 por ciento 2,66-7,84) y en el pabellón A OR 3,82 (IC95 por ciento 2,33-6,25). Conclusiones: Los síntomas predominantes fueron cefalea, irritación oculary dolor abdominal. La cercanía a la zona de exposición del cilindro y la dispersión de los vapores tóxicos influyeron para afectar mayormente a la escuela y a aquellos que ocupaban aulas en pisos superiores y el pabellón A. La legislación peruana debe contemplar el problema del manejo clandestino de residuos peligrosos.

Objectives: To describe clinical and epidemiological features of cases of acute intoxication caused by ethyl acrylate due to clandestine management of a container with this substance in an urban area in Comas District, Lima, Peru, in November 2002. Materials and methods: Analytical cross sectional study performed in residents and school population near the affected area. A survey was performed in every exposed person. Cases were defined as those people presenting with headache, eye irritation, nausea, abdominal pain, and intense pruritus. Accidents were characterized according to time of occurrence, space, and affected person(s). Exposure factors favoring the presence of affected persons were explored in a nearby school. Data was input in Epi Info v 6.0, and it was analyzed using STATA v 8.0 software. Results: 456 residents and 326 school students were interviewed. General attack rate was 21,9%, 46,6% at the nearby school, and 4,2% in surrounding households. Predominating symptoms were headache, 56%, eye irritation, 47%, abdominal pain, 42%. 23% of all affected persons required hospitalization. Staying in the upper floors in the nearby school was a risk factor for being affected, with an odds ratio (OR) reported as 4,54 (95% confidence interval [CI]: 2,66–7,84), and particularly in the «A¼ wing the OR was 3,82 (95% IC: 2,33 – 6,25). Conclusions: Predominant symptoms for acute intoxication caused by ethyl acrylate exposure were headache, eye irritation, and abdominal pain. Being near to the exposure area and dispersion of toxic fumes influenced the attack rate, mostly affecting the nearby school and those students in the upper floors and the «A¼ wing. Peruvian law should be stricter with respect to management of dangerous waste.