[Panniculitis during BRAF inhibitor and/or MEK inhibitor therapy: A new case report and literature review]. / Hypodermite sous inhibiteur de BRAF et/ou inhibiteur de MEK : revue de la littérature à partir d'une nouvelle observation.

INTRODUCTION: BRAF inhibitors±MEK inhibitors can cause panniculitis. Since the initial case described in 2012 by Zimmer et al., some sixty further cases have been reported. Based on a clinical study and a recent and complete review of the literature, we set out in detail the characteristics of panniculitis occurring during BRAF and MEK inhibition therapy as well as the treatment thereof. PATIENTS AND METHODS: A 25-year-old-patient followed for multi-metastatic melanoma and taking dabrafenib and trametinib consulted for the appearance, twenty-two days after the start of targeted therapy (TT), of panniculitis of the legs and forearms possibly induced by the TT after other causes had been ruled out. The TT had been continued following dose reduction and corticoid therapy for ten days, and complete resolution occurred after fifteen days. RESULTS: Fifty-three cases of panniculitis during BRAF±MEK inhibition therapy were analysed. The condition occurred mainly with BRAF inhibitors alone (especially vemurafenib), but it was also described with three combinations of BRAF and MEK inhibitors, regardless of age (median: 45 years), with a M/F ratio of 0.51, and in 50 % of cases, it occurred within the first month (time to onset: between 1 and 480 days). Non-specific biopsy is useful to rule out differential diagnoses. Symptomatic anti-inflammatory treatment, whether systemic or topical, may be given. In the absence of signs of severity, the TT may be continued. CONCLUSION: When panniculitis occurs during BRAF±MEK inhibitor therapy, the causal role of the TT must be considered after full etiological investigation. It is essential to determine whether a causal relationship exists in order to avoid unwarranted cessation of treatment.

DEGRO practical guideline for partial-breast irradiation.

PURPOSE: This consensus statement from the Breast Cancer Working Group of the German Society for Radiation Oncology (DEGRO) aims to define practical guidelines for accelerated partial-breast irradiation (APBI). METHODS: Recent recommendations for relevant aspects of APBI were summarized and a panel of experts reviewed all the relevant literature. Panel members of the DEGRO experts participated in a series of conferences, supplemented their clinical experience, performed a literature review, and formulated recommendations for implementing APBI in clinical routine, focusing on patient selection, target definition, and treatment technique. RESULTS: Appropriate patient selection, target definition for different APBI techniques, and basic rules for appropriate APBI techniques for clinical routine outside of clinical trials are described. Detailed recommendations for APBI in daily practice, including dose constraints, are given. CONCLUSION: Guidelines are mandatory to assure optimal results of APBI using different techniques.

DEGRO practical guidelines for radiotherapy of breast cancer VI: therapy of locoregional breast cancer recurrences.

OBJECTIVE: To update the practical guidelines for radiotherapy of patients with locoregional breast cancer recurrences based on the current German interdisciplinary S3 guidelines 2012. METHODS: A comprehensive survey of the literature using the search phrases "locoregional breast cancer recurrence", "chest wall recurrence", "local recurrence", "regional recurrence", and "breast cancer" was performed, using the limits "clinical trials", "randomized trials", "meta-analysis", "systematic review", and "guidelines". CONCLUSIONS: Patients with isolated in-breast or regional breast cancer recurrences should be treated with curative intent. Mastectomy is the standard of care for patients with ipsilateral breast tumor recurrence. In a subset of patients, a second breast conservation followed by partial breast irradiation (PBI) is an appropriate alternative to mastectomy. If a second breast conservation is performed, additional irradiation should be mandatory. The largest reirradiation experience base exists for multicatheter brachytherapy; however, prospective clinical trials are needed to clearly define selection criteria, long-term local control, and toxicity. Following primary mastectomy, patients with resectable locoregional breast cancer recurrences should receive multimodality therapy including systemic therapy, surgery, and radiation +/- hyperthermia. This approach results in high local control rates and long-term survival is achieved in a subset of patients. In radiation-naive patients with unresectable locoregional recurrences, radiation therapy is mandatory. In previously irradiated patients with a high risk of a second local recurrence after surgical resection or in patients with unresectable recurrences, reirradiation should be strongly considered. Indication and dose concepts depend on the time interval to first radiotherapy, presence of late radiation effects, and concurrent or sequential systemic treatment. Combination with hyperthermia can further improve tumor control. In patients with isolated axillary or supraclavicular recurrence, durable disease control is best achieved with multimodality therapy including surgery and radiotherapy. Radiation therapy significantly improves local control and should be applied whenever feasible.

DEGRO practical guidelines: radiotherapy of breast cancer III--radiotherapy of the lymphatic pathways.

AIM: The purpose of this work is to update the practical guidelines for adjuvant radiotherapy of the regional lymphatics of breast cancer published in 2008 by the breast cancer expert panel of the German Society of Radiation Oncology (DEGRO). METHODS: A comprehensive survey of the literature concerning regional nodal irradiation (RNI) was performed using the following search terms: "breast cancer", "radiotherapy", "regional node irradiation". Recent randomized trials were analyzed for outcome as well as for differences in target definition. Field arrangements in the different studies were reproduced and superimposed on CT slices with individually contoured node areas. Moreover, data from recently published meta-analyses and guidelines of international breast cancer societies, yielding new aspects compared to 2008, provided the basis for defining recommendations according to the criteria of evidence-based medicine. In addition to the more general statements of the German interdisciplinary S3 guidelines updated in 2012, this paper addresses indications, targeting, and techniques of radiotherapy of the lymphatic pathways after surgery for breast cancer. RESULTS: International guidelines reveal substantial differences regarding indications for RNI. Patients with 1-3 positive nodes seem to profit from RNI compared to whole breast (WBI) or chest wall irradiation alone, both with regard to locoregional control and disease-free survival. Irradiation of the regional lymphatics including axillary, supraclavicular, and internal mammary nodes provided a small but significant survival benefit in recent randomized trials and one meta-analysis. Lymph node irradiation yields comparable tumor control in comparison to axillary lymph node dissection (ALND), while reducing the rate of lymph edema. Data concerning the impact of 1-2 macroscopically affected sentinel node (SN) or microscopic metastases on prognosis are conflicting. CONCLUSION: Recent data suggest that the current restrictive use of RNI should be scrutinized because the risk-benefit relationship appears to shift towards an improvement of outcome.

Treatment planning after hydrogel injection during radiotherapy of prostate cancer.

PURPOSE: Imaging for treatment planning shortly after hydrogel injection is optimal for practical purposes, reducing the number of appointments. The aim was to evaluate the actual difference between early and late imaging. PATIENTS AND METHODS: Treatment planning computed tomography (CT) was performed shortly after injection of 10 ml hydrogel (CT1) and 1-2 weeks later (CT2) for 3 patients. The hydrogel was injected via the transperineal approach after dissecting the space between the prostate and rectum with a saline/lidocaine solution of at least 20-ml. Hydrogel volume and distances between the prostate and rectal wall were compared. Intensity-modulated radiotherapy (IMRT) plans up to a dose of 78 Gy were generated (rectum V70 < 20 %, rectum V50 < 50 %; with the rectum including hydrogel volume for planning). RESULTS: A mean planning treatment volume of 104 cm(3) resulted for a prostate volume of 37 cm(3). Hydrogel volumes of 30 and 10 cm(3) were determined in CT1 and CT2, respectively. Distances between the prostate and rectal wall at the levels of the base, middle, and apex were 1.7 cm, 1.6 cm, 1.5 cm in CT1 and 1.3 cm, 1.2 cm, 0.8 cm in CT2, respectively, corresponding to a mean decrease of 24, 25, and 47 %. A small overlap between the PTV and the rectum was found only in 1 patient in CT2 (0.2 cm(3)). The resulting mean rectum (without hydrogel) V75, V70, V60, V50 increased from 0 %, 0 %, 0.6 %, 10 % in CT1 to 0.1 %, 1.2 %, 6 %, 20 % in CT2, respectively. CONCLUSION: Treatment planning based on imaging shortly after hydrogel injection overestimates the actual hydrogel volume during the treatment as a result of not-yet-absorbed saline solution and air bubbles.

Quality of life after intensity-modulated radiotherapy for prostate cancer with a hydrogel spacer. Matched-pair analysis.

BACKGROUND: Hydrogel spacer is an innovative method to protect the rectal wall during prostate cancer radiotherapy. Clinical effects are not well known. METHODS: Patients have been surveyed before, at the last day, and 2-3 months after radiotherapy using a validated questionnaire (Expanded Prostate Cancer Index Composite). Median dose to the prostate in the spacer subgroup (SP) was 78 Gy in 2 Gy fractions. The results were independently compared with two matched-pair subgroups (treated conventionally without spacer): 3D conformal 70.2 Gy in 1.8 Gy fractions (3DCRT) and intensity-modulated radiotherapy (IMRT) 76 Gy in 2 Gy fractions. There were 28 patients in each of the three groups. RESULTS: Baseline mean bowel bother scores were 96 points in all subgroups. Similar mean changes (SP 16, 3DCRT 14, IMRT 17 points) were observed at the end of radiotherapy. The smallest difference resulted in the spacer subgroup 2-3 months after radiotherapy (SP 2, 3DCRT 8, IMRT 6 points). Bowel bother scores were only significantly different in comparison to baseline levels in the spacer subgroup. The percentage of patients reporting moderate/big bother with specific symptoms did not increase for any item (urgency, frequency, diarrhoea, incontinence, bloody stools, pain). CONCLUSION: Moderate bowel quality-of-life changes can be expected during radiotherapy irrespective of spacer application or total dose. Advantages with a spacer can be expected a few weeks after treatment.

Integrated boost IMRT with FET-PET-adapted local dose escalation in glioblastomas. Results of a prospective phase II study.

PURPOSE: Dose escalations above 60 Gy based on MRI have not led to prognostic benefits in glioblastoma patients yet. With positron emission tomography (PET) using [(18)F]fluorethyl-L-tyrosine (FET), tumor coverage can be optimized with the option of regional dose escalation in the area of viable tumor tissue. METHODS AND MATERIALS: In a prospective phase II study (January 2008 to December 2009), 22 patients (median age 55 years) received radiochemotherapy after surgery. The radiotherapy was performed as an MRI and FET-PET-based integrated-boost intensity-modulated radiotherapy (IMRT). The prescribed dose was 72 and 60 Gy (single dose 2.4 and 2.0 Gy, respectively) for the FET-PET- and MR-based PTV-FET((72 Gy)) and PTV-MR((60 Gy)). FET-PET and MRI were performed routinely for follow-up. Quality of life and cognitive aspects were recorded by the EORTC-QLQ-C30/QLQ Brain20 and Mini-Mental Status Examination (MMSE), while the therapy-related toxicity was recorded using the CTC3.0 and RTOG scores. RESULTS: Median overall survival (OS) and disease-free survival (DFS) were 14.8 and 7.8 months, respectively. All local relapses were detected at least partly within the 95% dose volume of PTV-MR((60 Gy)). No relevant radiotherapy-related side effects were observed (excepted alopecia). In 2 patients, a pseudoprogression was observed in the MRI. Tumor progression could be excluded by FET-PET and was confirmed in further MRI and FET-PET imaging. No significant changes were observed in MMSE scores and in the EORTC QLQ-C30/QLQ-Brain20 questionnaires. CONCLUSION: Our dose escalation concept with a total dose of 72 Gy, based on FET-PET, did not lead to a survival benefit. Acute and late toxicity were not increased, compared with historical controls and published dose-escalation studies.

[Solitary iris metastasis from breast cancer. Effective local therapy with electron beam irradiation]. / Solitäre Irismetastase bei Mammakarzinom. Wirksame lokale Therapie durch Elektronenbestrahlung.

BACKGROUND: The prevalence of intraocular metastases from breast cancer is approximately 4-5%. Solitary metastases of the iris are rare. We report on successful treatment of a solitary iris metastasis using electron beam irradiation. CASE REPORT: A 30-year-old patient presented with an amelanotic tumor of the iris and the anterior chamber angle of her right amblyopic eye. The patient had undergone left-sided breast-conserving surgery and lymph node dissection 3 years before followed by chemotherapy and radiotherapy. The iris tumor was considered a metastasis. Fractionated electron beam irradiation was performed applying a total dose of 50 Gy in fractions of 5 x 2 Gy/week, electrons (9 MeV). The iris metastasis was completely resolved 13 months after radiotherapy. Until now no signs of cataract have been detected and visual acuity has remained stable. CONCLUSION: Electron beam irradiation of this iris metastasis was an effective treatment for preserving visual acuity and ocular function with tolerable acute toxicity and so far no adverse side effects.

Radiation recall dermatitis from docetaxel.

BACKGROUND: Experiences with inflammatory skin reactions after treatment with docetaxel and prior exposure to radiotherapy like a recall phenomenon are very rare. We present the case of an uncommon and severe skin reaction after docetaxel application and prior radiotherapy. PATIENT AND METHODS: A 40-year-old female was treated with an upper body irradiation with electrons because of relapsed breast cancer. In addition, because of metastases of brain and bone she received radiotherapy on the whole brain and the left pelvis. One week after radiotherapy weekly chemotherapy with docetaxel was started. RESULTS: Radiotherapy was well tolerated. There was a cutaneous erythema RTOG grade 1. After second application of docetaxel the patient developed a severe skin erythema, after fourth application confluent desquamations exactly demarcated the previously irradiated skin area. After discontinuation of docetaxel and after antiinflammatory treatment the skin reactions improved rapidly. CONCLUSION: In our opinion the severe skin reaction was clearly associated with the application of docetaxel like a recall phenomenon after previous radiotherapy. In case of severe skin reaction after this therapy it is important to know the possibility of recall phenomenon.