Juliette Thariat

Management of choroidal metastases

BACKGROUND Choroidal metastases (CM) are the most common malignant intraocular lesion observed in up to 4-12% of necropsy series of patients with solid cancer. The spectrum of presentations varies from prevalent CM in disseminated cancer to isolated CM. CM are responsible for visual deterioration. Depending on the primary cancer, estimated life expectancy, overall cancer presentation and ocular symptoms, the management of CM varies widely. We address the multidisciplinary management of CM and technical aspects of radiotherapy. MATERIAL AND METHODS A systematic review of literature was performed from 1974 to 2014. RESULTS Choroidal metastases occur preferentially in breast and lung carcinomas but are reported in all cancer types. The standard treatment remains external beam radiotherapy, applying 30Gy in 10 fractions or 40Gy in 20 fractions. The reported complete response and improved visual acuity rates are 80% and 57% to 89%, respectively. Some chemotherapy or new targeted therapy regimens yield promising CM response rates. DISCUSSION Radiation therapy consistently shows rapid symptom alleviation, yield excellent local control and functional outcomes. However, there are only few reports on late toxicities after 6months given the unfavorable prognostic of CM patients. Selected patients may live more than two years, underlying the need to better assess mean and long term outcomes. Some authors have favored exclusive systemic strategies with omission of irradiation. The current literature suffers from the scarcity of prospective trials. Duration of tumor response following systemic therapy is rarely reported but appears less favorable as compared to radiotherapy. Systemic treatments may be proposed for pauci-symptomatic CM in a polymetastatic context while radiation therapy remains necessary in symptomatic CM either upfront or as an alternating treatment. Focalized radiation like brachytherapy and proton therapy may be proposed for isolated CM with long disease-free interval between primary and CM, as these techniques have the potential to yield better tumor and functional outcomes in patients with long life expectancy.

Impact of dose-rate on the low-dose hyper-radiosensitivity and induced radioresistance (HRS/IRR) response

Abstract Purpose: To ask whether dose-rate influences low-dose hyper- radiosensitivity and induced radioresistance (HRS/IRR) response in rat colon progressive (PRO) and regressive (REG) cells. Methods: Clonogenic survival was applied to tumorigenic PRO and non-tumorigenic REG cells irradiated with 60Co γ-rays at 0.0025–500 mGy.min−1. Both clonogenic survival and non-homologous end-joining (NHEJ) pathway involved in DNA double-strand breaks (DSB) repair assays were applied to PRO cells irradiated at 25 mGy.min−1 with 75 kV X-rays only. Results: Irrespective of dose-rates, marked HRS/IRR responses were observed in PRO but not in REG cells. For PRO cells, the doses at which HRS and IRR responses are maximal were dependent on dose-rate; conversely exposure times during which HRS and IRR responses are maximal (tHRSmax and tIRRmax) were independent of dose-rate. The tHRSmax and tIRRmax values were 23 ± 5 s and 66 ± 7 s (mean ± standard error of the mean [SEM], n = 7), in agreement with literature data. Repair data show that tHRSmax may correspond to exposure time during which NHEJ is deficient while tIRRmax may correspond to exposure time during which NHEJ is complete. Conclusion: HRS response may be maximal if exposure times are shorter than tHRSmax irrespective of dose, dose-rate and cellular model. Potential application of HRS response in radiotherapy is discussed.

Radio-anatomy of the superior vena cava syndrome and therapeutic orientations

Superior vena cava syndrome (SVCS) groups all the signs secondary to the obstruction of superior vena cava drainage and the increase in the venous pressure in the territories upstream. There are two major causes of SVCS: malignant, dominated by bronchopulmonary cancer, and benign, often secondary to the presence of poorly positioned implantable venous devices. CT scan is the key examination for the exploration of SVCS. It specifies the characteristics of the stenosis, its aetiology and detects collateral venous routes. Scannography reconstructions provide a true map of the obstacle, indispensable in planning the endovascular treatment.

Management of thyroid nodules on US with benign or atypical cytological features.

The diagnosis of thyroid nodule is based on the ultrasound examination and TIRADS (Thyroid Imaging Reporting and Database System), which classifies the risk of malignancy according to ultrasound criteria [1]. This determines the management of the patient, the cornerstone of which is ultrasound-guided fine needle aspiration, which allows the thyroid nodule to be classified into one of six cytological categories associated with a risk of cancer and the diagnostic and therapeutic action to be taken according to the Bethesda reporting system of 2010 [2]. Highly suspicious TIRADS ultrasound signs must be strictly defined to avoid reducing the specificity and positive predictive value of the score.

The liquid biopsy: a tool for a combined diagnostic and theranostic approach for care of a patient with late-stage lung carcinoma presenting with bilateral ocular metastases

ABSTRACT Introduction: Liquid biopsies (LB) are used routinely in clinical practice in two situations for late stage non-small-cell lung cancer (NSCLC) patients, (i) at the initial diagnosis when looking for activating mutations in EGFR in the absence of analyzable tissue DNA and, (ii) during tumor progression on a tyrosine kinase inhibitor treatment to look for the resistance mutation T790M in EGFR. LB is not presently recommended in daily practice for the diagnosis of NSCLC. Areas covered: We report the diagnosis of a NSCLC in a patient with bilateral ocular metastases after detection of a deletion in exon 19 of EGFR when using plasma DNA. Without histological analysis, the origin of the primary ocular metastasis was uncertain. In this context, a LB showing an activating mutation in EGFR and circulating tumor cells positive for TTF1 led to the diagnosis of NSCLC and targeted therapy. Expert commentary: When no tumor tissue sample is available a LB can be used to diagnose for metastatic NSCLC, when a mutation in EGFR is identified. While a tissue biopsy is the gold standard approach for the diagnosis of a NSCLC and for identification of activating mutations, LB can exceptionally provide both a diagnosis of the primitive tumor and indicate appropriate therapy based on a molecular analysis.

Dosimetrical and radiobiological approach to manage the dosimetric shift in the transition of dose calculation algorithm in radiation oncology: how to improve high quality treatment and avoid unexpected outcomes?

BackgroundFor a given prescribed dose of radiotherapy, with the successive generations of dose calculation algorithms, more monitor units (MUs) are generally needed. This is due to the implementation of successive improvements in dose calculation: better heterogeneity correction and more accurate estimation of secondary electron transport contribution. More recently, there is the possibility to report the dose-to-medium, physically more accurate compared to the dose-to-water as the reference one. This last point is a recent concern and the main focus of this study.MethodsIn this paper, we propose steps for a general analysis procedure to estimate the dosimetric alterations, and the potential clinical changes, between a reference algorithm and a new one. This includes dosimetric parameters, gamma index, radiobiology indices based on equivalent uniform dose concept and statistics with bootstrap simulation. Finally, we provide a general recommendation on the clinical use of new algorithms regarding the dose prescription or dose limits to the organs at risks.ResultsThe dosimetrical and radiobiological data showed a significant effect, which might exceed 5–10%, of the calculation method on the dose the distribution and clinical outcomes for lung cancer patients. Wilcoxon signed rank paired comparisons indicated that the delivered dose in MUs was significantly increased (> 2%) using more advanced dose calculation methods as compared to the reference one.ConclusionThis paper illustrates and explains the use of dosimetrical, radiobiologcal and statistical tests for dosimetric comparisons in radiotherapy. The change of dose calculation algorithm may induce a dosimetric shift, which has to be evaluated by the physicists and the oncologists. This includes the impact on tumor control and on the risk of toxicity based on normal tissue dose constraints. In fact, the alteration in dose distribution makes it hard to keep exactly the same tumor control probability along with the same normal tissue complication probability.

Impact of the NTCP modeling on medical decision to select eligible patient for proton therapy: the usefulness of EUD as an indicator to rank modern photon vs proton treatment plans

Abstract Purpose: The aim of this study is to evaluate the impact of normal tissue complication probability (NTCP)-based radiobiological models on the estimated risk for late radiation lung damages. The second goal is to propose a medical decision-making approach to select the eligible patient for particle therapy. Materials and methods: Fourteen pediatric patients undergoing cranio-spinal irradiation were evaluated. For each patient, two treatment plans were generated using photon and proton therapy with the same dose prescriptions. Late radiation damage to lung was estimated using three NTCP concepts: the Lyman-Kutcher-Burman, the equivalent uniform dose (EUD) and the mean lung dose according to the quantitative analysis of normal tissue effects in the clinic QUANTEC review. Wilcoxon paired test was used to calculate p-value. Results: Proton therapy achieved lower lung EUD (Gy). The average NTCP values were significantly lower with proton plans, p < .05, using the three NTCP concepts. However, applying the same TD50/5 using radiobiological models to compare NTCP from proton and photon therapy, the ΔNTCP was not a convincing method to measure the potential benefit of proton therapy. Late radiation pneumonitis estimated from the mean lung dose model correlated with QUANTEC data better. Conclusions: Treatment effectiveness assessed on NTCP reduction depends on radiobiological predictions and parameters used as inputs for in silico evaluation. Because estimates of absolute NTCP values from LKB and GN models are imprecise due to EUD ≪ TD50/5, a reduction of the EUD value with proton plans would better predict a reduction of dose/toxicity. The EUD concept appears as a robust radiobiological surrogate of the dose distribution to select the optimal patient’s plan.

Radiothérapie des cancers du sein inflammatoires

BACKGROUND Inflammatory breast cancer accounts for 1-5% of all breast cancers. It is associated with a poor prognosis, because of an increased risk to develop metastases in comparison with all breast malignancies. The treatment is multimodal. We have evaluated the role of radiotherapy: indications, techniques and impact for local control and overall survival. METHOD The series of the literature with more than 40 patients irradiated for inflammatory breast cancer published since 1995 were analyzed. RESULTS Chemotherapy was always delivered first. Adjuvant radiotherapy was associated with local control and overall survival at 10 years of 63-92% and 51-64 respectively. Without surgery, local control was 65% and overal survival 38% at 10years. Results of concomitant radiochemotherapy were reported: the studies were heterogenous. Modalities of radiotherapy were detailed with respect to dose and fractionation, target-volumes and technical considerations (including bolus). CONCLUSION The multimodal strategy comprises systematically radiotherapy with an evaluation of tumor response to maximise resecability.

Cataract Avoidance With Proton Therapy in Ocular Melanomas

Purpose The lens is a radiosensitive organ. Any dose of cephalic irradiation can give rise to radiation-induced cataracts. Contrary to other forms of radiotherapy, proton therapy (PT) can spare all or part of the lens due to accurate dose deposition. We investigated whether a lens-sparing approach was relevant to avoid cataracts in uveal melanoma patients. Methods Patients were referred for PT from onco-ophthalmologists of private and academic institutions. Patients without preexisting cataracts or implants were entered in a prospective database. Dose thresholds responsible for cataracts were investigated in volumes of lens or lens periphery. Lens opacifications and de novo vision-impairing cataracts (VICs) had biannual follow up by ophthalmologists blinded to lens dose. Correlations between dose-volume relationships and VICs were assessed using univariate/multivariate regressions. Results Between 1991 and 2015, 1696 uveal melanoma patients were consecutively treated with PT. After a median follow up of 48 months, 14.4% and 8.7% of patients had cataracts and VIC within median times of 19 and 28 months, respectively. Median values of mean lens and lens periphery doses were 1.1 (radiobiologically effective [RBE] dose in photon-equivalent grays [GyRBE]) and 6.5 GyRBE, respectively. The lens received no dose in 25% of the patients. At an irradiated lens volume of ≤5%, there was no significantly increased risk for VIC below a dose of 10 GyRBE. Conclusions A lens-sparing approach is feasible and results not only in reduced need for cataract surgery but also in better fundus-based tumor control. Reassessment of radioprotection rules for lens dose thresholds may follow.