Report of long-term follow-up in a randomized trial comparing radiation therapy and radiation therapy plus hyperthermia to metastatic lymphnodes in stage IV head and neck patients

Purpose: The treatment of inoperable metastatic lymphnodes in patients with head and neck cancer represents a therapeutic challenge. Clinical results using conventional radiation therapy are disappointing; on the other hand, the evaluation of recent innovative radiotherapeutic methods is still pending. The end points of this analysis were focused on long-term local control, on its potential influence on survival, and on late toxicity of a previously reported randomized Phase III study comparing conventionally fractionated radical irradiation alone or combined with local hyperthermia in fixed and inoperable metastatic neck lymphnodes. Methods and Materials: The medical records of 41 patients (44 nodes) with advanced locoregional Stage IV squamous cell cancer of the head and neck and randomized to treatment in the period 1985-1986 with irradiation alone ( 22 23 evaluable nodes) or combined with external hyperthermia ( 18 21 evaluable nodes), were re-evaluated. Results: The statistically significant difference observed in "early" response (p = 0.0164) in favor of the combined treatment results in improved 5-year actuarial nodal control (p = 0.015). Clinical improvement noted in tumor control positively affects survival, leading to a statistically significant difference in survival at 5 years (p = 0.02). With respect to side effects, no clearly enhanced acute or late toxicity has been found; as severe late effects, two patients with bone necroses possibly related to the combined treatment have been observed. Thermal analysis failed to show a significant correlation between heating parameters and the end points of the study. Conclusion: This report with 5-year follow-up confirms the efficacy and the absence of severe toxicity of the combination of radical radiation and hyperthermia in the treatment of metastatic lymphnodes in Stage IV squamous cell carcinoma of the head and neck

Numerical Simulation of the Medical Linear Accelerator Electron Beams Absorption by ABS-Plastic doped with Metal

In this paper the numerical simulation results of the dose spatial distribution of the medical electron beams in ABS-plastic doped with different concentrations of lead and zinc are shown. The dependences of the test material density on the lead and zinc mass concentrations are illustrated. The depth dose distributions of the medical electron beams in the modified ABS-plastic for three energies 6 MeV, 12 MeV and 20 MeV are tested. The electron beam shapes in the transverse plane in ABS-plastic doped with different concentrations of lead and zinc are presented

Combinatorial optimisation in radiotherapy treatment planning

The goal of radiotherapy is to cover a target area with a desired radiation dose while keeping the exposition of non-target areas as low as possible in order to reduce radiation side effects. In the case of Intensity Modulated Proton Therapy (IMPT), the dose distribution is typically designed via a treatment planning optimisation process based on classical optimisation algorithms on some objective functions. We investigate the planning optimisation problem under the point of view of the Theory of Complexity in general and, in particular, of the Combinatorial Optimisation Theory. We firstly give a formal definition of a simplified version of the problem that is in the complexity class NPO. We prove that above version is computationally hard, i.e. it belongs to the class NPO\PTAS if NP not equal P. We show how Combinatorial Optimisation Theory can give valuable tools, both conceptual and practical, in treatment plan definition, opening the way for new deterministic algorithms with bounded time complexity which have to support the technological evolution up to adaptive plans exploiting near real time solutions

Randomised trial of proton vs. carbon ion radiation therapy in patients with low and intermediate grade chondrosarcoma of the skull base, clinical phase III study

<p/> <p>Background</p> <p>Low and intermediate grade chondrosarcomas are relative rare bone tumours. About 5-12% of all chondrosarcomas are localized in base of skull region. Low grade chondrosarcoma has a low incidence of distant metastasis but is potentially lethal disease. Therefore, local therapy is of crucial importance in the treatment of skull base chondrosarcomas. Surgical resection is the primary treatment standard. Unfortunately the late diagnosis and diagnosis at the extensive stage are common due to the slow and asymptomatic growth of the lesions. Consequently, complete resection is hindered due to close proximity to critical and hence dose limiting organs such as optic nerves, chiasm and brainstem. Adjuvant or additional radiation therapy is very important for the improvement of local control rates in the primary treatment. Proton therapy is the gold standard in the treatment of skull base chondrosarcomas. However, high-LET (linear energy transfer) beams such as carbon ions theoretically offer advantages by enhanced biologic effectiveness in slow-growing tumours.</p> <p>Methods/Design</p> <p>The study is a prospective randomised active-controlled clinical phase III trial. The trial will be carried out at Heidelberger Ionenstrahl-Therapie (HIT) centre as monocentric trial.</p> <p>Patients with skull base chondrosarcomas will be randomised to either proton or carbon ion radiation therapy. As a standard, patients will undergo non-invasive, rigid immobilization and target volume definition will be carried out based on CT and MRI data. The biologically isoeffective target dose to the PTV (planning target volume) in carbon ion treatment will be 60 Gy E ± 5% and 70 Gy E ± 5% (standard dose) in proton therapy respectively. The 5 year local-progression free survival (LPFS) rate will be analysed as primary end point. Overall survival, progression free and metastasis free survival, patterns of recurrence, local control rate and morbidity are the secondary end points.</p> <p>Discussion</p> <p>Up to now it was impossible to compare two different particle therapies, i.e. protons and carbon ions, directly at the same facility in connection with the treatment of low grade skull base chondrosarcomas.</p> <p>This trial is a phase III study to demonstrate that carbon ion radiotherapy (experimental treatment) is not relevantly inferior and at least as good as proton radiotherapy (standard treatment) with respect to 5 year LPFS in the treatment of chondrosarcomas. Additionally, we expect less toxicity in the carbon ion treatment arm.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov identifier: NCT01182753</p

Early and late skin reactions to radiotherapy for breast cancer and their correlation with radiation-induced DNA damage in lymphocytes

INTRODUCTION: Radiotherapy outcomes might be further improved by a greater understanding of the individual variations in normal tissue reactions that determine tolerance. Most published studies on radiation toxicity have been performed retrospectively. Our prospective study was launched in 1996 to measure the in vitro radiosensitivity of peripheral blood lymphocytes before treatment with radical radiotherapy in patients with breast cancer, and to assess the early and the late radiation skin side effects in the same group of patients. We prospectively recruited consecutive breast cancer patients receiving radiation therapy after breast surgery. To evaluate whether early and late side effects of radiotherapy can be predicted by the assay, a study was conducted of the association between the results of in vitro radiosensitivity tests and acute and late adverse radiation effects. METHODS: Intrinsic molecular radiosensitivity was measured by using an initial radiation-induced DNA damage assay on lymphocytes obtained from breast cancer patients before radiotherapy. Acute reactions were assessed in 108 of these patients on the last treatment day. Late morbidity was assessed after 7 years of follow-up in some of these patients. The Radiation Therapy Oncology Group (RTOG) morbidity score system was used for both assessments. RESULTS: Radiosensitivity values obtained using the in vitro test showed no relation with the acute or late adverse skin reactions observed. There was no evidence of a relation between acute and late normal tissue reactions assessed in the same patients. A positive relation was found between the treatment volume and both early and late side effects. CONCLUSION: After radiation treatment, a number of cells containing major changes can have a long survival and disappear very slowly, becoming a chronic focus of immunological system stimulation. This stimulation can produce, in a stochastic manner, late radiation-related adverse effects of varying severity. Further research is warranted to identify the major determinants of normal tissue radiation response to make it possible to individualize treatments and improve the outcome of radiotherapy in cancer patients

ICAR: endoscopic skull‐base surgery

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