Dose compensation based on biological effectiveness due to interruption time for photon radiation therapy.

OBJECTIVE: To evaluate the biological effectiveness of dose associated with interruption time; and propose the dose compensation method based on biological effectiveness when an interruption occurs during photon radiation therapy. METHODS: The lineal energy distribution for human salivary gland tumor was calculated by Monte Carlo simulation using a photon beam. The biological dose (Dbio) was estimated using the microdosimetric kinetic model. The dose compensating factor with the physical dose for the difference of the Dbio with and without interruption (Δ) was derived. The interruption time (τ) was varied to 0.1, 0.2, 0.3, 0.4, 0.5, 1, 2, 3, 4, 5, 10, 20, 30, 40, 50, 75, and 120 min. The dose per fraction and dose rate varied from 2 to 8 Gy and 0.1 to 24 Gy/min, respectively. RESULTS: The maximum Δ with 1 Gy/min occurred when the interruption occurred at half the dose. The Δ with 1 Gy/min at half of the dose was over 3% for τ >= 20 min for 2 Gy, τ = 10 min for 5 Gy, and τ = 10 min for 8 Gy. The maximum difference of the Δ due to the dose rate was within 3% for 2 and 5 Gy, and achieving values of 4.0% for 8 Gy. The dose compensating factor was larger with a high dose per fraction and high-dose rate beams. CONCLUSION: A loss of biological effectiveness occurs due to interruption. Our proposal method could correct for the unexpected decrease of the biological effectiveness caused by interruption time. ADVANCES IN KNOWLEDGE: For photon radiotherapy, the interruption causes the sublethal damage repair. The current study proposed the dose compensation method for the decrease of the biological effect by the interruption.

Reformulation of a clinical-dose system for carbon-ion radiotherapy treatment planning at the National Institute of Radiological Sciences, Japan.

At the National Institute of Radiological Sciences (NIRS), more than 8,000 patients have been treated for various tumors with carbon-ion (C-ion) radiotherapy in the past 20 years based on a radiobiologically defined clinical-dose system. Through clinical experience, including extensive dose escalation studies, optimum dose-fractionation protocols have been established for respective tumors, which may be considered as the standards in C-ion radiotherapy. Although the therapeutic appropriateness of the clinical-dose system has been widely demonstrated by clinical results, the system incorporates several oversimplifications such as dose-independent relative biological effectiveness (RBE), empirical nuclear fragmentation model, and use of dose-averaged linear energy transfer to represent the spectrum of particles. We took the opportunity to update the clinical-dose system at the time we started clinical treatment with pencil beam scanning, a new beam delivery method, in 2011. The requirements for the updated system were to correct the oversimplifications made in the original system, while harmonizing with the original system to maintain the established dose-fractionation protocols. In the updated system, the radiation quality of the therapeutic C-ion beam was derived with Monte Carlo simulations, and its biological effectiveness was predicted with a theoretical model. We selected the most used C-ion beam with αr = 0.764 Gy(-1) and ß = 0.0615 Gy(-2) as reference radiation for RBE. The C-equivalent biological dose distribution is designed to allow the prescribed survival of tumor cells of the human salivary gland (HSG) in entire spread-out Bragg peak (SOBP) region, with consideration to the dose dependence of the RBE. This C-equivalent biological dose distribution is scaled to a clinical dose distribution to harmonize with our clinical experiences with C-ion radiotherapy. Treatment plans were made with the original and the updated clinical-dose systems, and both physical and clinical dose distributions were compared with regard to the prescribed dose level, beam energy, and SOBP width. Both systems provided uniform clinical dose distributions within the targets consistent with the prescriptions. The mean physical doses delivered to targets by the updated system agreed with the doses by the original system within ± 1.5% for all tested conditions. The updated system reflects the physical and biological characteristics of the therapeutic C-ion beam more accurately than the original system, while at the same time allowing the continued use of the dose-fractionation protocols established with the original system at NIRS.

Radiation therapy administration and survival in stage I/II extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue.

PURPOSE: To determine the factors associated with the use of radiation therapy and associated survival outcomes in early-stage marginal zone lymphoma of the mucosa-associated lymphoid tissue (MALT). METHODS AND MATERIALS: We extracted data on adult patients with stage I/II MALT lymphoma diagnoses between 1998 and 2010 recorded in the Surveillance, Epidemiology, and End Results (SEER) database. We studied factors associated with radiation therapy administration in a logistic regression model and described the cumulative incidence of lymphoma-related death (LRD) according to receipt of the treatment. The association of radiation therapy with survival was explored in multivariate models with adjustment for immortal time bias. RESULTS: Of the 7774 identified patients, 36% received radiation therapy as part of the initial course of treatment. Older patients; black or Hispanic men; white, Hispanic, and black women; and socioeconomically disadvantaged and underinsured patients had a significantly lower chance of receiving radiation therapy. Radiation therapy administration was associated with a lower chance of LRD in most sites. In cutaneous, ocular, and salivary MALT lymphomas, the 5-year estimate of LRD after radiation therapy was 0%. The association of radiation therapy with overall survival in different lymphoma sites was heterogeneous, and statistically significant in cutaneous (hazard ratio 0.45, P=.009) and ocular (hazard ratio 0.47, P<.0001) locations after multivariate adjustment. CONCLUSIONS: Demographic factors are associated with the use of radiation therapy in MALT lymphoma. Clinicians should be sensitive to those disparities because the administration of radiation therapy may be associated with improved survival, particularly in cutaneous and ocular lymphomas.

Assessment of early toxicity and response in patients treated with proton and carbon ion therapy at the Heidelberg ion therapy center using the raster scanning technique.

UNLABELLED: PUROPOSE: To asses early toxicity and response in 118 patients treated with scanned ion beams to validate the safety of intensity-controlled raster scanning at the Heidelberg Ion Therapy Center. PATIENTS AND METHODS: Between November 2009 and June 2010, we treated 118 patients with proton and carbon ion radiotherapy (RT) using active beam delivery. The main indications included skull base chordomas and chondrosarcomas, salivary gland tumors, and gliomas. We evaluated early toxicity within 6 weeks after RT and the initial clinical and radiologic response for quality assurance in our new facility. RESULTS: In all 118 patients, few side effects were observed, in particular, no high numbers of severe acute toxicity were found. In general, the patients treated with particle therapy alone showed only a few single side effects, mainly Radiation Therapy Oncology Group/Common Terminology Criteria grade 1. The most frequent side effects and cumulative incidence of single side effects were observed in the head-and-neck patients treated with particle therapy as a boost and photon intensity-modulated RT. The toxicities included common radiation-attributed reactions known from photon RT, including mucositis, dysphagia, and skin erythema. The most predominant imaging responses were observed in patients with high-grade gliomas and those with salivary gland tumors. For skull base tumors, imaging showed a stable tumor outline in most patients. Thirteen patients showed improvement of pre-existing clinical symptoms. CONCLUSIONS: Side effects related to particle treatment were rare, and the overall tolerability of the treatment was shown. The initial response was promising. The data have confirmed the safe delivery of carbon ions and protons at the newly opened Heidelberg facility.

Effect of radiotherapy interruptions on survival in medicare enrollees with local and regional head-and-neck cancer.

PURPOSE: To investigate whether interruptions in radiotherapy are associated with decreased survival in a population-based sample of head-and-neck cancer patients. METHODS AND MATERIALS: Using the Surveillance, Epidemiology, and End Results-Medicare linked database we identified Medicare beneficiaries aged 66 years and older diagnosed with local-regional head-and-neck cancer during the period 1997-2003. We examined claims records of 3864 patients completing radiotherapy for the presence of one or more 5-30-day interruption(s) in therapy. We then performed Cox regression analyses to estimate the association between therapy interruptions and survival. RESULTS: Patients with laryngeal tumors who experienced an interruption in radiotherapy had a 68% (95% confidence interval, 41-200%) increased risk of death, compared with patients with no interruptions. Patients with nasal cavity, nasopharynx, oral, salivary gland, and sinus tumors had similar associations between interruptions and increased risk of death, but these did not reach statistical significance because of small sample sizes. CONCLUSIONS: Treatment interruptions seem to influence survival time among patients with laryngeal tumors completing a full course of radiotherapy. At all head-and-neck sites, the association between interruptions and survival is sensitive to confounding by stage and other treatments. Further research is needed to develop methods to identify patients most susceptible to interruption-induced mortality.

Efficacité de la neutronthérapie pour le traitement des tumeurs malignes des glandes salivaires / Effectiveness of neutron therapy for the treatment of malignant tumors of the salivary glands

INTRODUCTION: Les neutrons sont employés à des fins thérapeu-tiques depuis quatre décennies. L'avantage qu'offre cette technologie découle des caracté-ristiques des rayons émis, et plus précisément de leur capacité à transférer une grande quantité d'énergie aux structures biologiques qu'elles traversent. Cette propriété permet de détruire les cellules tumorales ou d'y provoquer des dom-mages difficilement réparables. Après différentes phases d'utilisation, influencées tant par le per-fectionnement du matériel de neutronthérapie que par le bilan global de son efficacité, nous assis-tons actuellement à une stabilisation, voire à une diminution du nombre de patients traités, et ce, en raison de la raréfaction de la technologie et d'un choix plus sélectif des tumeurs à traiter. C'est dans ce contexte que la Régie de l'assu-rance maladie du Québec (RAMQ) a demandé à l'AETMIS d'étudier la pertinence et l'efficacité. de la neutronthérapie pour le traitement des cancers des glandes salivaires (le plus souvent des carcinomes adénoïdes kystiques de la paro-tide) avec envahissement des tissus mous cervi-caux, des sinus et de la base du crâne. La Régie demandait également à l'AETMIS de préciser si cette technologie a une visée palliative ou cura-tive et, dans ce dernier cas, quels sont les taux de survie. La présente évaluation repose principalement sur l'examen d'un rapport publié en 1995 par une agence d'évaluation, des données scientifi-ques qui se sont ajoutées depuis (jusqu'en mars 2003), ainsi que de lignes directrices appuyées par des données probantes portant sur la prise en charge des patients atteints de tumeurs malignes des glandes salivaires. MÉTHODE: La présente évaluation repose principalement sur l'examen d'un rapport publié en 1995 par une agence d'évaluation, des données scientifi-ques qui se sont ajoutées depuis (jusqu'en mars 2003) ainsi que de lignes directrices appuyées par des données probantes portant sur la prise en charge des patients atteints de tumeurs malignes. CONCLUSION: L'efficacité de la neutronthérapie n'est bien éta-blie que pour le traitement des tumeurs des glan-des salivaires inopérables ou inextirpables, quel que soit leur degré de malignité ou leur stade évolutif, et pour celui des tumeurs résiduelles volumineuses après résection chirurgicale. Dans le premier cas, la neutronthérapie employée seule constitue l'option thérapeutique à privi-légier, principalement pour les carcinomes adénoïdes kystiques non résécables de glandes salivaires principales ou accessoires. Il est mani-feste que la visée palliative ressort pour les tu-meurs de stade évolutif avancé. Dans le cas des gros reliquats tumoraux, la neutronthérapie est l'une des options possibles de la radiothérapie.

Preclinical biological assessment of proton and carbon ion beams at Hyogo Ion Beam Medical Center.

PURPOSE: To assess the biologic effects of proton and carbon ion beams before clinical use. METHODS AND MATERIALS: Cultured cells from human salivary gland cancer (HSG cells) were irradiated at 5 points along a 190 MeV per nucleon proton and a 320 MeV per nucleon carbon ion beam, with Bragg peaks modulated to 6 cm widths. A linac 4 MV X-ray was used as a reference. Relative biologic effectiveness (RBE) values at each point were calculated from survival curves. Cells were also irradiated in a cell-stack phantom to identify that localized cell deaths were observed at predefined depth. Total body irradiation of C3H/He mice was performed, and the number of regenerating crypts per jejunal section was compared to calculate intestinal RBE values. For carbon ion and referential 4 MV X-ray beams, mouse right legs were irradiated by four-fractional treatment and followed up for skin reaction scoring. RESULTS: RBE values calculated from cell survival curves at the dose that would reduce cell survival to 10% (D10) ranged from 1.01 to 1.05 for protons and from 1.23 to 2.56 for carbon ions. The cell-stack phantom irradiation revealed localized cell deaths at predefined depth. The intestinal RBE values ranged from 1.01 to 1.08 for protons and from 1.15 to 1.88 for carbon ions. The skin RBE value was 2.16 at C320/6 cm spread-out Bragg peak (SOBP) center. CONCLUSION: The radiobiologic measurements of proton and carbon ion beams at Hyogo Ion Beam Medical Center are consistent with previous reports using proton beams in clinical settings and carbon ion beams with similar linear energy transfer (LET) values.

[Tonsillar carcinoma--clinical assessment and analysis of treatment results]. / Rak migdalka podniebiennego--ocena kliniczna i analiza wyników leczenia.

The aim of the study was an evaluation of the clinical signs and treatment results of the patients with tonsillar cancer treated in the ENT Clinic Medical University in Lódz during 10 years (1985-1994). In this study we analysed retrospectively the data of 40 subjects (52% of all group 76 patients). Twenty four patients (55%) had tumor with T3-T4 stage and 21 patients (52.5%)--palpable lymph neck nodes. The most frequent treatment modality was combined therapy (surgery with radio/chemotherapy) introduced in 25 persons (62.5%), surgery alone was performed in 10 cases (25%). Distant metastases developed in 6 patients (15%) and the second primary neoplasm in 5 patients (12.5%). We obtained 30% five years survival rate. We stress the importance of careful clinical assessment before planning the treatment.

Economic analysis of amifostine as adjunctive support for patients with advanced head and neck cancer: preliminary results from a randomized phase II clinical trial from Germany.

In a randomized phase II trial in Germany, we investigated the clinical and economic impact of amifostine protection against the hematological and oral toxicities of carboplatin administered concurrently with standard fractions of radiotherapy. 28 patients with squamous cell carcinomas of the head and neck received adjunctive or primary radiotherapy (5 days per week with daily fractions of 2 Gy, up to a total dose of 60 Gy) in conjunction with carboplatin (70 mg/m2) on days 1-5 and days 21-26. All patients received radiation encompassing at least 75% of the major salivary glands. Patients were randomized to receive radiation and carboplatin (RCT) alone or RCT preceded by rapid infusion of amifostine (500 mg) on days carboplatin was administered. The 14 patients who received amifostine, in comparison to 14 patients in the control arm, had significantly fewer episodes of grade 3 or 4 thrombocytopenia (p = 0.001), mucositis (p = 0.001), and xerostomia (p = 0.001). The patients receiving amifostine accrued significantly lower supportive care costs for resources related to infection ($241 vs. $1,275, p < 0.01), red blood cell and platelet support ($286 vs. $1,276 p = 0.06) alimentation ($343 vs. $894, p = .01), and hospitalization ($286 vs. $2,429, p < 0.01). Overall, including the costs of amifostine, mean per patient supportive care costs were $4,401 for the amifostine group and $5,873 (p = .02) for the control group. Our results from a randomized phase II trial indicate that selective cytoprotection with amifostine potentially offers clinical and economic benefits in patients with advanced head and neck cancer receiving radiochemotherapy. Additional economic studies alongside randomized phase III trials and from other countries are needed.