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Title: Novel technologies and theoretical models in radiation therapy of cancer patients using 6.3 MeV fast neutrons produced by U-120 cyclotron

Abstract

The analysis of clinical use of neutron therapy with 6 MeV fast neutrons compared to conventional radiation therapy was carried out. The experience of using neutron and mixed neutron and photon therapy in patients with different radio-resistant malignant tumors shows the necessity of further studies and development of the novel approaches to densely-ionizing radiation. The results of dosimetry and radiobiological studies have been the basis for planning clinical programs for neutron therapy. Clinical trials over the past 30 years have shown that neutron therapy successfully destroys radio-resistant cancers, including salivary gland tumors, adenoidcystic carcinoma, inoperable sarcomas, locally advanced head and neck tumors, and locally advanced prostate cancer. Radiation therapy with 6.3 MeV fast neutrons used alone and in combination with photon therapy resulted in improved long-term treatment outcomes in patients with radio-resistant malignant tumors.

Authors:
;  [1]; ; ;  [1];  [2]
  1. Tomsk Cancer Research Institute, Kooperativny Street 5, Tomsk, 634050 (Russian Federation)
  2. (Russian Federation)
Publication Date:
OSTI Identifier:
22608284
Resource Type:
Journal Article
Resource Relation:
Journal Name: AIP Conference Proceedings; Journal Volume: 1760; Journal Issue: 1; Conference: PC'16: International conference on physics of cancer: Interdisciplinary problems and clinical applications 2016, Tomsk (Russian Federation), 22-25 Mar 2016; Other Information: (c) 2016 Author(s); Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; CARCINOMAS; CLINICAL TRIALS; COMPARATIVE EVALUATIONS; CYCLOTRONS; DOSIMETRY; FAST NEUTRONS; HEAD; IONIZING RADIATIONS; MEV RANGE 01-10; NECK; NEUTRON THERAPY; PATIENTS; PHOTONS; PLANNING; PROSTATE; SALIVARY GLANDS; SARCOMAS

Citation Formats

Musabaeva, L. I., E-mail: musabaevaLI@oncology.tomsk.ru, Lisin, V. A., E-mail: Lisin@oncology.tomsk.ru, Startseva, Zh. A., E-mail: zhanna.alex@rambler.ru, Gribova, O. V., E-mail: gribova79@mail.ru, Velikaya, V. V., E-mail: viktoria.v.v@inbox.ru, and National Research Tomsk Polytechnic University, Lenin Avenue 30, Tomsk, 634050. Novel technologies and theoretical models in radiation therapy of cancer patients using 6.3 MeV fast neutrons produced by U-120 cyclotron. United States: N. p., 2016. Web. doi:10.1063/1.4960269.
Musabaeva, L. I., E-mail: musabaevaLI@oncology.tomsk.ru, Lisin, V. A., E-mail: Lisin@oncology.tomsk.ru, Startseva, Zh. A., E-mail: zhanna.alex@rambler.ru, Gribova, O. V., E-mail: gribova79@mail.ru, Velikaya, V. V., E-mail: viktoria.v.v@inbox.ru, & National Research Tomsk Polytechnic University, Lenin Avenue 30, Tomsk, 634050. Novel technologies and theoretical models in radiation therapy of cancer patients using 6.3 MeV fast neutrons produced by U-120 cyclotron. United States. doi:10.1063/1.4960269.
Musabaeva, L. I., E-mail: musabaevaLI@oncology.tomsk.ru, Lisin, V. A., E-mail: Lisin@oncology.tomsk.ru, Startseva, Zh. A., E-mail: zhanna.alex@rambler.ru, Gribova, O. V., E-mail: gribova79@mail.ru, Velikaya, V. V., E-mail: viktoria.v.v@inbox.ru, and National Research Tomsk Polytechnic University, Lenin Avenue 30, Tomsk, 634050. 2016. "Novel technologies and theoretical models in radiation therapy of cancer patients using 6.3 MeV fast neutrons produced by U-120 cyclotron". United States. doi:10.1063/1.4960269.
@article{osti_22608284,
title = {Novel technologies and theoretical models in radiation therapy of cancer patients using 6.3 MeV fast neutrons produced by U-120 cyclotron},
author = {Musabaeva, L. I., E-mail: musabaevaLI@oncology.tomsk.ru and Lisin, V. A., E-mail: Lisin@oncology.tomsk.ru and Startseva, Zh. A., E-mail: zhanna.alex@rambler.ru and Gribova, O. V., E-mail: gribova79@mail.ru and Velikaya, V. V., E-mail: viktoria.v.v@inbox.ru and National Research Tomsk Polytechnic University, Lenin Avenue 30, Tomsk, 634050},
abstractNote = {The analysis of clinical use of neutron therapy with 6 MeV fast neutrons compared to conventional radiation therapy was carried out. The experience of using neutron and mixed neutron and photon therapy in patients with different radio-resistant malignant tumors shows the necessity of further studies and development of the novel approaches to densely-ionizing radiation. The results of dosimetry and radiobiological studies have been the basis for planning clinical programs for neutron therapy. Clinical trials over the past 30 years have shown that neutron therapy successfully destroys radio-resistant cancers, including salivary gland tumors, adenoidcystic carcinoma, inoperable sarcomas, locally advanced head and neck tumors, and locally advanced prostate cancer. Radiation therapy with 6.3 MeV fast neutrons used alone and in combination with photon therapy resulted in improved long-term treatment outcomes in patients with radio-resistant malignant tumors.},
doi = {10.1063/1.4960269},
journal = {AIP Conference Proceedings},
number = 1,
volume = 1760,
place = {United States},
year = 2016,
month = 8
}
  • Purpose: To evaluate the rate of gastrointestinal (GI) toxicity of neoadjuvant chemoradiation with capecitabine, oxaliplatin, and intensity modulated radiation therapy (IMRT) in cT3-4 rectal cancer. Methods and Materials: Patients with localized, nonmetastatic T3 or T4 rectal cancer <12 cm from the anal verge were enrolled in a prospective, multi-institutional, single-arm study of preoperative chemoradiation. Patients received 45 Gy with IMRT in 25 fractions, followed by a 3-dimensional conformal boost of 5.4 Gy in 3 fractions with concurrent capecitabine/oxaliplatin (CAPOX). Surgery was performed 4 to 8 weeks after the completion of therapy. Patients were recommended to receive FOLFOX chemotherapy after surgery. The primary endpoint ofmore » the study was acute grade 2 to 5 GI toxicity. Seventy-one patients provided 80% probability to detect at least a 12% reduction in the specified GI toxicity with the treatment of CAPOX and IMRT, at a significance level of .10 (1-sided). Results: Seventy-nine patients were accrued, of whom 68 were evaluable. Sixty-one patients (89.7%) had cT3 disease, and 37 (54.4%) had cN (+) disease. Postoperative chemotherapy was given to 42 of 68 patients. Fifty-eight patients had target contours drawn per protocol, 5 patients with acceptable variation, and 5 patients with unacceptable variations. Thirty-five patients (51.5%) experienced grade ≥2 GI toxicity, 12 patients (17.6%) experienced grade 3 or 4 diarrhea, and pCR was achieved in 10 patients (14.7%). With a median follow-up time of 3.98 years, the 4-year rate of locoregional failure was 7.4% (95% confidence interval [CI]: 1.0%-13.7%). The 4-year rates of OS and DFS were 82.9% (95% CI: 70.1%-90.6%) and 60.6% (95% CI: 47.5%-71.4%), respectively. Conclusion: The use of IMRT in neoadjuvant chemoradiation for rectal cancer did not reduce the rate of GI toxicity.« less
  • Purpose: To identify prognostic biomarkers in pancreatic cancer using high-throughput quantitative image analysis. Methods and Materials: In this institutional review board–approved study, we retrospectively analyzed images and outcomes for 139 locally advanced pancreatic cancer patients treated with stereotactic body radiation therapy (SBRT). The overall population was split into a training cohort (n=90) and a validation cohort (n=49) according to the time of treatment. We extracted quantitative imaging characteristics from pre-SBRT {sup 18}F-fluorodeoxyglucose positron emission tomography, including statistical, morphologic, and texture features. A Cox proportional hazard regression model was built to predict overall survival (OS) in the training cohort using 162more » robust image features. To avoid over-fitting, we applied the elastic net to obtain a sparse set of image features, whose linear combination constitutes a prognostic imaging signature. Univariate and multivariate Cox regression analyses were used to evaluate the association with OS, and concordance index (CI) was used to evaluate the survival prediction accuracy. Results: The prognostic imaging signature included 7 features characterizing different tumor phenotypes, including shape, intensity, and texture. On the validation cohort, univariate analysis showed that this prognostic signature was significantly associated with OS (P=.002, hazard ratio 2.74), which improved upon conventional imaging predictors including tumor volume, maximum standardized uptake value, and total legion glycolysis (P=.018-.028, hazard ratio 1.51-1.57). On multivariate analysis, the proposed signature was the only significant prognostic index (P=.037, hazard ratio 3.72) when adjusted for conventional imaging and clinical factors (P=.123-.870, hazard ratio 0.53-1.30). In terms of CI, the proposed signature scored 0.66 and was significantly better than competing prognostic indices (CI 0.48-0.64, Wilcoxon rank sum test P<1e-6). Conclusion: Quantitative analysis identified novel {sup 18}F-fluorodeoxyglucose positron emission tomography image features that showed improved prognostic value over conventional imaging metrics. If validated in large, prospective cohorts, the new prognostic signature might be used to identify patients for individualized risk-adaptive therapy.« less
  • The possibilities offered for activation analysis by using cyclotron-produced fast neutrons are investigated for the elements Mg, Al, Si, P, Zr, and Mo. Neutrons were produced by bombarding a thick beryllium target with 10- to 50-MeV deuterons. The use of a cyclotron in fast-neutron activation analysis has the advantages that rather high fast-neutron fluxes are available, and that, because of the variability of the neutron-energy spectra, optimum conditions with respect to sensitivity and interferences can be chosen. The experimental sensitivities obtained for Mg, Al, Si, P, and Zr range from 0.74 to 5.5 dpm/ng ..mu..A. These sensitivities are better bymore » a factor of up to several hundred in comparison with data obtainable for 14-MeV neutrons. The extent of the interferences is, excluding some few exceptions, at about the same level for both techniques. 10 figures, 3 tables.« less
  • Purpose: This study quantifies tumor shape variability in head-and-neck cancer patients during radiation therapy using implanted markers. Methods and Materials: Twenty-seven patients with oropharyngeal tumors treated with (chemo)radiation were included. Helical gold markers (0.35 Multiplication-Sign 2 mm, 3-10/patient, average 6) were implanted around the tumor. Markers were identified on planning computed tomography (CT) and daily cone beam CT (CBCT). After bony anatomy registration, the daily vector length on CBCT in reference to the planning CT and daily marker movement perpendicular to the gross tumor volume (GTV) surface at planning CT (d{sub normal}) of each marker were analyzed. Time trends weremore » assessed with linear regression of the {sub markers}. In 2 patients, 2 markers were implanted in normal tissue to evaluate migration by measuring intermarker distances. Results: Marker implantation was feasible without complications. Three-dimensional vectors (4827 measurements, mean 0.23 cm, interquartile ratio 0.24 cm) were highest in base of tongue sublocalization (P<.001) and bulky tumors (vectors exceeded 0.5 cm in 5.7% [0-20 mL], 12.0% [21-40 mL], and 21.7% [{>=}41 mL], respectively [P<.001] of measurements). The measured inward time trend in 11/27 patients correlated with the visual observed marker pattern. In patients with an outward trend (5/27) or no trend (11/27), visual observation showed predominantly an inhomogeneous pattern. Remarkably, in 6 patients, outward marker movement was observed in the posterior pharyngeal wall. The difference in distance between normal tissue markers (1 SD) was 0.05-0.06 cm without time trend, indicating that implanted markers did not migrate. Conclusions: During head-and-neck radiation therapy, normal tissue markers remained stable. Changes in position of tumor markers depended on sublocalization and tumor volume. Large differences in marker patterns between patients as well as within patients were observed. Based on our study, the cranial and caudal border in the posterior pharyngeal wall are at highest risk to be covered insufficiently. Furthermore, implanted markers could help identify patients with an actual shrinkage of the GTV who might benefit from mid-radiation therapy redelineation to reduce toxicity.« less