Linear energy transfer-guided optimization in intensity modulated proton therapy: feasibility study and clinical potential. 2013

Drosoula Giantsoudi, and Clemens Grassberger, and David Craft, and Andrzej Niemierko, and Alexei Trofimov, and Harald Paganetti
Department of Radiation Oncology, Massachusetts General Hospital & Harvard Medical School, Boston, Massachusetts, USA. dgiantsoudi@partners.org

OBJECTIVE To investigate the feasibility and potential clinical benefit of linear energy transfer (LET) guided plan optimization in intensity modulated proton therapy (IMPT). METHODS A multicriteria optimization (MCO) module was used to generate a series of Pareto-optimal IMPT base plans (BPs), corresponding to defined objectives, for 5 patients with head-and-neck cancer and 2 with pancreatic cancer. A Monte Carlo platform was used to calculate dose and LET distributions for each BP. A custom-designed MCO navigation module allowed the user to interpolate between BPs to produce deliverable Pareto-optimal solutions. Differences among the BPs were evaluated for each patient, based on dose-volume and LET-volume histograms and 3-dimensional distributions. An LET-based relative biological effectiveness (RBE) model was used to evaluate the potential clinical benefit when navigating the space of Pareto-optimal BPs. RESULTS The mean LET values for the target varied up to 30% among the BPs for the head-and-neck patients and up to 14% for the pancreatic cancer patients. Variations were more prominent in organs at risk (OARs), where mean LET values differed by a factor of up to 2 among the BPs for the same patient. An inverse relation between dose and LET distributions for the OARs was typically observed. Accounting for LET-dependent variable RBE values, a potential improvement on RBE-weighted dose of up to 40%, averaged over several structures under study, was noticed during MCO navigation. CONCLUSIONS We present a novel strategy for optimizing proton therapy to maximize dose-averaged LET in tumor targets while simultaneously minimizing dose-averaged LET in normal tissue structures. MCO BPs show substantial LET variations, leading to potentially significant differences in RBE-weighted doses. Pareto-surface navigation, using both dose and LET distributions for guidance, provides the means for evaluating a large variety of deliverable plans and aids in identifying the clinically optimal solution.

UI MeSH Term Description Entries
D009010 Monte Carlo Method In statistics, a technique for numerically approximating the solution of a mathematical problem by studying the distribution of some random variable, often generated by a computer. The name alludes to the randomness characteristic of the games of chance played at the gambling casinos in Monte Carlo. (From Random House Unabridged Dictionary, 2d ed, 1993) Method, Monte Carlo
D010190 Pancreatic Neoplasms Tumors or cancer of the PANCREAS. Depending on the types of ISLET CELLS present in the tumors, various hormones can be secreted: GLUCAGON from PANCREATIC ALPHA CELLS; INSULIN from PANCREATIC BETA CELLS; and SOMATOSTATIN from the SOMATOSTATIN-SECRETING CELLS. Most are malignant except the insulin-producing tumors (INSULINOMA). Cancer of Pancreas,Pancreatic Cancer,Cancer of the Pancreas,Neoplasms, Pancreatic,Pancreas Cancer,Pancreas Neoplasms,Pancreatic Acinar Carcinoma,Pancreatic Carcinoma,Acinar Carcinoma, Pancreatic,Acinar Carcinomas, Pancreatic,Cancer, Pancreas,Cancer, Pancreatic,Cancers, Pancreas,Cancers, Pancreatic,Carcinoma, Pancreatic,Carcinoma, Pancreatic Acinar,Carcinomas, Pancreatic,Carcinomas, Pancreatic Acinar,Neoplasm, Pancreas,Neoplasm, Pancreatic,Neoplasms, Pancreas,Pancreas Cancers,Pancreas Neoplasm,Pancreatic Acinar Carcinomas,Pancreatic Cancers,Pancreatic Carcinomas,Pancreatic Neoplasm
D011859 Radiography Examination of any part of the body for diagnostic purposes by means of X-RAYS or GAMMA RAYS, recording the image on a sensitized surface (such as photographic film). Radiology, Diagnostic X-Ray,Roentgenography,X-Ray, Diagnostic,Diagnostic X-Ray,Diagnostic X-Ray Radiology,X-Ray Radiology, Diagnostic,Diagnostic X Ray,Diagnostic X Ray Radiology,Diagnostic X-Rays,Radiology, Diagnostic X Ray,X Ray Radiology, Diagnostic,X Ray, Diagnostic,X-Rays, Diagnostic
D011879 Radiotherapy Dosage The total amount of radiation absorbed by tissues as a result of radiotherapy. Dosage, Radiotherapy,Dosages, Radiotherapy,Radiotherapy Dosages
D011880 Radiotherapy Planning, Computer-Assisted Computer-assisted mathematical calculations of beam angles, intensities of radiation, and duration of irradiation in radiotherapy. Computer-Assisted Radiotherapy Planning,Dosimetry Calculations, Computer-Assisted,Planning, Computer-Assisted Radiotherapy,Calculation, Computer-Assisted Dosimetry,Calculations, Computer-Assisted Dosimetry,Computer Assisted Radiotherapy Planning,Computer-Assisted Dosimetry Calculation,Computer-Assisted Dosimetry Calculations,Dosimetry Calculation, Computer-Assisted,Dosimetry Calculations, Computer Assisted,Planning, Computer Assisted Radiotherapy,Radiotherapy Planning, Computer Assisted
D012062 Relative Biological Effectiveness The ratio of radiation dosages required to produce identical change based on a formula comparing other types of radiation with that of gamma or roentgen rays. Biological Effectiveness, Relative,Effectiveness, Biologic Relative,Effectiveness, Biological Relative,Relative Biologic Effectiveness,Biologic Effectiveness, Relative,Biologic Relative Effectiveness,Biological Relative Effectiveness,Effectiveness, Relative Biologic,Effectiveness, Relative Biological,Relative Effectiveness, Biologic
D002817 Chordoma A malignant tumor arising from the embryonic remains of the notochord. It is also called chordocarcinoma, chordoepithelioma, and notochordoma. (Dorland, 27th ed) Chordomas
D005240 Feasibility Studies Studies to determine the advantages or disadvantages, practicability, or capability of accomplishing a projected plan, study, or project. Feasibility Study,Studies, Feasibility,Study, Feasibility
D006258 Head and Neck Neoplasms Soft tissue tumors or cancer arising from the mucosal surfaces of the LIP; oral cavity; PHARYNX; LARYNX; and cervical esophagus. Other sites included are the NOSE and PARANASAL SINUSES; SALIVARY GLANDS; THYROID GLAND and PARATHYROID GLANDS; and MELANOMA and non-melanoma skin cancers of the head and neck. (from Holland et al., Cancer Medicine, 4th ed, p1651) Cancer of Head and Neck,Head Cancer,Head Neoplasm,Head and Neck Cancer,Head and Neck Neoplasm,Neck Cancer,Neck Neoplasm,Neck Neoplasms,Neoplasms, Upper Aerodigestive Tract,UADT Neoplasm,Upper Aerodigestive Tract Neoplasm,Upper Aerodigestive Tract Neoplasms,Cancer of Head,Cancer of Neck,Cancer of the Head,Cancer of the Head and Neck,Cancer of the Neck,Head Neoplasms,Head, Neck Neoplasms,Neoplasms, Head,Neoplasms, Head and Neck,Neoplasms, Neck,UADT Neoplasms,Cancer, Head,Cancer, Neck,Cancers, Head,Cancers, Neck,Head Cancers,Neck Cancers,Neoplasm, Head,Neoplasm, Neck,Neoplasm, UADT,Neoplasms, UADT
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man

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