The use of the normal tissue non-complication probability (NTCP0) in the safety evaluations as a new alternative of assessing the side-effects of the radiation oncology treatments.

PURPOSE: To encourage the use of the NTCP0 for evaluating safety as a new alternative of assessing the S-Es of the radiation oncology treatments; and the use of the 'NTCP0cal' methodology that calculates/estimates NTCP0. METHOD: Revisions of studies related to use of the NTCP in the evaluations of S-Es. Development of the first version of the Matlab application of our methodology, which provides three options, two of them employ the well-known aspects of a phenomenological model, or the relationship with the TNTCP; where NTCP0 = 100%-TNTCP; and the third option determines NTCP0 from an assumed NTCP discrete probabilistic distribution from the binomial distribution, where one of its parameters is automatically defined from a databased of the Disease locations Vs. Late complications. RESULT: As result of revisions of some QUANTEC studies, we can say that: (1) The majority of current NTCP models are DVH-based; (2) The risk of toxicity is the way of evaluating the S-Es of the radiation oncology treatments; and (3) The NTCP are used mainly for evaluations of individual or principal complications or Endpoints of the radiation treatments. The 'NTCP0cal' Matlab application developed in this study has three calculation options. Two of the options provide additional graphical information about the distributions. CONCLUSIONS: The NTCP0 is a new radiobiological concept, its introduction let to correct some current P + and UTCP formulations, and will allow evaluating S-Es in whatever activity involving ionizing radiation, like radiation treatments; and its phenomenological model function of dose prescribed (D = n*d) will allow calculating values of NTCP0 for a range of dose per fraction (d) in a treatment with a determined number of fractions (n), or for range of n for a constant d. The DVH is irrelevant for this model. For whatever radiation treatment given to a population of similar patients under similar circumstances, the NTCP0 is calculated as ratio of the number of patients without acute/late complications and total of them. When this number is unknown, then NTCP0 can be obtained using the 'NTCP0cal' application.

The use of the normal tissue non-complication probability (NTCP0) methodology as a new alternative of assessing side-effects in brachytherapy treatments.

Background: The NTCP methodology evaluating side-effects (S-Es) was initially used in radiotherapy (RT), and later was extended to brachytherapy (BT). The NTCP0 methodology has been recently introduced in RT. Given the advantages, this methodology could replace NTCP. Materials and methods: Revisions of studies related to use of NTCP in the evaluations of S-Es in BT. Development of the first versions of two Matlab applications of the NTCP0 methodology. These applications have three options. Two of them employ the well-known aspects of a phenomenological model, or the probabilistic relationship between NTCP0 and total NTCP (TNTCP) that is the sum(NTCP(x i )) i: i th complication i:1..nc: Number of complications; where NTCP0 = 100% - TNTCP; and the third option assumes a NTCP(xi) discrete probabilistic distribution generated by the binomial distribution, where one of its parameters is automatically obtained from a databased of the Disease locations Vs. Late complications. Results: The NTCP0cal and NTCP0calDr Matlab applications have been developed, and respectively used for fractional continuous low dose-rate BT. Conclusions: NTCP0 is defined as the ratio of the number of patients without acute/late complications and total of them, and also can be obtained using our Matlab applications. NTCP0 works do not disregard the last 10-15 years of NTCP research; but NTCP0 was not considered during these years. A generic example was used for showing the variations of the late complications and NTCP0 for a BT treatment of a constant number of fractions and six different dose per fraction values.

Implications of the Harmonization of [18F]FDG-PET/CT Imaging for Response Assessment of Treatment in Radiotherapy Planning.

The purpose of this work is to present useful recommendations for the use of [18F]FDG-PET/CT imaging in radiotherapy planning and monitoring under different versions of EARL accreditation for harmonization of PET devices. A proof-of-concept experiment designed on an anthropomorphic phantom was carried out to establish the most suitable interpolation methods of the PET images in the different steps of the planning procedure. Based on PET/CT images obtained by using these optimal interpolations for the old EARL accreditation (EARL1) and for the new one (EARL2), the treatment plannings of representative actual clinical cases were calculated, and the clinical implications of the resulting differences were analyzed. As expected, EARL2 provided smaller volumes with higher resolution than EARL1. The increase in the size of the reconstructed volumes with EARL1 accreditation caused high doses in the organs at risk and in the regions adjacent to the target volumes. EARL2 accreditation allowed an improvement in the accuracy of the PET imaging precision, allowing more personalized radiotherapy. This work provides recommendations for those centers that intend to benefit from the new accreditation, EARL2, and can help build confidence of those that must continue working under the EARL1 accreditation.

Proposals of models for new formulations of the current complication-free cure (P+) and uncomplicated tumor control probability (UTCP) concepts, and total normal tissue complication probability of late complications.

This study proposes phenomenological models for total normal tissue complication probability (TNTCP) and NTCP0. NTCP0 is a new acronym for reformulating the current complication-free cure (P+) and uncomplicated tumor control probability (UTCP) concepts, and TNTCP will reformulate the current NTCP involving multiple organs at risks. The current probabilistic concepts are incoherently formulated with mathematical operations of tumor control probability (TCP) and normal tissue complication probability (NTCP) that are associated with different stochastic processes and random variables. NTCP0 is equal to NTCP0 (normal tissue non-complication probability) that is calculated as the ratio of a number of patients of a population without late complications and a total of them. As a cumulative distribution function (CDF) of late complications, TNTCP = sum(NTCPi), where NTCPi is the NTCP of the ith late complication. TNTCP is also a new acronym, and the probabilistic complement of NTCP0, then NTCP0 = 100% - TNTCP. The NTCP0/TNTCP (D(d)) proposing models are based on the relationship between the NTCP0/TNTCP and total dose (D = n×d; where d = dose per fraction, and n = number of fractions). TNTCP(D) model will be correlated with LKB model (the normal CDF) that is an increasing function; and NTCP0(D) model with a decreasing function, which additionally will define clear limits of three possible regions for NTCP0: 0 and 100% deterministic, and a stochastic. These models are function D, which is widely used for characterizing radiation therapies.

Accurate, robust and harmonized implementation of morpho-functional imaging in treatment planning for personalized radiotherapy.

In this work we present a methodology able to use harmonized PET/CT imaging in dose painting by number (DPBN) approach by means of a robust and accurate treatment planning system. Image processing and treatment planning were performed by using a Matlab-based platform, called CARMEN, in which a full Monte Carlo simulation is included. Linear programming formulation was developed for a voxel-by-voxel robust optimization and a specific direct aperture optimization was designed for an efficient adaptive radiotherapy implementation. DPBN approach with our methodology was tested to reduce the uncertainties associated with both, the absolute value and the relative value of the information in the functional image. For the same H&N case, a single robust treatment was planned for dose prescription maps corresponding to standardized uptake value distributions from two different image reconstruction protocols: One to fulfill EARL accreditation for harmonization of [18F]FDG PET/CT image, and the other one to use the highest available spatial resolution. Also, a robust treatment was planned to fulfill dose prescription maps corresponding to both approaches, the dose painting by contour based on volumes and our voxel-by-voxel DPBN. Adaptive planning was also carried out to check the suitability of our proposal. Different plans showed robustness to cover a range of scenarios for implementation of harmonizing strategies by using the highest available resolution. Also, robustness associated to discretization level of dose prescription according to the use of contours or numbers was achieved. All plans showed excellent quality index histogram and quality factors below 2%. Efficient solution for adaptive radiotherapy based directly on changes in functional image was obtained. We proved that by using voxel-by-voxel DPBN approach it is possible to overcome typical drawbacks linked to PET/CT images, providing to the clinical specialist confidence enough for routinely implementation of functional imaging for personalized radiotherapy.

Amiloidosis traqueobronquial difusa: uso de radioterapia local externa como modalidad de tratamiento / External Beam Radiation Therapy: A Treatment Modality in Diffuse Tracheobronchial Amyloidosis

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