Normal Tissue Control Probability Research Articles

PO-1956 Normal Tissue Control Probability evaluation of photon versus proton therapy for left breast cancer

PO-1956 Normal Tissue Control Probability evaluation of photon versus proton therapy for left breast cancer

Automatic Radiobiological Comparison of Radiation Therapy Plans: An Application to Gastric Cancer.

(1) Aim: This study was conducted to radiobiologically compare radiotherapy plans for gastric cancer with a newly developed software tool. (2) Methods: Treatment planning was performed on two computational phantoms simulating adult male and female patients. Three-dimensional conformal radiotherapy (3D-CRT), intensity-modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) plans for gastric cancer were generated with three-photon beam energies. The equivalent uniform dose (EUD), tumor control probability (TCP) of the target and normal tissue control probability (NTCP) of eight different critical organs were calculated. A new software was employed for these calculations using the EUD-based model and dose-volume-histogram data. (3) Results: The IMRT and VMAT plan led to TCPs of 51.3-51.5%, whereas 3D-CRT gave values up to 50.2%. The intensity-modulated techniques resulted in NTCPs of (5.3 × 10-6-3.3 × 10-1)%. The corresponding NTCPs from 3D-CRT were (3.4 × 10-7-7.4 × 10-1)%. The above biological indices were automatically calculated in less than 40 s with the software. (4) Conclusions: The direct and quick radiobiological evaluation of radiotherapy plans is feasible using the new software tool. The IMRT and VMAT reduced the probability of the appearance of late effects in most of the surrounding critical organs and slightly increased the TCP compared to 3D-CRT.

Dosimetric analysis of cervical cancer stage IIB patients treated with volumetric modulated arc therapy using plan uncertainty parameters module of Varian Eclipse treatment planning system

Introduction. The present study aims to investigate the dosimetric and radiobiological impact of patient setup errors (PSE) on the target and organs at risk (OAR) of the cervix carcinoma stage IIB patients treated with volumetric-modulated arc therapy (VMAT) delivery technique using plan uncertainty parameters module of Varian Eclipse treatment planning system and in-house developed DVH Analyzer program. Materials and Methods. A total of 976 VMAT plans were generated to simulate the PSE in the base plan that varies from −10 mm to 10 mm in a step size of 1 mm in x– (lateral), y– (craniocaudal), and z– (anteroposterior) directions. The different OAR and tumor (PTV) volumes were delineated in each case. Various plan quality metrics, such as conformity index (CI) and homogeneity index (HI), as well as radiobiological quantities, such as tumor control probability (TCP) and normal tissue control probability (NTCP), were calculated from the DVH bands generated from the cohort of treatment plans associated with each patient case, using an in-house developed ‘DVH Analyzer’ program. The extracted parameters were statistically analyzed and compared with the base plan’s dosimetric parameters having no PSE. Results. The maximum variation of (i) 2.4%, 21.5%, 0.8%, 2.5% in D2cc of bladder, rectum, small bowel and sigmoid colon respectively; (ii) 19.3% and 18.9% in Dmax of the left and right femoral heads (iii) 16.9% in D95% of PTV (iv) 12.1% in NTCP of sigmoid colon were observed with change of PSE in all directions. TCP was found to be considerably affected for PSEs larger than 4 mm in x+, y+, z+ directions and 7 mm in x-, y- and z- directions, respectively. Conclusion. This study presents the effect of PSE on TCP and NTCP for the cervix carcinoma cases treated with VMAT technique and also recommends daily image guidance to mitigate the effects of PSE.

RADT-30. COPLANAR AND NON-COPLANAR VMAT ARC SETTING FOR GLIOBLASTOMA MULTIFORME – DOSIMETRIC AND RADIOBIOLOGICAL COMPARISONS

Abstract OBJECTIVES To evaluate three different arc arrangements in glioblastoma multiforme (GBM) treatment planning. METHODS Eighteen GBM patients were replanned by using one full arc (1FA), two full coplanar arcs (2FA), and three full non- coplanar arcs (3FA). Dose-volume histograms (DVHs) were used to calculate conformity (CI), homogeneity (HI) and gradient indices (GI), the dose received by 5% (D5%) and 95% (D95%) of the planning target volume (PTV) and maximum (Dmax) and minimum (Dmin) absorbed dose for organs at risk (OARs), including normal brain (brain excluding PTV). General equivalent uniform dose (gEUD) for both PTV and OARs and EUD based tumor control probability (TCP) and normal tissue control probability (NTCP) were calculated as radiobiological parameters. Monitor units (MUs) were also computed and compared. RESULTS All three plans resulted in similar conformity, while 2FA resulted in a better homogeneity than 1FA (0.06vs. 0.07, p=0.007). 2FA vs. 1FA dose analysis for PTV revealed a lower D5% (61.28 vs. 61.37 Gy, p=0.014), a higher D95% (58.7 vs. 58.47 Gy, p=0.008) and a higher TCP (37.73 vs.37.38%, p=0.008). The utilization of 3FA did not significantly change the outcome of PTV but managed to decrease GI in comparison to both 1FA and 2FA (4.11 vs. 5.19 and 5.49, p< 0.05). Regarding NB, 1FA scored a higher Dmax than 2FA (62.32 vs. 61.98 Gy, p=0.005), while 3FA scored a higher Dmin than 1FA and 2FA (2.52 vs. 1.08 and 1.10 Gy, p< 0.05). No difference in NB NTCP was noted between techniques. Furthermore, 3FA yielded more MUs when compared to coplanar patters (566.74 vs. 486.78, p= 0.015 for 1FA and 495.98, p=0.019 for 2FA). CONCLUSION Although all three approaches resulted in clinical admissible outcome, the utilization of complex non-coplanar arrangement resulted in a stepper dose fall off but did not improve PTV results and increased machine MUs.

P159] Design and application of a metric to perform routinely quality assurance of dose plans

Purpose In this work a suitable metric named dosimetric quality index (DQI) for quality assurance of dose planning performance is developed and implemented by means of statistical control process tools. We analyzed its robustness and reliability in performing good quality dosimetries while monitoring the process in order to progressively improve them. Methods The DQI definition relies on the radiobiological concept that an optimal dosimetry should maximize the Tumor Control Probability (TCP) while minimizing the Normal Tissue Control Probability (NTCP). A series of 126 intermediate risk prostate cancer dosimetries provides the database from which distributions of minimum dose to PTV, and mean dose to rectum, bladder and femoral heads have been obtained in order to create a DQI set, assumed as the initial reference state (IRS), according to the expression: DQI = TCP Π ( 1 - NTCP ) For statistical control purposes, a lower DQI limit has been assessed by generating dosimetries of different quality levels using MC methods based on the real distributions of the aforementioned variables. We consider the dosimetries in the 5% lower quartile of the DQI probability function distribution as improvable, and we analyze its features. Results The statistical analysis shows that dosimetries with a DQI smaller than the DQI lower limit are characterized by having more than two OR with mean doses bigger than the mean of the corresponding IRS distributions. Also, if the minimum dose to the PTV is smaller than the mean of the IRS distribution, and at least one OR is over irradiated, the dosimetry may have as well a DQI smaller than the DQI lower limit. The DQI statistical control process tool provides a time evolution visualization of the quality dosimetries. Conclusions A radiobiological based control quality metric, DQI, has been designed and utilized to statistically perform a quality assurance of dose plans. The DQI helps to improve the dosimetry before its evaluation by the physician, and therefore may be a routinely used, time saving procedure. Better and better quality dosimetries may be achieved by progressively raising the overall DQI value and eventually, changing the IRS to a higher quality level.

Viability of Noncoplanar VMAT for liver SBRT compared with coplanar VMAT and beam orientation optimized 4π IMRT

PurposeThe 4π static noncoplanar radiation therapy delivery technique has demonstrated better normal tissue sparing and dose conformity than the clinically used volumetric modulated arc therapy (VMAT). It is unclear whether this is a fundamental limitation of VMAT delivery or the coplanar nature of its typical clinical plans. The dosimetry and the limits of normal tissue toxicity constrained dose escalation of coplanar VMAT, noncoplanar VMAT and 4π radiation therapy are quantified in this study. Methods and materialsClinical stereotactic body radiation therapy plans for 20 liver patients receiving 30 to 60 Gy using coplanar VMAT (cVMAT) were replanned using 3 to 4 partial noncoplanar arcs (nVMAT) and 4π with 20 intensity modulated noncoplanar fields. The conformity number, homogeneity index, 50% dose spillage volume, normal liver volume receiving >15 Gy, dose to organs at risk (OARs), and tumor control probability were compared for all 3 treatment plans. The maximum tolerable dose yielding a normal liver normal tissue control probability <1%, 5%, and 10% was calculated with the Lyman-Kutcher-Burman model for each plan as well as the resulting survival fractions at 1, 2, 3, and 4 years. ResultsCompared with cVMAT, the nVMAT and 4π plans reduced liver volume receiving >15 Gy by an average of 5 cm3 and 80 cm3, respectively. 4π reduced the 50% dose spillage volume by ∼23% compared with both VMAT plans, and either significantly decreased or maintained OAR doses. The 4π maximum tolerable doses and survival fractions were significantly higher than both cVMAT and nVMAT (P < .05) for all normal liver normal tissue control probability limits used in this study. ConclusionsThe 4π technique provides significantly better OAR sparing than both cVMAT and nVMAT and enables more clinically relevant dose escalation for tumor local control. Therefore, despite the current accessibility of nVMAT, it is not a viable alternative to 4π for liver SBRT.

Testing the Assessment of New Radiation Oncology Technology and Treatments framework using the evaluation of post-prostatectomy radiotherapy techniques.

We tested the ability of the Assessment of New Radiation Oncology Technology and Treatments framework to determine the clinical efficacy and safety of intensity-modulated radiation therapy (IMRT) compared with 3-dimensional radiation therapy (3DCRT) for post-prostatectomy radiation therapy (PPRT) to support its timely health economic evaluation. Treatment plans produced using FROGG guidelines provided dosimetry parameters for both techniques at 64 Gy and 70 Gy and were also used to model early and late outcome probabilities. Clinical parameters were derived from early toxicity and quality of life patient data, systematic literature review and expert opinion. Dosimetry parameters were correlated with the measures of clinical efficacy and safety. Data from two patient cohorts (29 and 27 respectively) were collected within the project timeframe, providing evidence for acute toxicity and quality of life, and dosimetric comparisons. Relative rates of tumour control probability (TCP) and normal tissue control probability (NTCP) modelling were readily derived from the planning exercise and demonstrated advantages in uncomplicated TCP for IMRT over 3DCRT, predominantly due to normal tissue sparing. The safety of IMRT delivery was demonstrated with TCP uncompromised by IMRT protocol violations, which achieved rectal sparing only by reducing minimum target dose and coverage. Sources of desk-top and patient-based evidence were successfully used to demonstrate potential improved clinical efficacy and safety of applying dose escalation using IMRT instead of 3DCRT in PPRT.

SU‐E‐T‐580: On the Significance of Model Based Dosimetry for Breast and Head and Neck 192Ir HDR Brachytherapy

Purpose:To assess the dosimetric and radiobiological differences between TG43‐based and model‐based dosimetry in the treatment planning of 192Ir HDR brachytherapy for breast and head and neck cancer.Methods:Two cohorts of 57 Accelerated Partial Breast Irradiation (APBI) and 22 head and neck (H&amp;N) patients with oral cavity carcinoma were studied. Dosimetry for the treatment plans was performed using the TG43 algorithm of the Oncentra Brachy v4.4 treatment planning system (TPS). Corresponding Monte Carlo (MC) simulations were performed using MCNP6 with input files automatically prepared by the BrachyGuide software tool from DICOM RT plan data. TG43 and MC data were compared in terms of % dose differences, Dose Volume Histograms (DVHs) and related indices of clinical interest for the Planning Target Volume (PTV) and the Organs‐At‐Risk (OARs). A radiobiological analysis was also performed using the Equivalent Uniform Dose (EUD), mean survival fraction (S) and Tumor Control Probability (TCP) for the PTV, and the Normal Tissue Control Probability (N TCP) and the generalized EUD (gEUD) for the OARs. Significance testing of the observed differences performed using the Wilcoxon paired sample test.Results:Differences between TG43 and MC DVH indices, associated with the increased corresponding local % dose differences observed, were statistically significant. This is mainly attributed to their consistency however, since TG43 agrees closely with MC for the majority of DVH and radiobiological parameters in both patient cohorts. Differences varied considerably among patients only for the ipsilateral lung and ribs in the APBI cohort, with a strong correlation to target location.Conclusion:While the consistency and magnitude of differences in the majority of clinically relevant DVH indices imply that no change is needed in the treatment planning practice, individualized dosimetry improves accuracy and addresses instances of inter‐patient variability observed.Research co‐financed by the ESF and Greek funds through the Operational Program Education and Lifelong Learning Investing in Knowledge Society of the NSRF. Research Funding Program Aristeia. Nucletron, an Elekta company (Veenendaal, The Netherlands) is gratefully acknowledged for providing Oncentra Brachy v4.4 for research purposes.

A multicentre observational study evaluating image-guided radiotherapy for more accurate partial-breast intensity-modulated radiotherapy: comparison with standard imaging technique

BackgroundWhole-breast radiotherapy (WBRT) is the standard treatment for breast cancer following breast-conserving surgery. Evidence shows that tumour recurrences occur near the original cancer: the tumour bed. New treatment developments include increasing dose to the tumour bed during WBRT (synchronous integrated boost) and irradiating only the region around the tumour bed, for patients at high and low risk of tumour recurrence, respectively. Currently, standard imaging uses bony anatomy to ensure accurate delivery of WBRT. It is debatable whether or not more targeted treatments such as synchronous integrated boost and partial-breast radiotherapy require image-guided radiotherapy (IGRT) focusing on implanted tumour bed clips (clip-based IGRT).ObjectivesPrimary – to compare accuracy of patient set-up using standard imaging compared with clip-based IGRT. Secondary – comparison of imaging techniques using (1) tumour bed radiotherapy safety margins, (2) volume of breast tissue irradiated around tumour bed, (3) estimated breast toxicity following development of a normal tissue control probability model and (4) time taken.DesignMulticentre observational study embedded within a national randomised trial: IMPORT-HIGH (Intensity Modulated and Partial Organ Radiotherapy – HIGHer-risk patient group) testing synchronous integrated boost and using clip-based IGRT.SettingFive radiotherapy departments, participating in IMPORT-HIGH.ParticipantsTwo-hundred and eighteen patients receiving breast radiotherapy within IMPORT-HIGH.InterventionsThere was no direct intervention in patients’ treatment. Experimental and control intervention were clip-based IGRT and standard imaging, respectively. IMPORT-HIGH patients received clip-based IGRT as routine; standard imaging data were obtained from clip-based IGRT images.Main outcome measuresDifference in (1) set-up errors, (2) safety margins, (3) volume of breast tissue irradiated, (4) breast toxicity and (5) time, between clip-based IGRT and standard imaging.ResultsThe primary outcome of overall mean difference in clip-based IGRT and standard imaging using daily set-up errors was 2–2.6 mm (p &lt; 0.001). Heterogeneity testing between centres found a statistically significant difference in set-up errors at one centre. For four centres (179 patients), clip-based IGRT gave a mean decrease in the systematic set-up error of between 1 mm and 2 mm compared with standard imaging. Secondary outcomes were as follows: clip-based IGRT and standard imaging safety margins were less than 5 mm and 8 mm, respectively. Using clip-based IGRT, the median volume of tissue receiving 95% of prescribed boost dose decreased by 29 cm3(range 11–193 cm3) compared with standard imaging. Difference in median time required to perform clip-based IGRT compared with standard imaging was X-ray imaging technique dependent (range 8–76 seconds). It was not possible to estimate differences in breast toxicity, the normal tissue control probability model indicated that for breast fibrosis maximum radiotherapy dose is more important than volume of tissue irradiated.Conclusions and implications for clinical practiceMargins of less than 8 mm cannot be used safely without clip-based IGRT for patients receiving concomitant tumour bed boost, as there is a risk of geographical miss of the tumour bed being treated. In principle, smaller but accurately placed margins may influence local control and toxicity rates, but this needs to be evaluated from mature clinical trial data in the future.FundingThe National Institute for Health Research Efficacy and Mechanism Evaluation programme.

SU-D-16A-04: Accuracy of Treatment Plan TCP and NTCP Values as Determined Via Treatment Course Delivery Simulations

Purpose: To to determine if tumor control probability (TCP) and normal tissue control probability (NTCP) values computed on the treatment planning image are representative of TCP/NTCP distributions resulting from probable positioning variations encountered during external-beam radiotherapy. Methods: We compare TCP/NTCP as typically computed on the planning PTV/OARs with distributions of those parameters computed for CTV/OARs via treatment delivery simulations which include the effect of patient organ deformations for a group of 19 prostate IMRT pseudocases. Planning objectives specified 78 Gy to PTV1=prostate CTV+5 mm margin, 66 Gy to PTV2=seminal vesicles+8 mm margin, and multiple bladder/rectum OAR objectives to achieve typical clinical OAR sparing. TCP were computed using the Poisson Model while NTCPs used the Lyman-Kutcher-Bruman model. For each patient, 1000 30-fraction virtual treatment courses were simulated with each fractional pseudo- time-oftreatment anatomy sampled from a principle component analysis patient deformation model. Dose for each virtual treatment-course was determined via deformable summation of dose from the individual fractions. CTVTCP/ OAR-NTCP values were computed for each treatment course, statistically analyzed, and compared with the planning PTV-TCP/OARNTCP values. Results: Mean TCP from the simulations differed by 5% for 12/19 patients and >10% for 4/19 patients. Similarly, mean rectum NTCP differed by >5% for 12/19 patients, >10% for 4/19 patients. Both mean bladder and mean rectum NTCP differed by >5% for 10/19 patients and by >10% for 2/19 patients. For several patients, planned NTCP was less than the minimum or more than the maximum from the treatment course simulations. Conclusion: Treatment course simulations yield TCP values that are similar to planned values, while OAR NTCPs differ significantly, indicating the need for probabilistic methods or PRVs for OAR risk assessment. Presenting author receives support from Philips Medical Systems.

SU‐C‐211‐06: A New Treatment Plan Quality Index for NPC SIB‐IMRT

Purpose: To proposed a new plan quality index to fasten the evaluation and comparison of the competing multi‐isocenter SIB‐IMRT (intensity modulated radiotherapy with simultaneous integrated boost) plans for NPC (Nasopharyngeal Cancer) patients. Methods: Multi‐isocenter SIB‐IMRT plans at 2.5 Gy/fraction for GTV (gross tumor volume) and 2.0 Gy/fraction for CTVs (clinical tumor volume) with different OAR (Organ at Risk) constraint levels were generated with BrainSCAN 5.2 and m3 MLC. DVH (dose volume histogram) were read from treatment planning system by custom software (written with Matlab 7.1). Various items was read and calculated. A plan filter matrix with variable plan quality items was introduced to filter plans that fail to satisfy the customed criteria. PTV plan quality indices including TC (target coverage), V93, HI (homogeneity index), TCP (tumor control probability), and OAR plan quality indices including NTCP (normal tissue control probability), V26, and V32 of parotids were calculated for qualified plans. A unique composite plan quality index (CPQI) was proposed based on the relative weight of these indices to evaluate and compare plans. Plan ranking results were compared with physician's evaluation results to verify the accuracy of this new plan quality index. Results: The average CPQI values for plans with OAR constraint level of low, normal, high, and PTV only were 0.22±0.08, 0.49±0.077, 0.71±0.062, and −0.21±0.16, respectively. There were significant differences between these plan quality indices (One‐way ANOVA test, p&lt;0.01). This consistent with physician's ranking results with 99.3% OAR high plans accepted. Conclusions: Plan filter matrix was able to fasten the plan evaluation process. The new matrix plan quality index CPQI showed good consistence with physician ranking results, it is a promising tool for optimal plan selection.

Dose- and LET-painting with particle therapy

Tumour hypoxia is one of the limiting factors in obtaining tumour control in radiotherapy. The high-LET region of a beam of heavy charged particles such as carbon ions is located in the distal part of the Bragg peak. A modulated or spread out Bragg peak (SOBP) is a weighted function of several Bragg peaks at various energies, which however results in a dilution of the dose-average LET in the target volume. Here, we investigate the possibility to redistribute the LET by dedicated treatment plan optimisation, in order to maximise LET in the target volume. This may be a strategy to potentially overcome hypoxia along with dose escalation or dose painting. The high-LET region can be shaped in very different ways, while maintaining the distribution of the absorbed dose or biological effective dose. Treatment plans involving only carbon ion beams, show very different LET distributions depending on how the fields are arranged. Alternatively, a LET boost can be applied in multi-modal treatment planning, such as combining carbon ions with protons and/or photons. For such mixed radiation modalities, significant “LET boosts” can be achieved at nearly arbitrary positions within the target volume. Following the general understanding of the relationship between hypoxia, LET and the oxygen enhancement ratio (OER), we conclude, that an additional therapeutic advantage can be achieved by confining the high-LET part of the radiation in hypoxic compartments of the tumour, and applying low-LET radiation to the normoxic tissue. We also anticipate that additional advantages may be achieved by deliberate sparing of normal tissue from high LET regions. Consequently, treatment planning based on simultaneous dose and LET optimisation has a potential to achieve higher tumour control and/or reduced normal tissue control probability (NTCP).

The Comparison of Treatment Plans.

Abstract The comparison of plans, once done by looking from one isodose plot to another, has become in hyper-dimensional planning a sophisticated matter. I have described here a number of tools that support plan evaluation and comparison, namely: 1.1. Side-by-side display of dose distributions: using color-wash to represent dose; displays on any section, transverse, sagittal, coronal, oblique; ostensive (mouse-driven cursor) interrogation of dose at a point; pan and zoom to highlight a specified volume of interest. 2.2. Dose-volume histograms: cumulative and (optionally) differential; with superposed constraint points. 3.3. Dose statistics: minimum, mean, maximum dose to a volume of interest; minimum dose received by a specified proportion of a VOI; proportion of a VOI which receives at least a specified dose; numerical score based on deviation from specified dose or dose-volume constraint. 4.4. Biophysical models: tumor control probability; normal tissue control probability. The greater complexity that this tool kit implies has, of course, its downside: although the clinician has much more useful information at his or her fingertips, it can take longer to use it. For this reason I have emphasized here the importance of speed and inter-activity in the programs and of tools to help users in the evaluation process. These are becoming increasingly available in the new generation of treatment-planning programs; pressure from the consumer is needed to keep researchers on their toes and manufacturers responsive!

An assessment of Biologically-based Optimization (BORT) in the IMRT era

The purpose of this study was to investigate the role of biological-based IMRT (BORT) in treatment planning development; more specifically, to assess the possible advantages of BORT over the classic 3-dimensional conformal radiation therapy (3DRT) and dose-based IMRT based on quantitative and qualitative indices. Three clinical cases are presented to evaluate the differences of BORT, IMRT, and 3DRT. 3DRT, IMRT, and BORT plans were generated for each case using a commercially available treatment planning system (Pinnacle by Philips). The plans were compared by evaluating biological endpoints such as tumor control probability (TCP), normal tissue control probability (NTCP), and uncomplicated tumor control probability (P+), as well as isodose line distribution, dose-volume histograms (DVHs), and dose uniformity. In all cases of this study, BORT yielded improved isodose coverage and P+. Our preliminary results suggest that BORT could play an important role in treatment planning optimization, especially as biological models and predictive assays become more accurate. Further case studies are needed to establish a definitive role for this type of optimization.

Inverse and forward optimization of one- and two-dimensional intensity-modulated radiation therapy-based treatment of concave-shaped planning target volumes: the case of prostate cancer.

Intensity-modulated radiation therapy (IMRT) was suggested as a suitable technique to protect the rectal wall, while maintaining a satisfactory planning target volume (PTV) irradiation in the case of high-dose radiotherapy of prostate cancer. However, up to now, few investigations tried to estimate the expected benefit with respect to conventional three-dimensional (3D) conformal radiotherapy (CRT). Estimating the expected clinical gain coming from both 1D and 2D IMRT against 3DCRT, in the case of prostate cancer by mean of radiobiological models. In order to enhance the impact of IMRT, the case of concave-shaped PTV including prostate and seminal vesicles (P+SV) was considered. Five patients with concave-shaped PTV including P+SV were selected. Two different sets of constraints were applied during planning: in the first one a quite large inhomogeneity of the dose distribution within the PTV was accepted (set (a)); in the other set (set (b)) a greater homogeneity was required. Tumor control probability (TCP) and normal tissue control probability (NTCP) indices were calculated through the Webb-Nahum and the Lyman-Kutcher models, respectively. Considering a dose interval from 64.8 to 100.8 Gy, the value giving a 5% NTCP for the rectum was found (D(NTCP(rectum)=5%)) using two different methods, and the corresponding TCP(NTCP(rectum)=5%) and NTCP(NTCP(rectum)=5%) for the other critical structures were derived. With the first method, the inverse optimization of the plans was performed just at a fixed 75.6 Gy ICRU dose; with the second method (applied to 2/5 patients) inverse treatment plannings were re-optimized at many dose levels (from 64.8 to 108 Gy with 3.6 Gy intervals). In this case, three different values of alpha/beta (10, 3, 1.5)were used for TCP calculation. The 3DCRT plan consisted of a 3-fields technique; in the IMRT plans, five equi-spaced beams were applied. The Helios Inverse Planning software from Varian was used for both the 2D IMRT and the 1D IMRT inverse optimization, the last one being performed fixing only one available pair of leaves for modulation. A previously proposed forward 1D IMRT 'class solution' technique was also considered, keeping the same irradiation geometry of the inversely optimized IMRT techniques. With the first method, the average gains in TCP(NTCP(rectum)=5%) of the 2D IMRT technique, with respect 3DCRT, were 10.3 and 7.8%, depending on the choice of the DVHs constraints during the inverse optimization procedure (set (a) and set (b), respectively). The average gain (DeltaTCP(NTCP(rectum)=5%)) coming from the inverse 1D IMRT optimization was 5.0%, when fixing the set (b) DVHs constraints. Concerning the forward 1D IMRT optimization, the average gain in TCP(NTCP(rectum)=5%) was 4.5%. The gain was found to be correlated with the degree of overlapping between rectum and PTV. When comparing 2D IMRT and 1D IMRT, in the case of the more realistic set (b) constraints, DeltaTCP(NTCP(rectum)=5%) was always less than 3%, excepting one patient with a very large overlap region. Basing our choice on this result, the second method was applied to this patient and one of the remaining. Through the inverse re-optimization of the treatment plans at each dose level, the gain in TCP(NTCP(rectum)=5%) of the inverse 2D technique was significantly higher than the ones obtained by applying the first method (concerning the two patients: +6.1% and +2.4%), while no significant benefit was found for inverse 1D. The impact of changing the alpha/beta ratio was less evident in the patient with the lower gain in TCP(NTCP(rectum)=5%). The expected benefit due to IMRT with respect to 3DCRT seems to be relevant when the overlap between PTV and rectum is high. Moreover, the difference between the inverse 2D and the simpler inverse or forward 1D IMRT techniques resulted in being relatively modest, with the exception of one patient, having a very large overlap between rectum and PTV. Optimizing the inverse planning at each dose level to find TCP(NTCP(rectum)=5%)e level to find TCP(NTCP(rectum)=5%) can improve the performances of inverse 2D IMRT, against a significant increase of the time for planning. These results suggest the importance of selecting the patients that could have significant benefit from the application of IMRT.

The comparison of treatment plans

The comparison of plans, once done by looking from one isodose plot to another, has become in hyper-dimensional planning a sophisticated matter. I have described here a number of tools that support plan evaluation and comparison, namely: 1. 1. Side-by-side display of dose distributions: using color-wash to represent dose; displays on any section, transverse, sagittal, coronal, oblique; ostensive (mouse-driven cursor) interrogation of dose at a point; pan and zoom to highlight a specified volume of interest. 2. 2. Dose-volume histograms: cumulative and (optionally) differential; with superposed constraint points. 3. 3. Dose statistics: minimum, mean, maximum dose to a volume of interest; minimum dose received by a specified proportion of a VOI; proportion of a VOI which receives at least a specified dose; numerical score based on deviation from specified dose or dose-volume constraint. 4. 4. Biophysical models: tumor control probability; normal tissue control probability. The greater complexity that this tool kit implies has, of course, its downside: although the clinician has much more useful information at his or her fingertips, it can take longer to use it. For this reason I have emphasized here the importance of speed and inter-activity in the programs and of tools to help users in the evaluation process. These are becoming increasingly available in the new generation of treatment-planning programs; pressure from the consumer is needed to keep researchers on their toes and manufacturers responsive!