Normal tissue complication probability

Background and purpose-A tumor subvolume-based, risk-adaptive optimization strategy is presented. Methods and materials-Risk-adaptive optimization employs a biological objective function instead of an objective function based on physical dose constraints. Using this biological objective function, TCP is maximized for different tumor risk regions while at the same time minimizing NTCP for organs at risk (OAR). The feasibility of risk-adaptive optimization was investigated for a variety of tumor subvolume geometries, risk-levels, and slopes of the TCP curve. Furthermore, the impact of a correlation parameter, δ, between TCP and NTCP on risk-adaptive optimization was investigated. Results-Employing risk-adaptive optimization, it is possible in a prostate cancer model to increase EUD by up to 35.4 Gy in tumor subvolumes having the highest risk classification without increasing predicted normal tissue complications in organs at risk. For all tumor subvolume geometries investigated, we found that the EUD to high-risk tumor subvolumes could be increased significantly without increasing normal tissue complications above those expected from a treatment plan aiming for uniform dose coverage of the PTV. We furthermore found that the tumor subvolume with the highest risk classification had the largest influence on the design of the risk-adaptive dose distribution. The parameter δ had little effect on risk-adaptive optimization. However, the clinical parameters D 50 and γ 50 that represent the risk classification of subtumor volumes had the largest impact on risk-adaptive optimization. Conclusions-On the whole, risk-adaptive optimization yields heterogeneous dose distributions that match the risk level distribution of different subvolumes within the tumor volume.

The 3D-CRT plan could be further improved if a better choice of beam angles was made. The 3D-CRT plans were able to meet the RTOG criteria, which suggests the added time and expense of IMRT planning was not justified for these cases. However, it is true that allowing the TPS to work toward the RTOG criteria achieved a more homogeneous dose inside the target volume. To rationalize the use of IMRT treatment when a 3D conformal plan would suffice, the FCCC criteria could be used to fully exploit the benefits IMRT offers.

and 0.9916. The values of R 2 and l i were found to be 0.9867 & 0.0316 for V 100 ; 0.9988 & 0.0148 for V 150 ; 0.9958 & 0.00148 for V 200 , respectively. The values of l i are a function of T 1/2edema , hence the increase in V i with time is less pronounced when T 1/2edema changes from 4 to 30 days. Using the values of a=0.04 Gy -1 , b=0.027 Gy -2 and Tr = 1.9 hr (half repair time of sublethal damage in the prostate cells) at the 4 th week, the SF for D 90 and D 100 changes from 4.96Â10 -4 to 12.82Â10 -4 and 6.11Â10 -2 to 8.84Â10 -2 for change in T 1/2edema from 4 days to 30 days. This corresponds with a change in BED from 195.5 Gy to 171.87 Gy and 75.7 Gy to 66.6 Gy, respectively. Conclusions: Values of various dosimetric parameters investigated in this study increased with increasing post-implant time and attains optimal values in 4 weeks. But due to the short half life of 131 Cs seeds and longer T 1/2edema the improvement in dosimetric and radiobiological parameter is less. Therefore it is important to account for the effect of edema at the time of implant by defining seed positions by using post-needle volumes or by compensating for this edema on preplans.

Entropy as a quality descriptor for the dose distribution — theory and practice for the patient target volume The most common and established way to evaluate the quality of a radiotherapy plan is to use the dose-volume histogram (DVH). The evaluation of the DVH, however, is a subjective procedure. This may not be crucial as long as the two plans are significantly different. In the case of several plans obtained with different planning or optimisation strategies the differences are often subtle and therefore a more objective comparison method is desirable. A commonly used approach is based on evaluation of the conformity index, however we show how it can fail for plans of similar quality. Therefore we propose a new method based on the similarity of DVH to statistical distributions, which can be characterised uniquely by their entropy. The concept is defined separately for target volumes, where it is derived from the Fermi-like distribution, and for organs at risk, where the tradition...

The purpose of the study was to investigate the potential of direct machine parameter optimization (DMPO) to achieve parotid sparing without compromising target coverage in IMRT of oropharyngeal cancer as compared to fluence modulation with subsequent leaf sequencing (IM) and forward planned two-step arc therapy (IMAT). IMRT plans were generated for 10 oropharyngeal cancer patients using DMPO and IM. The resulting dose volume histograms (DVH) were evaluated with regard to compliance with the dose volume objectives (DVO) and plan quality. DMPO met the DVO for the targets better than IM, but violated the DVO to the parotids in some cases. DMPO provided better target coverage and dose homogeneity than IM and was comparable to IMAT. Dose to the parotids (23Gy) was significantly lower than for IMAT (48Gy), but somewhat higher than for IM (20Gy). Parotid sparing with IM was, however, only achieved at the cost of target coverage and homogeneity. DMPO allows achieving parotid sparing in the treatment of oropharyngeal cancer without compromising target coverage and dose homogeneity in the target as compared to two-step IMAT. Better overall plan quality can be delivered with less monitor units than with IM.

Radioiodine has been in use for over 60 years as a treatment for hyperthyroidism. Major changes in clinical practice have led to accurate dosimetry capable of avoiding the risks of adverse effects and the optimization of the treatment. The aim of this study was to test the capability of a radiobiological model, based on normal tissue complication probability ͑NTCP͒, to predict the outcome after oral therapeutic 131 I administration. Following dosimetric study, 79 patients underwent treatment for hyperthyroidism using radioiodine and then 67 had at least a one-year follow up. The delivered dose was calculated using the MIRD formula, taking into account the measured maximum uptake of administered iodine transferred to the thyroid, U0, and the effective clearance rate, T eff and target mass. The dose was converted to normalized total dose delivered at 2 Gy per fraction ͑NTD 2 ͒. Furthermore, the method to take into account the reduction of the mass of the gland during radioiodine therapy was also applied. The clinical outcome and dosimetric parameters were analyzed in order to study the dose-response relationship for hypothyroidism. The TD 50 and m parameters of the NTCP model approach were then estimated using the likelihood method. The TD 50 , expressed as NTD 2 , resulted in 60 Gy ͑95% C.I.: 45-75 Gy͒ and 96 Gy ͑95% C.I.: 86-109 Gy͒ for patients affected by Graves or autonomous/multinodular disease, respectively. This supports the clinical evidence that Graves' disease should be characterized by more radiosensitive cells compared to autonomous nodules. The m parameter for all patients was 0.27 ͑95% C.I.: 0.22-0.36͒. These parameters were compared with those reported in the literature for hypothyroidism induced after external beam radiotherapy. The NTCP model correctly predicted the clinical outcome after the therapeutic administration of radioiodine in our series.

Purpose: To report on the potential benefits of swallowing-sparing intensity-modulated radiation therapy (SW-IMRT) in the first 100 SW-IMRT treated patients, as well as on the factors that influence the potential benefit of SW-IMRT relative to standard parotid sparing (ST)-IMRT. Material and methods: One hundred consecutive head and neck cancer patients, scheduled for primary radiotherapy, were included in this prospective cohort study. For each patient, ST-IMRT and SW-IMRT treatment plans were created. All patients were eventually treated with SW-IMRT. Objectives for SW-IMRT were identical to those with ST-IMRT, with additional objectives to spare the swallowing organs at risk (SWOARs). After 20 patients, interim results were evaluated by a multidisciplinary committee. Results: The mean gain of SW-IMRT relative to ST-IMRT in the first 20 patients was less than expected based on our previous planning comparative study. A critical review of all plans revealed that the results with SW-IMRT could be improved by: (1) gaining experience and attempting to reduce SWOAR dose as much as possible; (2) accepting a moderate shift of dose to unspecified tissues; (3) maximizing SWOAR sparing while keeping PTV coverage exactly according to protocol. In the additional 80 patients, the mean dose to the various SWOARs was further reduced significantly compared to ST-IMRT. Dose reductions with SW-IMRT were largest for patients who received neck irradiation, had a tumour located in the larynx, oropharynx, nasopharynx or oral cavity, and had <75% overlap between SWOARs and PTVs. The mean absolute reduction in predicted physician-rated RTOG grade 2-4 swallowing dysfunction for patients numbered 21-100 was 6.1%, ranging from 0.0% to 17.2%. Conclusions: The benefit of SW-IMRT depends significantly on neck radiotherapy, tumour site and the amount of overlap between SWOARs and PTVs. Optimal clinical introduction requires a detailed evaluation and comparison between the standard (ST-IMRT) and new technique (SW-IMRT) in order to fully exploit the potential benefits.

Purpose: To determine the pattern of changes of rectum and bladder structures during conformal therapy of T3 prostate cancer and the impact of these changes on the accuracy of the dose-volume histograms (DVHs) and normal tissue complication probabilities (NTCPs) of these organs, based on the planning computed tomography (CT) scan only. Methods and Materials: For 11 T3 prostate cancer patients treated with conformal therapy, three repeat CT scans were made in Weeks 2, 4, and 6 of the treatment. The bony anatomy was aligned with the planning CT scan, using three dimensional (3D) chamfer matching. The internal and external surfaces of rectum and bladder were contoured in each scan. Three volumes were calculated for each organ: solid organ (including filling), filling, and wall volume. DVHs and NTCPs were calculated for all structures. Results: The solid organ and filling volumes varied considerably between patients and within a patient and they decreased with increasing treatment time. The largest patient variation was seen for patients with large initial filling volumes. The variations of rectum and bladder wall volumes during treatment were 9 and 17% (1 standard deviation (SD)), respectively, with no time trend. The changes of the high dose (~80 and 90% of the prescribed dose) volumes of the rectum in response to rectum filling differences were proportional to the whole rectum volume changes. The variation of the high-dose rectum wall volume was relatively small (14%, 1 SD). As a result, the NTCPs of rectum and rectum wall were the same overall and the variation of the NTCPs during treatment was about 14% (1 SD) and not correlated with rectum filling. The variation of the high-dose bladder volumes (about 14%, 1 SD) was smaller than the variation of the whole bladder volumes (30%, 1 SD). The high-dose bladder wall volume decreased significantly due to wall distention as the bladder filling increased. As a result of this complex pattern, the variation of NTCPs of bladder (85%, 1 SD) and bladder wall (88%, 1 SD) during treatment was large and significantly correlated with bladder filling. Conclusions: The planning CT scan overestimates rectum and bladder filling during treatment. Furthermore, the variation of filling is so large that only the wall structures have relatively constant volumes during treatment. For the rectum wall, the DVHs and NTCPs, as estimated from the initial scan, are representative for the whole treatment, because no correlation was seen between these parameters and organ filling. For the bladder wall, however, such a correlation was present and consequently, the initial bladder wall DVHs and NTCPs can only be representative for the whole treatment, if the bladder filling can be kept reasonably constant during treatment. Conformal radiation therapy, Dose-volume histograms, Prostate cancer.

To assess the potential of composite minimax robust optimization (CMRO) compared to planning target volume (PTV)-based optimization for head and neck cancer (HNC) patients treated with volumetric modulated arc therapy (VMAT). Ten HNC patients previously treated with a PTV-based VMAT plan were studied. In addition to the PTV-plan a VMAT plan was created with CMRO. For both plans an adapted planning strategy was also investigated, including a plan adaptation during the third week of treatment. The PTV-plans and CMRO-plans (adapted and non-adapted) were evaluated by means of the estimated actually given dose (EAGD). Therefore, the dose was calculated on daily acquired CBCTs, mapped onto the planning CT and accumulated. The plans were compared by dosimetric parameters and normal tissue complication probabilities (NTCPs) for tube feeding dependence, grade 2-4 dysphagia and xerostomia. The accuracy of CBCT-based dose accumulation was further quantified by comparisons of dose accumulation on weekly verification CTs. On average, CMRO significantly increased (1.5 Gy) the D 98% of the EAGD to the clinical target volume and significantly decreased the mean dose of the ipsilateral parotid (2.8 Gy), inferior pharynx constrictor muscle (0.7 Gy) and the oral cavity (0.8 Gy). This translated into significantly reduced NTCP of tube feeding dependence (0.9%) and xerostomia (2.8%). The differences in EAGD derived from evaluation CTs or CBCTs were minimal. Minimax robust optimization led to improved target coverage and dose reduction in organs at risk in HNC patients treated with VMAT.

To assess the potential of composite minimax robust optimization (CMRO) compared to planning target volume (PTV)-based optimization for head and neck cancer (HNC) patients treated with volumetric modulated arc therapy (VMAT). Ten HNC patients previously treated with a PTV-based VMAT plan were studied. In addition to the PTV-plan a VMAT plan was created with CMRO. For both plans an adapted planning strategy was also investigated, including a plan adaptation during the third week of treatment. The PTV-plans and CMRO-plans (adapted and non-adapted) were evaluated by means of the estimated actually given dose (EAGD). Therefore, the dose was calculated on daily acquired CBCTs, mapped onto the planning CT and accumulated. The plans were compared by dosimetric parameters and normal tissue complication probabilities (NTCPs) for tube feeding dependence, grade 2-4 dysphagia and xerostomia. The accuracy of CBCT-based dose accumulation was further quantified by comparisons of dose accumulation on weekly verification CTs. On average, CMRO significantly increased (1.5 Gy) the D 98% of the EAGD to the clinical target volume and significantly decreased the mean dose of the ipsilateral parotid (2.8 Gy), inferior pharynx constrictor muscle (0.7 Gy) and the oral cavity (0.8 Gy). This translated into significantly reduced NTCP of tube feeding dependence (0.9%) and xerostomia (2.8%). The differences in EAGD derived from evaluation CTs or CBCTs were minimal. Minimax robust optimization led to improved target coverage and dose reduction in organs at risk in HNC patients treated with VMAT.

Purpose: Intensity-modulated radiotherapy (IMRT) with photon beams is currently pursued in many clinics. Theoretically, inclusion of intensity-and energy-modulated high-energy electron beams (15-50 MeV) offers additional possibilities to improve radiotherapy treatments of deep-seated tumors. In this study the added value of high-energy electron beams in IMRT treatments was investigated. Methods and Materials: In a comparative treatment planning study, conventional treatment plans and various types of IMRT plans were constructed for four clinical cases (cancer of the bladder, pancreas, chordoma of the sacrum, and breast). The conventional plans were used for the actual treatment of the patients. The IMRT plans were optimized using the Orbit optimization code (Lo ¨f et al., 2000) with a radiobiologic objective function. The IMRT plans were either photon or combined electron and photon beam plans, with or without dose homogeneity constraints assuming standard or increased radiosensitivities of organs at risk. Results: Large improvements in expected treatment outcome are found using IMRT plans compared to conventional plans, but differences in tumor control probability (TCP) and normal tissue complication probabilities (NTCP) values between IMRT plans with and without electrons are small. However, the use of electrons improves the dose-volume histograms for organs at risk, especially at lower dose levels (e.g., 0 -40 Gy). Conclusions: This preliminary study indicates that addition of higher energy electrons to IMRT can only marginally improve treatment outcome for the selected cases. The dose-volume histograms of organs at risk show improvements for IMRT with higher energy electrons, which may reduce tumor induction but does not substantially reduce NTCP.

The shift from conventional two-dimensional (2D) to three-dimensional (3D)conformal target definition and dose-planning seems to have introduced volumetric as well as geometric changes. The purpose of this study was to compare coverage of computed tomography (CT)-based breast and boost planning target volumes (PTV), absolute volumes irradiated, and dose delivered to the organs at risk with conventional 2D and 3D-conformal breast conserving radiotherapy. Methods: Twenty-five patients with left-sided breast cancer were subject of CT-guided target definition and 3D-conformal dose-planning, and conventionally defined target volumes and treatment plans were reconstructed on the planning CT. Accumulated dose-distributions were calculated for the conventional and 3D-conformal dose-plans, taking into account a prescribed dose of 50 Gy for the breast plans and 16 Gy for the boost plans. Results: With conventional treatment plans, CT-based breast and boost PTVs received the intended dose in 78% and 32% of the patients, respectively, and smaller volumes received the prescribed breast and boost doses compared with 3D-conformal dose-planning. The mean lung dose, the volume of the lungs receiving > 20 Gy, the mean heart dose, and volume of the heart receiving > 30 Gy were significantly less with conventional treatment plans. Specific areas within the breast and boost PTVs systematically received a lower than intended dose with conventional treatment plans. The shift towards CT-guided target definition and planning as the golden standard for breast conserving radiotherapy has resulted in improved target coverage at the cost of larger irradiated volumes and an increased dose delivered to organs at risk. Tissue is now included into the breast and boost target volumes that was never explicitly defined or included with conventional treatment. Therefore, a coherent definition of the breast and boost target volumes is needed, based on clinical data confirming tumour control probability and normal tissue complication probability with the use of 3D-conformal radiotherapy.

Purpose: To report on the potential benefits of swallowing-sparing intensity-modulated radiation therapy (SW-IMRT) in the first 100 SW-IMRT treated patients, as well as on the factors that influence the potential benefit of SW-IMRT relative to standard parotid sparing (ST)-IMRT. Material and methods: One hundred consecutive head and neck cancer patients, scheduled for primary radiotherapy, were included in this prospective cohort study. For each patient, ST-IMRT and SW-IMRT treatment plans were created. All patients were eventually treated with SW-IMRT. Objectives for SW-IMRT were identical to those with ST-IMRT, with additional objectives to spare the swallowing organs at risk (SWOARs). After 20 patients, interim results were evaluated by a multidisciplinary committee. Results: The mean gain of SW-IMRT relative to ST-IMRT in the first 20 patients was less than expected based on our previous planning comparative study. A critical review of all plans revealed that the results with SW-IMRT could be improved by: (1) gaining experience and attempting to reduce SWOAR dose as much as possible; (2) accepting a moderate shift of dose to unspecified tissues; (3) maximizing SWOAR sparing while keeping PTV coverage exactly according to protocol. In the additional 80 patients, the mean dose to the various SWOARs was further reduced significantly compared to ST-IMRT. Dose reductions with SW-IMRT were largest for patients who received neck irradiation, had a tumour located in the larynx, oropharynx, nasopharynx or oral cavity, and had <75% overlap between SWOARs and PTVs. The mean absolute reduction in predicted physician-rated RTOG grade 2-4 swallowing dysfunction for patients numbered 21-100 was 6.1%, ranging from 0.0% to 17.2%. Conclusions: The benefit of SW-IMRT depends significantly on neck radiotherapy, tumour site and the amount of overlap between SWOARs and PTVs. Optimal clinical introduction requires a detailed evaluation and comparison between the standard (ST-IMRT) and new technique (SW-IMRT) in order to fully exploit the potential benefits.

Biological images (PET, SPECT, fMRI, etc.) provide three-dimensional biological data (proliferation, cell density, hypoxy, choline/citrate, etc)(1). The implementation of this information in a tratmentplan leads to the irradiation of target subvolumes with higher dose. For that a TPS has to be able to realise an inhomogeneous doseprescription. In this work we investigate the response of the inverse monte carlo TPS IKO (2) to an inhomogeneous prescribed dose distribution. 1 Methods and Materials In this work the inverse TPS IKO (2) is used for op- timisation. For first investigations nine different lat- tices wirh lattice constants from 1.5 cm to 9.5 cm are defined and treated as PTV in a RW3-Phantom. The modulation-transfer-function (mtf) is evaluated. Fi- nally one to five small islands are defined as sub- volumes within a prostate and treated by a 7 field prostate plan (figure2). The volumes differ from 2.0 cm 3 to 4.4 cm 3 . The prescribed Dose for these volumes is increased to m...

Radiotherapy has an important role in the treatment of prostate cancer. Three-dimensional conformal radiation therapy (3D-CRT), intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) techniques are all applied for this purpose. However, the risk of secondary radiation-induced bladder cancer is significantly elevated in irradiated patients compared surgery-only or watchful waiting groups. There are also reports of risk of secondary cancer with low doses to normal tissues. This study was designed to compare received volumes of low doses among 3D-CRT, IMRT and VMAT techniques for prostate patients. Ten prostate cancer patients were selected retrospectively for this planning study. Treatment plans were generated using 3D-CRT, IMRT and VMAT techniques. Conformity index (CI), homogenity index (HI), receiving 5 Gy of the volume (V5%), receiving 2 Gy of the volume (V2%), receiving 1 Gy of the volume (V1%) and monitor units (MUs) were compared. This study confirms that VMAT has slightly better CI while thev olume of low doses was higher. VMAT had lower MUs than IMRT. 3D-CRT had the lowest MU, CI and HI. If target coverage and normal tissue sparing are comparable between different treatment techniques, the risk of second malignancy should be a important factor in the selection of treatment.

Aims and Objectives: Aims and objectives of this study are to get the best fit of the normal tissue tolerance doses to the NTCP model of the linear quadratic model. To compute the NTCP, the modified form of the Poisson cell kill model of NTCP, based on linear quadratic model, is used. The model has been applied to compute the parameters of the NTCP model using clinical tolerance doses of various normal tissues / organs extracted from published reports of various authors. The normal tissue tolerance doses are calculated for partial volumes of the organs using the values of above-said parameters for published data on normal tissue tolerance doses. In this article, a graphical representation of the computed NTCP for bladder, brain, heart and rectum is presented. A fairly good correspondence is found between the curves of 2 sets of data for brain, heart and rectum. Hence the model may, therefore, be used to interpolate clinical data to provide an estimate of NTCP for these organs for any altered fractionated treatment schedule.

Purpose: Recent observations have shown that there are regional variations in radiation response in mouse lung as measured by functional assays. Furthermore, there are both in-field and out-of-field effects in radiationinduced lung damage as observed by DNA assay in rats. The purpose of this work is: (a) to examine mice lethality data following partial volume lung irradiation to assess the possibility of directional or regional effects, (b) to evaluate the correlation between mice lethality data and DNA damage assayed by micronuclei production in rat lung, and (c) to re-interpret mice lethality considering the existence of directional effects in lung cellular response to partial volume irradiation. Methods and Materials: The lethality data for mice, generated at the M. D. Anderson Cancer Center, Houston, and micronuclei yield data for rats obtained at Princess Margaret Hospital, Toronto, were used. A radiobiological model that allows for out-of-field and in-field effects for lung cell damage and lung response was developed. This model is based on the observation of DNA damage in shielded parts of rat lung that was assumed relevant to cell lethality and consequently overall lung response. Results: While the experimental data indicated directional or regional volume effects, the applicability of dose and volume as sole predictors of lung response to radiation was found to be unreliable for lower lung (base) irradiation in mice. This conforms well to rat lung response where micronuclei were observed in shielded apical parts of lung following base irradiation. The radiobiological model, which was specifically developed to account for the lung response outside of primary irradiated volume, provides a good fit to mice lethality data, using parameters inferred from rat micronuclei data. Conclusion: Response to lung irradiation in rodents, in particular, elevated sensitivity to base irradiation, can be interpreted with a hypothesis of in-field and out-of-field effects for cellular response. If the existence of these effects for lung is subsequently proven in humans, it will require the incorporation of geometrical and directional information in normal tissue complication probability calculations for lung. These considerations are ignored in present approaches based only on conventional dose-volume histograms.

Purpose: To investigate methods of reporting and analyzing statistical uncertainties in doses to targets and normal tissues in Monte Carlo (MC)-based treatment planning. Methods and Materials: Methods for quantifying statistical uncertainties in dose, such as uncertainty specification to specific dose points, or to volume-based regions, were analyzed in MC-based treatment planning for 5 lung cancer patients. The effect of statistical uncertainties on target and normal tissue dose indices was evaluated. The concept of uncertainty volume histograms for targets and organs at risk was examined, along with its utility, in conjunction with dose volume histograms, in assessing the acceptability of the statistical precision in dose distributions. The uncertainty evaluation tools were extended to four-dimensional planning for application on multiple instances of the patient geometry. All calculations were performed using the Dose Planning Method MC code. Results: For targets, generalized equivalent uniform doses and mean target doses converged at 150 million simulated histories, corresponding to relative uncertainties of less than 2% in the mean target doses. For the normal lung tissue (a volume-effect organ), mean lung dose and normal tissue complication probability converged at 150 million histories despite the large range in the relative organ uncertainty volume histograms. For "serial" normal tissues such as the spinal cord, large fluctuations exist in point dose relative uncertainties. Conclusions: The tools presented here provide useful means for evaluating statistical precision in MC-based dose distributions. Tradeoffs between uncertainties in doses to targets, volume-effect organs, and "serial" normal tissues must be considered carefully in determining acceptable levels of statistical precision in MC-computed dose distributions.

Intensity modulated radiation therapy (IMRT) guided by PET/CT imaging with respiratory gating was employed to dose escalate in patients with non-small cell lung cancer (NSCLC), using accelerated fractionation with induction chemotherapies. One patient developed a grade 5 pneumonitis and the study was halted at 84 Gy in 35 fractions.

The histogram analysis in radiation therapy (HART) software has been widely used for the research in intensity modulation radiation therapy (IMRT) treatments in cancer. The common application of HART is the precise and efficient dose volume histogram (DVH) analysis of structures in IMRT plans(Med Phys.35(6), p.2812 (2008)). The tool has been further developed with additional features, such as multi-dimensional dose histogram (MDH) computational module, dose response modeling (DRM), treatment plan-indices (TPIs) evaluation techniques, and biological modeling based outcome analysis (BOA) options. Methods and Materials: Matlab based codes were designed to read RTOG data formats exported from the Pinnacle 3 treatment planning system (TPS; Philips Healthcare, Best, Netherlands), and to write into a simpler HART format. HART computes the MDH differential data utilizing the information on the dose-grid values and the coordinates of a given structure in the TPS. MDH is applicable to evaluate spatial DVH and dose-surface histogram (DSH). The DRM utilizes the polynomial models for cumulative DVH in order to simulate the optimal dose response models for structures. The TPI assesses IMRT and stereotactic radiosurgery (SRS) plans by evaluating 10 different plan-indices as reported in literature. Similarly the POA feature can be used for evaluations of IMRT plans using various biological modeling (NTCP and TCP). DVH analysis results extracted by HART, can also be exported into customizable output formats. Results: HART offers MDH computational capability, DRM simulations, a noble TPI evaluation technique, a simpler POA feature, and the DVH analysis module for IMRT plans. MDH computations and DRM simulations for an IMRT plan were accomplished relatively in 15-30 minutes with the clock speed of 1.8 GHz and 2 GB RAM support. The MDH and DVH analysis results were validated with the Pinnacle 3 data. Conclusions: Several applications have been incorporated into a simpler, user-friendly, and automated software package (HART). We have also implemented an open-source mechanism for various users. We expect to develop HART for various applications in radiotherapy research, and its expansion to other TPSs.

This work aims to evaluate the predictive strength of the relative seriality, parallel and Lyman-Kutcher-Burman (LKB) normal tissue complication probability (NTCP) models regarding the incidence of radiation pneumonitis (RP), in a group of patients following lung cancer radiotherapy and also to examine their correlation with pulmonary function tests (PFTs). The study was based on 47 patients who received radiation therapy for stage III non-small-cell lung cancer. For each patient, lung dose volume histograms (DVHs) and the clinical treatment outcome were available. Clinical symptoms, radiological findings and pulmonary function tests incorporated in a post-treatment followup period of 18 months were used to assess the manifestation of radiation induced complications. Thirteen of the 47 patients were scored as having radiation induced pneumonitis, with RTOG criteria grade 3 and 28 of the 47 with RTOG criteria grade 2. Using this material, different methods of estimating the likelihood of radiation effects were evaluated, by analysing patient data based on their full dose distributions and associating the calculated complication rates with the clinical follow-up records. Lungs were evaluated as a paired organ as well as individual lungs. Of the NTCP models examined in the overall group considering the dose distribution in the ipsilateral lung, all models were able to predict radiation induced pneumonitis only in the case of grade 2 radiation pneumonitis score, with the LKB model giving the best results (χ 2 -test: probability of agreement between the observed and predicted

Purpose: To report on the potential benefits of swallowing-sparing intensity-modulated radiation therapy (SW-IMRT) in the first 100 SW-IMRT treated patients, as well as on the factors that influence the potential benefit of SW-IMRT relative to standard parotid sparing (ST)-IMRT. Material and methods: One hundred consecutive head and neck cancer patients, scheduled for primary radiotherapy, were included in this prospective cohort study. For each patient, ST-IMRT and SW-IMRT treatment plans were created. All patients were eventually treated with SW-IMRT. Objectives for SW-IMRT were identical to those with ST-IMRT, with additional objectives to spare the swallowing organs at risk (SWOARs). After 20 patients, interim results were evaluated by a multidisciplinary committee. Results: The mean gain of SW-IMRT relative to ST-IMRT in the first 20 patients was less than expected based on our previous planning comparative study. A critical review of all plans revealed that the results with SW-IMRT could be improved by: (1) gaining experience and attempting to reduce SWOAR dose as much as possible; (2) accepting a moderate shift of dose to unspecified tissues; (3) maximizing SWOAR sparing while keeping PTV coverage exactly according to protocol. In the additional 80 patients, the mean dose to the various SWOARs was further reduced significantly compared to ST-IMRT. Dose reductions with SW-IMRT were largest for patients who received neck irradiation, had a tumour located in the larynx, oropharynx, nasopharynx or oral cavity, and had <75% overlap between SWOARs and PTVs. The mean absolute reduction in predicted physician-rated RTOG grade 2-4 swallowing dysfunction for patients numbered 21-100 was 6.1%, ranging from 0.0% to 17.2%. Conclusions: The benefit of SW-IMRT depends significantly on neck radiotherapy, tumour site and the amount of overlap between SWOARs and PTVs. Optimal clinical introduction requires a detailed evaluation and comparison between the standard (ST-IMRT) and new technique (SW-IMRT) in order to fully exploit the potential benefits.

Background: Concurrent chemoradiation is one of the major treatments for locally advanced rectal cancer. As radiation therapy suppresses the bone marrow, it is essential to quantify the dose received by the pelvic bone marrow (PBM), which constitutes about 50% of the hematopoietic bone marrow. Methods: A prospective study conducted in 50 patients with locally advanced rectal cancer treated with long course concurrent chemoradiation. All the patients were followed up with weekly complete blood count for assessing hematological toxicities and were graded. PBM was contoured and subdivided into ilium bone marrow (IBM), lower pelvis bone marrow (LPBM) and lumbosacral bone marrow (LSBM). Volumes of bone marrow receiving different doses were quantified. Results: Among the 50 patients, 40 (80%) developed acute bone marrow toxicity, during the course of treatment. Highest grade of bone marrow toxicity developed in 20 (40%) patients which was grade 2. Compared to grade 1, grade 2 neutropenia patients exhibited significantly higher levels of V10 to V40 (p<0.05) in PBM and significantly higher levels of V20 in IBM and LSBM. In LPBM, compared to grade 1 leukopenia and neutropenia, grade 2 leukopenia and neutropenia exhibited significantly higher levels of V10 and V20 (p<0.05). Conclusions: Increased PBM V10 to V40, IBM V20, LSBM V20, LPBM V10 and V20 were significantly related to the higher grades of neutropenia in locally advanced rectal cancer patients undergoing long course concurrent chemoradiation. Increased LPBM V10 and V20 were also significantly related with higher grades of leukopenia

To achieve the optimal treatment goal, radiobiological parameters have to evaluate and predict the outcome of this treatment plan in terms of both TCP and NTCP. Different types of radiobiological model were used to achieve prescribed treatment dose of radiation during the tumor control. Where TCP models play an important role in order to achieve desired dose to the tumor. A suitable NTCP model was theoretically found among different models that can be used in treatment plan evaluation. Theoretically, six different radiobiological dose response models were analyzed in this project. Lyman-Kutcher-Burman, Critical element, critical volume, Relative Seriality, Parallel architecture, Weibull distribution models were analyzed from the derivation. All models were discussed elaborately with its various parameters and were used in the calculation of normal tissue complication probability during the treatment in radiotherapy. Further, all models were compared with each other. The models denote the dose for 50% complication probability (D50) parameters is the most commonly used radiobiological models for the normal tissues. The functional subunit response models (critical element & Relative seriality, Critical Volume, parallel architecture) are used in the derivation of the formulae for the normal tissue. Since all complicated NTCP model predict same as the simple NTCP model that is Lyman-Kutcher-Burman model as well as it is computationally efficient. Also Lyman-Kutcher-Burman model can be used in different treatment planning system incorporating with other model. For this reason, our suggested model is Lyman-Kutcher-Burman NTCP model which can be used in treatment plan evaluation. After analyzing six different model of NTCP, finding of the study is the treatment plan evaluation in where Lyman-Kutcher-Burman model is the best model for biological plan evaluation.

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Background: This paper analyses normal tissue sparing capability of radiation treatment techniques in Hodgkin's lymphoma with large treatment volume. Methods: 10 patients with supradiaphragmatic Hodgkin's lymphoma and planning target volume (PTV) larger than 900 cm 3 were evaluated. Two plans were simulated for each patient using 6 MV X-rays: a conventional multi-leaf (MLC) parallel-opposed (AP-PA) plan, and the same plan with additional MLC shaped segments (forward planned intensity modulated radiation therapy, FPIMRT). In order to compare plans, dose-volume histograms (DVHs) of PTV, lungs, heart, spinal cord, breast, and thyroid were analyzed. The Inhomogeneity Coefficient (IC), the PTV receiving 95% of the prescription dose (V95), the normal tissue complication probability (NTCP) and dose-volume parameters for the OARs were determined. Results: the PTV coverage was improved (mean V95 AP-PA = 95.9 and IC AP-PA = 0.4 vs. V95 FPIMRT = 96.8 and IC FPIMRT = 0.31, p ≤ 0.05) by the FPIMRT technique compared to the conventional one. At the same time, NTCPs of lung, spinal cord and thyroid, and the volume of lung and thyroid receiving ≥ 30 Gy resulted significantly reduced when using the FPIMRT technique. Conclusions: The FPIMRT technique can represent a very useful and, at the same time, simple method for improving PTV conformity while saving critical organs when large fields are needed as in Hodgkin's lymphoma.

ventricle and overlapping with the interventricular septum and the right ventricle. Conclusion: The VBA highlighted subregions with dose differences associated with RILD in both heart and lungs. The S .05 lung cluster shares a similar parenchymal position with analogous statistical structure found by Palma et al. 2016 on a different patient cohort (Hodgkin lymphoma) treated with different RT beam arrangement, thus supporting preliminarily reported patterns of the VBA findings on lung toxicity. Furthermore, the first inclusion of covariates within a dosimetric statistical model that faces the multiple comparison problem expands the potential of VBA, thus paving the way to a reliable VBA of radiation-induced toxicity in datasets with strong correlation of the outcome with non-dosimetric variables.

The standard treatment for stage I non-small cell lung cancer (NSCLC) is lobectomy. However, a considerable number of patients are not eligible for standard lung surgery due to poor pulmonary function or comorbidities. We evaluated the efficacy and tolerability of intensitymodulated stereotactic radiotherapy (IMSRT) with moderate hypofractionation for these patients. Twelve patients were selected for IMSRT. 4D-CT planning was performed by gating CT-scanning positioning. The applied doses ranged between 10x4.5 Gy (80% ID) (N=1), 12x4.5 Gy (95% ID) (N=1) and 10x5.5 Gy (95% ID) (N=10). Long-term follow-up was performed including spirometry and CT for evaluation of local, locoregional and distant control. Even in patients with poor pulmonary function IMRST was safe and well tolerated. No severe acute adverse effects were observed. Estimated local control at 2 years was 90%. Moreover, IMSRT does not induce a significant deterioration of pulmonary function. IMRST is safe and feasible even for patients with very poor pulmonary function. The applied dose provides a high local control rate, although the biological equivalent dose (BED) is lower compared to the average of other SRT regimens. Therefore, IMRST may be an efficient alternative for all NSCLC stage I patients with contraindications to standard lobectomy especially in patients with small tumors in highrisk localisations.

Background and purpose: The aim of our study was to elaborate a suitable model on bladder late toxicity in prostate cancer (PC) patients treated by radiotherapy with volumetric technique. Materials and methods: PC patients treated between September 2010 and April 2017 were included in the analysis. An observational study was performed collecting late toxicity data of any grade, according to RTOG and CTCAE 4.03 scales, cumulative dose volumes histograms were exported for each patient. Vdose, the value of dose to a specific volume of organ at risk (OAR), impact was analyzed through the Mann–Whitney rank-sum test. Logistic regression was used as the final model. The model performance was estimated by taking 1000 samples with replacement from the original dataset and calculating the AUC average. In addition, the calibration plot (Hosmer–Lemeshow goodness-of-fit test) was used to evaluate the performance of internal validation. RStudio Software version 3.3.1 and an in house developed sof...

2nd ESTRO Forum 2013 S457 deviations was related to the beam energy, i.e. larger deviations were observed for the higher beam energy. The overall treatment time calculated with superposition was 5-7 % longer in comparison to the calculation of convolution, and the coverage of PTV, in terms of 95% isodose, was better (up to 18%). Hot spots were lower for superposition plans for both low and high energies. Conclusions: Convolution algorithms are not adequate for dose calculations in the presence of and inside low density inhomogeneities, while the superposition algorithm showed better agreement for all cases.Convolution algorithm overestimates the delivered dose, which leads to the underdosage of the target volume in reality. This applies both to lower energy and even more to higher energy beams. Differences between doses calculated with superposition and convolution algorithms are primarily due to changes in electron transport in the lungs, which is not adequately taken into account by convolution algorithm. Following these findings, and recommendations from the literature all lung patients is planned with superposition algorithm. Acknowledgement: The work has been supported by IAEA through the national SRB6006 and regional RER 6023 technical cooperation project. EP-1215 The effect of photon energy on the intensity-modulated radiation therapy (IMRT) plans for prostate cancer

Background and purpose: Recent investigations demonstrated a significant correlation between rectal dose-volume patterns and late rectal toxicity. The reduction of the DVH to a value expressing the probability of complication would be suitable. To fit different normal tissue complication probability (NTCP) models to clinical outcome on late rectal bleeding after external beam radiotherapy (RT) for prostate cancer. Patients and methods: Rectal dose-volume histograms of the rectum (DVH) and clinical records of 547 prostate cancer patients (pts) pooled from five institutions previously collected and analyzed were considered. All patients were treated in supine position with 3 or 4-field techniques: 123 patients received an ICRU dose between 64 and 70 Gy, 255 patients between 70 and 74 Gy and 169 patients between 74 and 79.2 Gy; 457/547 patients were treated with conformal RT and 203/547 underwent radical prostatectomy before RT. Minimum follow-up was 18 months. Patients were considered as bleeders if showing grade 2/3 late bleeding (slightly modified RTOG/EORTC scoring system) within 18 months after the end of RT. Four NTCP models were considered: (a) the Lyman model with DVH reduced to the equivalent uniform dose (LEUD, coincident with the classical Lyman-Kutcher-Burman, LKB, model), (b) logistic with DVH reduced to EUD (LOGEUD), (c) Poisson coupled to EUD reduction scheme and (d) relative seriality (RS). The parameters for the different models were fit to the patient data using a maximum likelihood analysis. The 68% confidence intervals (CI) of each parameter were also derived. Results: Forty six out of five hundred and forty seven patients experienced grade 2/3 late bleeding: 38/46 developed rectal bleeding within 18 months and were then considered as bleeders The risk of rectal bleeding can be well calculated with a 'smooth' function of EUD (with a seriality parameter n equal to 0.23 (CI 0.05), best fit result). Using LEUD the relationship between EUD and NTCP can be described with a TD50 of 81.9 Gy (CI 1.8 Gy) and a steepness parameter m of 0.19 (CI 0.01); when using LOGEUD, TD50 is 82.2 Gy and k is 7.85. Best fit parameters for RS are sZ0.49, gZ1.69, TD50Z83.1 Gy. Qualitative as well as quantitative comparisons (chisquared statistics, PZ0.005) show that the models fit the observed complication rates very well. The results found in the overall population were substantially confirmed in the subgroup of radically treated patients (LEUD: nZ0.24 mZ0.14 TD50Z75.8 Gy). If considering just the grade 3 bleeders (nZ9) the best fit is found in correspondence of a n-value around 0.06, suggesting that for severe bleeding the rectum is more serial.

To estimate the dosimetric impact of residual setup errors on parotid sparing in head-and-neck (H&N) intensity-modulated treatments and to evaluate the effect of employing an PRV (planning organ-at-risk volume) margin for the parotid gland. Patients and Methods: Ten patients treated for H&N cancer were considered. A nine-beam intensity-modulated radiotherapy (IMRT) was planned for each patient. A second optimization was performed prescribing dose constraint to the PRV of the parotid gland. Systematic setup errors of 2 mm, 3 mm, and 5 mm were simulated. The dose-volume histograms of the shifted and reference plans were compared with regard to mean parotid gland dose (MPD), normal-tissue complication probability (NTCP), and coverage of the clinical target volume (V 95% and equivalent uniform dose [EUD]); the sensitivity of parotid sparing on setup error was evaluated with a probability-based approach. Results: MPD increased by 3.4%/mm and 3.0%/mm for displacements in the craniocaudal and lateral direction and by 0.7%/ mm for displacements in the anterior-posterior direction. The probability to irradiate the parotid with a mean dose > 30 Gy was > 50%, for setup errors in cranial and lateral direction and < 10% in the anterior-posterior direction. The addition of a PRV margin improved parotid sparing, with a relative reduction in NTCP of 14%. The PRV margin compensates for setup errors of 3 mm and 5 mm (MPD ≤ 30 Gy in 87% and 60% of cases), without affecting clinical target volume coverage (V 95% and EUD variations < 1% and < 1 Gy). Conclusion: The parotid gland is more sensitive to craniocaudal and lateral displacements. A setup error of 2 mm guarantees an MPD ≤ 30 Gy in most cases, without adding a PRV margin. If greater displacements are expected/accepted, an adequate PRV margin could be used to meet the clinical parotid gland constraint of 30 Gy, without affecting target volume coverage.

To develop a predictive multivariate normal tissue complication probability (NTCP) model for radiation-induced heart valvular damage (RVD). The influence of combined heart-lung irradiation on RVD development was included. Multivariate logistic regression modeling with the least absolute shrinkage and selection operator (LASSO) was used to build an NTCP model to predict RVD based on a cohort of 90 Hodgkin lymphoma patients treated with sequential chemo-radiation therapy. In addition to heart irradiation factors, clinical variables, along with left and right lung dose-volume histogram statistics, were included in the analysis. To avoid overfitting, 10-fold cross-validation (CV) was used for LASSO logistic regression modeling, with 50 reshuffled cycles. Model performance was assessed using the area under the receiver operating characteristic (ROC) curve (AUC) and Spearman&#39;s correlation coefficient (Rs). At a median follow-up time of 55 months (range 12-92 months) after the end of r...

Although larger multivariate studies are necessary to determine the precise effect of different chemotherapy agents, the study by Tsujino et al. (1) allows us to estimate roughly the additional risk for patients to develop radiation pneumonitis when concurrent treatment with chemotherapy is applied. Dose-response curves such as in Fig. 1 will be valuable for the optimization of radiation treatment of the increasing number of lung cancer patients receiving concurrent chemoradiation.

Radiation therapy dosimetry software now frequently incorporates biological predictions of the probability of normal tissue complications. This study investigates whether the length of normal structure outlined affects a normal tissue complication probability (NTCP) for that structure. It also researches the effect of any change in the dose parameter used to produce a 50% probability of a complication (the TD 50) on the calculated NTCP, as this is related to the clinical observations. An NTCP was calculated for rectum and bladder on a sample of prostate cases receiving external beam radiation therapy. The length of the organs at risk was varied and the NTCP recalculated for each different length using the same treatment plan. Large variations of up to 80% in NTCP for different delineated lengths of organ for a given TD 50 were observed. Changing the TD 50 dose altered the calculated NTCP and the relative size of the variation in the values. This parameter will need further investigation; a standardized delineated length of 2 cm beyond the beam edge for normal structures is recommended. Interpatient and interinstitution plan comparison using dose volume histograms and/or normal tissue complication probabilities will be compromised until such standardization occurs.

Background Accurate localisation of the lumpectomy cavity (LC) volume is one of the most critical points in 3D-conformal Partial breast irradiation (3D-APBI) treatment planning because the irradiated volume is restricted to a small breast volume. Here, we studied the role of the placement of surgical clips at the 4 cardinal points of the lumpectomy cavity in target delineation. Methods Forty CT-based 3D-APBI plans were retrieved on which a total of 4 radiation oncologists, two trainee and two experienced physicians, outlined the lumpectomy cavity. The inter-observer variability of LC contouring was assessed when the CTV was defined as the delineation that encompassed both surgical clips and remodelled breast tissue. Results The conformity index of tumour bed delineation was significantly improved by the placement of surgical clips within the LC (median at 0.65). Furthermore, a better conformity index of LC was observed according to the experience of the physicians (median CI = 0.55 ...

Purpose-We previously showed that 75% of radiation therapy (RT) failures in patients with unresectable esophageal cancer are in the gross tumor volume (GTV). We performed a planning study to evaluate if a simultaneous integrated boost (SIB) technique could selectively deliver a boost dose of radiation to the GTV in patients with esophageal cancer. Methods and Materials-Treatment plans were generated using four different approaches (two-dimensional conformal RT [2D-CRT] to 50.4 Gy or 64.8 Gy, intensity-modulated RT [IMRT] to 50.4 Gy, and SIB-IMRT to 64.8 Gy) and optimized for 10 patients with distal esophageal cancer. All plans were constructed to deliver the target dose in 28 fractions using heterogeneity corrections. Isodose distributions were evaluated for target coverage and normal tissue exposure. Results-The 50.4-Gy IMRT plan was associated with significant reductions in mean cardiac, pulmonary, and hepatic doses relative to the 50.4-Gy 2D-CRT plan. The 64.8-Gy SIB-IMRT plan produced a 28% increase in GTV dose and the same normal tissue doses as the 50.4-Gy IMRT plan; compared with the 50.4-Gy 2D-CRT plan, the 64.8-Gy SIB-IMRT produced significant dose reductions to all critical structures (heart, lung, liver, and spinal cord). Conclusions-The use of SIB-IMRT allowed us to selectively increase the dose to the GTV, the area at highest risk of failure, while simultaneously reducing the dose to the normal heart, lung, and liver. Clinical implications warrant systematic evaluation.

Background: Nowadays, radiation therapy plays an important role in the treatment of breast cancer. The important point is the optimal control of the tumor along with the protection of organs at risk. This study aims to investigate and compare the radiobiological factors of the tumor and organs at risk in two different radiation therapy techniques of breast cancer.Methods: Ten left-sided breast cancer patients with breast-conservative surgery were selected for this study. Three-dimensional treatment planning was performed using CT scan images of the patients using PCRT 3D software. Two different tangential external beam techniques were compared: first, dual-isocentric technique (DIT) with two isocentre, one on the breast tissue, and the other one on the supraclavicular lymph nodes and second, a mono-isocentric technique (MIT) with one isocentre at the intersection of the tangential and the supraclavicular field. The total prescribed dose was 5000 cGy per 25 fractions. Dose-volume his...

Purpose: Reirradiation in the scalp area can be challenging given the proximity to organs at risk (OARs), such as the eye and brain. Our aim is to evaluate the dosimetric differences of volumetric modulated arc therapy (VMAT) and electron beam therapy (EBT) compared with 3-dimensional proton beam therapy (PBT). Patients and Methods: We evaluated a patient with recurrent angiosarcoma of the left temporal scalp after prior surgical resections and radiation therapy to 60 Gy in 30 fractions who needed reirradiation. We generated VMAT, EBT, and PBT plans using the Pinnacle Treatment Planning System (TPS). Both VMAT and EBT plans used a skin bolus, whereas no bolus was used for the proton plan. Doses to the OARs, including cochlea, eyes, lens, lacrimal glands, optic nerves, optic chiasm, pituitary gland, and underlying brain, were compared. Results: The reirradiation treatment dose was 60 Gy(RBE). Target volume coverage was comparable in all plans. Compared with VMAT and EBT, the PBT plan...

vs 70). A composite DDR pathway biomarker was defined as positive enrichment in damage checkpoint, DSB repair, BER, NER, and MMR. Results: We found that there are distinct clusters of DDR pathway patterns within the cohort. DDR pathway enrichment is only weakly correlated with the clinical variables of age, Gleason score, and prostate-specific antigen (Spearman rho 0.20) and is much more strongly correlated with AR pathway enrichment (Spearman rho up to 0.82). Many of the individual pathways have statistically significant association between positive pathway enrichment and increased metastatic progression risk (5/8 DDR pathways with odds ratios [ORs] 1.41e1.78) and worse overall survival (8/ 8, ORs Z 1.51e2.23) on univariate and multivariate analysis. The composite DDR pathway biomarker showed improved prognostic performance for metastatic progression risk (OR Z 2.09 [1.33, 3.28]), but not for overall survival (OR Z 2.07 [1.31, 3.27]). Interestingly, this metastatic progression prognostic significance is driven by patients <70 years old (6/ 8, ORs Z 1.40e1.90), while there was no prognostic significance in patients 70 (P > .2). Conclusion: Patient-level DDR pathway profiling revealed distinct pathway enrichment clusters. Individual DDR pathways and a composite DDR pathway biomarker showed strong prognostic performance with the long-term outcomes of metastatic progression and overall survival that may be useful for risk stratification of high-risk prostate cancer patients.

external beam RT followed by a brachytherapy boost with (N = 2,723) or without (N = 986) a median duration of 4.2 (IQR 3.3-5.5) months of neoadjuvant HT between 1991 and 2006. 70% of men had unfavorable-risk disease (Gleason score 7 or above; PSA 10 ng/mL or above; or clinical stage T2b or above). A Cox regression multivariable analysis was performed assessing whether WP as compared to PORT affected the risk of ACM, adjusting for age, cardiovascular comorbidity, HT use, year of treatment, and known PC prognostic factors. A formal test for interaction between the radiation treatment volume and HT use was performed. Results: After a median follow-up of 3.3 years, there were a total of 561 deaths. Within the interaction model, the use of WPRT as compared to PORT was significantly associated with a decreased risk of ACM (adjusted hazard ratio [AHR] 0.58, 95% confidence interval [CI], 0.38-0.89, p = 0.01). Similarly, HT use was significantly associated with a decreased risk of ACM (AHR 0.71, 95% CI, 0.58-0.90, p = 0.004). An interaction term consisting of WPRT and HT use was also noted to be significant (AHR 1.61, 95% CI, 1.004-2.58, p = 0.048). When compared to men treated with PORT without HT, there was a significantly decreased risk of ACM in men treated with either WPRT without HT (p = 0.01) or PORT with HT (p = 0.004) as well as in men treated with both WPRT and HT (p = 0.005). However, there was no significant decrease in the risk of ACM in men treated with both WPRT and HT when compared to men treated with either WPRT without HT (p = 0.51) or PORT with HT (p = 0.53). Conclusions: The use of either WPRT or the addition of short-course HT to PORT is associated with a decreased risk of ACM in men treated for PC, but there is no additive or synergistic benefit to combining both. These findings suggest that the shared mechanism for this risk reduction by either WPRT or short-course HT use is sterilization of micrometastatic disease within pelvic lymph nodes.

external beam RT followed by a brachytherapy boost with (N = 2,723) or without (N = 986) a median duration of 4.2 (IQR 3.3-5.5) months of neoadjuvant HT between 1991 and 2006. 70% of men had unfavorable-risk disease (Gleason score 7 or above; PSA 10 ng/mL or above; or clinical stage T2b or above). A Cox regression multivariable analysis was performed assessing whether WP as compared to PORT affected the risk of ACM, adjusting for age, cardiovascular comorbidity, HT use, year of treatment, and known PC prognostic factors. A formal test for interaction between the radiation treatment volume and HT use was performed. Results: After a median follow-up of 3.3 years, there were a total of 561 deaths. Within the interaction model, the use of WPRT as compared to PORT was significantly associated with a decreased risk of ACM (adjusted hazard ratio [AHR] 0.58, 95% confidence interval [CI], 0.38-0.89, p = 0.01). Similarly, HT use was significantly associated with a decreased risk of ACM (AHR 0.71, 95% CI, 0.58-0.90, p = 0.004). An interaction term consisting of WPRT and HT use was also noted to be significant (AHR 1.61, 95% CI, 1.004-2.58, p = 0.048). When compared to men treated with PORT without HT, there was a significantly decreased risk of ACM in men treated with either WPRT without HT (p = 0.01) or PORT with HT (p = 0.004) as well as in men treated with both WPRT and HT (p = 0.005). However, there was no significant decrease in the risk of ACM in men treated with both WPRT and HT when compared to men treated with either WPRT without HT (p = 0.51) or PORT with HT (p = 0.53). Conclusions: The use of either WPRT or the addition of short-course HT to PORT is associated with a decreased risk of ACM in men treated for PC, but there is no additive or synergistic benefit to combining both. These findings suggest that the shared mechanism for this risk reduction by either WPRT or short-course HT use is sterilization of micrometastatic disease within pelvic lymph nodes.

Background: Hepatocellular carcinoma with inferior vena cava invasion is a rare but fatal condition of disease progression. The aim of this study was to analyze the results of treatment for hepatocellular carcinoma with inferior vena cava invasion by three-dimensional conformal radiation therapy. Methods: From 1990 to 2006, 18 histopathologically confirmed hepatocellular carcinoma patients with inferior vena cava invasion who were unsuitable for surgery were treated by three-dimensional conformal radiation therapy at our hospital with two to four static or dynamic conformal arc fields. Results: A median total tumor dose of 50 Gy (range 30-60 Gy) was delivered. The progression-free rate was 91.6% among the patients in whom follow-up computed tomography was obtained. Actuarial survival at 1 year was 33.3%, and the median survival period was 5.6 months. Conclusions: Three-dimensional conformal radiation therapy might offer a chance of long survival for a part of the hepatocellular carcinoma patients with inferior vena cava invasion, since a third of such patients survived more than a year. Additional treatments should be considered to prevent distant metastases and hepatic functional deterioration after threedimensional conformal radiation therapy.