Comprehensive 3DCRT Hypofractionated Radiotherapy Schedule for Localized Prostate Adenocarcinoma in the Era of IMRT: Dosimetric and Endoscopic Analysis.

Background: Moderate hypofractionated radiotherapy (MHRT) has emerged as the preferred treatment modality for localized prostate cancer based on randomized controlled studies regarding efficacy and toxicity using contemporary radiotherapy techniques. In the setting of MHRT, available data on dosimetric parameters and late rectal toxicity are limited. Aim: To present the effects of MHRT on late rectal toxicity while conducting an extensive dosimetric analysis in conjunction with rectoscopy results. Methods: This is a prospective study including patients with intermediate-risk prostate adenocarcinoma. All patients were treated with MHRT 44 Gy in 16 fractions to the seminal vesicles and to the prostate, followed by a sequential boost to the prostate alone of 16.5 Gy in 6 fractions delivered with three-dimensional conformal radiation therapy (3DCRT). Acute and late toxicity were assessed. Endoscopy was performed at baseline, every 3 months post-therapy for the first year, and every 6 months for the year after. The Vienna Rectoscopy Score (VRS) was used to assess rectal mucosal injury related to radiotherapy. Dosimetric analysis for the rectum, rectal wall, and its subsegments (upper, mid, and low 1/3) was performed. Results: Between September 2015 and December 2019, 20 patients enrolled. Grade 1 late gastrointestinal toxicity occurred in 10% of the patients, whereas 5% had a grade ≥2. Twelve months post radiotherapy: 4 (20%) patients had VRS 1; 2 (10%) patients had VRS 2; 1(5%) patient had VRS 3. 24 months post radiotherapy, VRS 1 was observed in 4 patients (20%) and VRS 2 in 3 (15%) patients. The dosimetric analysis demonstrated noticeable variations between the rectum, rectal wall, and rectal wall subsegments. The dosimetric analysis of the rectum, rectal wall, and its mid and low segments with respect to rectoscopy findings showed that the higher dose endpoints V52.17Gy and V56.52Gy are associated with rectal mucosal injury. Conclusions: A thorough delineation of the rectal wall and its subsegments, together with the dosimetric analysis of these structures, may reduce late rectal toxicity. Dosimetric parameters such as V52.17Gy and V56.52Gy were identified to have a significant impact on rectal mucosal injury; additional dose endpoint validation and its relation to late GI toxicity is needed.

Dosimetric predictors for genitourinary toxicity in MR-guided stereotactic body radiation therapy (SBRT): Substructure with fraction-wise analysis.

BACKGROUND: MR-guided radiation therapy (MRgRT) systems provide superior soft tissue contrast than x-ray based systems and can acquire real-time cine for treatment gating. These features allow treatment planning margins to be reduced, allowing for improved critical structure sparing and reduced treatment toxicity. Despite this improvement, genitourinary (GU) toxicity continues to affect many patients. PURPOSE: (1) To identify dosimetric predictors, potentially in combination with clinical parameters, of GU toxicity following SBRT by leveraging MRgRT to accurately monitor daily dose, beyond predicted dose calculated during planning. (2) Improve awareness of toxicity-sensitive bladder substructures, specifically the trigone and urethra. METHODS: Sixty-nine prostate cancer patients (NCT04384770 clinical trial) were treated on a ViewRay MRIdian MRgRT system, with 40 Gy prescribed to 95% of the PTV in over five fractions. Overall, 17 (24.6%) prostate patients reported acute grade 2 GU toxicity. The CTV, PTV, bladder, bladder wall, trigone, urethra, rectum, and rectal wall were contoured on the planning and daily treatment MRIs. Planning and daily treatment DVHs (0.1 Gy increments), organ doses (min, max, mean), and organ volumes were recorded. Daily dose was estimated by transferring the planning dose distributions to the daily MRI based on the daily setup alignment. Patients were partitioned into a training (55) and testing set (14). Dose features were pre-filtered using a t-test followed by maximum relevance minimum redundancy (MRMR) algorithm. Logistic regression was investigated with regularization to select dosimetric predictors. Specifically, two approaches: time-group least absolute shrinkage and selection (LASSO), and interactive grouped greedy algorithm (IGA) were investigated. Shared features across the planning and five treatment fractions were grouped to encourage consistency and stability. The conventional flat non-temporally grouped LASSO was also evaluated to provide a solid benchmark. After feature selection, a final logistic regression model was trained. Dosimetric regression models were compared to a clinical regression model with only clinical parameters (age, baseline IPSS, prostate gland size, ADT usage, etc.) and a hybrid model, combining the best performing dosimetric features with the clinical parameters, was evaluated. Final model performance was evaluated on the testing set using accuracy, sensitivity, and specificity determined by the optimal threshold of the training set. RESULTS: IGA had the best testing performance with an accuracy/sensitivity/specificity of 0.79/0.67/0.82, selecting 12 groups covering the bladder (V19.8 Gy, V20.5 Gy), bladder wall (19.7 Gy), trigone (15.9, 18.2, 43.3 Gy), urethra (V41.4 Gy, V41.7 Gy), CTV (V41.9 Gy), rectum (V8.5 Gy), and rectal wall (1.2, 44.1 Gy) dose features. Absolute bladder V19.8 Gy and V20.5 Gy were the most important features, followed by relative trigone 15.9  and 18.2 Gy. Inclusion of clinical parameters in the hybrid model with IGA did not significantly change regression performance. CONCLUSION: Overall, IGA feature selection resulted in the best GU toxicity prediction performance. This exploratory study demonstrated the feasibility of identification and analysis of dosimetric toxicity predictors with awareness to sensitive substructures and daily dose to potentially provide consistent and stable dosimetric metrics to guide treatment planning. Further patient accruement is warranted to further assess dosimetric predictor and perform validation.

Patient specific quality assurance of volumetric modulated arc therapy of synchronous bilateral breast cancer.

Synchronous bilateral breast cancers (SBBC) present a considerable issue in external beam radiotherapy because of large fields size and large target volumes. Mono-isocentric volumetric modulated arc therapy (VMAT) appears as an appropriate irradiation technique for these types of tumors. The aim of this study was to demonstrate the utility of a 3D DVH pretreatment quality assurance program in VMAT of SBBC cases. Twenty SBBC patients who underwent radiation therapy in our department were retrospectively enrolled in this study. Fifteen patients were treated exclusively to the mammary glands. Five patients benefited from a dose boost on the tumor bed (60Gy). Nine patients were irradiated on the supraclavicular nodes (50Gy). This dose was delivered in 25 fractions and integrated boost was used when appropriate. Depending on the complexity of the treatment plans; 2 or 4 arcs VMAT plans were used in a mono-isocentric technique. The patient specific quality assurance (PSQA) was evaluated using COMPASS measured data, COMPASS reconstructed (CR) and COMPASS computed (CC) dose compared to treatment planning system (TPS) dose. Clinical evaluation was based on DVH metrics for target volumes and organ at risks. The maximum average dose deviation between TPS, CC, and CR was below 3%. The paired t-test between TPS, CC, and CR shows a strong agreement (p < 0.001). The 3DVH dose distribution comparison between TPS and COMPASS were also performed with good gamma score for global analysis. COMPASS was successfully evaluated as a 3DVH pretreatment system for SBBC despite the large fields size and complex target volumes. It allows the verification of the plan in 3D patient anatomy and the evaluation of dose discrepancies.

Effects of lymphopenia on survival in proton therapy with chemotherapy for non-small cell lung cancer.

Lymphocytes play an important role in the cancer immune system. In the present study, we aimed to evaluate the associations of lymphopenia during proton beam therapy (PBT) and concurrent chemotherapy with clinical outcomes and to determine whether lung or bone is more influential on lymphopenia during PBT. Data from 41 patients with stage III non-small cell lung cancer (NSCLC) who received PBT of 74 GyE with concurrent chemotherapy between 2007 and 2017 were reviewed retrospectively. The correlation between dosimetry parameters obtained from dose-volume histograms of the bone and lung and lymphopenia during PBT were analyzed. Minimum absolute lymphocyte count (ALCmin) and maximum neutrophil/lymphocyte ratio (NLRmax) were used as indicators of lymphopenia. Bone V5-20 and lung V5-50 were significantly correlated with the ALCmin and NLRmax during PBT. Multivariable analysis showed that the NLRmax, but not the ALCmin, was associated with overall survival (OS), progression-free survival (PFS) and distant metastasis-free survival (DMFS). The 3-year rates of OS, PFS and DMFS of patients with a low (≤ 6.3) versus high (> 6.3) NLRmax were 73.9% vs 44.4% (P = 0.042), 26.1% vs 5.6% (P = 0.022) and 39.1% vs 5.6% (P < 0.001), respectively. Lung V20 was significantly associated with DMFS on multivariable analyses (hazard ratio: 1.094, P = 0.008), whereas bone V5 had no impact on survival outcomes. We concluded that the NLRmax was a better prognostic indicator than the ALCmin, and the lung dose had more influence than the bone dose on the main survival outcomes in stage III NSCLC patients treated with PBT combined with concurrent chemotherapy.

Determining the Occurrence of Hypothyroidism Following Treatment With Radiation Therapy in Head and Neck Carcinoma Patients and the Associated Role of Risk Factors and Dose-Volume Histograms: A Prospective Study.

Background Head and neck carcinomas are one of the most common malignancies in developing countries including India. Most patients are treated with radiotherapy. Although post-radiotherapy hypothyroidism is a known complication, data regarding its incidence and factors influencing it are scarce. This study aimed to determine the incidence of post-radiotherapy hypothyroidism in head and neck carcinoma patients treated with radiotherapy and the factors influencing it. Methodology Patients with head and neck carcinomas treated with radiotherapy as one of the modalities were included in this study. Thyroid function tests were done, and quality of life questionnaires were completed before treatment and during follow-up. Dose-volume histogram (DVH), demographic data, and disease-related parameters were compared. Results Out of the 95 patients screened, 14 were found to be hypothyroid prior to the commencement of radiotherapy and were excluded. With a median follow-up duration of 34 weeks, 29.6% developed hypothyroidism, with 19% developing it in the first year. On univariate and multivariate analysis of the DVH of the thyroid gland, volume receiving 50 Gy (V50), dose received to 50% volume (D50), and the mean dose (more than 50 Gy) were found to be significantly associated with hypothyroidism. Conclusions Hypothyroidism is a significant comorbid factor in Indian patients with head and neck carcinomas. The incidence of post-radiotherapy hypothyroidism is significant and occurs early compared to the western population leading to significant deterioration in the quality of life. Parameters such as the volume of the thyroid gland, V50, D50, and mean dose to the thyroid gland influence the incidence of hypothyroidism. The use of appropriate constraints can significantly prevent radiotherapy-induced hypothyroidism.

Comparison of acute gastrointestinal toxicities between 3-dimensional conformal radiotherapy and intensity-modulated radiotherapy including prophylactic regions in chemoradiotherapy with S-1 for pancreatic cancer-importance of dose volume histogram parameters in the stomach as the predictive factors.

The purpose of this study was to compare acute gastrointestinal (GI) toxicities in patients who underwent 3-dimensional conformal radiotherapy (3DCRT) and intensity-modulated radiotherapy (IMRT) in chemoradiotherapy (CRT) with S-1 including prophylactic regions for pancreatic cancer. We also investigated the predictive factor of acute GI toxicities in dose volume histogram (DVH) parameters. Patients who received CRT with S-1 for pancreatic cancer between January 2014 and March 2021 were included. Radiotherapy (RT) with a total dose of 50-54 Gy was delivered. We examined the differences in the frequencies of acute GI toxicity of grade 2 or higher and DVH parameters of the stomach (ST) and duodenum (DU) between the 3DCRT group and the IMRT group. The RT-related predictive factors of acute GI toxicities were investigated by univariate and multivariate analyses. There were 25 patients in the 3DCRT group and 31 patients in the IMRT group. The frequencies of acute GI toxicity of G2 or higher were 36% in the 3DCRT group and 9.7% in the IMRT group (p = 0.035). ST V50 was the most predictive factor (p = 0.001), and the incidences of acute GI toxicity of G2 or higher in ST V50 ≥ 4.1 cc and < 4.1cc were 43.7% and 7.7%, respectively. ST V40 was also a significant predictive factor of acute GI toxicity (p = 0.002). IMRT could reduce acute GI toxicities in CRT with S-1 including prophylactic regions for pancreatic cancer. Acute GI toxicities may be affected by moderate to high doses to the ST.

Development and Validation of a Comprehensive Multivariate Dosimetric Model for Predicting Late Genitourinary Toxicity Following Prostate Cancer Stereotactic Body Radiotherapy.

Purpose: Dosimetric predictors of toxicity after Stereotactic Body Radiation Therapy (SBRT) are not well-established. We sought to develop a multivariate model that predicts Common Terminology Criteria for Adverse Events (CTCAE) late grade 2 or greater genitourinary (GU) toxicity by interrogating the entire dose-volume histogram (DVH) from a large cohort of prostate cancer patients treated with SBRT on prospective trials. Methods: Three hundred and thirty-nine patients with late CTCAE toxicity data treated with prostate SBRT were identified and analyzed. All patients received 40 Gy in five fractions, every other day, using volumetric modulated arc therapy. For each patient, we examined 910 candidate dosimetric features including maximum dose, volumes of each organ [CTV, organs at risk (OARs)], V100%, and other granular volumetric/dosimetric indices at varying volumetric/dosimetric values from the entire DVH as well as ADT use to model and predict toxicity from SBRT. Training and validation subsets were generated with 90 and 10% of the patients in our cohort, respectively. Predictive accuracy was assessed by calculating the area under the receiver operating curve (AROC). Univariate analysis with student t-test was first performed on each candidate DVH feature. We subsequently performed advanced machine-learning multivariate analyses including classification and regression tree (CART), random forest, boosted tree, and multilayer neural network. Results: Median follow-up time was 32.3 months (range 3-98.9 months). Late grade ≥2 GU toxicity occurred in 20.1% of patients in our series. No single dosimetric parameter had an AROC for predicting late grade ≥2 GU toxicity on univariate analysis that exceeded 0.599. Optimized CART modestly improved prediction accuracy, with an AROC of 0.601, whereas other machine learning approaches did not improve upon univariate analyses. Conclusions: CART-based machine learning multivariate analyses drawing from 910 dosimetric features and ADT use modestly improves upon clinical prediction of late GU toxicity alone, yielding an AROC of 0.601. Biologic predictors may enhance predictive models for identifying patients at risk for late toxicity after SBRT.

Vertebral body irradiation during chemoradiation therapy for esophageal cancer contributes to acute bone marrow toxicity.

BACKGROUND: Hematologic toxicity (HT) commonly occurs during chemoradiation therapy (CRT) for esophageal cancer. We sought to determine radiation doses that correlate with declines in blood counts due to vertebral body (VB) irradiation during CRT. METHODS: We analyzed 53 esophageal cancer patients who were treated with weekly neoadjuvant carboplatin, paclitaxel and RT with weekly complete blood counts (CBC) available during treatment. HTs were graded according to the Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0). Dose volume histogram (DVH) parameters of Vx, defined as percentage of entire bony vertebra (body, pedicles, laminae, processes) receiving at least x Gy of radiation, were collected for VB V5 (VBV5), VBV10-VBV60 in increments of 10, and mean vertebral dose (MVD). Linear and logistic regressions were performed to identify associations between leukopenia nadirs and DVH parameters. Receiver operator curves identified thresholds to avoid grade ≥3 leukopenia. RESULTS: A proportion of 32.1% of patients (n=17) developed grade 3 leukopenia and 5.7% (n=3) developed grade 4 leukopenia. VBV5, VBV10, VBV20, VBV30, and MVD were significantly associated with worsening leukopenia on univariate and multivariate analysis. Associations with leukopenia were not seen with VBV40 and VBV50 DVH values. Thresholds to avoid grade ≥3 leukopenia were VBV10 <49.1%, VBV20 <45.6%, and MVD <17.2 Gy. CONCLUSIONS: VBV5, VBV10, VBV20, VBV30 associate with leukopenia during CRT for esophageal cancer patients. Improved radiation sparing of the VB may decrease HT and may improve tolerability of concurrent chemotherapy and allow for intensification of systemic therapy during RT.

First report on extended distance between tumor lesion and adjacent organs at risk using interventionally applied balloon catheters: a simple procedure to optimize clinical target volume covering effective isodose in interstitial high-dose-rate brachytherapy of liver malignomas.

PURPOSE: Organs at risk (OARs), which are very close to a clinical target volume (CTV), can compromise effective tumor irradiation. The present study investigated the feasibility and safety of a novel approach, in particular, the extent of the dosimetric effect of distancing CTV from adjacent OARs by means of interventionally applied balloon catheters. MATERIAL AND METHODS: Patients with peripheral hepatic malignancies, in whom the critical proximity of an OAR to the CTV in the assessment by contrast-enhanced magnetic resonance imaging (MRI) scans and the preplanning process were included. Additionally, patients underwent placement of an interventional balloon catheter during computed tomography (CT)-guided application of interstitial brachytherapy (iBT) catheters inserted into the tissue between hepatic capsule and adjacent OAR. The virtual position of an OAR without balloon catheter was anticipated and contoured in addition to contouring of CTV and OAR. The calculated dose values for CTV as well as 1 cc of the relevant OAR (D1cc) with and without balloon were recorded. The D1cc of the realized irradiation plan was statistically compared to the D1cc of the virtually contoured OARs. RESULTS: In 31 cases, at least one balloon catheter was administered. The mean D1cc of the OAR in the group with balloon(s) was 12.6 Gy compared with 16 Gy in the virtual cohort without the device, therefore significantly lower (p < 0.001). Overall, there were no acute complications. Severe (> 2 CTCAEv4.03) late complications observed in 3/31 (9.6%) patients during follow-up period after brachytherapy were most certainly not due to the balloon application. Side effects were probably associated with pre-existing serious diseases and potentially additional local late effects of the irradiation in general rather than with the balloon catheters. CONCLUSIONS: The distancing of the adjacent OARs allows a higher D100 value of CTV, therefore allowing for more efficient local control.

[Impact of DVH Outliers Registered in Knowledge-based Planning on Volumetric Modulated Arc Therapy Treatment Planning for Prostate Cancer].

RapidPlan, a knowledge-based planning software, uses a model library containing the dose-volume histogram (DVH) of previous treatment plans, and it automatically provides optimization objectives based on a trained model to future patients for volumetric modulated arc therapy treatment planning. However, it is unknown how DVH outliers registered in models influence the resulting plans. The purpose of this study was to investigate the effect of DVH outliers on the resulting quality of RapidPlan knowledge-based plans generated for patients with prostate cancer. First, 123 plans for patients with prostate cancer were used to populate the initial model (modelall). Next, modelall-20 and modelall-40 were created by excluding DVH outliers of bladder optimization contours 20 and 40 patients from modelall, respectively. These models were used to create plans for a 20-patient. The plans created using modelall-40 showed reductions of D30% and D50% in the bladder wall dose, and the DVH shape excluding outliers were affected. However, there were no significant differences in monitor units, target doses, or bladder wall doses between each treatment plan. Thus, we have shown that removal of DVH outliers from models does not affect the quality of plans created by the model.

Analysis of repeated proton beam therapy for patients with hepatocellular carcinoma.

PURPOSE: To evaluate the feasibility and efficacy of repeated proton beam therapy (PBT) and to analyze the dose-volume relationship. PATIENTS AND METHODS: A retrospective analysis was performed in 83 patients who received definitive repeated PBT. Proton beams were delivered with expiratory gating. The numbers of treatment courses were 2, 3, and 4 in 68, 12, and 3 patients, respectively. MIM software was used for dose analysis. RESULTS: The planned median total dose was 70.5 GyE for all tumors and the median doses for the 1st, 2nd, 3rd and 4th treatments were 71.0, 70.0, 70.0, and 69.3 GyE, respectively. There was no severe acute toxicity, and no radiation-induced liver dysfunction (RILD) was observed. The median overall survival (OS) period from the first PBT was 61months (95% CI: 50-71months), and the 2- and 5-year OS rates were 87.5% (95%CI: 80.2-94.8%) and 49.4% (95%CI: 37.6-61.2%), respectively. The maximal delivered dose to the liver ranged from 66.7 to 248.1 GyE (mean: 124.93 GyE) and the mean liver dose ranged from 5.4 to 66.5 GyE (mean: 24.23 GyE). CONCLUSION: Repeated PBT was well tolerated and safe, even though the liver doses in many patients deviated substantially from well-known critical levels for RILD.

Correlative study of dose to thyroid and incidence of subsequent dysfunction after head and neck radiation.

BACKGROUND: Thyroid dysfunction is common after radiotherapy (RT) for patients with head and neck cancers. We attempted to discover RT dose parameters that correspond with RT-induced thyroid dysfunction. METHODS: Records of 102 patients who received RT from 2008 to 2010 were reviewed with respect to thyroid function. Abnormalities were grouped in 2 ways: (1) none, transient, or permanent; and (2) overt or subclinical. RESULTS: At median follow-up of 33.5 months, incidence of any thyroid abnormality was 39.2% (women vs men - 50% vs 35%). Permanent dysfunction was seen in 24.5% with higher incidence in women versus men (42.9% vs 17.6%; p = .0081). Permanent abnormalities most strongly correlated with D50% (p = .0275). V50Gy also correlated with thyroid dysfunction post-RT (p = .0316). Concurrent chemotherapy increased permanent dysfunction (p = .0008). CONCLUSION: Achieving D50% <50 Gy, V50 <50%, and mean dose <54.58 Gy during RT planning may decrease the incidence; whereas female sex and concurrent chemotherapy seem to increase the risk of RT-induced hypothyroidism. © 2016 Wiley Periodicals, Inc. Head Neck 39: 548-554, 2017.

A new mathematical approach for handling DVH criteria in IMRT planning.

The appropriate handling of planning criteria on the cumulative dose-volume histogram (DVH) is a highly problematic issue in intensity-modulated radiation therapy (IMRT) plan optimization. The nonconvexity of DVH criteria and globality of the resulting optimization problems complicate the design of suitable optimization methods, which feature numerical efficiency, reliable convergence and optimality of the results. This work examines the mathematical structure of DVH criteria and proves the valuable properties of isotonicity/antitonicity, connectedness, invexity and sufficiency of the KKT condition. These properties facilitate the use of efficient and goal-oriented optimization methods. An exemplary algorithmic realization with feasible direction methods gives rise to a functional framework for interactive IMRT planning on DVH criteria. Numerical examples on real world planning cases prove its practical capability.

Analysis of acute radiation injury in non-small cell lung cancer treated by three-dimensional conformal radiotherapy / 中华放射医学与防护杂志

Objective To analyze the influencing factors with radiation induced injury of nonsmall cell lung cancer(NSCLC)treated by three-dimensional conformal radiotherapy,in order to supply he reference criteria for optimize the treatment planning of NSCLC, further to improve the local control rate and quality of life of NSCLC patitents.Method From Aug 2000 to Dec 2004,107 NSCLC patients received three-dimensional conformal radiotherapy were enrolled in this study.In all the patients,48 patients accepted three dimensional conformal radiotherapy(3D-CRT),the other 59 patients accepted conventional radiotherapy(CRT)before later-course of 3D-CRT.All of the patients received the prescription dose between 60-78 Gy and the median dose 66 Gy.Results In the 107 patients,the rate of radiation induced injury was 62.6%.and the rate of≥2 grade was 38.3%.23 cases were classified in grade 2,14 cases in grade 3,4 cases in grade 4.Univariate analysis showed chronic obstructive pulmonary disease,number of beams field,lung mean dose,lung V5-V40 were important influencing factors on radiation induced injury.Further more,lung mean dose,lung V20 and chronic obstructive lung disease were likely to be the independent factors of radiation induced injury by Logistic model.Conclusions lung mean dose,chronic obstructive lung disease and lung V20 were the independent influencing factors on irradiated induced injury.

Development of Conformal Radiotherapy with Respiratory Gate Device / 대한방사선종양학회지

PURPOSE: 3D conformal radiotherapy, the optimum dose delivered to the tumor and provided the risk of normal tissue unless marginal miss, was restricted by organ motion. For tumors in the thorax and abdomen, the planning target volume (PTV) is decided including the margin for movement of tumor volumes during treatment due to patients breathing. We designed the respiratory gating radiotherapy device (RGRD) for using during CT simulation, dose planning and beam delivery at identical breathing period conditions. Using RGRD, reducing the treatment margin for organ (thorax or abdomen) motion due to breathing and improve dose distribution for 3D conformal radiotherapy. MATERIALS AND METHODS: The internal organ motion data for lung cancer patients were obtained by examining the diaphragm in the supine position to find the position dependency. We made a respiratory gating radiotherapy device (RGRD) that is composed of a strip band, drug sensor, micro switch, and a connected on-off switch in a LINAC control box. During same breathing period by RGRD, spiral CT scan, virtual simulation, and 3D dose planing for lung cancer patients were performed, without an extended PTV margin for free breathing, and then the dose was delivered at the same positions. We calculated effective volumes and normal tissue complication probabilities (NTCP) using dose volume histograms for normal lung, and analyzed changes in doses associated with selected NTCP levels and tumor control probabilities (TCP) at these new dose levels. The effects of 3D conformal radiotherapy by RGRD were evaluated with DVH (Dose Volume Histogram), TCP, NTCP and dose statistics. RESULTS: The average movement of a diaphragm was 1.5 cm in the supine position when patients breathed freely. Depending on the location of the tumor, the magnitude of the PTV margin needs to be extended from 1 cm to 3 cm, which can greatly increase normal tissue irradiation, and hence, results in increase of the normal tissue complications probability. Simple and precise RGRD is very easy to setup on patients and is sensitive to length variation (+2 mm), it also delivers on-off information to patients and the LINAC machine. We evaluated the treatment plans of patients who had received conformal partial organ lung irradiation for the treatment of thorax malignancies. Using RGRD, the PTV margin by free breathing can be reduced about 2 cm for moving organs by breathing. TCP values are almost the same values (4-5% increased) for lung cancer regardless of increasing the PTV margin to 2.0 cm but NTCP values are rapidly increased (60-70% increased) for upon extending PTV margins by 2.0 cm. CONCLUSION: Internal organ motion due to breathing can be reduced effectively using our simple RGRD. This method can be used in clinical treatments to reduce organ motion induced margin, thereby reducing normal tissue irradiation. Using treatment planning software, the dose to normal tissues was analyzed by comparing dose statistics with and without RGRD. Potential benefits of radiotherapy derived from reduction or elimination of planning target volume (PTV) margins associated with patient breathing through the evaluation of the lung cancer patients treated with 3D conformal radiotherapy.