Lung Normal Tissue Complication Probability Research Articles

Radiobiological evaluation of hypo-fractionated breast cancer radiotherapy regimens in comparison with conventional approaches

Abstract Purpose: This study compares tumor control probability (TCP) and normal tissue complication probability (NTCP) across different hypo-fractionated (HypoRT) and conventional breast radiotherapy regimens using radiobiological models. Materials and methods: Computed tomography data from 30 patients with left breast-conserving surgery were used to evaluate three HypoRT regimens (39 Gy and 41·6 Gy in 13 fractions, and 40 Gy in 15 fractions) and a conventional regimen (50 Gy in 25 fractions). Dose-volume histograms (DVHs) were extracted for radiobiological calculations using Equivalent Uniform Dose (EUD) and Poisson models for TCP, and EUD and LKB (Lyman-Kutcher-Burman) models for NTCP. Results: Conventional treatment achieved significantly higher TCP (95%) than all HypoRT regimens (p < 0·001), with no significant differences between HypoRT regimens (p > 0·05. The 39 Gy/13 fraction regimen showed the lowest lung NTCP (p < 0·05). HypoRT regimens had significantly lower NTCP for the lungs and heart compared to the conventional regimen (p < 0·01). TCP and NTCP values from Poisson and LKB models were higher than those from the EUD model (p < 0·01). Conclusion: HypoRT regimens reduced NTCP, with the lowest values in the regime of 39 Gy/13 fractions regimen, though the conventional regimen had higher TCP.

An Agent-Based Model of Radiation-Induced Lung Fibrosis.

Early- and late-phase radiation-induced lung injuries, namely pneumonitis and lung fibrosis (RILF), severely constrain the maximum dose and irradiated volume in thoracic radiotherapy. As the most radiosensitive targets, epithelial cells respond to radiation either by undergoing apoptosis or switching to a senescent phenotype that triggers the immune system and damages surrounding healthy cells. Unresolved inflammation stimulates mesenchymal cells' proliferation and extracellular matrix (ECM) secretion, which irreversibly stiffens the alveolar walls and leads to respiratory failure. Although a thorough understanding is lacking, RILF and idiopathic pulmonary fibrosis share multiple pathways and would mutually benefit from further insights into disease progression. Furthermore, current normal tissue complication probability (NTCP) models rely on clinical experience to set tolerance doses for organs at risk and leave aside mechanistic interpretations of the undergoing processes. To these aims, we implemented a 3D agent-based model (ABM) of an alveolar duct that simulates cell dynamics and substance diffusion following radiation injury. Emphasis was placed on cell repopulation, senescent clearance, and intra/inter-alveolar bystander senescence while tracking ECM deposition. Our ABM successfully replicates early and late fibrotic response patterns reported in the literature along with the ECM sigmoidal dose-response curve. Moreover, surrogate measures of RILF severity via a custom indicator show qualitative agreement with published fibrosis indices. Finally, our ABM provides a fully mechanistic alveolar survival curve highlighting the need to include bystander damage in lung NTCP models.

Normal tissue complication probabilities of lung SABR patients from a UK centre and its implication on personalised radiotherapy

Abstract Introduction: This work reports on the normal tissue complication probabilities (NTCP) from a UK cohort of previously treated peripheral lung SABR patients (n = 198) supplementing our previous publication on tumour control probabilities (TCP). Each patient was recalculated for alternative schedules. Materials and Methods: NTCP for 3 (54 Gy), 5 (55 and 60 Gy) and 8 (50 Gy) fraction (#) schemes were calculated with the Lyman Kutcher Burman (LKB) model in the software platform ‘Biosuite’ (Version 12·01) for lung and chest wall. Patients treated with 5 # or 8 # were then recomputed for alternative fractionations and doses (3 # and 5 #, for both 55 Gy and 60 Gy). Results: The mean lung NTCP (NTCPLUNG, for the outcome of radiation pneumonitis) was 2·8% (range 0·6 – 10·6). The mean chest wall NTCP (NTCPCW, for the outcome of rib fracture) was 1·4% (range 0·0–55·9). There were no statistically significant differences observed between male and female, tumour status or fractionation groups except for the NTCPLUNG between 5 # and 3 #. When recalculating NTCP and TCP individually, for 8 # patients, no differences were observed between mean TCP, NTCPLUNG or NTCPCW compared with 3 # or 5 # indicating that fractionation reduction is possible. Parity was observed between the 60 Gy group when recalculated for 55 Gy. For the 60 Gy in 5 # group, the NTCPCW increased significantly when recalculated for 3 #. Conclusion: NTCPs achievable with current UK planning techniques have been presented indicating SABR Consortium compliant centres are likely to have low complication population risks (< 3 %). 5 # schedules could be justified for 8 # patients, thereby reducing the number of treatment visits. Where there is a large overlap of PTV and chest wall, this indicates an NTCP/TCP calculation is required to investigate if fractionation reduction is individually appropriate.

A Comparison of Isotoxic Dose-escalated Radiotherapy in Lung Cancer with Moderate Deep Inspiration Breath Hold, Mid-ventilation and Internal Target Volume Techniques

AimsWith interest in normal tissue sparing and dose-escalated radiotherapy in the treatment of inoperable locally advanced non-small cell lung cancer, this study investigated the impact of motion-managed moderate deep inspiration breath hold (mDIBH) on normal tissue sparing and dose-escalation potential and compared this to planning with a four-dimensional motion-encompassing internal target volume or motion-compensating mid-ventilation approach. Materials and methodsTwenty-one patients underwent four-dimensional and mDIBH planning computed tomography scans. Internal and mid-ventilation target volumes were generated on the four-dimensional scan, with mDIBH target volumes generated on the mDIBH scan. Isotoxic target dose-escalation guidelines were used to generate six plans per patient: three with a target dose cap and three without. Target dose-escalation potential, normal tissue complication probability and differences in pre-specified dose-volume metrics were evaluated for the three motion-management techniques. ResultsThe mean total lung volume was significantly greater with mDIBH compared with four-dimensional scans. Lung dose (mean and V21 Gy) and mean heart dose were significantly reduced with mDIBH in comparison with four-dimensional-based approaches, and this translated to a significant reduction in heart and lung normal tissue complication probability with mDIBH. In 20/21 patients, the trial target prescription dose cap of 79.2 Gy was achievable with all motion-management techniques. ConclusionmDIBH aids lung and heart dose sparing in isotoxic dose-escalated radiotherapy compared with four-dimensional planning techniques. Given concerns about lung and cardiac toxicity, particularly in an era of consolidation immunotherapy, reduced normal tissue doses may be advantageous for treatment tolerance and outcome.

Reduction of heart and lung normal tissue complication probability using automatic beam angle optimization and more generic optimization objectives for breast radiotherapy.

During breast cancer radiotherapy, sparing of healthy tissue is desired. The effect of automatic beam angle optimization and generic dose fall-off objectives on dose and normal tissue complication probabilities was studied. In all patients, dose to lungs and heart showed a mean reduction of 0.4 Gy (range 0.1–1.3 Gy) and 0.2 Gy (range −0.2–0.7 Gy), respectively. These lower doses led to a statistically significant lower cumulative cardiac and lung cancer mortality risk. For smoking patients 40–45 years of age who continue to smoke, it would lead to a reduction from 3.2% ± 0.7% to 2.7% ± 0.6% (p < 0.001).

Cone-Beam-CT Guided Adaptive Radiotherapy for Locally Advanced Non-small Cell Lung Cancer Enables Quality Assurance and Superior Sparing of Healthy Lung.

PurposeTo evaluate the potential of cone-beam-CT (CB-CT) guided adaptive radiotherapy (ART) for locally advanced non-small cell lung cancer (NSCLC) for sparing of surrounding organs-at-risk (OAR).Materials and MethodsIn 10 patients with locally advanced NSCLC, daily CB-CT imaging was acquired during radio- (n = 4) or radiochemotherapy (n = 6) for simulation of ART. Patients were treated with conventionally fractionated intensity-modulated radiotherapy (IMRT) with total doses of 60–66 Gy (pPlan) (311 fraction CB-CTs). OAR were segmented on every daily CB-CT and the tumor volumes were modified weekly depending on tumor changes. Doses actually delivered were recalculated on daily images (dPlan), and voxel-wise dose accumulation was performed using a deformable registration algorithm. For simulation of ART, treatment plans were adapted using the new contours and re-optimized weekly (aPlan).ResultsCB-CT showed continuous tumor regression of 1.1 ± 0.4% per day, leading to a residual gross tumor volume (GTV) of 65.3 ± 13.4% after 6 weeks of radiotherapy (p = 0.005). Corresponding PTVs decreased to 83.7 ± 7.8% (p = 0.005). In the actually delivered plans (dPlan), both conformity (p = 0.005) and homogeneity (p = 0.059) indices were impaired compared to the initial plans (pPlan). This resulted in higher actual lung doses than planned: V20Gy was 34.6 ± 6.8% instead of 32.8 ± 4.9% (p = 0.066), mean lung dose was 19.0 ± 3.1 Gy instead of 17.9 ± 2.5 Gy (p = 0.013). The generalized equivalent uniform dose (gEUD) of the lung was 18.9 ± 3.1 Gy instead of 17.8 ± 2.5 Gy (p = 0.013), leading to an increased lung normal tissue complication probability (NTCP) of 15.2 ± 13.9% instead of 9.6 ± 7.3% (p = 0.017). Weekly plan adaptation enabled decreased lung V20Gy of 31.6 ± 6.2% (−3.0%, p = 0.007), decreased mean lung dose of 17.7 ± 2.9 Gy (−1.3 Gy, p = 0.005), and decreased lung gEUD of 17.6 ± 2.9 Gy (−1.3 Gy, p = 0.005). Thus, resulting lung NTCP was reduced to 10.0 ± 9.5% (−5.2%, p = 0.005). Target volume coverage represented by conformity and homogeneity indices could be improved by weekly plan adaptation (CI: p = 0.007, HI: p = 0.114) and reached levels of the initial plan (CI: p = 0.721, HI: p = 0.333).ConclusionIGRT with CB-CT detects continuous GTV and PTV changes. CB-CT-guided ART for locally advanced NSCLC is feasible and enables superior sparing of healthy lung at high levels of plan conformity.

Ipsilateral lung normal tissue complication probability parameters for different dose calculation algorithms in radiotherapy of breast cancer.

Different dose calculation algorithms (DCAs) predict different dose distributions for the same treatment. Awareness of optimal model parameters is vital for estimating normal tissue complication probability (NTCP) for different algorithms. The aim is to determine the NTCP parameter values for different DCAs in left-sided breast radiotherapy, using the Lyman-Kutcher-Burman (LKB) model. First, the methodology recommended by International Atomic Energy Agency TEC-DOC 1583 was used to establish the accuracy of dose calculations of different DCAs including: Monte Carlo (MC) and collapsed cone algorithms implemented in Monaco, pencil beam convolution (PBC) and analytical anisotropic algorithm (AAA) implemented in Eclipse, and superposition and Clarkson algorithms implemented in PCRT3D treatment planning systems (TPSs). Then, treatment planning of 15 patients with left-sided breast cancer was performed by the mentioned DCAs and NTCP of the left-lung normal tissue were calculated for each patient individually, using the LKB model. For the PB algorithm, the NTCP parameters were taken from previously published values and new model parameters obtained for each DCA, using the iterative least squares methods. For all cases and DCAs, NTCP computation with the same model parameters resulted in >15% deviation in NTCP values. The new NTCP model parameters were classified according to the algorithm type. Thus, the discrepancy of NTCP computations was reduced up to 5% after utilizing adjusted model parameters. This paper confirms that the NTCP values for a given treatment type are different for the different DCAs. Thus, it is essential to introduce appropriate NTCP parameter values according to DCA adopted in TPS, to obtain a more precise estimation of lung NTCP. Hence, new parameter values, classified according to the DCAs, must be determined before introducing NTCP estimation in clinical practice.

Rectum and lung normal tissue complication probability: a retrospective analysis depending on different numbers of fractions and different dose-limits

Rectum and lung normal tissue complication probability: a retrospective analysis depending on different numbers of fractions and different dose-limits

NTCP Model for Radiation Pneumonitis after Stereotactic Body Radiation Therapy in Non-Small Cell Lung Cancer Patients

Radiation pneumonitis (RP) is a dose limiting toxicity in stereotactic body radiation therapy (SBRT) for early stage non-small cell lung cancer (NSCLC). Currently there is no consensus on which lung dosimetric parameter would best predict RP. This study aimed to determine the optimal lung dosimetric parameter for predicting RP in SBRT using a lung normal tissue complication probability (NTCP) model. A total of 339 early-stage NSCLC patients with SBRT were included in the study. Total lung minus gross tumor volume was used to calculate lung dose volume histogram. V5Gy, V10Gy, V20Gy, V30Gy, as well as generalized equivalent uniform dose (EUD) with “a”=1 to 6 were calculated as representative lung dosimetric parameters. RP1 (RP>=1), RP2 (RP>=2), RP3 (RP>=3) were used as the toxicity endpoint, respectively. Maximum log likelihood (MLL) was used to determine the optimal lung dosimetric parameter for the logistic NTCP model with D50 and γ50 as fitting parameters. The RP>=1 was reported in 91 (27%) patients, RP>=2 in 34 (10%) patients and RP>=3 in 19 (6%) patients. V20Gy was the best lung dosimetric parameter for predicting RP>=1, with V50=16.5 % ± 95% CI (8.6%, 24.3%). EUD (a=5) was the best parameter for RP>=2, with D50=46.7 (Gy) ± 95% CI (30.8 Gy, 62.5 Gy). EUD (a=3) was the best for RP>=3, with D50=30.9 (Gy) ± 95% CI (24.4 Gy, 37.4 Gy). Considering 30%, 15% and 10% of RP for RP1, RP2, and RP3 as the acceptable toxicity rate, respectively, the cutting lung dosimetric parameter should be V20Gy < 7.2%, EUD (a=5) < 28.3 Gy, and EUD (a=3) < 19.0 Gy. With the NTCP analysis of RP endpoints, V20Gy, EUD (a=5), and EUD (a=3) appear to be the best predictors for RP1, RP2 and RP3 following SBRT for NSCLC patients. The cutting off dosimetric parameters for 30% RP1, 15% RP2 and 10% RP3 are 7.2%, 28.3 Gy and 19.0 Gy, respectively.

P1.14-014 Comparative Evaluation of VMAT & 3D-CRT in Locally Advanced NSCLC: Is There Any Radiobiological Advantage?

Our aim was comparative dosimetric evaluation of volumetric modulated arc therapy (VMAT) and 3-dimensional conformal radiotherapy (3D-CRT) in patients with locally advanced non-small cell lung cancer (LA-NSCLC) and to confirm whether this dosimetric benefit translates into a radiobiological advantage with respect to tumor control probability (TCP) and normal-tissue complication probability (NTCP) and finally to generate an algorithm and software to integrate the radiobiological component during plan evaluation and quality assurance. A total of 25 3D-CRT naïve patients of LA-NSCLC, treated with radical radiotherapy were included in this study. We used copies of the Eclipse plan data, organized in separate study treatment courses. For each course, new VMAT plans were generated using the standard provincial dose-volume constraints. The DVH parameters for PTV (planning target volume), lung-GTV (gross tumor volume subtracted from lung), heart, esophagus and spine were reviewed and then the TCP and NTCP values for these regions of interest (ROI), cardio-pulmonary toxicity index i.e. C.P.T.I (∑i NTCPi; i=1-2 representing heart, lung), morbidity index i.e. M.I (∑i NTCPi; i=1-4 representing heart, esophagus, lung and spinal cord) and therapeutic gain (defined as the value of TCP when M.I=0; i.e. TG=TCP(1-M.I)) values were generated. The resulting data sets were compared using the Weltch two sample t-test and p <0.05 was accepted as significant. Parameters were calculated using DVH data exported from the Eclipse and software written in the “R” programming language. The user interface has been developed with the “shiny” “R” web library. Dosimetric parameters included V98% and D99% of PTV, V50Gy of esophagus and mean dose to esophagus, V45Gy of spinal cord, V30Gy and mean dose of heart and V20Gy, V10Gy and V5Gy and mean dose of (lung-GTV). The radiobiological metrics included TCP, NTCP of heart, esophagus, lung and spinal cord, C.P.T.I, M.I and therapeutic gain. Dosimetric evaluation did not show any significant difference in V98% (p=0.169) and D99% (p=0.797) of PTV between VMAT and 3D-CRT, however, there was significant improvement in V50Gy of esophagus (p=0.039), V45Gy of spinal cord (p=0.003) and V30Gy of heart (p=0.038) with VMAT. V10Gy of (lung-GTV) was higher with VMAT (p=0.019). The rest of the dosimetric parameters were not significantly different two modalities. TCP was better with 3D-CRT (p<0.0001) while NTCP of heart (p=0.028), esophagus (p=0.053) and spinal cord (p=0.001) was substantially improved with VMAT. There was no difference in NTCP of lung between two modalities. Overall C.P.T.I (p=0.039), M.I (p=0.019) was remarkably lower and therapeutic gain (p=0.005) was significantly better with VMAT. The study reveals that although TCP is higher with 3D-CRT, majority of the NTCP parameters including C.P.T.I and M.I are substantially improved with VMAT even in 3D-CRT naïve patients. The overall therapeutic gain is therefore notably higher with VMAT which emphasizes its potential to achieve superior oncologic outcome in patients with LA-NSCLC.

Limiting the risk of cardiac toxicity with esophageal-sparing intensity modulated radiotherapy for locally advanced lung cancers.

Intensity modulated radiotherapy (IMRT) is routinely utilized in the treatment of locally advanced non-small cell lung cancer (NSCLC). RTOG 0617 found that overall survival was impacted by increased low (5 Gy) and intermediate (30 Gy) cardiac doses. We evaluated the impact of esophageal-sparing IMRT on cardiac doses with and without the heart considered in the planning process and predicted toxicity compared to 3D-conventional radiotherapy (3DCRT). Ten consecutive patients with N2 Stage III NSCLC treated to 60 Gy in 30 fractions, between February 2012 and September 2014, were evaluated. For each patient, 3DCRT and esophageal-sparing IMRT plans were generated. IMRT plans were then created with and without the heart considered in the optimization process. To compare plans, the dose delivered to 95% and 99% of the target (D95% and D99%), and doses to the esophagus, lung and heart were compared by determining the volume receiving X dose (VXGy) and the normal tissue complication probability (NTCP) calculated. IMRT reduced maximum esophagus dose to below 60 Gy in all patients and produced significant reductions to V50Gy, V40Gy and esophageal NTCP. The cost of this reduction was a non-statistically, non-clinically significant increase in low dose (5 Gy) lung exposure that did not worsen lung NTCP. IMRT plans produced significant cardiac sparing, with the amount of improvement correlating to the amount of heart overlapping with the target. When included in plan optimization, for selected patients further sparing of the heart and improvement in heart NTCP was possible. Esophageal-sparing IMRT can significantly spare the heart even if it is not considered in the optimization process. Further sparing can be achieved if plan optimization constrains low and intermediate heart doses, without compromising lung doses.

Exploring spatial overlap of high-uptake regions derived from dual tracer positron emission tomography-computer tomography imaging using 18F-fluorodeoxyglucose and 18F-fluorodeoxythymidine in nonsmall cell lung cancer patients: a prospective pilot study.

Interest is growing in radiotherapy to nonuniformly boost radioresistant regions within nonsmall cell lung cancer (NSCLC) using molecular imaging techniques. The complexity of tumor behavior is beyond the ability of any single radiotracer to reveal. We hold dual tracer positron emission tomography–computer tomography (PET/CT) imaging with fluorodeoxyglucose (FDG) and fluorodeoxythymidine (FLT) for NSCLC patients to offer an integrated overlook of tumor biological behaviors quantitatively and localizationally, which may help biological target volume delineation and subvolume boost.Pathological confirmed that NSCLC patients were eligible. FDG and FLT PET/CT were performed for each patient before anticancer treatment and coregistrated for analysis. Maximum and mean standardized uptake values (SUVmax and SUVmean) were calculated automatically. Metabolic volumes (MVs) were delineated by a fixed 50% of SUVmax in FDG PET/CT and proliferative volumes (PVs) were delineated by 50% to 90% of SUVmax with 10% interval in FLT PET/CT. Overlap ratio (OR) were determined as overlapped volume between MV and PV divided PV. Conventional contrast-enhanced CT-based intensity-modulated radiotherapy (IMRT) plans with and without additional PET/CT-guided subtarget boost were made for each of the 5 typical NSCLC patients. Dosimetric parameters derived from dose–volume histogram, tumor control probability (TCP), and normal tissue complication probability (NTCP) of lung, esophagus, heart, and spinal cord were calculated and compared.Thirty-one patients were prospectively included and 23 were selected for analysis. Totally, 23 primary diseases, 41 metastatic lymph nodes, and 15 metastatic lesions were positive in dual PET/CTs and included for analysis. Median ORs increased from 58.61% to 93.12% under thresholds of 50% of SUVmax in FDG PET/CT and increased thresholds from 50% to 90% of SUVmax in FLT PET/CT. Based on conventional IMRT, additional boost to union of high FDG (determined by 50% SUVmax) and FLT (determined by 80% SUVmax) uptake subtargets exhibited higher TCP without significant elevated NTCP of lung, esophagus, spinal cord, and heart.Dual tracer PET/CT of FDG and FLT is suggested for NSCLC patients to guide tumor target delineation in clinical practice. FDG PET/CT is necessary whereas FLT PET/CT may be optional when guiding tumor target delineation clinically. Additional information from randomized trials is required to validate.

Impact of Integrating Pet-Ct in Radiotherapy Planning of Non-small Cell Carcinoma Lung: Dosimetric and Radiobiological Comparison

The integration of PET and CT scans allows the simultaneous use of biologic and anatomic imaging data for better delineating tumor and sparing normal critical structures. The aim of this study is to assess the impact on target volume delineation using CT vs. PETCT based plans, and to determine radiobiological effect on tumor and normal tissue by comparing Tumor control probability (TCP) & normal tissue complication probability (NTCP) of CT & PET-CT based plans. 15 patients of inoperable NSCLC planned for radical radiotherapy, underwent a planning CT scan of the thorax. Target volumes were contoured. Later PETCT images with the auto contoured MTV (Metabolic target volume) images, were fused with the planning CT images. Margins were similarly given to PETMTV for the generation of PET CTV and PET PTV. 3 Dimensional conformal radiotherapy (3DCRT) plans were made on the planning CT images and the planning PETCT images, and were compared dosimetrically and radio biologically. The study shows that the use of PETCT resulted in significant decrease in PETCT generated MTV versus GTV delineated on CT. Also, there was statistical significant decrease in the volume of the normal lung irradiated in terms of V40 and the MLD. TCP for PETCT based plans was significantly higher than that with CT based plans. Also, PETCT based planning resulted in a statistically significant decrease in the NTCP for lung and spinal cord. Therefore, the study concludes that incorporation of PETCT into radiotherapy planning of NSCLC is technically feasible and dosimetrically appealing strategy for patient treatment.

Radiobiological Determination of Dose Escalation and Normal Tissue Toxicity in Definitive Chemoradiation Therapy for Esophageal Cancer

PurposeThis study investigated the trade-off in tumor coverage and organ-at-risk sparing when applying dose escalation for concurrent chemoradiation therapy (CRT) of mid-esophageal cancer, using radiobiological modeling to estimate local control and normal tissue toxicity.Methods and MaterialsTwenty-one patients with mid-esophageal cancer were selected from the SCOPE1 database (International Standard Randomised Controlled Trials number 47718479), with a mean planning target volume (PTV) of 327 cm3. A boost volume, PTV2 (GTV + 0.5 cm margin), was created. Radiobiological modeling of tumor control probability (TCP) estimated the dose required for a clinically significant (+20%) increase in local control as 62.5 Gy/25 fractions. A RapidArc (RA) plan with a simultaneously integrated boost (SIB) to PTV2 (RA62.5) was compared to a standard dose plan of 50 Gy/25 fractions (RA50). Dose-volume metrics and estimates of normal tissue complication probability (NTCP) for heart and lungs were compared.ResultsClinically acceptable dose escalation was feasible for 16 of 21 patients, with significant gains (>18%) in tumor control from 38.2% (RA50) to 56.3% (RA62.5), and only a small increase in predicted toxicity: median heart NTCP 4.4% (RA50) versus 5.6% (RA62.5) P<.001 and median lung NTCP 6.5% (RA50) versus 7.5% (RA62.5) P<.001.ConclusionsDose escalation to the GTV to improve local control is possible when overlap between PTV and organ-at-risk (<8% heart volume and <2.5% lung volume overlap for this study) generates only negligible increase in lung or heart toxicity. These predictions from radiobiological modeling should be tested in future clinical trials.

The impact of inter-fraction set-up errors on the probability of pulmonary and cardiac complication in left-sided breast cancer patients

AbstractPurposeThis study evaluated the impact of patient set-up errors on the probability of pulmonary and cardiac complications in the irradiation of left-sided breast cancer.Methods and materialsUsing the CMS XiO Version 4·6 radiotherapy planning system's normal tissue complication probability (NTCP) algorithm and the Lyman–Kutcher–Burman model, we calculated the dose–volume histograms (DVH) indices for the ipsilateral lung and heart and the resultant NTCP for radiation-induced pneumonitis and excess cardiac mortality in 12 left-sided breast cancer patients.ResultsIsocentric shifts in the posterior direction had the greatest effect on the lung V20, heart V25, and mean and maximum doses to the lung and the heart. DVH results show that the ipsilateral lung V20 tolerance was exceeded in 58% of the patients after 1 cm posterior shifts. Similarly, the heart V25 tolerance was exceeded after 1 cm antero-posterior and left–right isocentric shifts in 70% of the patients. The baseline NTCPs for radiation-induced pneumonitis ranged from 0·73% to 3·4%, with a mean value of 1·7%. The maximum reported NTCP for radiation-induced pneumonitis was 5·8% (mean 2·6%) after 1 cm posterior isocentric shift. The NTCP for excess cardiac mortality were 0% in 100% of the patients (n = 12) before and after set-up error simulations.ConclusionsSet-up errors in left-sided breast cancer patients have a statistically significant impact on the Lung NTCPs and DVH indices. However, with a central lung distance of 3 cm or less (CLD &lt; 3 cm), and a maximum heart distance of 1·5 cm or less (MHD &lt; 1·5 cm), the treatment plans could tolerate set-up errors of up to 1 cm without any change in the NTCP to the heart.

Acute radiation pneumonitis after conformational radiotherapy for nonsmall cell lung cancer: Clinical, dosimetric, and associated-treatment risk factors

Conformational thoracic radiotherapy (CTR) is a key-treatment in locally advanced nonsmall cell lung cancer (LA-NSCLC). Acute radiation pneumonitis (ARP) is one of the major complications. To evaluate the predictors of ARP after CTR in the treatment of LA-NSCLC. A total of 47 consecutive patients (pts) were treated with CTR for LA-NSCLC and retrospectively analyzed. The mean total dose of radiation therapy (RT) was 65 Gy, with respiratory gating (RG) in 19 cases. Induction and concomitant chemotherapy was performed in 33 pts (70%) and 41 pts (87%), respectively. Eleven pts (23%) had an ARP resulting in death for one pt. In univariate analysis, age, sex, pretherapeutic value of forced expiratory volume (FEV), not-gated radiotherapy and type of concomitant chemotherapy did not appear as contributing factors in contrast to the administration of induction gemcitabine ( p = 0.03). The occurrence of ARP was significantly associated with nontumor lung volumes irradiated to 13 Gy (V13, p = 0.04), 20 Gy (V20, p = 0.02), and 25 Gy (V25, p = 0.006), the mean lung dose ( p = 0.008) and lung normal tissue complication probability (NTCP) ( p = 0.004). In multivariate logistic regression analysis, the occurrence of ARP was significantly associated with age >75 years (odds ratio (OR) = 16.72, confidence interval (CI) 95% 1.77-157.87) and administration of induction gemcitabine (OR = 18.08, CI 95% 1.09-300.08). ARP is a common acute complication, requiring close posttreatment follow-up, particularly for elderly patients. The use of gemcitabine before radiation should be avoided. The benefits and risks of CTR must be carefully analyzed, according to the dosimetric parameters.

Cancers bronchiques non à petites cellules : facteurs prédictifs de survenue de pneumopathie radique

PurposeTo evaluate the predictors of acute radiation pneumonitis after conformal thoracic radiotherapy in the treatment of locally advanced non-small cell lung cancer. Patients and methodsForty-seven consecutive patients were treated with conformal thoracic irradiation for locally advanced non-small cell lung cancer and retrospectively analysed. The mean total dose of radiotherapy was 65Gy with respiratory gating in 19 cases. Neoadjuvant and concomitant chemotherapy was performed in 33 patients (70%) and 41 patients (87%) respectively. ResultsEleven patients (23%) had an acute radiation pneumonitis, resulting in death for one patient. In univariate analysis, age, sex, pretherapeutic value of forced expiratory volume, non-gated radiotherapy and type of concomitant chemotherapy did not appear as contributing factors in contrast to the administration of neoadjuvant gemcitabine (P=0.03). The occurrence of acute radiation pneumonitis was significantly associated with non-tumour lung volumes irradiated to 13Gy (V13, P=0.04), 20Gy (V20, P=0.02) and 25Gy (V25, P=0.006), the mean lung dose (P=0.008) and lung normal tissue complication probability (P=0.004). In multivariate logistic regression analysis, the occurrence of acute radiation pneumonitis was significantly associated with age above 75 years (odds ratio [OR]=16.72 ; P=0.02) and with administration of neoadjuvant gemcitabine (OR=18.08, P=0.04). ConclusionAcute radiation pneumonitis is a common acute side effect of the conformal thoracic radiotherapy of locally advanced non-small cell lung cancer, requiring close post-treatment follow-up, particularly for elderly patients. The use of gemcitabine before radiation should be avoided. The benefits and risks of conformal thoracic radiotherapy must be carefully analyzed in view of the dosimetric parameters obtained.

An evaluation of three dimensional conformal radiation therapy versus intensity modulated radiation therapy in radical chemoradiation of esophageal cancer: A dosimetric study

Aims: To evaluate the feasibility whether intensity-modulated radiotherapy (IMRT) can be used to reduce doses to normal thoracic structures than three-dimensional conformal radiotherapy (3DCRT) in treating esophageal cancer and to compare normal tissue complication probability (NTCP) for lung between two treatment plans. Materials and Methods: A prospective study was carried out from 2009 to 2011, in which 15 inoperable patients of esophageal cancer who were suitable for radical chemoradiation were enrolled. All patients were treated with 3DCRT. In first phase, patients were treated with external beam radiation therapy (EBRT) dose of 36Gy in 20 fractions in 4 weeks, along with concurrent weekly chemotherapy with cisplatinum and 5-fluorouracil (5 FU). In second phase, boost dose of 18Gy in 10 fractions in 2 weeks was given. An IMRT plan was generated for each patient. Plan sum of both the 3D CRT and IMRT plans were compared. Doses to critical structures and NTCP for lung were compared between 3DCRT and IMRT plans. Results: The mean lung dose and volumes of lung receiving 20 Gy, 10 Gy, and 5 Gy (V20, V10, and V5) were significantly lower with 3DCRT plans as compared to IMRT plans. The mean dose to heart and spinal cord was higher in 3DCRT arm. There was no difference in dose distribution to the liver between the 3D CRT and IMRT techniques. The NTCP for lung was lower with 3D CRT than IMRT. Conclusion: IMRT technique needs further dosimetric study as well as further clinical trials before implication of this technique replacing 3D CRT technique with escalated dose for the treatment of esophageal cancer in our setup. IMRT using seven fields provided no improvement over 3DCRT.

Intensity Modulated Radiation Therapy (IMRT) Target Volume and Dosimetric Planning in Treatment of Locally Advanced Non-small Cell Lung Cancer

Objective To assess elective nodal irradiation(ENI) and involved field irradiation(IFI) target volume and dosimetric distribution and to obtain the optional intensity modulated radiation therapy(IMRT) planning for locally advanced non-small cell lung cancer(LA-NSCLC).Methods Two different plannings: ENI and IFI were designed to assess the dosimetric distribution of target volume and normal tissues for 27 patients with LA-NSCLC confirmed through pathology.Dose volume histograms(DVHs),target volume conformal index(CI),tumor control probability(TCP),normal tissue irradiation dose and normal tissue complication probability(NTCP) were used to assess the IMRT planning.Results The maximum dose,minimum dose,average dose,CI,and TCP of GTV by IFI and ENI were 77.1 Gy vs.73.9 Gy,67.3 Gy vs.63.6 Gy,70.9 Gy vs.67.1 Gy,0.82 vs.0.73,96.7% vs.93.1%,respectively(P0.05).The average dose,total lung volume received radiation exceeding 20 Gy(V20) and NTCP of lung were 13.2 Gy vs.16.0 Gy,22.1% vs.24.7%,5.2% vs.5.8%,respectively(P0.05).The total esophagus volume received radiation exceeding 45 Gy(V45) by IFI and ENI were 16.3% vs.21.7%,however the length of esophagus(total circumference) treated with greater than 45 Gy(LETT45),average dose of heart and the maximum dose of spinal cord had no different significantly between IFI and ENI respectively(P 0.05).Conclusion Target volume dosimetric distribution of IFI is significantly better than ENI.Therefore,we suggest IFI in patients with LA-NSCLC.

Intensity-Modulated Radiotherapy for Locally Advanced Non–Small-Cell Lung Cancer: A Dose-Escalation Planning Study

To evaluate the potential for dose escalation with intensity-modulated radiotherapy (IMRT) in positron emission tomography-based radiotherapy planning for locally advanced non-small-cell lung cancer (LA-NSCLC). For 35 LA-NSCLC patients, three-dimensional conformal radiotherapy and IMRT plans were made to a prescription dose (PD) of 66 Gy in 2-Gy fractions. Dose escalation was performed toward the maximal PD using secondary endpoint constraints for the lung, spinal cord, and heart, with de-escalation according to defined esophageal tolerance. Dose calculation was performed using the Eclipse pencil beam algorithm, and all plans were recalculated using a collapsed cone algorithm. The normal tissue complication probabilities were calculated for the lung (Grade 2 pneumonitis) and esophagus (acute toxicity, grade 2 or greater, and late toxicity). IMRT resulted in statistically significant decreases in the mean lung (p <.0001) and maximal spinal cord (p = .002 and 0005) doses, allowing an average increase in the PD of 8.6-14.2 Gy (p ≤.0001). This advantage was lost after de-escalation within the defined esophageal dose limits. The lung normal tissue complication probabilities were significantly lower for IMRT (p <.0001), even after dose escalation. For esophageal toxicity, IMRT significantly decreased the acute NTCP values at the low dose levels (p = .0009 and p <.0001). After maximal dose escalation, late esophageal tolerance became critical (p <.0001), especially when using IMRT, owing to the parallel increases in the esophageal dose and PD. In LA-NSCLC, IMRT offers the potential to significantly escalate the PD, dependent on the lung and spinal cord tolerance. However, parallel increases in the esophageal dose abolished the advantage, even when using collapsed cone algorithms. This is important to consider in the context of concomitant chemoradiotherapy schedules using IMRT.