Increase In Normal Tissue Complication Probability Research Articles

The Promising Treatment Schedule of Concurrent Chemoradiotherapy for Stage III Non-small Cell Lung Cancer: Alternative for Conventional Fractionation Using Mathematical Analysis.

To evaluate treatment schedules involving concurrent chemoradiotherapy in stage III non-small cell lung cancer (NSCLC) using the tumor control probability (TCP) and normal tissue complication probability (NTCP) parameters. The standard schedules were compared with two types of schedules, the dose escalation and the short-term schedules. Standard schedules were 60-74 Gy in 30-37 fractions. The dose escalation schedules with hypofractionation and hyperfractionation were 69 Gy in 30 fractions and 69.6 Gy in 58 fractions, respectively, twice per day (b.i.d). The short-term schedules were concomitant boost, 64 Gy in 40 fractions b.i.d. and the accelerated radiotherapy schedule, 57.6 Gy in 36 fractions, three fractions per day (t.i.d). The average TCP for the short-term schedules was more than 16% in two tumor models; however, the TCP for standard and dose escalation schedules was less than 5%. In each organ, the increase in NTCP for the short-term schedule compared with standard schedules was less than 15%. The short-term schedules had an advantage over standard schedules for NSCLC.

Influence of respiratory motion management technique on radiation pneumonitis risk with robotic stereotactic body radiation therapy.

Purpose/ObjectivesFor lung stereotactic body radiation therapy (SBRT), real‐time tumor tracking (RTT) allows for less radiation to normal lung compared to the internal target volume (ITV) method of respiratory motion management. To quantify the advantage of RTT, we examined the difference in radiation pneumonitis risk between these two techniques using a normal tissue complication probability (NTCP) model.Materials/Method20 lung SBRT treatment plans using RTT were replanned with the ITV method using respiratory motion information from a 4D‐CT image acquired at the original simulation. Risk of symptomatic radiation pneumonitis was calculated for both plans using a previously derived NTCP model. Features available before treatment planning that identified significant increase in NTCP with ITV versus RTT plans were identified.ResultsPrescription dose to the planning target volume (PTV) ranged from 22 to 60 Gy in 1–5 fractions. The median tumor diameter was 3.5 cm (range 2.1–5.5 cm) with a median volume of 14.5 mL (range 3.6–59.9 mL). The median increase in PTV volume from RTT to ITV plans was 17.1 mL (range 3.5–72.4 mL), and the median increase in PTV/lung volume ratio was 0.46% (range 0.13–1.98%). Mean lung dose and percentage dose–volumes were significantly higher in ITV plans at all levels tested. The median NTCP was 5.1% for RTT plans and 8.9% for ITV plans, with a median difference of 1.9% (range 0.4–25.5%, pairwise P < 0.001). Increases in NTCP between plans were best predicted by increases in PTV volume and PTV/lung volume ratio.ConclusionsThe use of RTT decreased the risk of radiation pneumonitis in all plans. However, for most patients the risk reduction was minimal. Differences in plan PTV volume and PTV/lung volume ratio may identify patients who would benefit from RTT technique before completing treatment planning.

SU‐F‐T‐97: Outlier Identification in Radiation Therapy Knowledge Modeling

Purpose:To investigate the impact of outliers on knowledge modeling in radiation therapy, and develop a systematic workflow for identifying and analyzing geometric and dosimetric outliers using pelvic cases.Methods:Four groups (G1‐G4) of pelvic plans were included: G1 (37 prostate cases), G2 (37 prostate plus lymph node cases), and G3 (37 prostate bed cases) are all clinical IMRT cases. G4 are 10 plans outside G1 re‐planned with dynamic‐arc to simulate dosimetric outliers. The workflow involves 2 steps: 1. identify geometric outliers, assess impact and clean up; 2. identify dosimetric outliers, assess impact and clean up.1. A baseline model was trained with all G1 cases. G2/G3 cases were then individually added to the baseline model as geometric outliers. The impact on the model was assessed by comparing leverage statistic of inliers (G1) and outliers (G2/G3). Receiver‐operating‐characteristics (ROC) analysis was performed to determine optimal threshold. 2. A separate baseline model was trained with 32 G1 cases. Each G4 case (dosimetric outliers) was then progressively added to perturb this model. DVH predictions were performed using these perturbed models for remaining 5 G1 cases. Normal tissue complication probability (NTCP) calculated from predicted DVH were used to evaluate dosimetric outliers’ impact.Results:The leverage of inliers and outliers was significantly different. The Area‐Under‐Curve (AUC) for differentiating G2 from G1 was 0.94 (threshold: 0.22) for bladder; and 0.80 (threshold: 0.10) for rectum. For differentiating G3 from G1, the AUC (threshold) was 0.68 (0.09) for bladder, 0.76 (0.08) for rectum. Significant increase in NTCP started from models with 4 dosimetric outliers for bladder (p&lt;0.05), and with only 1 dosimetric outlier for rectum (p&lt;0.05).Conclusion:We established a systematic workflow for identifying and analyzing geometric and dosimetric outliers, and investigated statistical metrics for detecting. Results validated the necessity for outlier detection and clean‐up to enhance model quality in clinical practice.Research Grant: Varian master research grant

The effect of dose escalation on gastric toxicity when treating lower oesophageal tumours: a radiobiological investigation.

PurposeUsing radiobiological modelling to estimate normal tissue toxicity, this study investigates the effects of dose escalation for concurrent chemoradiation therapy (CRT) in lower third oesophageal tumours on the stomach.Methods and materials10 patients with lower third oesophageal cancer were selected from the SCOPE 1 database (ISCRT47718479) with a mean planning target volume (PTV) of 348 cm3. The original 3D conformal plans (50Gy3D) were compared to newly created RapidArc plans of 50GyRA and 60GyRA, the latter using a simultaneous integrated boost (SIB) technique using a boost volume, PTV2. Dose-volume metrics and estimates of normal tissue complication probability (NTCP) were compared.ResultsThere was a significant increase in NTCP of the stomach wall when moving from the 50GyRA to the 60GyRA plans (11–17 %, Wilcoxon signed rank test, p = 0.01). There was a strong correlation between the NTCP values of the stomach wall and the volume of the stomach wall/PTV 1 and stomach wall/PTV2 overlap structures (R = 0.80 and R = 0.82 respectively) for the 60GyRA plans.ConclusionRadiobiological modelling suggests that increasing the prescribed dose to 60Gy may be associated with a significantly increased risk of toxicity to the stomach. It is recommended that stomach toxicity be closely monitored when treating patients with lower third oesophageal tumours with 60Gy.

Image Guidance-Based Target Volume Margin Expansion in IMRT of Head and Neck Cancer.

This study quantifies the setup uncertainties to optimize the planning target volume (PTV) margin based on daily image guidance, its dosimetric impact, and radiobiological implication for intensity-modulated radiation therapy (IMRT) in head and neck cancer. Ten patients were retrospectively chosen who had been treated with IMRT and with daily image-guided radiation therapy (IGRT). The daily setup errors of the 10 patients from on-board imaging for the entire treatment were analyzed. Planning target volumes were generated by expanding the clinical target volumes (CTVs) with 0 to 10 mm margins. The IMRT plans with the same dose-volume constraints were created in an Eclipse treatment planning system. The effect of volume expansion was analyzed with biological indices such as tumor control probability, normal tissue complication probability (NTCP), and equivalent uniform dose. Analysis of 906 daily setup corrections using daily IGRT showed that 98% of the daily setups are within ± 5 mm. The relative increase in PTV-CTV volume from 0 to 10 mm margins provides nearly 4-fold volume increase and is linearly related to monitor unit (MU). The increase in MU is about 5%/mm margin increase. The relative increase in NTCP of parotids from 5 to 10 mm margins is 3.2 ± 1.15. Increase in PTV margin increases extra tissue volume with a corresponding increase in MU for treatment and NTCP values. Even a small margin increase (eg, 1 mm) may result in increase of more than 20% in relative extra volume and 15% in NTCP value of organs at risk (OARs). With image guidance, the setup uncertainty could be achieved within ± 5 mm for 98% of the treatments, and a margin <5 mm for PTV may seem desirable to reduce the extra tissue irradiated, but at the expense of a more demanding setup accuracy.

A Split-organ Delineation Approach for Dose Optimisation for Intensity-modulated Radiotherapy for Advanced T-stage Nasopharyngeal Carcinoma

Aims To assess the dosimetric effect of using a split-organ delineation approach during intensity-modulated radiotherapy (IMRT) treatment planning for advanced T-stage nasopharyngeal carcinoma (NPC). Materials and methods Twenty NPC patients with T3–4 tumours were studied. A reference (REF) IMRT plan was generated based on a standard treatment planning protocol, with a set of user-defined dose constraints for optimisation. An investigative (INV) IMRT plan was then generated based on the same protocol, but treating several organs at risk (OARs; parotid glands, temporal lobes, cochlea, auditory nerves and planning organ at risk volume [PRV] of the brainstem) as split organs consisting of target-overlapping and non-target-overlapping sub-segments. These sub-segments were assigned independent dose constraints. The REF and INV plans were compared with respect to target coverage and OAR sparing. Target coverage was evaluated by the D min (minimum dose), V 66/ V 60 (percentage volume of gross target volume [GTV]/planning target volume [PTV] receiving 66 Gy/60 Gy), target conformity index (CI), and tumour control probability (TCP). The sparing of OARs was evaluated by the commonly used dose end points for the respective OAR, and normal tissue complication probability (NTCP). Results For PTV coverage, the INV plan was superior to the REF plan in terms of D min ( P = 0.000), CI ( P = 0.005) and TCP ( P = 0.002). This is attributed to an increase in dose to the PTV-OAR overlapping sub-segments. Regarding the sparing of OARs, there was a significant reduction in the mean dose of the parotid glands ( P = 0.002), and a slight, but non-significant, increase in NTCP of the temporal lobes, cochlea and brainstem. Conclusions Using a split-organ delineation approach in IMRT treatment planning for advanced T-stage NPC, a significant improvement in the target coverage and TCP could be achieved, whereas the mean dose of the parotid was reduced significantly. There was insignificant change in the NTCP of the temporal lobe, parotid gland, cochlea and brainstem, but a significant change in the NTCP of the auditory nerve. The approach provides the planner extra room to manipulate the dose constraints during optimisation, and to obtain the desired result in less attempts. This approach also has the potential to be used in a broader context for IMRT planning for other tumour sites.

On the radiobiological impact of metal artifacts in head-and-neck IMRT in terms of tumor control probability (TCP) and normal tissue complication probability (NTCP)

To investigate the effects of distorted head-and-neck (H&N) intensity-modulated radiation therapy (IMRT) dose distributions (hot and cold spots) on normal tissue complication probability (NTCP) and tumor control probability (TCP) due to dental-metal artifacts. Five patients' IMRT treatment plans have been analyzed, employing five different planning image data-sets: (a) uncorrected (UC); (b) homogeneous uncorrected (HUC); (c) sinogram completion corrected (SCC); (d) minimum-value-corrected (MVC); and (e) streak-artifact-reduction including minimum-value-correction (SAR-MVC), which has been taken as the reference data-set. The effects on NTCP and TCP were evaluated using the Lyman-NTCP model and the Logistic-TCP model, respectively. When compared to the predicted NTCP obtained using the reference data-set, the treatment plan based on the original CT data-set (UC) yielded an increase in NTCP of 3.2 and 2.0% for the spared parotid gland and the spinal cord, respectively. While for the treatment plans based on the MVC CT data-set the NTCP increased by a 1.1% and a 0.1% for the spared parotid glands and the spinal cord, respectively. In addition, the MVC correction method showed a reduction in TCP for target volumes (MVC: delta TCP = -0.6% vs. UC: delta TCP = -1.9%) with respect to that of the reference CT data-set. Our results indicate that the presence of dental-metal-artifacts in H&N planning CT data-sets has an impact on the estimates of TCP and NTCP. In particular dental-metal-artifacts lead to an increase in NTCP for the spared parotid glands and a slight decrease in TCP for target volumes.

Diffusion Tensor Imaging: Possible Implications for Radiotherapy Treatment Planning of Patients with High-grade Glioma

Radiotherapy treatment planning for high-grade gliomas (HGG) is hampered by the inability to image peri-tumoural white-matter infiltration. Diffusion tensor imaging (DTI) is an imaging technique that seems to show white-matter abnormalities resulting from tumour infiltration that cannot be visualised by conventional computed tomography or magnetic resonance imaging (MRI). We propose a new term, the image-based high-risk volume (IHV) for such abnormalities, which are distinct from the gross-tumour volume (GTV). For IHV based on DTI, we use the term IHVDTI. This study assesses the value of DTI for the individualisation of radiotherapy treatment planning for patients with HGG. Seven patients with biopsy-proven HGG were included in a theoretical planning exercise, comparing standard planning techniques with individualised plans based on DTI. Standard plans were generated using a 2.5 cm clinical target volume (CTV) margin added to the GTV. For DTI-based plans, the CTV was generated by adding a 1 cm margin to the IHVDTI. Estimates of normal tissue complication probability (NTCP) were calculated and used to estimate the level of dose escalation that could be achieved using the DTI-based plans. The use of DTI resulted in non-uniform margins being added to the GTV to encompass areas at high risk of tumour involvement, but, in six out of seven cases, the IHVDTI was encapsulated by the standard CTV margin. In all cases, DTI could be used to reduce the size of the planning-target volume (PTV) (mean 35%, range 18-46%), resulting in escalated doses (mean 67 Gy, range 64-74 Gy), with NTCP levels that matched the conventional treatment plans. DTI can be used to individualise radiotherapy target volumes, and reduction in the CTV permits modest dose escalation without an increase in NTCP. DTI may also be helpful in stratifying patients according to the degree of white-matter infiltration.