RECOMMENDATION FOR A CONTOURING METHOD AND ATLAS OF ORGANS AT RISK IN NASOPHARYNGEAL CARCINOMA PATIENTS RECEIVING INTENSITY-MODULATED RADIOTHERAPYRadiotherapy and Oncology; Volume 110 (2014); 390-397

Reference :

OVERVIEW

INTRODUCTION

METHODS AND MATERIALS

RESULTS

DISCUSSION

CONCLUSION

INTRODUCTION

Radiation Therapy is the preferred therapeutic treatment modality for Non-Metastatic Nasopharyngeal Carcinoma (NPC)

Intensity Modulated Radiation Therapy (IMRT) is the preferred modality in view of dose escalation to the primary with sparing of the organs at risk (OAR)

Accurate delineation and precise dosage of the target volume and the organs at risk are keys to a successful radiotherapy

INTRODUCTION

The normal tissues close to the nasopharynx which need to be spared for proper functioning are the organs at risk (OARs) Temporal lobe Brainstem Spinal cord Optic Nerve Optic chiasm Parotid gland Submandibular gland Pituitary

INTRODUCTION

Accurate and consistent OAR delineation is important in NPC treatment planning for adequate target volume coverage and reduction of dose to the OARs

However, large variations are observed while contouring the OARs

Also different contouring methods are available in the literature which further increase the inhomogeneity in contouring the OARs and thus leads to dose inhomogeneity

The diversity in OAR delineation leads to unmatched Dosimetric analyses and prevents side effect correlation studies

INTRODUCTION

The variation in OAR delineation mainly depends on : Diversity of Subjective interpretations Variations in actual contouring

This study focused mainly on the diversities in subjective interpretation

METHODS AND MATERIALS

METHODS AND MATERIALS

Different OAR contouring methods were identified

Applied on 41 patients with non- metastatic NPC for treatment with IMRT (March 2011 – September 2011)

Retrospective analysis of 21 patients with NPC treated with IMRT (November 2004 – November 2006) and developing unilateral temporal lobe necrosis (TLN) was done

The area under Receiver Operating Characteristic (ROC) for these 21 patients with 2 temporal lobe contouring methods were compared and a more reasonable contouring method for temporal lobe was obtained

DELINEATION METHODS

Literature search of OAR delineation in head and neck cancers showed 2-4 contouring methods for middle ear, inner ear, temporal lobe, parotid gland and spinal cord

Search done on PubMed

Papers published till end of November 2012

DELINEATION METHODS

Total 553 papers were identified and out of these 5, 30, 13, 7, and 7 papers were found to be relevant for temporal lobe, parotid gland, spinal cord, inner ear and middle ear respectively

For other OARs, different contouring methods were referred based on human anatomy and CT and MRI based sectional anatomical references

DELINEATION METHODS

Temporal lobe contouring – 2 methods were used

Method 1 : Brain tissue outside the sylvian fissure and basal ganglia, excluding the

parahippocampus gyrus and hippocampus

Method 2 : Temporal lobe including the parahippocampal gyrus and hippocampus, excluding

the basal ganglia and insula

DELINEATION METHODS

Middle ear contouring – 3 methods Contouring the combination of tympanum and Eustachian tube (ET) Contouring the tympanum and bony part of the ET respectively Contouring the ET, tympanic cavity and mastoid process, respectively

Inner ear contouring – 4 methods

Spinal cord contouring – 2 methods Contouring the true spinal cord Contouring the bony limits of spinal canal

APPLICATION OF DIFFERENT CONTOURING METHODS Gross Tumor Volume (GTV)

Clinical Target Volume (CTV)

Atlas based auto segmentation for primary OAR delineation (ABAS Version 2.01, ELEKTA)

The contouring was modified manually

3mm margin for planning Target Volume (PTV) and Planning at Risk volume (PRV)

In accordance with ICRU 50, 62 and 83

APPLICATION OF DIFFERENT CONTOURING METHODS Dose to PTV : 70 Gy at 2.12 Gy per fraction (5 fractions per week)

For comparison of various contouring methods Volume of all organs Mean dose (Dmean) for the parotid gland, middle and inner ear D1 of PRV (Dx/xcc, the minimum dose received by the ‘‘hottest’’ x% or x ml of

the structure) for the spinal cord and temporal lobe

SELECTION OF TEMPORAL LOBE CONTOURING METHOD Retrospective analysis of dosimetric parameters in 21 NPC patients with

unilateral TLN who underwent IMRT between November 2004 and November 2006

Median follow-up time was 45 months (range: 38–63 months)

Latency of TLN was 35 months (range: 25–57 months) after completion of radiotherapy

MRI findings were independently reviewed by two radiologists

SELECTION OF TEMPORAL LOBE CONTOURING METHOD A diagnosis of TLN was made if the MRI presented following signs :

White matter lesions (WMLs) - homogeneous lesions in the white matter Solid, enhanced nodules with or without a necrotic centre and finger signs Cysts of round or oval lesions

Tumor recurrence or metastasis of tumor was excluded.

STATISTICAL ANALYSIS

SPSS 16.0

Friedman test to compare middle/inner ear Dmean

Paired-t test to compare parotid gland volume and Dmean

Paired-t test to compare spinal cord volume and D1 of PRV

Wilcoxon-test to compare temporal lobe volume, and D1 of PRV

STATISTICAL ANALYSIS For the 21 patients with unilateral TLN, 3 steps were adopted

Paired-t test

Multivariate analysis using the binary logistic regression model

Areas under the ROC curves

Used to compare all the dosimetric parameters between the temporal lobes with

and without radiation-induced damage for every method :

D1–D60, D1–D40 cc, V10 to V75, D1–D60 of PRV, and V20–V75 of the PRV at five units

intervals

Used to identify the most relevant parameters associated with TLN

Of the most relevant parameters from the two contouring methods were compared to select a more reasonable contouring

method

D1 of PRV was identified as the most relevant parameter for TLN for both methods

Method 2 had a slightly larger area under the ROC curve than method 1 (0.86 vs. 0.85)

64 Gy was the critical point for the D1 of PRV

There was no significant difference between the areas under the ROC curves of the two contouring methods (p = 0.27)

RESULTS

RESULTS

Significant differences in the volume and selected parameters of all organs were observed using different contouring methods (p < 0.05)

Significant differences between the ipsilateral and contralateral temporal lobe were observed for all dosimetric parameters (p < 0.05)

RESULTS

Based on the anatomic definition and pathogenesis of radiation induced injury, a contouring method was recommended for : Temporal lobe Middle ear Inner ear Parotid gland Spinal cord

For other organs whose contouring is rarely described, it was recommended to outline the whole organ according to their anatomic definition

RESULTS

The middle ear, inner ear and Temporomandibular joint (TMJ) should be delineated on the bone window

The temporal lobe and brainstem on the brain window

However, the lateral boundary of the temporal lobe and other organs should be delineated on the soft tissue window

RESULTS

Temporal lobe : Should include the hippocampus, parahippocampal gyrus and uncus

The basal ganglia and insula are located anteriorly and superiorly to the hippocampus and parahippocampal gyrus and should be excluded

Spinal cord : Visible true spinal cord should be contoured from the foramen magnum (the level of the odontoid process of the axis) to 2 cm below the inferior edge of the head of the collarbone

Parotid gland : Whole gland should be outlined including the CTV, but not the GTV

1: Cerebellum2: Raphe dorsalis 3: Parahippocampal gyrus 4: Temporal pole 5: Inferior temporal gyrus 6: Occipital gyrus7: Hippocampus8: Amygdala9: Middle temporal gyrus 10: Superior temporal gyrus11: Insula12: Orbitofrontal gyrus13: Inferior parietal lobule14: Thalamus15: Superior parietal lobule16: Post‐ and precentral operculum17: Anterior cingulate gyrus18: Posterior cingulate gyrus19: Inferior, middle and superior frontal gyri

RESULTS

Middle ear : The tympanic cavity and bony part of the Eustachian Tube (ET) should be contoured individually

The tympanic cavity is delineated Laterally by the tympanic membrane, defined by the ligature between the two

bony structures with an increased density along the anterior and posterior walls of the most medial aspect of the outer air canal

the sharp narrow region connected anteriorly to the ET, and the interface between the temporal bone and air at all other walls

Inner ear : Delineation of the cochlea and Internal Auditory Canal (IAC) should be done individually

The cochlea is located anteriorly to the IAC

1: Cochlea (basal turn)2: Tensor tympani muscle3: Manubrium of malleus4: Facial nerve canal5: Stapedius muscle6: Round window

DISCUSSION

DISCUSSION

Accurate and consistent OAR delineation is important for proper execution of an IMRT plan

Nelms et al* : The most variable contours in head and neck cancer are the brainstem, parotid gland and spinal cord - These had a consistency score of 70/100.

The contouring variations occur both due to subjective diversity in OAR interpretation and variations in actual anatomical contouring

This study focused on subjective OAR interpretation

This study showed that various contouring methods will lead to different dosimetric parameters * Benjamin E. Nelms, Wolfgang A. Tomé, Greg Robinson, James Wheeler, Variations in the

Contouring of Organs at Risk: Test Case From a Patient With Oropharyngeal Cancer, International Journal of Radiation Oncology*Biology*Physics, Volume 82, Issue 1, 1 January 2012, Pages 368-378, ISSN 0360-3016, http://dx.doi.org/10.1016/j.ijrobp.2010.10.019

DISCUSSION

Radiation-induced temporal lobe injury : Characterized by TLN Observed in around 1-5% patients of NPC after radiotherapy D1 of PRV was the most relevant dosimetric parameter for TLN 64 Gy was the critical dose, similar to the 65 Gy limit recommended by RTOG 0225

protocol

The area under the ROC curves was not significantly different between the two contouring methods

This may be explained as follows: The D1 of PRV is mainly impacted by the inferior and medial aspect of the temporal

lobe, where TLN is mostly observed. Both methods included the inferior and medial aspect

DISCUSSION

Method 2 was recommended for contouring the temporal lobe for the following reasons :

The hippocampus and parahippocampal gyrus are located close to the target volume, in which the TLN usually occurred (13/21 in this study), while in the basal ganglia and insula rarely occurred (1/21 in this study)

The symptoms of TLN such as decreased memory, acalculia et al. are correlated with the damage to the hippocampus and parahippocampal gyrus

DISCUSSION

Radiation-induced middle ear damage : Characterized by otitis media with effusion (OME) 26–40% NPC patients within 5 years after radiotherapy Two factors contributed to OME:

damage to the ET, tensor veli palatini muscle, cartilage or nerves direct radiation damage leading to non-infectious inflammation

The injuries of ET and tympanic cavity (including the otosteon) are relevant to the development of OME and should be contoured and protected individually

DISCUSSION

Sensorineural Hearing loss : Due to inner ear radiation injury Morbidity rates of 11-57% Precise mechanism is obscure and contributed also by the concurrent

chemotherapy

The recommendation to contour the cochlea and IAC individually is based on inner ear function

DISCUSSION

Radiation-induced xerostomia : Mainly seen due to radiation damage to the parotid gland

Contouring the whole salivary gland minus the GTV may be more suitable for getting the better dosimetric parameters that correspond with the change of salivary function after radiotherapy

DISCUSSION

This atlas was based mainly on CT scan and referred to MRI

MRI has a better resolution for soft tissue, and is usually used to diagnose the soft tissue disease Glands, muscles and other soft tissues should be contoured by referring to MRI

CT can more reliably indicate bone boundaries and joint structures the TMJ, middle / inner ear and mandible, which are mainly defined by bone limit,

could be contoured based on CT alone

CONCLUSIONS

CONCLUSIONS

Different OARs contouring methods result in different Dosimetric parameters

A contouring guideline is necessary to facilitate the generation of uniform and comparable dosimetric parameters

The present atlas, based on anatomic definitions and the pathogenesis of radiation-induced injury, may help reach a consensus on subjective interpretation of the OARs delineation to reduce inter institutional differences in NPC patients

COMPLETE ATLAS OF OAR DELINEATION IN HNC