Search tips
Search criteria 


Logo of brjradiolSubmitSubscribeAboutBJR
Br J Radiol. 2012 August; 85(1016): 1070–1077.
PMCID: PMC3587103

Interobserver variation in parotid gland delineation: a study of its impact on intensity-modulated radiotherapy solutions with a systematic review of the literature

S W Loo, FRCR, W M C Martin, FRCR, P Smith, BSc, S Cherian, FRCR, and T W Roques, FRCR



This study evaluates the interobserver variation in parotid gland delineation and its impact on intensity-modulated radiotherapy (IMRT) solutions.


The CT volumetric data sets of 10 patients with oropharyngeal squamous cell carcinoma who had been treated with parotid-sparing IMRT were used. Four radiation oncologists and three radiologists delineated the parotid gland that had been spared using IMRT. The dose–volume histogram (DVH) for each study contour was calculated using the IMRT plan actually delivered for that patient. This was compared with the original DVH obtained when the plan was used clinically.


70 study contours were analysed. The mean parotid dose achieved during the actual treatment was within 10% of 24 Gy for all cases. Using the study contours, the mean parotid dose obtained was within 10% of 24 Gy for only 53% of volumes by radiation oncologists and 55% of volumes by radiologists. The parotid DVHs of 46% of the study contours were sufficiently different from those used clinically, such that a different IMRT plan would have been produced.


Interobserver variation in parotid gland delineation is significant. Further studies are required to determine ways of improving the interobserver consistency in parotid gland definition.

Permanent xerostomia is one of the most prevalent and debilitating long-term adverse effects of radiotherapy for head and neck squamous cell carcinoma (HNSCC) [1,2]. It has a negative impact on patients' quality of life and oral health, and can lead to difficulties in chewing and swallowing [3-5]. It can also affect speech and taste, and predisposes these patients to dental caries, oral infections, mucosal ulcerations and osteoradionecrosis of the mandible [6]. The parotid glands are the largest of the salivary glands. In the stimulated state, they contribute more than two-thirds of the total salivary output. They are situated close to the Level II cervical lymph nodes, parapharyngeal space, tonsillar fossae and soft palate, and are likely to receive a significant dose when oropharyngeal cancers are treated with radiotherapy. Salivary flow from the parotid is affected by the radiation dose received and the volume of the gland irradiated. Several parameters of the parotid dose–volume–response relationship have been investigated. The one that seems to correlate best with long-term saliva production is the mean dose to the parotid [7-10]. An accepted target is to keep the mean dose below 24 Gy to preserve unstimulated salivary flow.

Intensity-modulated radiotherapy (IMRT) delivers highly conformal radiation to the planning target volumes (PTVs), while sparing adjacent uninvolved organs at risk (OARs) such as the parotid glands. Prospective randomised trials and non-randomised clinical studies have shown IMRT to be superior to conventional two-dimensional radiotherapy in the preservation of long-term parotid function [11,12]. As a result, parotid-sparing IMRT has become the standard technique for delivering radiotherapy for oropharyngeal cancer.

Accurate delineation of target volumes and OARs is essential for the success of IMRT. Interobserver variation in gross tumour volume (GTV) definition has been shown to be large and clinically significant for many tumour types, including HNSCC [13-17]. There is variation between individuals and groups such as oncologists and radiologists. Variation in parotid gland delineation can potentially offset the benefits of parotid-sparing IMRT.

The objective of this study is to evaluate the interobserver variation in parotid gland delineation and to determine its impact on IMRT solutions.

Methods and materials

Patient selection

The CT volumetric data sets of 10 patients with Stage IV squamous cell carcinoma of the oropharynx were used in this study. All patients had N2a/b disease and were deemed at risk of harbouring microscopic disease in the contralateral neck. All had been treated with IMRT to a dose of 65 Gy in 30 fractions to the GTV and high-risk clinical target volume (CTV), and 54 Gy in 30 fractions to the lower-risk uninvolved nodal regions. The constraint for the parotid gland contralateral to the GTV was a mean dose of <24 Gy.

These data sets were selected from our database on the basis that the dose constraints to the PTVs and the spinal cord planning OAR volume (PRV) had been met, and the mean dose to the spared parotid gland was within 10% of the target of 24 Gy. In these cases, a small change in the parotid contour may potentially result in a significant difference to the plan accepted for treatment.

Imaging protocol

Planning images were obtained using a high-speed single-slice spiral CT scanner (GE Healthcare, Waukesha, WI). They were acquired with a 3-mm slice thickness reconstructed every 3 mm and subsequently transferred via DICOM (NEMA, Rosslyn, VA) to the Eclipse (Varian, Palo Alto, CA) radiotherapy treatment planning system. All data were made anonymous and stored under separate profiles.

Volume delineation

Four consultant radiation oncologists and three consultant radiologists with 2–15 years of experience in head and neck oncology participated in the study. A tutorial was provided for those participants who were unfamiliar with the treatment planning system. For each patient, participants were given relevant clinical information. All diagnostic radiological investigations, including contrast-enhanced MRI, were also made available electronically via PACS (Picture Archiving and Communications System). Participants were allowed access to an atlas of head and neck anatomy and imaging. They were asked to independently delineate the parotid gland that had been spared with IMRT on the axial CT images. This was done without reference to the PTV contours. The window levels for all CT images could be altered during volume delineation.

Data and statistical analysis

The dose distribution of the actual IMRT treatment plan was superimposed on each study contour to allow their DVHs to be derived. These were compared to the original DVH obtained when the plan was used clinically. The interobserver variation in the parotid contours was examined both quantitatively and qualitatively for each patient. The Jaccard coefficient is defined as the ratio of the volume of intersection or overlap to the encompassing volume for any two parotid contours (Figure 1). The conformity index was then calculated for each patient by averaging the Jaccard coefficient between all possible pairs of contours for that patient [18]. The conformity index could therefore range between zero (no overlap between contours) and one (identical contours), and was determined separately for radiation oncologists and radiologists.

Figure 1
Diagrammatic representation of the Jaccard coefficient for two parotid delineations A and B. The Jaccard coefficient is defined as the ratio of the volume of intersection or the overlapping volume between A and B (A∩B) to the encompassing volume ...

Search strategy used for systematic review

A literature search was performed in PubMed using the keywords “parotid”, “radiotherapy”, and “variation” or “variability”. Articles published in English between 1990 and 2010 were reviewed.


A total of 70 study contours were available for analysis. The mean conformity index was 0.66 (range 0.46–0.73) among radiologists and 0.52 (range 0.26–0.61) among oncologists.

The mean parotid dose achieved during the actual treatment ranged from 22.1 to 25.2 Gy (median 23 Gy) and were all within 10% of 24 Gy. Using the study contours, the mean parotid dose obtained was within 10% of 24 Gy for only 53% of volumes by radiation oncologists and 55% of volumes by radiologists. Mean dose was within 20% of 24 Gy for 80 and 90% of the volumes, respectively. Overall, only 53% of all study contours achieved a mean parotid dose within 10% of 24 Gy, and 20% had mean doses >26.4 Gy (10% above 24 Gy). The mean doses obtained and the volumes of the “actual” treatment plans and all study parotid contours are shown in Tables 1 and and2,2, respectively. Figures 2 and and33 demonstrates the mean doses obtained by radiation oncologists and radiologists, respectively, for all 10 data sets.

Figure 2
Graph showing the mean parotid doses obtained by radiation oncologists for all ten data sets.
Figure 3
Graph showing the mean parotid doses obtained by radiologists for all ten data sets.
Table 1
Mean parotid doses for study contours and the doses in the actual treatment plans (Gy)
Table 2
Volumes of study contours delineated by all seven observers (cm3)

When the study contours were analysed qualitatively, the greatest degree of variation consistently appeared in the medial edge of the deep lobe, the anterior border of the superficial lobe, and the superior and inferior margins of the parotid gland. Figure 4 is an axial CT image showing the study contours of all seven participants for one parotid gland.

Figure 4
Axial CT image showing the study contours of the seven observers for one parotid gland. (a) Radiologists; (b) radiation oncologists.

Discussion and literature review

Radiotherapy is the main non-surgical treatment for patients with HNSCC. One of the commonest long-term adverse effects following such treatment is xerostomia. IMRT results in better dose conformation to the PTV and improved sparing of adjacent uninvolved normal tissues compared with conventional radiotherapy. Numerous studies showed a reduction in the incidence and severity of xerostomia following parotid-sparing IMRT [19-30], with post-treatment recovery of saliva production and resultant improvement in patient-reported quality of life [31]. Three randomised controlled trials comparing parotid-sparing IMRT and conventional radiotherapy were reported [12,32,33]. The PARSPORT study [32] was a multicentre trial which recruited 94 patients with oropharyngeal or hypopharyngeal squamous cell carcinoma. Treatment consisted of either parotid-sparing IMRT or CT-planned three-dimensional conformal radiotherapy using parallel-opposed lateral fields, with no concurrent chemotherapy. One of the planning constraints for parotid-sparing IMRT was a mean dose of <24 Gy to the entire contralateral parotid gland. In this study, IMRT resulted in a lower mean dose to the contralateral parotid, and this translated into a reduced incidence of Grade 2 or worse xerostomia at 12 and 24 months following treatment completion, assessed using the LENT SOMA (Late Effects of Normal Tissues Subjective–Objective Management Analytic) and the Radiation Therapy Oncology Group (RTOG) scoring systems. The IMRT arm also contained a higher proportion of patients with both stimulated and unstimulated saliva flow from the contralateral parotid post treatment. Patient-reported outcomes in favour of IMRT were observed. As a result, parotid-sparing IMRT has now become the current treatment of choice for patients with head and neck cancer who are likely to receive significant radiation doses to both parotid glands with conventional radiotherapy [34].

Accurate delineation of target volumes and OARs is critical to the success of IMRT. Its inverse planning process involves defining PTVs and OARs, stipulating constraints on the DVHs of each of these structures and optimising the treatment plan to meet these constraints with an iterative process. It creates high dose gradients between the PTVs and OARs. Interobserver variation in the delineation of target volumes and OARs may thus potentially result in underdosing of tumours, overdosing of OARs or both. For a relatively small structure such as the parotid gland with a steep dose gradient across, a slight change in its contour can lead to a significant alteration in its DVH and the ability of the treatment plan to meet the stipulated constraint.

This study demonstrates the presence of interobserver variation in parotid delineation and highlights its effect on IMRT solutions. Only half of all study contours achieved a mean parotid dose within 10% of 24 Gy when they were evaluated using the actual IMRT plans delivered to the patients. The parotid DVHs of 46% of the study contours were sufficiently different from those used clinically, such that a different IMRT plan would have been produced. The mean doses for 18% of study contours were greater than 26.4 Gy.

Interobserver variation in GTV and CTV delineation in HNSCC has been extensively studied [13,35-41]. By contrast, there have been few studies looking at interobserver variation in OAR definition in head and neck radiotherapy [42]. Geets et al [43] noted interobserver variation when parotid glands were delineated on CT and MRI. Even though MRI of the parotid gland provided excellent spatial resolution and soft-tissue contrast was not affected by dental artefact and allowed more accurate definition of the deep lobe, interobserver variation was found to be comparable between CT and MRI. Thus, coregistering the planning CT with MRI acquired in the treatment position may not offer any advantage, although the average parotid volumes were smaller when delineated with MRI than with CT [43]. These results are in contrast to those of another study which showed a reduction in interobserver variation with the addition of MRI, especially in patients with dental artefact on CT images [44]. Better reproducibility was noted in GTV delineation compared with that of the parotid [43], yet interobserver variation in GTV delineation has been much more extensively studied. This may be owing to clinicians' perception that accurate definition of the GTV is more critical to the success of IMRT and that differences in parotid delineation may not be relevant. Ultimately, the significance of interobserver variation in parotid definition can best be demonstrated by its effect on the DVH when the treatment plan is applied. In this study, we established the importance of accurate delineation of the parotid gland given that differences in its contour may have impacted on IMRT dose solutions in almost half the cases.

Qualitatively, a high degree of variation was noted in the delineation of the deep lobe of the parotid glands. This is important from a dosimetric perspective because the mean gland dose that can be achieved depends on the proximity of the parotid to the PTV and the extent of parotid–PTV overlap [45-47]. Both of these factors can be affected by variations in the delineation of the deep lobe of the parotid gland. Parotid sparing remains possible if the PTV overlaps <20% of the entire gland volume [48].

Parotid-sparing IMRT is currently used to treat patients with locally advanced HNSCC, with the expectation that the mean parotid dose as determined from its DVH predicts xerostomia, a physiological end point. In the absence of pathological correlation with imaging, it is impossible to establish with certainty where the actual parotid is. Our study highlights the difficulties in accurately delineating the parotid and has implications for the interpretation of previous research that helped establish 24 Gy as the threshold mean parotid dose for the preservation of unstimulated saliva flow. In the pivotal study by Eisbruch et al [7] that defined the dose, volume and function relationships for the parotid, no details were provided on the methods used to outline the parotid glands. Uncertainties in parotid gland definition in that study may have led to an inaccurate correlation between the parotid DVH and xerostomia, and the threshold dose of 24 Gy thus obtained for unstimulated salivary flow may be misleading. A different dose threshold of 32 Gy was identified in a separate study [8]. Others failed to detect such a threshold, instead demonstrating a linear correlation between the mean parotid dose and post-radiotherapy salivary flow [49]. These discrepancies might have been caused by interstudy variation in parotid definition. In addition, variation in parotid delineation may also lead to a disparity between the true mean dose received in vivo and that calculated from the treatment plan, and therefore the actual sparing of the parotid glands may not be as effective as intended. Rather than assume that a mean dose of <24 Gy predicts parotid sparing, radiotherapy centres practising parotid-sparing IMRT should prospectively correlate parotid DVHs obtained from contours outlined at their centres with saliva measurements and evaluations using the RTOG/European Organisation for Research and Treatment of Cancer late radiation morbidity scoring for xerostomia [50].

Apart from interobserver variation in its delineation, other factors can also affect the radiation dose to the parotid gland. Volumetric and positional changes in patients' anatomy occur during head and neck radiotherapy as a result of weight loss, tissue oedema, and shrinkage of tumour and normal structures [51-54]. This, together with daily set-up variations, has an impact on the mean dose received by the parotid gland [55]. In a study by O'Daniel et al [56] using an integrated CT–linear accelerator and deformable image registration to compute cumulative dose distribution, the mean dose “delivered” to the contralateral parotid was found to be at least 5 Gy higher than the planned dose in 27% of patients, using alignment to mark on the immobilisation mask and weekly portal imaging. This increase in mean parotid dose was due to both uncertainties in patient set-up and radiation-induced reduction in tumour and parotid volumes, with a medial shift of the parotids' centre of volumes into the high-dose region [52,56-58]. The effect of set-up uncertainties on the parotid dose distribution can be reduced via the use of daily image-guided radiotherapy (IGRT) or the addition of a PRV margin [59,60]. Adaptive radiotherapy (ART) can also result in more effective sparing of the parotid gland by taking tumour and normal tissue changes into account, with subsequent modification of the original IMRT plans [61]. This technique is still under evaluation. Preliminary data from a prospective study conducted at MD Anderson Cancer Center suggest that ART is both feasible and reduces the mean dose to the contralateral parotid compared with IGRT alone [62].

Contrary to prevalent belief, the introduction and use of contouring guidelines did not consistently lead to a reduction in interobserver variation in target volume definition among radiation oncologists [63-65]. This may be secondary to interclinician differences in guideline and imaging interpretation. Although guidelines exist for delineation of the parotid gland, there is no published evidence to show that its use reduces interobserver variation [66]. Apart from contouring guidelines, other measures that may help improve interobserver consistency in OAR definition include introduction of protocol-based one-on-one training [67] and use of automatic atlas-based segmentation via deformable image registration [68-70]. In addition, evaluation and identification of features associated with low conformity between observers can be useful in educating clinicians [71] and improving existing delineation guidelines and protocols. Further studies are required to determine the effectiveness of these measures in reducing interobserver variation in parotid gland delineation.

This study is limited in using a relatively small number of patient data sets, with parotid delineations performed by clinicians from a single institution. While it would be interesting to replicate the study in other institutions, all the oncologists who participated in the current study were experienced in volume definition for conformal radiotherapy, and the radiologists were experienced in the interpretation of head and neck imaging. We believe the participants are likely to be representative of their peers.


This study demonstrates significant interobserver variation in parotid delineation for head and neck IMRT. Further studies are required to establish ways of reducing this variation, which will allow more accurate determination of the dose–volume–effect relationship for the parotid gland.


1. Epstein JB, Emerton S, Kolbinson DA, Le ND, Phillips N, Stevenson-Moore P, et al. Quality of life and oral function following radiotherapy for head and neck cancer. Head Neck 1999;21:1–11 [PubMed]
2. Nguyen NP, Sallah S, Karlsson U, Antoine JE. Combined chemotherapy and radiation therapy for head and neck malignancies: quality of life issues. Cancer 2002;94:1131–41 [PubMed]
3. Chambers MS, Garden AS, Kies MS, Martin JW. Radiation-induced xerostomia in patients with head and neck cancer: pathogenesis, impact on quality of life, and management. Head Neck 2004;26:796–807 [PubMed]
4. McMillan AS, Pow EH, Leung WK, Wong MC, Kwong DL. Oral health-related quality of life in southern Chinese following radiotherapy for nasopharyngeal carcinoma. J Oral Rehabil 2004;31:600–8 [PubMed]
5. Jellema AP, Slotman BJ, Doornaert P, Leemans CR, Langendijk JA. Impact of radiation-induced xerostomia on quality of life after primary radiotherapy among patients with head and neck cancer. Int J Radiat Oncol Biol Phys 2007;69:751–60 [PubMed]
6. Cooper JS, Fu K, Marks J, Silverman S. Late effects of radiation therapy in the head and neck region. Int J Radiat Oncol Biol Phys 1995;31:1141–64 [PubMed]
7. Eisbruch A, Ten Haken RK, Kim HM, Marsh LH, Ship JA. Dose, volume, and function relationships in parotid salivary glands following conformal and intensity-modulated irradiation of head and neck cancer. Int J Radiat Oncol Biol Phys 1999;45:577–87 [PubMed]
8. Chao KS, Deasy JO, Markman J, Haynie J, Perez CA, Purdy JA, et al. A prospective study of salivary function sparing in patients with head-and-neck cancers receiving intensity-modulated or three-dimensional radiation therapy: initial results. Int J Radiat Oncol Biol Phys 2001;49:907–16 [PubMed]
9. Roesink JM, Schipper M, Busschers W, Raaijmakers CP, Terhaard CH. A comparison of mean parotid gland dose with measures of parotid gland function after radiotherapy for head-and-neck cancer: implications for future trials. Int J Radiat Oncol Biol Phys 2005;63:1006–9 [PubMed]
10. Houweling AC, Philippens MEP, Dijkema T, Roesink JM, Terhaard CHJ, Schilstra C, et al. A comparison of dose-response models for the parotid gland in a large group of head-and-neck cancer patients. Int J Radiat Oncol Biol Phys 2010;76:1259–65 [PubMed]
11. Braam PM, Terhaard CHJ, Roesink JM, Raaijmakers CPJ. Intensity-modulated radiotherapy significantly reduces xerostomia compared with conventional radiotherapy. Int J Radiat Oncol Biol Phys 2006;66:975–80 [PubMed]
12. Kam MK, Leung SF, Zee B, Chau RM, Suen JJ, Mo F, et al. Prospective randomized study of intensity-modulated radiotherapy on salivary gland function in early-stage nasopharyngeal carcinoma patients. J Clin Oncol 2007;25:4873–9 [PubMed]
13. Hermans R, Feron M, Bellon E, Dupont P, Van denBogaert W, Baert AL. Laryngeal tumor volume measurements determined with CT: a study on intra- and interobserver variability. Int J Radiat Oncol Biol Phys 1998;40:553–7 [PubMed]
14. Van deSteene J, Linthout N, de Mey J, Vinh-Hung V, Claassens C, Noppen M, et al. Definition of gross tumor volume in lung cancer: inter-observer variability. Radiother Oncol 2002;62:37–49 [PubMed]
15. Caldwell CB, Mah K, Ung YC, Danjoux CE, Balogh JM, Ganguli SN, et al. Observer variation in contouring gross tumor volume in patients with poorly defined non-small cell lung tumors on CT: the impact of 18-FDG-hybrid PET fusion. Int J Radiat Oncol Biol Phys 2001;51:923–31 [PubMed]
16. Tai P, Van Dyk J, Yu E, Battista J, Stitt L, Coad T. Variability of target volume delineation in cervical oesophageal cancer. Int J Radiat Oncol Biol Phys 1998;42:277–88 [PubMed]
17. Yamamoto M, Nagata Y, Okajima K, Ishigaki T, Murata R, Mizowaki T, et al. Differences in target outline delineation from CT scans of brain tumours using different methods and different observers. Radiother Oncol 1999;50:151–6 [PubMed]
18. Kouwenhoven E, Giezen M, Struikmans H. Measuring the similarity of target volume delineations independent of the number of observers. Phys Med Biol 2009;54:2863–73 [PubMed]
19. Chao KS, Majhail N, Huang CJ, Simpson JR, Perez CA, Haughey B, et al. Intensity-modulated radiation therapy reduces late salivary toxicity without compromising tumor control in patients with oropharyngeal carcinoma: a comparison with conventional techniques. Radiother Oncol 2001;61:275–80 [PubMed]
20. Pacholke HD, Amdur RJ, Morris CG, Li JG, Dempsey JF, Hinerman RW, et al. Late xerostomia after intensity-modulated radiation therapy versus conventional radiotherapy. Am J Clin Oncol 2005;28:351–8 [PubMed]
21. Graff P, Lapeyre M, Desandes E, Ortholan C, Bensadoun RJ, Alfonsi M, et al. Impact of intensity-modulated radiotherapy on health-related quality of life for head and neck cancer patients: matched-pair comparison with conventional radiotherapy. Int J Radiat Oncol Biol Phys 2007;67:1309–17 [PubMed]
22. van Rij CM, Oughlane-Heemsbergen WD, Ackerstaff AH, Lamers EA, Balm AJ, Rasch CR. Parotid gland sparing IMRT for head and neck cancer improves xerostomia related quality of life. Radiat Oncol 2008;3:41. [PMC free article] [PubMed]
23. Hsiung CY, Ting HM, Huang HY, Lee CH, Huang EY, Hsu HC. Parotid-sparing intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma: preserved parotid function after IMRT on quantitative salivary scintigraphy, and comparison with historical data after conventional radiotherapy. Int J Radiat Oncol Biol Phys 2006;66:454–61 [PubMed]
24. Munter MW, Hoffner S, Hof H, Herfarth KK, Haberkorn U, Rudat V, et al. Changes in salivary gland function after radiotherapy of head and neck tumors measured by quantitative pertechnetate scintigraphy: comparison of intensity-modulated radiotherapy and conventional radiation therapy with and without amifostine. Int J Radiat Oncol Biol Phys 2007;67:651–9 [PubMed]
25. Daly ME, Lieskovsky Y, Pawlicki T, Yau J, Pinto H, Kaplan M, et al. Evaluation of patterns of failure and subjective salivary function in patients treated with intensity modulated radiotherapy for head and neck squamous cell carcinoma. Head Neck 2007;29:211–20 [PubMed]
26. Rades D, Fehlauer F, Wroblesky J, Albers D, Schild SE, Schmidt R. Prognostic factors in head-and-neck cancer patients treated with surgery followed by intensity-modulated radiotherapy (IMRT), 3D-conformal radiotherapy, or conventional radiotherapy. Oral Oncol 2007;43:535–43 [PubMed]
27. Lee NY, de Arruda FF, Puri DR, Wolden SL, Narayana A, Mechalakos J, et al. A comparison of intensity-modulated radiation therapy and concomitant boost radiotherapy in the setting of concurrent chemotherapy for locally advanced oropharyngeal carcinoma. Int J Radiat Oncol Biol Phys 2006;66:966–74 [PubMed]
28. Jabbari S, Kim HM, Feng M, Lin A, Tsien C, Elshaikh M, et al. Matched case-control study of quality of life and xerostomia after intensity-modulated radiotherapy or standard radiotherapy for head-and-neck cancer: initial report. Int J Radiat Oncol Biol Phys 2005;63:725–31 [PubMed]
29. Rusthoven KE, Raben D, Ballonoff A, Kane M, Song JI, Chen C. Effect of radiation techniques in treatment of oropharynx cancer. Laryngoscope 2008;118:635–9 [PubMed]
30. Madani I, Vakaet L, Bonte K, Boterberg T, De Neve W. Intensity-modulated radiotherapy for cervical lymph node metastases from unknown primary cancer. Int J Radiat Oncol Biol Phys 2008;71:1158–66 [PubMed]
31. Lin A, Kim HM, Terrell JE, Dawson LA, Ship JA, Eisbruch A. Quality of life after parotid-sparing IMRT for head-and-neck cancer: a prospective longitudinal study. Int J Radiat Oncol Biol Phys 2003;57:61–70 [PubMed]
32. Nutting CM, Morden JP, Harrington KJ, Guerrero Urbano T, Bhide SA, Clark C, et al. Parotid-sparing intensity modulated versus conventional radiotherapy in head and neck cancer (PARSPORT): a phase 3 multicentre randomised controlled trial. Lancet Oncol 2011;12:127–36 [PMC free article] [PubMed]
33. Pow EH, Kwong DL, McMillan AS, Wong MC, Sham JS, Leung LH, et al. Xerostomia and quality of life after intensity-modulated radiotherapy vs. conventional radiotherapy for early-stage nasopharyngeal carcinoma: initial report on a randomized controlled clinical trial. Int J Radiat Oncol Biol Phys 2006;66:981–91 [PubMed]
34. Jensen SB, Pedersen AM, Vissink A, Andersen E, Brown CG, Davies AN, et al. A systematic review of salivary gland hypofunction and xerostomia induced by cancer therapies: management strategies and economic impact. Support Care Cancer 2010;18:1061–79 [PubMed]
35. Rasch C, Eisbruch A, Remeijer P, Bos L, Hoogeman M, van Herk M, et al. Irradiation of paranasal sinus tumors, a delineation and dose comparison study. Int J Radiat Oncol Biol Phys 2002;52:120–7 [PubMed]
36. Rasch CRN, Steenbakkers RJHM, Fitton I, Duppen JC, Nowak PJCM, Pameijer FA, et al. Decreased 3D observer variation with matched CT-MRI, for target delineation in nasopharyngeal cancer. Radiat Oncol 2010;5:21. [PMC free article] [PubMed]
37. Rasch C, Keus R, Pameijer FA, Koops W, de Ru V, Muller S, et al. The potential impact of CT-MRI matching on tumor volume delineation in advanced head and neck cancer. Int J Radiat Oncol Biol Phys 1997;39:841–8 [PubMed]
38. Chang CC, Chen MK, Wu HK, Liu MT. Nasopharyngeal carcinoma volume measurements determined with computed tomography: study of intraobserver and interobserver variability. J Otolaryngol 2002;31:361–5 [PubMed]
39. Riegel AC, Berson AM, Destian S, Ng T, Tena LB, Mitnick RJ, et al. Variability of gross tumor volume delineation in head-and-neck cancer using CT and PET/CT fusion. Int J Radiat Oncol Biol Phys 2006;65:726–32 [PubMed]
40. Cooper JS, Mukherji SK, Toledano AY, Beldon C, Schmalfuss IM, Amdur R, et al. An evaluation of the variability of tumor-shape definition derived by experienced observers from CT images of supraglottic carcinomas (ACRIN protocol 6658). Int J Radiat Oncol Biol Phys 2007;67:972–5 [PMC free article] [PubMed]
41. Breen SL, Publicover J, De Silva S, Pond G, Brock K, O'Sullivan B, et al. Intraobserver and interobserver variability in GTV delineation on FDG-PET-CT images of head and neck cancers. Int J Radiat Oncol Biol Phys 2007;68:763–70 [PubMed]
42. O'Daniel JC, Rosenthal DI, Garden AS, Barker JL, Ahamad A, Ang KK, et al. The effect of dental artifacts, contrast media, and experience on interobserver contouring variations in head and neck anatomy. Am J Clin Oncol 2007;30:191–8 [PubMed]
43. Geets X, Daisne JF, Arcangeli S, Coche E, De Poel M, Duprez T, et al. Inter-observer variability in the delineation of pharyngo-laryngeal tumor, parotid glands and cervical spinal cord: comparison between CT-scan and MRI. Radiother Oncol 2005;77:25–31 [PubMed]
44. Gardner M, Halimi P, Valinta D, Plantet MM, Alberini JL, Wartski M, et al. Use of single MRI and 18F-FDG PET-CT scans in both diagnosis and radiotherapy treatment planning in patients with head and neck cancer: advantage on target volume and critical organ delineation. Head Neck 2009;31:461–7 [PubMed]
45. Astreinidou E, Dehnad H, Terhaard CH, Raaijmakers CP. Level II lymph nodes and radiation-induced xerostomia. Int J Radiat Oncol Biol Phys 2004;58:124–31 [PubMed]
46. Vineberg KA, Eisbruch A, Coselmon MM, McShan DL, Kessler ML, Fraass BA. Is uniform target dose possible in IMRT plans in the head and neck? Int J Radiat Oncol Biol Phys 2002;52:1159–72 [PubMed]
47. Moore KL, Brame RS, Low DA, Mutic S. Experience-based quality control of clinical intensity-modulated radiotherapy planning. Int J Radiat Oncol Biol Phys 2011;81:545–51 [PubMed]
48. Hunt MA, Jackson A, Narayana A, Lee N. Geometric factors influencing dosimetric sparing of the parotid glands using IMRT. Int J Radiat Oncol Biol Phys 2006;66:296–304 [PubMed]
49. Roesink JM, Moerland MA, Battermann JJ, Hordijk GJ, Terhaard CH. Quantitative dose-volume response analysis of changes in parotid gland function after radiotherapy in the head-and-neck region. Int J Radiat Oncol Biol Phys 2001;51:938–46 [PubMed]
50. Cox JD, Stetz J, Pajak TF. Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC). Int J Radiat Oncol Biol Phys 1995;31:1341–6 [PubMed]
51. Castadot P, Geets X, Lee JA, Christian N, Gregoire V. Assessment by a deformable registration method of the volumetric and positional changes of target volumes and organs at risk in pharyngo-laryngeal tumors treated with concomitant chemo-radiation. Radiother Oncol 2010;95:209–17 [PubMed]
52. Barker JL, Jr, Garden AS, Ang KK, O'Daniel JC, Wang H, Court LE, et al. Quantification of volumetric and geometric changes occurring during fractionated radiotherapy for head-and-neck cancer using an integrated CT/linear accelerator system. Int J Radiat Oncol Biol Phys 2004;59:960–70 [PubMed]
53. Han C, Chen YJ, Liu A, Schultheiss TE, Wong JY. Actual dose variation of parotid glands and spinal cord for nasopharyngeal cancer patients during radiotherapy. Int J Radiat Oncol Biol Phys 2008;70:1256–62 [PubMed]
54. Wang ZH, Yan C, Zhang ZY, Zhang CP, Hu HS, Kirwan J, et al. Radiation-induced volume changes in parotid and submandibular glands in patients with head and neck cancer receiving postoperative radiotherapy: a longitudinal study. Laryngoscope 2009;119:1966–74 [PubMed]
55. Hong TS, Tome WA, Chappell RJ, Chinnaiyan P, Mehta MP, Harari PM. The impact of daily setup variations on head-and-neck intensity-modulated radiation therapy. Int J Radiat Oncol Biol Phys 2005;61:779–88 [PubMed]
56. O'Daniel JC, Garden AS, Schwartz DL, Wang H, Ang KK, Ahamad A, et al. Parotid gland dose in intensity-modulated radiotherapy for head and neck cancer: is what you plan what you get? Int J Radiat Oncol Biol Phys 2007;69:1290–6 [PMC free article] [PubMed]
57. Lee C, Langen KM, Lu W, Haimerl J, Schnarr E, Ruchala KJ, et al. Evaluation of geometric changes of parotid glands during head and neck cancer radiotherapy using daily MVCT and automatic deformable registration. Radiother Oncol 2008;89:81–8 [PubMed]
58. Robar JL, Day A, Clancey J, Kelly R, Yewondwossen M, Hollenhorst H, et al. Spatial and dosimetric variability of organs at risk in head-and-neck intensity-modulated radiotherapy. Int J Radiat Oncol Biol Phys 2007;68:1121–30 [PubMed]
59. Manning MA, Wu Q, Cardinale RM, Mohan R, Lauve AD, Kavanagh BD, et al. The effect of setup uncertainty on normal tissue sparing with IMRT for head-and-neck cancer. Int J Radiat Oncol Biol Phys 2001;51:1400–9 [PubMed]
60. Delana A, Menegotti L, Bolner A, Tomio L, Valentini A, Lohr F, et al. Impact of residual setup error on parotid gland dose in intensity-modulated radiation therapy with or without planning organ-at-risk margin. Strahlenther Onkol 2009;185:453–9 [PubMed]
61. Wu Q, Chi Y, Chen PY, Krauss DJ, Yan D, Martinez A. Adaptive replanning strategies accounting for shrinkage in head and neck IMRT. Int J Radiat Oncol Biol Phys 2009;75:924–32 [PubMed]
62. Schwartz DL, Dong L. Adaptive radiation therapy for head and neck cancer—can an old goal evolve into a new standard? J Oncol 2011;2011 article ID 690595 [PMC free article] [PubMed]
63. Wong EK, Truong PT, Kader HA, Nichol AM, Salter L, Petersen R, et al. Consistency in seroma contouring for partial breast radiotherapy: impact of guidelines. Int J Radiat Oncol Biol Phys 2006;66:372–6 [PubMed]
64. van Mourik AM, Elkhuizen PH, Minkema D, Duppen JC, Dutch YoungBoostStudyGroup. van Vliet-Vroegindeweij C. Multiinstitutional study on target volume delineation variation in breast radiotherapy in the presence of guidelines. Radiother Oncol 2010;94:286–91 [PubMed]
65. Fuller CD, Nijkamp J, Duppen JC, Rasch CRN, Thomas Jr CR, Wang SJ, et al. Prospective randomized double-blind pilot study of site-specific consensus atlas implementation for rectal cancer target volume delineation in the cooperative group setting. Int J Radiat Oncol Biol Phys 2011;79:481–9 [PMC free article] [PubMed]
66. van deWater TA, Bijl HP, Westerlaan HE, Langendijk JA. Delineation guidelines for organs at risk involved in radiation-induced salivary dysfunction and xerostomia. Radiother Oncol 2009;93:545–52 [PubMed]
67. Tai P, Van Dyk J, Battista J, Yu E, Stitt L, Tonita J, et al. Improving the consistency in cervical esophageal target volume definition by special training. Int J Radiat Oncol Biol Phys 2002;53:766–74 [PubMed]
68. Reed VK, Woodward WA, Zhang L, Strom EA, Perkins GH, Tereffe W, et al. Automatic segmentation of whole breast using atlas approach and deformable image registration. Int J Radiat Oncol Biol Phys 2009;73:1493–500 [PMC free article] [PubMed]
69. Stapleford LJ, Lawson JD, Perkins C, Edelman S, Davis L, McDonald MW, et al. Evaluation of automatic atlas-based lymph node segmentation for head-and-neck cancer. Int J Radiat Oncol Biol Phys 2010;77:959–66 [PubMed]
70. Chao KSC, Bhide S, Chen H, Asper J, Bush S, Franklin G, et al. Reduce in variation and improve efficiency of target volume delineation by a computer-assisted system using a deformable image registration approach. Int J Radiat Oncol Biol Phys 2007;68:1512–21 [PubMed]
71. Petersen RP, Truong PT, Kader HA, Berthelet E, Lee JC, Hilts ML, et al. Target volume delineation for partial breast radiotherapy planning: clinical characteristics associated with low interobserver concordance. Int J Radiat Oncol Biol Phys 2007;69:41–8 [PubMed]

Articles from The British Journal of Radiology are provided here courtesy of British Institute of Radiology