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ORIGINAL ARTICLE
Year : 2021  |  Volume : 17  |  Issue : 1  |  Page : 235-241

Study of volumetric and dosimetric changes during fractionated radiotherapy in head and neck cancers: A single centre experience


Department of Radiation Oncology, Cancer Research Institute, Himalayan Institute of Medical Sciences, Swami Rama Himalayan University, Dehradun, Uttarakhand, India

Date of Submission20-Mar-2020
Date of Decision31-May-2020
Date of Acceptance22-Jun-2020
Date of Web Publication15-Mar-2021

Correspondence Address:
Vipul Nautiyal
Associate Professor, Department of Radiation Oncology, Cancer Research Institute, Himalayan Institute of Medical Sciences, Swami Rama Himalayan University, Doiwala, Dehradun - 248 016, Uttarakhand
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jcrt.JCRT_350_20

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 > Abstract 


Aims and Objective: The assessment of volumetric and dosimetric changes in the head-and-neck cancer during fractionated radiotherapy by intensity-modulated radiotherapy (IMRT) technique.
Materials and Methods: A single-center prospective observational hospital-based study with a sample size of 20 cases of the head-and--neck squamous cell carcinoma over 1 year treated with chemoradiotherapy 66–70 Gy/33–35#@2 Gy/fraction with weekly cisplatin 35 mg/m2. After contouring of target volumes (TVs) and organs at risk (OARs) in initial computed tomography (CT) scan, all patients were planned and treated by the IMRT technique. We re-delineated the TVs and OARs in the second (CT15#) and third (CT30#) planning CT scan, and the initial plan was implemented in the re-CT scan dataset with the same optimization and doses. The volumetric and dosimetric changes during fractionated radiotherapy of TVs and OARs were evaluated and compared. Nonparametric Wilcoxon–signed-rank test was used to compare the means between each plan.
Results: For all 20 patients, plans were compared for volumetric and dosimetric parameters on repeat CT scans. The mean variation in gross tumor volume (GTV) and planning TV (PTV) was significant after 15 and 30 fractions of radiotherapy. On dosimetric evaluation, there was a significant increase in doses to GTV and OARs (parotid, spinal cord, and cochlea) with a significant P value. However, doses to the OARs were not exceeded the maximum tolerance limit.
Conclusion: This prospective single-center study concluded that two repeat imaging, along with re-planning improved TV coverage and decreased doses to the normal tissue. Larger studies with more sample sizes are required to set the criteria for replanning.

Keywords: Dosimetric and volumetric changes during radiotherapy, head-and-neck squamous cell carcinoma, intensity-modulated radiotherapy


How to cite this article:
Kumar V, Nautiyal V, Kant R, Gupta M, Bansal S, Ahmad M. Study of volumetric and dosimetric changes during fractionated radiotherapy in head and neck cancers: A single centre experience. J Can Res Ther 2021;17:235-41

How to cite this URL:
Kumar V, Nautiyal V, Kant R, Gupta M, Bansal S, Ahmad M. Study of volumetric and dosimetric changes during fractionated radiotherapy in head and neck cancers: A single centre experience. J Can Res Ther [serial online] 2021 [cited 2021 Apr 17];17:235-41. Available from: https://www.cancerjournal.net/text.asp?2021/17/1/235/311069




 > Introduction Top


The head-and-neck squamous cell carcinoma (HNSCC) is the sixth-leading cancer by incidence worldwide.[1] It is usually diagnosed in an advanced stage, and radiotherapy is an important therapeutic modality used either in the adjuvant or primary setting. Intensity-modulated radiotherapy (IMRT) has become the standard of care in treating head-and-neck (HN) cancers. It increases the therapeutic index by focussing radiation doses to the target volume (TV) and minimizing the radiation dose to normal tissue and organs at risk (OARs), thereby offering good loco-regional control and reduced toxicity.[2] In routine clinical practice, the initial IMRT plan is delivered for the whole course of radiotherapy. However during treatment, many patients have considerable anatomical changes[3] due to multiple factors such as weight loss, shrinkage of tumor, or nodal mass. By changing to one or more new plans during the radiation treatment,[4] these uncertainties can be corrected, and it reduces the doses to OARs and leads to improved quality of life (QOL). Re-planning reduces the mean dose to the parotid gland during IMRT in locally advanced HN carcinoma LAHNC.[5] The objective of this study was to assess the volumetric and dosimetric changes in TVs as well as in OARs after the 15th and 30th fractions of radiotherapy.


 > Materials and Methods Top


Patient selection

This prospective observational study was conducted over a period from January 2017 to January 2018. Twenty patients with a primary diagnosis of HNSCC were treated by IMRT technique. Volumetric changes and resultant dosimetric implications were documented by doing repeat contrast-enhanced computed tomography (CECT) and replanning. Patients were recruited after taking written informed consent and ethical clearance certificate from the institutional ethics committee. Eligibility criteria were histopathological proven HNSCC of the Oral cavity, oropharynx, hypopharynx, and larynx who are recommended for primary radiotherapy by the institutional tumor board; >18 years of age and ECOG PS I, II. Exclusion criteria were patients with recurrent or metastatic disease, history of surgery for primary disease, co-existing malignancy, ECOG PS >2, psychiatric illness, and tissue diagnosis other than squamous cell carcinoma. Dental evaluations were performed before starting the treatment of all patients.

Treatment planning

All patients were immobilized by orfit thermoplastic cast Prosthetic and Orthotic Clinic (POCL) with Headrest and shoulder traction. CECT data of the patient were acquired in 5-mm slice thickness on CT simulator unit (Somatom Emotion Duo, Siemens Healthcare Pvt. Ltd.) and acquired CT data set was reconstructed into 3-mm slice thickness and then transferred to the treatment planning system (Oncentra MasterPlan, Nucletron Pvt. Ltd.) through DICOM in local Area Networking system. TVs (gross tumor volume [GTV], CTV, and planning TV [PTV]) and OARs were delineated as per international commission on radiation units (ICRU) and measurements (ICRU 62, 83) on the CT scan images. Inverse planning algorithm was used to generate the IMRT plan for each patient's initial CT data set, and treatment delivery of the plan was made through the step and shoot technique. The volumetric doses to the TV and OARs were analyzed by the dose-volume histogram tool in the treatment planning system for final inverse IMRT (inverse-IMRT) treatment plan of each patient.

GTV representing gross disease and/or enlarged lymph nodes were recognized clinically on CT scan. Areas with a high risk of microscopic disease and a 1–1.5 cm margin around the GTV were included in the CTV primary and edited from the air, bone, and adjacent anatomical boundaries. Low-risk CTV includes drainage areas in the neck, which may harbor subclinical disease.

For PTV further 5 mm margin to CTV was given. High-risk CTV received 66–70 Gy and low-risk CTV received 54 Gy. The gross primary tumor and gross lymph nodes containing clinical/pathological or radiological evidence of disease were given a total dose of 66–-70 Gy in 33–35 [email protected] 2 Gy/fraction, along with weekly injection Cisplatin 35 mg/m2. We used 5–7 Gantry Angles beam arrangements for IMRT planning. Treatment was delivered once daily, 5 fractions/week, over 6.5–7 weeks. Portal images were acquired weekly and superimposed on a digital reconstructed radiograph image for treatment verification in the therapist system of LANTIS at the control console area of the Linear Accelerator (LINAC).

On the 15th and 30th fraction of radiotherapy, second (CT15#) and third (CT30#) CT scan images data were acquired with the same treatment planning reference points (TPRP). All new CT scan images were fused with the previous one, and re-delineation of TVs and OARs were done in second and third CT scan data set (CT15# and CT30#). Initial IMRT plan was imported on the CT15# and CT30# data set in the Oncentra Master Plan TPS. The treatment isocenter in the second and third CT data sets was made the same as in the initial plan with the help of TPRP. The beam arrangement and optimization values were also kept the same in both CT data and structure set. After that, dose calculations were performed in a new CT scan data set. The doses to the TVs and the OARs were recorded from the dose-volume histogram treatment plan analysis for the dosimetric comparison of the CT15# and CT30# plan with the initial one. Deformable image registrations were done in Oncentra MasterPlan, Nucletron Pvt. Ltd. The initial inverse IMRT plan was delivered for the whole course of radiotherapy in each patient. All patients were weekly assessed clinically in terms of Nutritional status of the patients, toxicities, blood parameters, and weight loss. All patients completed their radiation without any interruption. The dosimetric and volumetric changes of the Various TVs and OAR were evaluated and compared from the initial one.

Data management and statistical analysis

Interpretation and analysis of obtained results were carried out using software SPSS version 20 (IBM Corp., Armonk, N.Y.,USA) and electronic spreadsheets (MS Excel). The means between each plan was compared by the nonparametric Wilcoxon–signed-rank test, and it was statistically significant by P < 0.05.


 > Results Top


During Inverse IMRT treatment, dosimetric as well as volumetric changes were assessed in twenty patients having Locally advanced head and neck Squamous cell carcinoma (LAHNSCC).

The summary of the baseline characteristics is shown in [Table 1]. The mean age of the patient population was 64.5 years (range: 52–78 years). Among the various sites, majority of the patients had hypopharynx malignancies (nine patients–45%) while oropharyngeal, laryngeal, and oral cavity malignancies were seven, three, and one patient respectively.
Table 1: Baseline patient characteristics

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Volumetric analysis

[Figure 1] and [Figure 2] compare the TVs and Organ at risks (OARs) between 15 fractions and 30 fractions of radiotherapy. [Figure 3] shows a marked reduction in the gross tumor volume primary as well as the nodal site. Mean shrinkage of TVs and OARs (parotids and submandibular glands) after 15 fractions and 30 fractions of radiotherapy were statistically significant (P < 0.05).
Figure 1: Volumetric evaluation of the gross tumor volume during treatment (initial, after 15, and 30 fractions)

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Figure 2: Volumetric evaluation of the volume of ipsilateral and contralateral Parotid glands during treatment (initial, after 15 and 30 fractions)

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Figure 3: Regression of gross tumor volume during treatment (after 15 fractions)

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Dosimetric analysis

A summary of the dosimetric evaluation of TVs with regards to GTVprimary, GTVnodal, and PTV) are summarized in [Figure 4] and [Figure 5] and [Table 2]. On dosimetric evaluation, there was observed a significant increase in 95% of the prescribed dose to Gross disease (P < 0.05) after 15 fractions and 30 fractions of radiotherapy. The doses to the OARs (parotid, spinal cord, and cochlea) were also significantly increases after 15 and 30 fractions of radiotherapy but could not exceed the tolerance limit [Table 2]. Maximum dose to 2 cc volume (D2cc) of skin at initial, 15 fractions and 30 fractions were 68.87 Gy (range = 66–70.46), 69.94 (range = 68.2–72.1) and 70.35 (range = 69–72.40), respectively.
Figure 4: Dosimetric evaluation of the gross tumor volume primary for the original plan, after 15 and after 30 fractions during treatment

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Figure 5: Dosimetric evaluation of the gross tumor volume nodal for the original plan, after 15 and after 30 fractions during treatment

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Table 2: Dosimetric Evaluation of the Organ at Risks (Parotid Glands, Spinal Cord and Cochlea) during the course of Treatment (initial, after 15 and 30 fractions)

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The mean weight loss after the completion of external-beam radiation therapy (EBRT) in 6.5–7 weeks of duration was 8.52% and only two patients had >10% wt. loss. Out of 20 patients, 12 patients were put on nasogastric tube feeding for nutritional support. During the last week of radiotherapy, nine patients (45%) had developed radiation therapy (RT) oncology group Grade 2 mucositis, and eight patients (40%) had developed Grade 3 mucositis, whereas three patients (15%) had developed Grade 4 mucositis.

QOL for dryness (HNDR) and stickiness (HNSS) were assessed in 20 patients by using EORTC-HN-35 (Hindi version or English version) at baseline (before starting the radiotherapy), at 3, 6, and 12 months following treatment. The mean symptom score values for HNDR at baseline, 3, 6, and 12 months post-RT were 21.1, 44.4, 56.7, and 25, respectively. The mean symptom score values for HNSS at baseline, 3, 6, and 12 months post-RT were 17.8, 62.2, 64.4, and 20.8, respectively. Dryness and stickiness increased over 3–6 months in the follow-up but improved by 12 months; however, it could not reach the baseline.

On follow-up of 15 months, all 20 patients are alive, of which 16 patients are disease-free, 3 had locoregional failure, and one developed lung metastasis.


 > Discussion Top


The treatment of HNSCC has undergone a paradigm shift over the past two decades, with improvements in surgery, RT, and chemotherapy leading to better locoregional control, overall survival, and QOL.[6]

Changes in the TV and organ at risk during IMRT may lead to geographical miss and increase the doses to the OARs. There are several reasons of anatomical changes during radiotherapy such as shrinkage of the tumor, weight loss, and set-up errors. This can lead to a high dose to normal surrounding tissues. To overcome these geometrical errors, repeat imaging is necessary.[7]

The mean weight loss in our study was 8.52% during radiotherapy. Ho et al.[8] and Barker et al. also found a similar mean weight loss of 7.6% and 7.1%, respectively, during radiotherapy in their studies. Nutrition management is an essential part of the care of patients with HNC.[9] 12 patients (60%) required a nasogastric tube during radiotherapy treatment.

In the present study, patients were evaluated for volumetric and dosimetric changes in TVs and OARs after 15 and 30 fractions of radiotherapy. It showed statistically significant decreases in TVs. We also analyzed our initial plan in re-contoured CT scan (15 and 30 fractions) dataset. Higher doses would have been delivered to the shrunken TV and OARs. Hansen et al.,[4] Cheng et al.[10] and Morgan and Sher;[11] had also shown significantly increased 95% of the prescribed doses to the TVs and increased doses to the organ at risk, which was similar to our study.

In volumetric evolutions, the mean reduction of the TV and OARs (bilateral parotid and submandibular gland) after 15 and 30 fractions of EBRT were statistically significant (P < 0.05) in our study which is in concordance with Barker et al. and Cheng et al. (2012).[10] Cheng et al. reported shrinkage of GTV by 13.1%. Barker et al. also noted a regression in GTV by 69.5% during the whole treatment at 1.8%/day.[12] The study reported significant GTV regression of 72% during the entire treatment.

In this study, the mean volume of ipsilateral and contralateral parotids decreased during the course of treatment. The mean reduction in the volume of parotid after 30 fractions of treatment, the mean reduction was 24.3% for ipsilateral and 25.26% for contralateral parotid with a significant P value (<0.05). Brouwer et al.[13] also found a 26% average volume reduction in parotids. Ho et al.[8] similarly noted a mean reduction in the volume of ipsilateral and contralateral parotid by 29.7% and 28.4%, respectively. Wang et al.[14] documented mean reduction of 20.6% and 19.8% in the left and right parotid volume, respectively, whileHansen et al. (2006)[4] reported a volume reduction of 21.5% and 15.6% in left and right parotids with a significant P < 0.05. The observation by Lee et al.[15] showed a reduction in parotid volume with a median total loss of 21.3% volume by the end of 30 fractions, which parallels our results this is by virtue that the gland migrated medially with a median distance of 25.26 mm.

For submandibular gland mean reduction was 21.44% for ipsilateral and 24.20% for contralateral submandibular gland after 15 fractions of radiotherapy while after 30 fractions mean reduction was 27.17% for ipsilateral and 34.58% for contralateral submandibular gland with a significant P < 0.05. The study by Najim et al.[16] revealed that the mean volume of submandibular gland reduced to 7.1 ml at the completion of 30 fractions from 8.1 ml at the initiation, with mean volume reduction by 19.3%.

For dosimetric evolution, doses to the TVs were compared between the initial, 15, and 30 fractions plan. In terms of GTV primary and nodal; all the three parameters (D2%, D50%, and D95%) were increased with statistical significance. Similar results were obtained for PTV. Hansen et al.,[4] Wang et al.,[14] Cheng et al.,[10] and Burela et al.;[17] also observed similar results. However, some studies have shown conflicting results. Dewan et al.[18] and Castadot et al.[19] found that doses actually delivered to TVs did not significantly differ from planned doses.

In our study, the mean dose of ipsilateral parotids increased by 12.42% after 15 fractions and 23.5% after 30 fractions, while for contralateral parotid, it was 13.82% after 15 fractions and 22.87% after 30 fractions. Another study by Cheng et al.[10] also reported that after 15 fractions of radiation, there was an increase in dmedian of contralateral and ipsilateral parotids by 6.9% and 24.1%, respectively.

The major limitation of this study was the small number of patients. The certain parameter may be needed to know which patients may get benefit from mid-treatment re-planning so that that workload could be reduced, and cost-effectiveness could be achieved. This study exemplified the use of two repeat imaging and replanning, which are able to provide greater normal tissue sparing with improved TV coverage.


 > Conclusion Top


This prospective study supports to assess the volumetric and dosimetric changes with the help of repeat CT scans and replanning for HN IMRT patients. Although the sample size was small, our study has shown encouraging results with the use of two repeat imaging along with re-planning, which improved TV coverage and decreased doses to the normal tissue. Larger studies with more sample sizes are required to set the criteria for re-contouring and re-planning.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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Hansen EK, Bucci MK, Quivey JM, Weinberg V, Xia P. Repeat CT imaging and replanning during the course of IMRT for head-and-neck cancer. Int J Radiat Oncol Biol Phys 2006;64:355-62.  Back to cited text no. 4
    
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Ho KF, Marchant T, Moore C, Webster G, Rowbottom C, Penington H, et al. Monitoring dosimetric impact of weight loss with kilovoltage (kV) cone beam CT (CBCT) during parotid-sparing IMRT and concurrent chemotherapy. Int J Radiat Oncol Biol Phys 2012;82:e375-82.  Back to cited text no. 8
    
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Beltran M, Ramos M, Rovira JJ, Perez-Hoyos S, Sancho M, Puertas E, et al. Dose variations in tumor volumes and organs at risk during IMRT for head-and-neck cancer. J Appl Clin Med Phys 2012;13:3723.  Back to cited text no. 9
    
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Cheng HC, Wu VW, Ngan RK, Tang KW, Chan CC, Wong KH, et al. A prospective study on volumetric and dosimetric changes during intensity-modulated radiotherapy for nasopharyngeal carcinoma patients. Radiother Oncol 2012;104:317-23.  Back to cited text no. 10
    
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Morgan HE, Sher DJ. Adaptive radiotherapy for head and neck cancer. Cancers Head Neck 2020;5:1.  Back to cited text no. 11
    
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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.  Back to cited text no. 12
    
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Brouwer CL, Steenbakkers RJ, Langendijk JA, Sijtsema NM. Identifying patients who may benefit from adaptive radiotherapy: Does the literature on anatomic and dosimetric changes in head and neck organs at risk during radiotherapy provide information to help? Radiother Oncol 2015;115:285-94.  Back to cited text no. 13
    
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Wang W, Yang H, Hu W, Shan G, Ding W, Yu C, et al. Clinical study of the necessity of replanning before the 25th fraction during the course of intensity-modulated radiotherapy for patients with nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys 2010;77:617-21.  Back to cited text no. 14
    
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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.  Back to cited text no. 15
    
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Najim M, Perera L, Bendall L, Sykes JR, Gebski V, Cross S, et al. Volumetric and dosimetric changes to salivary glands during radiotherapy for head and neck cancer. Acta Oncol 2015;54:1691-3.  Back to cited text no. 16
    
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Burela N, Soni TP, Patni N, Natarajan T. Adaptive intensity-modulated radiotherapy in head-and-neck cancer: A volumetric and dosimetric study. J Cancer Res Ther 2019;15:533-8.  Back to cited text no. 17
    
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Dewan A, Sharma S, Dewan A, Srivastava H, Rawat S, Kakria A, et al. Impact of adaptive radiotherapy on locally advanced head and neck cancer – A dosimetric and volumetric study. Asian Pac J Cancer Prev 2016;17:985-92.  Back to cited text no. 18
    
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Castadot P, Geets X, Lee JA, Grégoire V. Adaptive functional image-guided IMRT in pharyngo-laryngeal squamous cell carcinoma: Is the gain in dose distribution worth the effort? Radiother Oncol 2011;101:343-50.  Back to cited text no. 19
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
 
 
    Tables

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