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ORIGINAL ARTICLE
Year : 2019  |  Volume : 15  |  Issue : 3  |  Page : 533-538

Adaptive intensity-modulated radiotherapy in head-and-neck cancer: A volumetric and dosimetric study


Department of Radiation Oncology, Bhagwan Mahaveer Cancer Hospital and Research Centre, Jaipur, Rajasthan, India

Date of Web Publication29-May-2019

Correspondence Address:
Dr. Nagarjuna Burela
Department of Radiation Oncology, Bhagwan Mahaveer Cancer Hospital and Research Centre, JLN Marg, Jaipur - 302 017, Rajasthan
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jcrt.JCRT_594_17

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 > Abstract 


Introduction and Objective: Anatomic and volumetric changes occur in head-and-neck cancer during fractionated radiotherapy (RT), and the actual dose received by patient is considerably different from the original plan. The purpose of this study is to evaluate volumetric and dosimetric changes occurring during radiation therapy.
Patients and Methods: Ten patients of locally advanced head-and-neck cancer, 6 oropharynx, 3 larynx, and 1 hypopharynx underwent computed tomography (CT) simulation before treatment and after 4 weeks during RT treatment. Original plan (OPLAN) was generated based on initial CT scan for the entire course of treatment. The initial plan is implemented on the second planning CT scan, and the dose distribution is recalculated. Beam configuration of OPLAN was applied onto the second CT scan and then hybrid plan (HPLAN30) was generated. RPLAN30 is the intensity-modulated RT replan generated on the second CT scan for the remaining 30 Gy. Dose and volume parameters between OPLAN30 (based on the first CT scan for the remaining 30 Gy), HPLAN30, and RPLAN30 were compared.
Results: The volume reduction of planning target volume (PTV), ipsilateral and contralateral parotid after 4 weeks of RT, was statistically significant (P < 0.05). D2% and V > 107% of PTV were higher in HPLAN than that of RPLAN (P < 0.05). Hybrid plans showed increase in delivered dose to spinal cord. Mid treatment replanning reduced doses to spinal cord (Dmax and D1%), which is statistically significant (P < 0.05). Mean doses to ipsilateral and contralateral parotid of RPLAN (21.4 Gy and 16.74 Gy, respectively) were reduced when compared to that of HPLAN (22.99 Gy and 22 Gy, respectively).
Conclusion: Interim CT scanning and replanning (adaptive) improves target volume coverage and normal tissue sparing.

Keywords: Adaptive radiotherapy, anatomic changes, dosimetric changes, head, intensity-modulated radiotherapy, neck cancer


How to cite this article:
Burela N, Soni TP, Patni N, Natarajan T. Adaptive intensity-modulated radiotherapy in head-and-neck cancer: A volumetric and dosimetric study. J Can Res Ther 2019;15:533-8

How to cite this URL:
Burela N, Soni TP, Patni N, Natarajan T. Adaptive intensity-modulated radiotherapy in head-and-neck cancer: A volumetric and dosimetric study. J Can Res Ther [serial online] 2019 [cited 2019 Aug 22];15:533-8. Available from: http://www.cancerjournal.net/text.asp?2019/15/3/533/244224




 > Introduction Top


Intensity-modulated radiotherapy (IMRT) has become the standard treatment in locally advanced head-and-neck cancer (LAHNC) because of its high conformality, with potential sparing of critical structures.[1],[2] During head-and-neck radiotherapy (RT), changes in anatomy occur during treatment course. Changes include shrinkage of tumor and normal tissues and positional shift of certain structures, which is due to response to radiation and combined chemotherapy.[3]

The planning target volume (PTV) includes margin for uncertainties in shape and motion of organs, beam geometry, and patient setup. However, this PTV does not account for weight loss, tumor shrinkage, and tissue edema (anatomical alterations).[4] Hence, little alteration in patient's anatomy and position results in huge dosimetric changes (lower dose to target volume and high dose to organ at risks [OARs]) because of sharp dose gradients between target volume (TV) and OARs in IMRT.[5] This might lead to increased complications and marginal recurrences. To minimize these limitations, the possible strategy is adaptive RT (ART), i.e., repeat imaging and replanning to adapt to actual patient anatomy.

In this study, we evaluated the dosimetric and volumetric changes occurring during IMRT treatment for LAHNC and also to estimate the benefits of adaptive radiation therapy.


 > Patients and Methods Top


Ten patients of Stage III-IVb LAHNC were analyzed prospectively between November 2015 and December 2016. Inclusion criteria were as follows: (i) Histologically proven squamous cell carcinoma of oropharynx, larynx, and hypopharynx; (ii) Age in the range of 18–70 years; and (iii) Eastern Cooperative Oncology Group performance score 0–2.

Primary objective

The primary objective was to evaluate the volumetric and dosimetric alterations occurring during RT treatment in LAHNC.

Treatment planning

All patients underwent RT treatment planning scan. A plain and contrast computed tomography (CT) scan for RT planning was done after immobilization with 5-clamp head-and-neck mask in treatment position as per departmental protocol. 3-mm slice thickness axial images from frontal sinus to carina were acquired and all data were sent through DICOM-Digital Imaging and Communications in Medicine to a workstation treatment planning system (TPS; Eclipse integrated treatment planning system, version 10) through local area network.

The primary tumor and abnormal lymph node in neck were delineated on CT images. The Clinical Target Volume (CTV) were named as CTV1- high risk volumes enclosing the gross tumor volumes; CTV2-low risk volumes of elective nodal regions. PTV margin of 5 mm was used for setup errors. Dose prescribed to PTV1 was 70Gy/35 fractions and PTV2 was 50Gy/25 fractions.

IMRT plans were generated with sliding window technique using nine coplanar equidistant fields of 6 MV energy. Optimizations and dose calculations were done with Eclipse version 10 (Varian Medical Systems). Treatment was delivered once daily, 5 days/week, over 7 weeks, using Varian (CLINAC iX) linear accelerator.

Adaptive radiotherapy–computed tomography re-simulation and intensity-modulated radiotherapy replanning

All patients were followed up once a week during treatment. The change in weight loss was monitored. After 4 weeks, re-CT simulation was done for each patient with new immobilization mask. Re-contouring of TV and OARs was done and noted. Original plan (OPLAN), i.e,. planning done on the first CT scan was implemented for the whole course of RT treatment. The initial plan is implemented on the second planning CT scan, and the dose distribution is recalculated. IMRT replan (RPLAN) was generated on the second CT scan to observe dosimetric changes. Beam configuration of OPLAN was applied onto the second CT scan and then hybrid plan (HPLAN) was generated. (HPLAN situation when no replanning would have occurred.)

Anatomical changes were compared between 2 scans after 4 weeks (20 fractions) of RT. To ensure dosimetric consistency between two plans, OPLAN30 (based on the first CT scan for the remaining 30 Gy) was compared to HPLAN30 (Hybrid plan for 30 Gy). To evaluate the effect of replanning on dosimetric outcome, HPLAN30 was compared with IMRT replan (RPLAN30). All these comparisons are for the remaining fractions delivered after the second CT scan. All patients underwent IMRT along with concurrent weekly injection of cisplatin.

Statistical analysis

Linear variables were summarized as mean and standard deviation as descriptive statistics. Between-group comparison of linear variables was done using unpaired t-test, whereas Wilcoxon rank sum test was used for paired observations of linear variables within the groups. P <0.05 was considered statistically significant. Med Calc version 12.2.1.0 software (MedCalc Software, Acacialaan 22, B-8400 Ostend, Belgium) was used for all statistical calculations.


 > Results Top


Patient characteristics are summarized in [Table 1].
Table 1: Patient characteristics

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Volumetric analysis

Comparison of volumes of PTV and OARs (parotids) between day 1 CT and mid CT scan was performed. Mean shrinkage of PTV and parotids (ipsilateral and contralateral) in mid treatment scan was statistically significant (P < 0.05).

Dosimetric analysis

Impact of anatomical changes in PTV and OARs on dosimetric outcome was evaluated. Dosimetric characteristics are summarized in [Table 2]. D98%/D95% (tumor coverage) on comparing OPLAN30 versus HPLAN30 (P = 0.098) and HPLAN30 versus RPLAN30 (P = 0.084) was statistically insignificant. There was a significant difference in D2% (OPLAN30 versus HPLAN30, P = 0.016 and HPLAN30 versus RLAN30, P = 0.015). On comparing planned and delivered doses, an increase on V107% was seen (P = 0.049). The comparison of dose distribution of TV of OPLAN, HPLAN, and RPLAN is shown in [Figure 1].
Table 2: Dosimetric evaluation for target volume, spinal cord, and parotids for original plan, hybrid plan, and replan; volumetric evaluation of target volume and parotids

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Figure 1: Comparison of dose distribution of target volume of original plan, hybrid plan, and replan

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Spinal cord

A significant increase in Dmax and D1% of spinal cord was seen in HPLAN30 when compared to that of OPLAN30 (P = 0.019). Replanning reduced Dmax and D1% of spinal cord (P = 0.004).

Parotid

Delivered (HPLAN) mean dose of contralateral parotid (22 ± 5.46 Gy) was higher than the planned (OPLAN) mean dose (20.30 ± 2.64 Gy), for which we further reduced the contralateral parotid mean dose by replanning (16.74 ± 7 Gy). A similar pattern was observed in ipsilateral parotid but was not significant.


 > Discussion Top


IMRT increases therapeutic ratio by increasing dose to target and reducing doses to OARs. Due to its high conformality, steep dose gradients exist around TV. A small change in anatomical/positional variations results in underdosage to TV and higher doses to OARs. In this study, we quantified changes occurring during RT treatment and the effect of replanning on dose distribution.

Weight loss is a common presentation during RT treatment in LAHNC. Ho et al. reported a 7.6% median weight loss during the entire course of treatment.[6] Bhandari et al., reported that 10% weight loss was observed after the 3rd week of RT.[1]

In comparison with the above studies, mean weight loss in our study was 7.99% in the first 4 weeks and three patients required nasogastric tube for nutritional support.

Marked anatomical changes have been observed during treatment either due to shrinkage of primary tumor and nodal volumes or weight loss. Vasquez Osorio et al. observed 25 ± 15% reduction in primary tumor volume in patients who underwent resimulation after 46 Gy.[7] In our study on comparison of PTV between the 1st and 2nd CT scan, there is significant reduction in mean PTV (146.3 cc, 13.1%, P = 0.034). These volumetric changes, i.e., reduction in volume is also seen in parotids. Due to weight loss or TV reduction, parotids shift medially into a high-dose region. Studies have observed significant volume loss of parotids during RT.[5],[6],[8],[9],[10],[11],[12],[13] Selected studies showing TV reduction and parotid volume contraction are depicted in [Table 3]. In the present study, there is a significant reduction in ipsilateral parotid (mean % decrease: −27.3%, P = 0.008) and contralateral parotid (−24.63%, P = 0.008) after 4 weeks.
Table 3: Studies reporting target volume and parotid volume contraction during radiotherapy treatment

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We have also evaluated the impact of anatomical modification on dosimetry. Dosimetric modifications between planned (OPLAN30), delivered (HPLAN30), and adaptive (RPLAN30) doses were performed. Delivered doses (D98%/D95%) did not significantly differ from planned doses to PTV but with a significant increase in D2% in HPLAN30 (P = 0.016), which was reduced by replanning (P = 0.015). In studies by Castadot et al. and Wu et al., there was no significant change between planned and delivered doses with respect to PTV coverage.[3],[13]

Spinal cord and parotids received more actual delivered dose than planned dose (P < 0.05) which could be reduced by replanning. Studies showing increase in dose to OARs (spinal cord and parotids) if not replanned and time for replanning are depicted in [Table 4]. Adaptive replanned doses (D2%) are significantly smaller than delivered doses. RPLAN30 for Dmax and D1% of spinal cord was significantly smaller than that of HPLAN30 (P = 0.004 and P = 0.008, respectively). In our study, mid treatment re-scanning and re-planning reduced doses to OARs. The increased doses to ipsilateral and contralateral parotid glands and spinal cord in hybrid plan (that we do not want) are 1.59 Gy, 1.7 Gy, and 3.3 Gy (Dmax), respectively. We reduced these extra doses to OARs by mid treatment replanning. Timing for replanning is a crucial challenge. There are no clear consensus guidelines for replanning. The timing for replanning is shown in [Table 4]. We have also analyzed skin doses and its clinical effect. The skin doses (Dmean) in OPLAN30, HPLAN30, and RPLAN30 are 10.88 Gy, 12.25 Gy, and 7.88 Gy, respectively. Nearly 80% of patients have Grade I and 20% have Grade II skin reactions.
Table 4: Studies reporting increased dose to organ at risks (spinal cord and parotids) if not replanned during treatment and studies showing timing for replanning

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 > Conclusion Top


This study evaluated the serial change in volume and dosimetric changes in TV and OARs in LAHNC patients receiving chemo-IMRT. The significant volume and dosimetric changes occur 4 weeks after commencing RT. The sharp dose gradients in IMRT force us to minimize uncertainties (anatomical and positional variations) to reduce geographic miss. ART by rescanning, recontouring, and replanning is required if necessary. Our study demonstrated the mid treatment re-CT simulation and adaptive planning reduced doses to OARs.[14],[15],[16],[17]

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 > References Top

1.
Bhandari V, Patel P, Gurjar OP, Gupta KL. Impact of repeat computerized tomography replans in the radiation therapy of head and neck cancers. J Med Phys 2014;39:164-8.  Back to cited text no. 1
[PUBMED]  [Full text]  
2.
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. 2
    
3.
Wu Q, Chi Y, Chen PY, Krauss DJ, Yan D, Martinez A, et al. Adaptive replanning strategies accounting for shrinkage in head and neck IMRT. Int J Radiat Oncol Biol Phys 2009;75:924-32.  Back to cited text no. 3
    
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Bhide SA, Davies M, Burke K, McNair HA, Hansen V, Barbachano Y, et al. Weekly volume and dosimetric changes during chemoradiotherapy with intensity-modulated radiation therapy for head and neck cancer: A prospective observational study. Int J Radiat Oncol Biol Phys 2010;76:1360-8.  Back to cited text no. 4
    
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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. 5
    
6.
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. 6
    
7.
Vásquez Osorio EM, Hoogeman MS, Al-Mamgani A, Teguh DN, Levendag PC, Heijmen BJ, et al. Local anatomic changes in parotid and submandibular glands during radiotherapy for oropharynx cancer and correlation with dose, studied in detail with nonrigid registration. Int J Radiat Oncol Biol Phys 2008;70:875-82.  Back to cited text no. 7
    
8.
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. 8
    
9.
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. 9
    
10.
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. 10
    
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Jensen AD, Nill S, Huber PE, Bendl R, Debus J, Münter MW, et al. A clinical concept for interfractional adaptive radiation therapy in the treatment of head and neck cancer. Int J Radiat Oncol Biol Phys 2012;82:590-6.  Back to cited text no. 11
    
12.
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.  Back to cited text no. 12
    
13.
Castadot P, Lee JA, Geets X, Grégoire V. Adaptive radiotherapy of head and neck cancer. Semin Radiat Oncol 2010;20:84-93.  Back to cited text no. 13
    
14.
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. 14
    
15.
Castelli J, Simon A, Louvel G, Henry O, Chajon E, Nassef M, et al. Impact of head and neck cancer adaptive radiotherapy to spare the parotid glands and decrease the risk of xerostomia. Radiat Oncol 2015;10:6.  Back to cited text no. 15
    
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Lee C, Langen KM, Lu W, Haimerl J, Schnarr E, Ruchala KJ, et al. Assessment of parotid gland dose changes during head and neck cancer radiotherapy using daily megavoltage computed tomography and deformable image registration. Int J Radiat Oncol Biol Phys 2008;71:1563-71.  Back to cited text no. 16
    
17.
Woodford C, Yartsev S, Dar AR, Bauman G, Van Dyk J. Adaptive radiotherapy planning on decreasing gross tumor volumes as seen on megavoltage computed tomography images. Int J Radiat Oncol Biol Phys 2007;69:1316-22.  Back to cited text no. 17
    


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  [Table 1], [Table 2], [Table 3], [Table 4]



 

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