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ORIGINAL ARTICLE
Year : 2020  |  Volume : 16  |  Issue : 3  |  Page : 565-568

Correlation of planning target volume with mucositis for head-and-neck cancer patients undergoing chemoradiation


Department of Radiation Oncology, MS Ramaiah Medical College and Hospital, Bengaluru, Karnataka, India

Date of Submission22-Jul-2019
Date of Decision05-Sep-2019
Date of Acceptance19-Dec-2019
Date of Web Publication18-Jul-2020

Correspondence Address:
Janaki Gururajachar Manur
Department of Radiation Oncology, MS Ramaiah Medical College and Hospital, Bengaluru, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jcrt.JCRT_511_19

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 > Abstract 


Context: Head-and-neck cancer patients undergoing chemoradiation.
Aims: The aim of the study was to see if there is any correlation between the planning target volume (PTV) and mucositis.
Settings and Design: This was a single-arm prospective study.
Subjects and Methods: A total of forty head-and-neck cancer patients undergoing chemoradiation were assessed for mucositis at the 5th week. The grades of mucositis were correlated with PTVs of low risk (54 Gy) and high risk (60–66 Gy).
Statistical Analysis Used: The data were analyzed using the statistical software, SPSS Inc. Release 2009, predictive analytics software statistics for windows version 20.0, Chicago. Log transformation was done as the data were skewed. Independent t-test was used to compare between the two grades of toxicity. P <0.01 was considered for statistical significance.
Results: The mean PTVlow risk was 522cc (228–771) and PTVhigh risk was 254cc (20–780). Grade II mucositis was seen in 27 (67%) patients and Grade III in 11 (28%) patients. The mean PTVlow risk was higher for patients, who had Grade III compared to Grade II mucositis (571 vs. 517 cc, P = 0.052).
Conclusions: The same was seen for PTVhigh risk(367 vs. 222 cc, P = 0.017). PTV is a better predictor of mucositis, and those patients with larger PTV require close monitoring and early intervention of mucositis.

Keywords: Chemoradiation, mucositis, planning target volume


How to cite this article:
Manur JG, Vidyasagar N. Correlation of planning target volume with mucositis for head-and-neck cancer patients undergoing chemoradiation. J Can Res Ther 2020;16:565-8

How to cite this URL:
Manur JG, Vidyasagar N. Correlation of planning target volume with mucositis for head-and-neck cancer patients undergoing chemoradiation. J Can Res Ther [serial online] 2020 [cited 2020 Aug 3];16:565-8. Available from: http://www.cancerjournal.net/text.asp?2020/16/3/565/289973




 > Introduction Top


Head-and-neck cancers are one of the most commonly occurring malignancies in India, and about 60%–80% of the patients present with a locally advanced disease as compared to 40% in other developed countries.[1] Radiation therapy forms an integral part of multimodality approach that is used to treat such malignancies. Mucositis is the most common side effect of radiation therapy in head-and-neck cancer patients seen in almost 90% of patients with varied severity.[2] Symptoms usually peak during the 4th to 5th week of radiation therapy when patients tend to become malnourished and even forego further treatment. The malnutrition prevalence rate as a result of mucositis in head-and-neck cancer patients is as high as 74.2%.[3] Approximately 20% of the cancer patients do not succumb to the tumor itself, but as a consequence of malnutrition. There are many articles published regarding the medical management and supportive care of different grades of mucositis; however, there are fewer studies done to look into the details of the planning parameters.

Over the past few decades, radiation therapy has undergone a major transition from conventional technique using bony anatomy to conformal technique using imaging. Although the stage, the dose, and fractionation remain the same, the tumor volume varies not only from patient to patient but also within a given stage. An increase in the size by 1 cm increases the volume eight times. In the present era of conformal radiation therapy, the tumor volume receiving the prescribed dose can be quantified on the planning computed tomography (CT) scan. Ahlawat et al.[4] and Rutkowski et al.[5] have studied the effect of gross primary and/or nodal tumor volume on the treatment outcome. Tomasz observed in a study on T2 supraglottic tumors treated with radiation that a tumor volume of >9.7 cm3 was associated with a lower local control (P = 0.03) and overall survival (OS) (P = 0.0001). A suggestion was made to include additional treatment such as chemotherapy for bigger tumors.[5]

The gross tumor volume is expanded to clinical target volume to include possible microscopic disease. This expansion depends on the individual site, natural spread of the disease, and the chances of nodal involvement and is unique to a given primary, and so the volume is different for different sites. The prescription is always to the planning target volume (PTV). Our study is an effort toward understanding the relationship between the PTV, the grade of toxicity, and its impact on tolerance to the treatment.


 > Subjects and Methods Top


Ours is a prospective study which included forty histologically proven head-and-neck cancer patients from October 2016 to March 2018. Based on a study by Ahlawat et al., considering power of 90% and alpha error of 1%, a sample size of 40 was decided.[4] Patients receiving radiotherapy to a minimum dose of 60 Gy were included in the study. Patients with nasopharyngeal and early glottis tumors, with previous history of irradiation, with second malignancies, and with severe uncontrolled comorbidities were excluded from the study.

The patients underwent complete blood count, renal function tests, liver function tests, and serum electrolytes, followed by two-dimensional echocardiogram, if patient was planned for concurrent chemotherapy. The patients underwent a CT-based simulation and planning. They were treated with external beam radiation therapy to a dose of 60–66 Gy to the high-risk PTV (PTVhigh risk) and 54 Gy to the low-risk PTV (PTVlow risk in 30–33 fractions using three-dimensional (3D) conformal radiation therapy (CRT)/intensity-modulated radiation therapy (IMRT) techniques on 6MV linear accelerator (LINAC) with or without chemotherapy. The PTV volumes in cc were recorded from the planning CT scan and at the end of 5 weeks; the mucositis was graded using radiation therapy oncology group (RTOG) acute toxicity criteria for mucous membrane of both oral cavity and laryngopharynx.[6] The PTV was correlated with mucositis at the 5th week.

Statistical analysis

The data were analyzed using statistical software, SPSS Inc. Predictive Analytics Software Statistics for Windows version 20.0, Chicago, Illinois, USA. Log transformation was done as the data were skewed. Independent t-test was used to compare between the two grades of toxicity. P <0.01 was considered for statistical significance.


 > Results Top


The patient characteristics are as summarized in [Table 1]. The mean age of the patients was 55 years. There were 32 male and 8 female patients in our study. There were eight patients with Stage II, 13 patients with Stage III, and 19 patients with Stage IVA malignancies. There were 11 patients with oral cavity, nine patients with oropharyngeal, 14 patients with hypopharyngeal, four patients with laryngeal, and one patient each of nasal cavity and paranasal sinus malignancies.
Table 1: Patient, tumor, and treatment characteristics

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Among the forty patients, 26 (65%) were treated with radical radiation, whereas 14 (35%) received adjuvant radiation. Thirty-one patients received concurrent chemotherapy and nine patients were treated with only radiation. Among 31 patients, 16 (51.6%) completed all the planned cycles of chemo, 11 (35.4%) received four and three received three cycles, and one patient received two cycles only. Twenty eight (70%) patients received cisplatin, one patient carboplatin, and other two patients received one cycle cisplatin and remaining cycles of carboplatin in view of poor tolerance to cisplatin. The reasons for not completing the schedule were electrolyte imbalance in three and poor tolerance in ten patients.

The mean PTVhigh risk was 254cc (20–781), and the mean PTVlow risk was 522cc (228–771). At the 5th week, two patients had Grade I, 27 (67.5%) had Grade II, and 11 (27.5%) patients had Grade III mucositis as shown in [Graph 1]. The mean PTVlow risk was higher for patients who had Grade III compared to Grade II mucositis (571 vs. 517 cc, P = 0.052). The same was seen for PTVhigh risk(367 vs. 222 cc, P = 0.017), as shown in [Table 2]. Furthermore, 20 out of 27 (74%) patients who developed Grade II mucositis had received minimum of four cycles compared to 6 out of 11 (54.5%) patients with Grade III mucositis with P = 0.18.
Table 2: Correlation of planning target volume with grade of toxicity

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By the end of the treatment, a weight loss of 5%–10% was seen in 31 (77.5%) patients and >10% weight loss was seen in 8 (20%) patients. Those who had >10% weight loss had higher PTV volume with P value of 0.68 for PTVhigh risk and 0.14 for PTVlow risk compared to those who had 5%–10% weight loss. Twelve patients required either percutaneous endoscopic gastrostomy (PEG) tube 9 (22.5%) or nasogastric tube 3 (7.5%) feeding. The mean PTVhigh risk was higher for those who needed nutritional support compared to those who did not (255 vs. 251 cc), P = 0.94. Similar observation was seen in comparing the PTVlow risk(542 vs. 513 cc), P = 0.56.


 > Discussion Top


This prospective study was done on forty patients treated with radical radiation therapy with or without chemotherapy. Their PTVhigh risk was correlated with the grades of mucositis. Similar studies were conducted by Ahlawat et al.,[4] Tsou et al.,[7] Chen et al.,[8] Strongin et al.,[9] In the study by Strongin et al., primary tumor volume was correlated with treatment outcome in 78 patients treated with chemoradiation and concluded that the gross tumor of <35cc, had a better progressionfree survival (61% vs. 33%, P = 0.004) and OS (84% vs. 41% P = 0.001).respectively. It was interesting that T and N stages were not significant predictor of the outcome.[9] TSou et al. correlated gross tumor volume with the OS and found that above a cutoff of 19cc, the survival dropped from 78.3% to 39.3%.[7] Chen et al. not only studied the outcome but also studied the mucositis like us.[8]

The American Joint Committee on Cancer tumor/node/metastasis (TNM) staging takes into account the size of the tumor to determine the stage of the disease but does not take the 3D tumor load into account, so patients with the same TNM stage may have different tumor volumes. In general, the outcomes are reported for a particular stage while Allen et al., in their study over 7 years of patients treated with 5 mm and 3 mm expansion to PTV, concluded that locoregional control was not different with 78% Vs 80% (P = 0.75) respectively. Marginal recurrence and Grade III mucositis in both groups of 5 mm versus 3 mm were similar. Gastrostomy tube requirement was 30% in both groups (P = 0.36) at the end of treatment with IMRT, and it did not depend on the T or N staging. In our study, 12 patients required nasogastric or PEG placement. Our observation was that increase in PTV increased the chances of Grade III mucositis and also requirement for additional nutritional support. We measured the actual volume while they spoke in terms of 5 mm versus 3 mm expansion.

Mallick et al. in their retrospective study of 103 patients concluded that a PTVhigh risk of >235cc and <235cc, PTVlow risk of >615cc and <615cc had a significantly higher (31% vs. 14.3%, P = 0.05; 38.6% vs. 6.5%v, P = 0.001) mucositis, respectively. They also observed that smaller PTV, CRT, or larger PTV was associated with 0%, 30.3%, 56.9% (P < 0.001) chances of >5% weight loss, respectively, between 1st day and at 1 month after completion of radiation. Similar findings were noted in our study also.[10]

An important observation was found when we correlated PTV and grades of mucositis with number of patients receiving four or more chemotherapy cycles. The mean PTV was lesser in patients getting Grade II compared to Grade III mucositis. Even though more patients had received four or more cycles in the Grade II mucositis group, the toxicity was not higher. Hence, the logical interpretation is that PTV is a stronger predictor of mucositis compared to the severity of chemotherapy. However, this needs to be studied with more patients.

The strength of our study is that this is a prospective study. Except for one patient, a minimum of three chemotherapy cycles were completed, and all patients completed radiotherapy as scheduled. One of our limitations is that we correlated at one point only, while subsequent assessment could have given us a better understanding.


 > Conclusions Top


In addition to the standard management of mucositis, the documentation of PTV volume during plan evaluation and close monitoring of patients with larger PTV helps in identifying those patients who are likely to have greater mucositis. Early intervention in terms of additional nutritional supplementation and titrating chemotherapy cycles for these patients helps in better compliance for treatment, which may translate to a better long-term outcome.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 > References Top

1.
Sarin R. Indian National Cancer Control Programme: Setting sight on shifting targets. J Cancer Res Ther 2005;1:240-8.  Back to cited text no. 1
    
2.
Carper E, Fleishman SB, McGuire M. Symptom management and supportive care for head and neck cancer patients. In: Harrison LB, Sessions RB, Hong WK, editors. Head and Neck Cancer: A Multidisciplinary Approach. Philadelphia: Lippincott, Williams, and Wilkins; 2004.  Back to cited text no. 2
    
3.
Kang WX, Li W, Huang SG, Dang Y, Gao H. Effects of nutritional intervention in head and neck cancer patients undergoing radiotherapy: A prospective randomized clinical trial. Mol Clin Oncol 2016;5:279-82.  Back to cited text no. 3
    
4.
Ahlawat P, Rawat S, Kakria A, Chauhan D, Tandon S, Jain S, et al. Tumor volumes: Predictors of early treatment response in locally advanced head and neck cancers treated with definitive chemoradiation. Int J Radiat Oncol Biol Phys 2012;82:1823-30.  Back to cited text no. 4
    
5.
Rutkowski TW, Maciejewski B, Kołosza Z, Wygoda A, Składowski K, Hejduk B, et al. The effect of tumor volume on radiotherapy outcome and correlation with other prognostic factors in patients with T2 supraglottic cancer. Contemp Oncol (Pozn) 2014;18:429-35.  Back to cited text no. 5
    
6.
Trotti A, Byhardt R, Stetz J, Gwede C, Corn B, Fu K, et al. Common toxicity criteria: Version 2.0. An improved reference for grading the acute effects of cancer treatment: Impact on radiotherapy. Int J Radiat Oncol Biol Phys 2000;47:13-47.  Back to cited text no. 6
    
7.
Tsou YA, Hua JH, Lin MH, Tsai MH. Analysis of prognostic factors of chemoradiation therapy for advanced hypopharyngeal cancer – Does tumor volume correlate with central necrosis and tumor pathology? ORL J Otorhinolaryngol Relat Spec 2006;68:206-12.  Back to cited text no. 7
    
8.
Chen AM, Yu Y, Daly ME, Farwell DG, Benedict SH, Purdy JA. Long-term experience with reduced planning target volume margins and intensity-modulated radiotherapy with daily image-guidance for head and neck cancer. Head Neck 2014;36:1766-72.  Back to cited text no. 8
    
9.
Strongin A, Yovino S, Taylor R, Wolf J, Cullen K, Zimrin A, et al. Primary tumor volume is an important predictor of clinical outcomes among patients with locally advanced squamous cell cancer of the head and neck treated with definitive chemoradiotherapy. Int J Radiat Oncol Biol Phys 2012;82:1823-30.  Back to cited text no. 9
    
10.
Mallick I, Gupta SK, Ray R, Sinha T, Sinha S, Achari R, et al. Predictors of weight loss during conformal radiotherapy for head and neck cancers – How important are planning target volumes? Clin Oncol (R Coll Radiol) 2013;25:557-63.  Back to cited text no. 10
    



 
 
    Tables

  [Table 1], [Table 2]



 

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