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Year : 2015  |  Volume : 4  |  Issue : 2  |  Page : 216-219

Do we need to spare central nervous system structures during head and neck cancer intensity modulated radiotherapy?

Department of Radiation Oncology, Medanta-The Medicity Hospital, Gurgaon, Haryana, India

Date of Web Publication9-Mar-2015

Correspondence Address:
Trinanjan Basu
Department of Radiation Oncology, Medanta The Medicity Hospital, Sec. 38, Gurgaon - 122 001, Haryana
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2278-0513.148914

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Introduction: Fatigue has always been a distressing symptom for patients of head and neck cancer (HNC) on radiotherapy. Although modern technologies like intensity modulated radiotherapy (IMRT) have been instrumental in reducing many of the distressing side-effects but the recent observation of increased fatigue has been a concern. Recent publications though very few hinted at possible correlation with dosage to central nervous system (CNS) structures. The current resource review highlights a very preliminary example of a futuristic approach. Materials and Methods: This retrospective analysis comprising of 20 HNC patients receiving either postoperative or radical radiotherapy by IMRT were evaluated with CNS dosage. The main organs contoured in planning computed tomography (CT) scan were brainstem (BS) and posterior fossa (PF) excluding BS. The dose received to these organs was recorded. The literature reported CNS structure dosage, which can probably cause increased fatigue was assessed. Results: Among the 20 nonnasopharyngeal HNC, 13 received radical radiotherapy and 7 had postoperative radiotherapy. Six patients had treatment gap varying between 2 and 10 days, mostly due to hematological toxicities and oral mucositis. The median volumes of PF and BS were 263.5 and 25.1 cc. Dmax for BS and PF ranged between 4.8 and 44.76 Gy and 23.8-63.2 Gy and the median Dmean for PF was 8.89 Gy. Conclusion: Future prospective analysis with inclusion of modified brief fatigue inventory scale and dosimetric evaluation of CNS structures would probably answer the necessity of sparing CNS structures and spare patients from excessive fatigue and related consequences.

Keywords: Central nervous system dosage, fatigue, head and neck cancer, intensity modulated radiotherapy

How to cite this article:
Basu T, Kataria T, Goyal S, Gupta D, Sharma K. Do we need to spare central nervous system structures during head and neck cancer intensity modulated radiotherapy?. Clin Cancer Investig J 2015;4:216-9

How to cite this URL:
Basu T, Kataria T, Goyal S, Gupta D, Sharma K. Do we need to spare central nervous system structures during head and neck cancer intensity modulated radiotherapy?. Clin Cancer Investig J [serial online] 2015 [cited 2020 Feb 22];4:216-9. Available from:

  Introduction Top

Since last 10 years intensity modulated radiotherapy (IMRT) has become a standard of care in the management of head and neck cancer (HNC). The prospective randomized data are favoring better toxicity profile and in the long-term an improved quality of life (QOL) has been the biggest boon. [1]

Fatigue is a known occurrence among HNC patients and factors like younger age, advanced stage, associated depressive symptoms and re irradiation have all been implicated. [2] The patterns of symptomatology although differ between survivors and nonsurvivors of HNC. A recent article analyzed these issues and among the survivors there is improvement in different symptoms over time and European Organization for Research and Treatment of Cancer (EORTC) QOLQ-C30 and H and N35 were able to address these issues. [3],[4] The dosimetric evaluation, especially related to radiotherapy technique has not been assessed in detail. Especially with IMRT newer organs at risk (OAR) and their acute and late effects have become paramount in deciding patients overall QOL. Though incidental, but an important finding from PARSPORT trial was excessive fatigue among IMRT patients. Gulliford et al. have analysed the dosimetric explanation in this group of patients. [5]

This preliminary resource review attempts at evaluating dosimetric parameters of the central nervous system (CNS) structures among 20 nonnasopharyngeal cancer patients undergoing IMRT.

  Materials and methods Top

Twenty patients of HNC receiving postoperative (n = 7) and radical radiotherapy (n = 13) with IMRT were retrospectively reviewed. There were 4 females and 16 male patients. The median age of the patients was 57.5 years. The primary disease sites were oral cavity, [6] oropharynx, [5] larynx [5] and hypopharynx. [1] The details of the diagnosis of these 20 patients are given in [Table 1]. The IMRT dose planned was between 60 and 70 Gy with conventional fractionation and concurrent chemotherapy as per high-risk features. The OAR concerned was delineated in radiotherapy planning scans. Standard contouring guideline was followed while contouring brainstem (BS) and posterior fossa (PF) excluding BS.
Table 1: Details of the diagnosis

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From the approved IMRT plans of these patients' volumes of BS and PF and maximum dose received to them as well as the mean dose received to PF were noted. The radiotherapy review charts for these patients and also the hospital electronic database were looked for to identify any treatment break, grade 3 or more mucositis and oral infection, hospitalization and other adverse events. The adverse events and treatment breaks were an indirect sign of excessive fatigue as has been reported by various literature.

  Results Top

Among the 20 nonnasopharyngeal HNC, 13 received radical radiotherapy, and 7 had postoperative radiotherapy. Fourteen patients received concurrent chemotherapy with 11 out of them received cisplatin. There were three patients who had neo-adjuvant chemotherapy as well. Six patients had treatment gap varying between 2 and 10 days, mostly due to hematological toxicities and oral mucositis. These details are elaborated in [Table 2].
Table 2: Demographic profiles of the patients

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The median volumes of PF and BS were 263.5 (range: 157-350) and 25.1 (range: 21-40.2) cc respectively. Dmax for BS and PF ranged between 4.8 and 44.76 Gy and 23.8-63.2 Gy respectively. Similarly, the Dmean for PF ranged between 1.5 and 21.15 Gy and median of D mean was 8.89 Gy. The details of these are given in [Table 3]. There were 6 out of 20 patients who had treatment break varying between 2 and 10 days excluding Saturdays and Sundays (conventional fractionation was 5 fractions per week from Monday to Friday). The reasons for treatment interruption were excessive generalized weakness in all of them and it was secondary to either extensive mucositis more than grade 3 or low blood counts. In addition, three patients had hospitalization due to inadequate oral intake and repeated oral infections.
Table 3: Dosimetric characteristics

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When the individual six patients with treatment break were reviewed, four of them had PF Dmean more than 10 Gy and BS Dmax over 40 Gy. The same has been found in the recent Gulliford et al. article from patients of PARSPORT trial. [5]

  Discussion Top

Gulliford et al. in their retrospective analysis of PARSPORT data have concluded "the excess fatigue reported in the IMRT arm of the trial may, at least in part, be attributed to the dose distribution to the PF, cerebellum and BS." [1],[5] This aspect of cancer related fatigue is definitely a new observation.

Cancer related fatigue although has been reported in several literature. Age, concurrent chemotherapy, low hemoglobin percentage and comorbidities have all been documented to be instrumental in causation. In 1998 Smets et al. have indicated that baseline pain and disease related disability can cause long-term fatigue among cancer patients. [6] The depression and fatigue symptoms increase during radiotherapy and about 50% patients of HNC experience them. [7],[8]

The prospective documentation of fatigue among HNC patients have already been validated with modified brief fatigue inventory (MBFI) scale. [9] The scale actually analyses various aspects of cancer-related fatigue with common questionnaires in Likert pattern. It is easy to administer and can record fatigue objectively. Compared to fatigue specific scale, QOL scales like EORTC QLQ-C30 and QLQ-H and N35 questionnaires also reports about improvement in fatigue over time. [4],[5],[10] Different scales have also identified concurrent chemoradiation to be responsible for increased fatigue among HNC patients. [11] A recent Indian study also supported EORTC QLQ-C15-PAL questionnaire and reported median score of 50 for fatigue. [8]

The uniqueness of Gulliford et al. study was the dosimetric explanation of excessive fatigue among HNC IMRT patients. Recently, Powell et al. also analyzed the fatigue and dosimetric correlation among nasopharyngeal patients and basal ganglia, pituitary and cerebellum were additional OAR with significance to grade 2 fatigue been established. [12] We believe that our short and preliminary report among 20 Indian HNC patients and dosimetric data of BS and PF was encouraging in view of its uniqueness and international similarity to published literature. The challenge would be to a prospectively document fatigue with validated MBFI and correlate them with a dose received to CNS structures. The meticulous target delineation of the CNS OAR and their effective sparing, if attempted can reduce cancer related fatigue among HNC patients. This might help in reducing untoward side effects of the treatment and will result in compliance and better outcome.

  Conclusion Top

Fatigue and dosimetric explanation of the same among HNC patients is an ideal option for future IMRT planning. The validation with MBFI would rather answer many patient felt needs and probability of them can be identified at baseline. Prospective studies with large sample size and serial MBFI measurement and dosimetry of CNS structures is the need of the hour.

  References Top

Nutting CM, Morden JP, Harrington KJ, Urbano TG, 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.  Back to cited text no. 1
Rogers LQ, Courneya KS, Robbins KT, Rao K, Malone J, Seiz A, et al. Factors associated with fatigue, sleep, and cognitive function among patients with head and neck cancer. Head Neck 2008;30:1310-7.  Back to cited text no. 2
Sherman AC, Simonton S, Adams DC, Vural E, Owens B, Hanna E. Assessing quality of life in patients with head and neck cancer: Cross-validation of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Head and Neck module (QLQ-H and N35). Arch Otolaryngol Head Neck Surg 2000;126:459-67.  Back to cited text no. 3
Bjordal K, de Graeff A, Fayers PM, Hammerlid E, van Pottelsberghe C, Curran D, et al. A 12 country field study of the EORTC QLQ-C30 (version 3.0) and the head and neck cancer specific module (EORTC QLQ-H and N35) in head and neck patients. EORTC Quality of Life Group. Eur J Cancer 2000;36:1796-807.  Back to cited text no. 4
Gulliford SL, Miah AB, Brennan S, McQuaid D, Clark CH, Partridge M, et al. Dosimetric explanations of fatigue in head and neck radiotherapy: An analysis from the PARSPORT Phase III trial. Radiother Oncol 2012;104:205-12.  Back to cited text no. 5
Aynehchi BB, Obourn C, Sundaram K, Bentsianov BL, Rosenfeld RM. Validation of the modified brief fatigue inventory in head and neck cancer patients. Otolaryngol Head Neck Surg 2013;148:69-74.  Back to cited text no. 6
Smets EM, Visser MR, Willems-Groot AF, Garssen B, Schuster-Uitterhoeve AL, de Haes JC. Fatigue and radiotherapy: (B) experience in patients 9 months following treatment. Br J Cancer 1998;78:907-12.  Back to cited text no. 7
Sawada NO, de Paula JM, Sonobe HM, Zago MM, Guerrero GP, Nicolussi AC. Depression, fatigue, and health-related quality of life in head and neck cancer patients: A prospective pilot study. Support Care Cancer 2012;20:2705-11.  Back to cited text no. 8
Gandhi AK, Roy S, Thakar A, Sharma A, Mohanti BK. Symptom burden and quality of life in advanced head and neck cancer patients: AIIMS study of 100 patients. Indian J Palliat Care 2014;20:189-93.  Back to cited text no. 9
[PUBMED]  Medknow Journal  
Verdonck-de Leeuw IM, Buffart LM, Heymans MW, Rietveld DH, Doornaert P, de Bree R, et al. The course of health-related quality of life in head and neck cancer patients treated with chemoradiation: A prospective cohort study. Radiother Oncol 2014;110:422-8.  Back to cited text no. 10
Rosenthal DI, Mendoza TR, Fuller CD, Hutcheson KA, Wang XS, Hanna EY, et al. Patterns of symptom burden during radiotherapy or concurrent chemoradiotherapy for head and neck cancer: A prospective analysis using the university of texas MD anderson cancer center symptom inventory - Head and neck module. Cancer 2014;120:1975-84.  Back to cited text no. 11
Powell C, Schick U, Morden JP, Gulliford SL, Miah AB, Bhide S, et al. Fatigue during chemoradiotherapy for nasopharyngeal cancer and its relationship to radiation dose distribution in the brain. Radiother Oncol 2014;110:416-21.  Back to cited text no. 12


  [Table 1], [Table 2], [Table 3]


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