|Year : 2016 | Volume
| Issue : 4 | Page : 483-486
Radical chemo-irradiation using intensity-modulated radiotherapy for locally advanced head and neck cancer in elderly patients: Experience from a tertiary care center in South India
JR Chalissery, PC Sudheeran, KM Varghese, K Venkatesan
Department of Radiation Oncology, Amala Institute of Medical Sciences, Thrissur, Kerala, India
|Date of Web Publication||21-Apr-2017|
Department of Radiation Oncology, Amala Institute of Medical Sciences, Thrissur, Kerala
Source of Support: None, Conflict of Interest: None
OBJECTIVE: To assess the feasibility, tolerance and response of radical chemo irradiation using Intensity modulated Radiotherapy [IMRT] in elderly patients [age >65] with locally advanced head and neck cancer. MATERIAL AND METHODS: Patients aged 65 and above [range 65 to 84years] registered in oncology outpatient unit in our institution between December 2011 to 2014, with stage III and IV head and neck cancer were treated with radical dose of radiotherapy using IMRT and concurrent chemotherapy with cisplatin 40mg/sq.m weekly. Response evaluation and toxicity profile assessment was done 6 to 8 weeks after completion of treatment and 3 monthly thereafter with median follow up of 3 years. RESULTS: Total number of patients analysed were 47. 43(91.5%) patients tolerated 66-.70Gy of radiotherapy and 4 or more cycles of weekly chemotherapy with cisplatin. First follow up evaluation at 6 to 8 weeks showed 81% patients having complete loco regional response. Grade III skin reaction and mucositis was noticed in 24% and 47% respectively. No grade III neutropenia observed. Median follow up of 3 years showed a complete local control in 53% and overall survival of 60%. CONCLUSION: Radical chemo irradiation with IMRT in elderly patients is a feasible option. Long term local control and overall survival benefits needs to be followed up.
Keywords: Chemo-irradiation, elderly, head and neck cancer, intensity-modulated radiation therapy
|How to cite this article:|
Chalissery J, Sudheeran P, Varghese K, Venkatesan K. Radical chemo-irradiation using intensity-modulated radiotherapy for locally advanced head and neck cancer in elderly patients: Experience from a tertiary care center in South India. Indian J Cancer 2016;53:483-6
|How to cite this URL:|
Chalissery J, Sudheeran P, Varghese K, Venkatesan K. Radical chemo-irradiation using intensity-modulated radiotherapy for locally advanced head and neck cancer in elderly patients: Experience from a tertiary care center in South India. Indian J Cancer [serial online] 2016 [cited 2020 Jan 29];53:483-6. Available from: http://www.indianjcancer.com/text.asp?2016/53/4/483/204785
| » Introduction|| |
Head and neck cancers are common in India and account for about 30% of cancers in males and about 13% in females. Worldwide, head and neck cancer accounts for more than 550,000 cases annually. Males are affected significantly more than females with a ratio ranging from 2:1 to 4:1. The incidence rate in males exceeds 20/100,000 in Indian subcontinent.,
A prevalence data of head and neck cancer in India shows that, 49% of patients are in fifty to sixty year age group and nearly 10% of patients belong to 70yrs and above. Management of a locally advanced head and neck cancer is always a challenge. Combined modality approach using radical radiotherapy and concurrent chemotherapy is considered to be the standard of care. An absolute survival benefit of 6.5% favoring concurrent chemoradiation was shown in meta-analysis of chemotherapy in head and neck cancer. All the clinical trials favoring chemoradiation included patients with a median age of <60 years.,,
According to the WHO data published in 2013, life expectancy in India is as follows: male 64.7, female 68.2, and total life expectancy is 66.4. In such situations, offering a combined modality treatment for an elderly person who is above 65 years is always questionable.
Apart from age factor, most of them have a lot of comorbidities that again affect their quality of life. Considering all these, elderly patients are treated with radical radiotherapy alone. With the help of modern techniques such as intensity-modulated radiation therapy (IMRT), toxicities of radiation treatment have been reduced significantly. This gives radiation oncologists the confidence for adding concurrent chemotherapy along with radical dose of radiation therapy. Hence, we at our center attempted giving concurrent chemotherapy even for elderly patients with locally advanced head and neck cancer who were undergoing IMRT.
| » Materials and Methods|| |
Patients registered in oncology outpatient clinic of our institution from December 2011 to December 2014, who satisfy the inclusion criteria (age >65 years; histologically proven inoperable squamous cell carcinoma of oral cavity, oropharynx, larynx, and hypopharynx of Stages III and IV  with performance score Eastern Co-operative Oncology Group of 0, 1, or 2 with normal liver, renal, and bone marrow function), were selected for the study. Those with sinonasal malignancies, parotid tumors, and nonsquamous cell carcinoma were not included in the study. A written informed consent for radical chemoirradiation was obtained from the patients. Pretreatment staging evaluation including clinical evaluation, biopsy from primary site or fine needle aspiration from clinically significant nodes, detailed ENT evaluation, computed tomography (CT) scan or magnetic resonance imaging (MRI) scan of head and neck, chest X-ray, and ultrasound abdomen was done. All patients had pre-RT dental consultation and clearance was obtained before starting radiotherapy. A cardiologist's opinion regarding the safety of cisplatin-based chemotherapy and hydration was taken for all patients before administering chemotherapy.
Toxicities and compliance to therapy during treatment period were recorded. The first follow-up was done after 6–8 weeks of treatment completion, and subsequent follow-ups were done 3 monthly for the first 2 years and 6 monthly thereafter.
All patients were treated with IMRT. Treatment planning was accomplished with the help of simulation CT scan done in treatment position. Patients were kept on a flat board with neck extended and immobilized with a thermoplastic mask. A contrast CT scan was acquired from vertex to mid-thorax up to the level of T6 vertebra with 3 mm slice thickness and zero pitch between the slices. The image set was transferred to radiotherapy treatment planning system, VARIAN Eclipse version 7 and 10.
Contouring of normal organs at risk was done according to the Radiation Therapy Oncology Group guidelines. The gross tumor volume (GTV) was contoured with the information from clinical evaluation findings and diagnostic CT or MRI scan findings. Clinical target volume (CTV) was defined as GTV plus microscopic disease areas. Combining a GTV expansion of 1.5–2 cm and high-risk nodal stations adjacent to involved nodes was done to create CTV1. CTV2 was considered low-risk nodal volume which was created according to the institutional protocol. An expansion of 0.5 cm was given to create PTV1 and PTV2. Dose prescribed was 60 Gy in 30 fractions to PTV1 (2 Gy/fraction) and 54 Gy in 30 fractions to PTV2 (1.8 Gy/fraction). Simultaneous intensity boost method was used for delivering this first phase of IMRT. After completing 30 fractions of treatment, a final boost dose of 10 Gy in 5 fractions was delivered to PTV boost volume created by giving 5 mm margin to GTV. A complete treatment plan dose would be 70 Gy in 35 fractions to PTV boost, 60 Gy in 30 fractions for PTV1, and 54 Gy in 30 fractions to PTV2.
Organs at risk were given dose constraints such as spinal cord maximum dose (Dmax) <45 Gy, brain stem (Dmax) <54 Gy, parotid mean dose (Dmean) <26 Gy, cochlea, optic nerve and optic chiasma (Dmax) <54 Gy, and temporomandibular joint (Dmax) <50 Gy.
IMRT planning was done with the help of treatment planning system Eclipse version 7 and 10. Algorithm used for inverse planning was AAA and Monte Carlo. Treatment plan was evaluated using dose-volume histograph and direct assessment of isodose distribution in each CT slice. PTV coverage of 95% volume covering 95%–100% of the prescribed dose was accepted, and dose constraints for normal organs at risk were also verified as mentioned before. Approved treatment plans are executed with the help of linear accelerators (Varian, Trilogy and Unique) using 6 MV X-rays. Treatment was delivered on a 5 days/week basis.
Cisplatin-based chemotherapy was planned for all patients. Dose given was 40 mg/m 2 on a weekly basis. Adequate hydration and premedication were given along with chemotherapy.
All patients were monitored weekly and assessment was done according to the Common Toxicity Criteria (Cancer Therapy Evaluation Program Common Toxicity Criteria, Version 2.0: DCTD, NCI, NIH, DHHS April 1999). Blood investigations - complete hemogram, renal and liver function tests were done on a weekly basis. Cisplatin was not administered if there was impairment in renal function.
Response assessment and follow-up
Response assessment was done by clinical evaluation and nasopharyngo-laryngoscopy. In suspicious cases, CT scan was done for confirmation of the response (Response Evaluation Criteria for Solid Tumours, version 1.0). All patients were advised to come for follow-up 6 weeks after treatment and for every 3 months in the 1st year, for every 6 months in the 2nd year, and every year thereafter. During follow-up visits, patients had clinical assessment and endoscopies to assess locoregional disease and also assessment for late radiation toxicities.
| » Results|| |
Majority of the patients who received radical chemo-irradiation in the age group above 65 years were men (male:female ratio - 40:7) and the median age was 70 years. All had locally advanced squamous cell carcinoma Stage III or IV. Majority had comorbidities including coronary artery disease, hypertension, and diabetes mellitus [Table 1].
The number of patients who had completed the full planned course of radiotherapy was 91.5% and the dose received by them ranged from 66 to 70 Gy. The number of cycles of chemotherapy received by the patients was in the range of 2–5 cycles and majority (91.5%) received 4 or more cycles of chemotherapy with weekly dose of cisplatin 40 mg/m 2. The total dose of cisplatin received by each patient during treatment period was also estimated. It was found that nearly 81% of patients tolerated 200 mg or more of cisplatin along with radiotherapy. Treatment duration ranges from 49 to 54 days. Gap given due to various reasons such as high-grade reactions or infections during treatment period was <1 week.
Major toxicities observed during treatment period were mucositis, skin reaction, and dysphagia [Table 2]. Grade III mucositis was observed in 47%, skin reaction in 24%, and dysphagia in 32% of patients. Neutropenia was rare and nearly 70% of the patients tolerated the chemotherapy without any significant neutropenia. Nearly 15% of patients developed Grade II neutropenia during the treatment period and no Grade III neutropenia was noticed. Few patients developed other systemic problems such as respiratory infection (4%), derangement of renal function (4%), and electrolyte imbalance (19%).
Responses of patients were assessed in each follow-up. The first assessment done at 6–8 weeks after completing the planned course of treatment showed 81% having complete response from the disease. Response rates vary in the subsequent follow-ups. A Kaplan–Meier graph was plotted to analyze the response in subsequent follow-ups [Figure 1]. Relation between the radical dose of radiotherapy and four or more cycles of chemotherapy receivers with complete response was evaluated. Among patients who received radical dose of radiotherapy, 88% showed complete response and 81% of patients who received four or more cycles of chemotherapy had complete response.
Regular follow-up of the patients was done and those found to have partial response or unable to complete the planned dose of radiotherapy were offered chemotherapy. Patients who recurred and developed secondary primaries were re-evaluated and treated as per their disease status. Median follow-up period was 36 months (range, 24–60 months). A survival curve was plotted with the help of follow-up data [Figure 2]. Three-year complete locoregional control was noticed in 53% of patients, and the overall survival was 60%.
| » Discussion|| |
Our data with 47 patients showed that concurrent chemo-irradiation is an effective tool in treating elderly patients with locally advanced head and neck cancer. There are few similar studies reported from other centers in India. However, they have included patients in Stage II to IV and multiple chemotherapy regimens had been tried in that series. Our study included patients with locally advanced head and neck cancer with Stage III and IV who definitely require a combined modality approach for better results in terms of local control and survival. Majority of the clinical trials we mentioned earlier used platinum-based chemotherapy regimens along with radiotherapy. Results of our study showed initial complete response rates of 81% which is better than earlier reported studies. Tolerance of patients for chemoirradiation was found to be encouraging. Nearly 91.5% of patients tolerated four or more cycles of concurrent chemotherapy and radical dose of radiotherapy, which was reflected well in their response to treatment.
In elderly patients, the treatment-related problems will affect their quality of life. Toxicities such as mucositis and associated pain and dysphagia cause major setbacks in their treatment compliance. Adequate measures to control pain and maintaining good nutritional support will be the ideal way to tackle this problem. Majority of the elderly population are particular about their dietary habits and they need an individualized approach to maintain it well. Early intervention during treatment will help to tackle this problem. Proper initiation of adequate analgesics and nutritional support with nasogastric tube feeding were found to be very effective in most of the patients.
IMRT is a very good tool to offer radical dose of radiotherapy in head and neck cancer. The major advantage of this technique, of achieving the dose constraints to various organs without compromising the dose distribution, can be much utilized for elderly patients. Toxicities such as mucositis, skin reaction, and dysphagia recorded in our study were lower than other standard head and neck studies., Achieving good dose homogeneity in all high-risk regions and avoiding high-dose regions in potentially painful sites can help the patients to maintain their normal diet without much difficulty.
Various chemotherapy regimens are being tried in locally advanced head and neck cancer. High-dose cisplatin alone or in combination with 5 fluorouracil was found to be the most commonly used concurrent chemotherapeutic agent. The incidence of Grade III neutropenia and other side effects was found to be high with those combinations. Elderly patients cannot tolerate these regimens due to their high rate of comorbidities. The benefit of using low-dose chemotherapy along with radiotherapy in head and neck cancer was also proven in few studies., Considering these situations, we tried low-dose weekly cisplatin in our elderly patients and it was found to be very well tolerated.
The 3-year follow-up data were also found to be very encouraging. Locoregional control was 53% and overall survival was 60%. These results are comparable with other reported standard trials.,,
Hence, by exploiting the benefits of IMRT technique and better efficacy of low-dose weekly cisplatin, this combination can be used in offering combined modality treatment for elderly patients (age >65) with locally advanced head and neck cancer. Their life expectancy and quality of life also can be maintained well with this type of combination.
| » Conclusion|| |
Option of combined modality treatment in locally advanced head and neck cancer for elderly patients is feasible. Judicious use of IMRT technique and ensuring a good dose distribution with careful analysis of treatment plan will help to deliver radical dose of radiation to elderly patients. A proper selection of concurrent chemotherapy regimens, preferably weekly cisplatin schedule, will be tolerated by these patients. Providing adequate nutritional support and managing symptoms during treatment period and later are the important factors to be considered.
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Conflicts of interest
There are no conflicts of interest.
| » References|| |
Sanghvi LD, Rao DN, Joshi S. Epidemiology of head and neck cancers. Seminars in Surgical Oncology 1989;5:305-9.
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics.CA Cancer J Clin 2011;61:69.
Bray F, Ren JS, Masuyer E, Ferlay SO. Global estimates of cancer prevalence for 27 sites in the adult population in 2008. Int J Cancer 2013;132:1133-45.
Lambert R, Sauvaget C, de Camargo Cancela M, Sankaranarayanan R SO Epidemiology of cancer from the oral cavity and oropharynx. Eur J Gastroenterol Hepatol 2011;23:633-41.
Abhinandan Bhattacharjee, A. Chakraborty, P. Purkaystha. Prevalence of head and neck cancers in the north east - an institutional study. Indian Journal of Otolaryngology and Head and Neck Surgery 2006;58:15-9.
Pignon JP, le Maà®tre A, Maillard E, et al
. Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): An update on 93 randomised trials and 17,346 patients. Radiother Oncol 2009;92:4–14.
Gilles Calais, Marc Alfonsi, Etienne Bardet, Christian Sire et al
Randomized Trial of Radiation Therapy Versus Concomitant Chemotherapy and Radiation Therapy for Advanced-Stage Oropharynx Carcinoma. J Natl Cancer Inst 1999;91:2081-6.
David J. Adelstein, Yi Li, George L. Adams, Henry Wagner, Jr, Julie A. Kish et al
An Intergroup Phase III Comparison of Standard Radiation Therapy and Two Schedules of Concurrent Chemoradiotherapy in Patients With Unresectable Squamous Cell Head and Neck Cancer. Journal of Clinical Oncology 2003;21:92-8.
Garden AS, Harris J, Vokes EE et al.
Preliminary results of radiation therapy Oncology group 97-03: A randomised pahse ii trial of concurrent radiation and chemotherapy for advanced squamous cell carcinoma of the head and neck. Journal of Clinical Oncology 2004;22:2856-64.
Edges SB, Compton CC. The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol 2010;17:1471-4.
Brouwera CL, Steenbakkersa RJMH, Bourhisb J, et al
. CT-based delineation of organs at risk in the head and neck region: DAHANCA, EORTC, GORTEC, HKNPCSG, NCIC CTG, NCRI, NRG Oncology and TROG consensus guidelines. Radiotherapy and Oncology. October 2015;117:83–90.
Kataria T, Gupta D, Bisht SS, et al
. Chemoradiation in elderly patients with head and neck cancers: a single institution experience. American Journal of Otolaryngology 2015;36:117–21.
Al-Sarraf M. Head and neck cancer: Present status and future prospects of adjuvant chemotherapy. Cancer Invest 1995;13:41-53.
Jeremic B, Shibamoto Y, Stanisavljevic B, Milojevic L, Milicic B, Nikolic N. Radiation therapy alone or with concurrent low-dose daily either Cisplatin or Carboplatin in locally advanced unresectable squamous cell carcinoma of the head and neck: a prospective randomized trial. Radiother Oncol. 1997;43:29-37.
Haselow RE, Warshaw MG, Oken MM, et al
. Radiation alone versus radiation with weekly low dose cisplatinum in unresectable cancer of the head and neck. In: Fee WE, Goepfert H, Johns ME, et al
, editors. Head and Neck Cancer. Toronto: BC Decker; 1990. p. 279-81.
[Figure 1], [Figure 2]
[Table 1], [Table 2]
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