Home About us Editorial board Ahead of print Current issue Search Archives Submit article Instructions Subscribe Contacts Login 


 
 Table of Contents  
ORIGINAL ARTICLE
Year : 2015  |  Volume : 11  |  Issue : 4  |  Page : 770-774

Conventional vs concomitant boost radiotherapy with concurrent cisplatin in advanced head and neck cancer


Department of Radiation Therapy and Oncology, Government Medical College and Hospital, Nagpur, Maharashtra, India

Date of Web Publication15-Feb-2016

Correspondence Address:
Sushil Dashrath Meshram
Department of Radiation Therapy and Oncology, Government Medical College and Hospital, Nagpur - 440 003, Maharashtra
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.154940

Rights and Permissions
 > Abstract 

Aim of Study: To compare outcome of concomitant boost therapy (CBT) with conventional radiotherapy with cisplatin as a radiosensitizer in advanced head and neck cancer.
Subjects and Methods: Prospective comparative study was undertaken. Patients were assigned alternately to ArmA (conventional arm) and ArmB (CBT arm), 30 in each arm and total 60 patients were enrolled.
Results: Out of 30 patients in conventional Arm A, 13 had complete response (CR; 43.33%), 9 had partial response (PR; 30%), three patients (10%) had stable disease (SD), and five patients (16.66%) had progressive disease (PD). In arm B out of 30 patients, 18 patients (60%) had CR, five patients (16.66%) had partial response (PR), four patients (13.33%) showed SD, and three patients (10%) had PD. There was no statistically significant difference between the two arms for CR (P - value = 0.196).
Conclusions: CBT can be used as an alternative to conventional RT in advanced head and neck cancers which minimize the total duration and the workload can be reduced. The locoregional control with CBT is comparable with the response of conventional RT.

Keywords: Concomitant boost technique, conventional radiotherapy, head and neck cancer


How to cite this article:
Meshram SD, Kamble KM, Diwan AK, Mohobia VK. Conventional vs concomitant boost radiotherapy with concurrent cisplatin in advanced head and neck cancer. J Can Res Ther 2015;11:770-4

How to cite this URL:
Meshram SD, Kamble KM, Diwan AK, Mohobia VK. Conventional vs concomitant boost radiotherapy with concurrent cisplatin in advanced head and neck cancer. J Can Res Ther [serial online] 2015 [cited 2019 Sep 21];11:770-4. Available from: http://www.cancerjournal.net/text.asp?2015/11/4/770/154940


 > Introduction Top


Head and neck cancer is the sixth most common type of cancer in the world, representing about 6% of all cancer cases. [1],[2] Males are affected significantly more than females with a ratio around 3:1. Buccal mucosa and tongue cancers are more common in the Indian subcontinent. [3],[4] Overall, 57.5% of global head and neck cancers occur in Asia, especially in India. Over 200,000 new cases and over 100,000 deaths occur each year in India. [5] It is accounted for 30% of all cancers. [6] The age standardized incidence rate is reported at 15.7 per 100,000 people, while most patients are between the age of 50 and 70 years. [7]

In the head and neck cancers, surgery and radiation therapy are curative treatments; while chemotherapy enhances the effects of irradiation, and routinely used as part of combined modality treatment. [8],[9] A locally advanced head and neck carcinoma, requires a multidisciplinary management. Primary surgery followed by adjuvant radio- and chemotherapy is considered as the standard approach. [9]

Conventional radiotherapy may not be the optimal treatment for head and neck squamous cell carcinomas. A major cause of failure in advanced rapidly growing tumors is the proliferation of clonogen cells. [10] To overcome this problem, various accelerated fractionation radiotherapy techniques came into practice but were associated with excessive acute reactions and therefore were not feasible. [10],[11] Concomitant boost therapy (CBT), despite being a variant of accelerated fractionation, is associated with minimal enhancement of acute reactions because it uses the concepts of accelerated fractionation while minimizing the volume of tissue that is irradiated with high doses. [11] Apart from this, it significantly reduces the total treatment time from 7 to 5 weeks. The aim of this study is to see the feasibility, tolerability, and comparison of CBT with conventional RT.


 > Subjects and methods Top


The study was carried out in the Department of Radiation Therapy and Oncology at our institute from November 2011 to October 2013. Total 60 patients were enrolled in this study, 30 in each arm, and a prospective study was carried out.

Inclusion criteria

  1. Histopathologically confirmed squamous cell carcinoma of head and neck cancer
  2. Union for International Cancer Control ( UICC) stage III and IVA
  3. No prior treatment in any form
  4. Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  5. Age less than 65 years
  6. No concurrent medical illness.


Exclusion criteria

  1. Patients having very large tumor size (T4)
  2. Large lymph node size (N3)
  3. Patients with distant metastasis (M1)
  4. Patients with nasopharyngeal cancer
  5. Pregnancy and lactating mothers.
All patients were made to undergo a complete pretreatment evaluation for the disease status. Radiological investigations were done to assess the extensions of disease. Computed tomography (CT) head and neck was done in selected patients.

A total dose of 63 Gy/35 fractions (180 cGy/fraction) for 7 weeks was planned for Arm A, while arm B received radiotherapy in the form of CBT to a total dose of 67.5 Gy/40 fractions. In this arm the large field was given 45 Gy/25 fractions (180 cGy/fraction) daily for 5 days a week for 5 weeks. The remaining 22.5 Gy/15 fractions (150 cGy/fraction) were given as a boost dose into the small field including primary and adjacent lymph node only. The boost was given every alternate day of the treatment, that is, on Monday, Wednesday, and Friday, after an interval of 4-6 h. Thus, total radiotherapy treatment was completed within 5 weeks. All patients in both the arms, received chemotherapy with inj. cisplatin 35 mg/m 2 weekly during the treatment for 6 weeks.

Acute toxicities due to radiation and chemotherapy were assessed weekly. The common acute toxicities were nausea and vomiting, mucositis, skin reaction, xerostomia, dysphagia, and dysgeusia. All acute toxicities were graded according to Common Terminology Criteria for Adverse Event (CTCAE) criteria version 4.0.

All the patients of both arms were evaluated after 1 month of completion of treatment. Local ultrasonography and CT was done for confirmation in selected cases. The overall response evaluation was done according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.0 criteria. Patients were followed-up at every 3 months for assessment of ECOG performance status, disease status, and complications.

Kaplan-Meier survival curve was plotted to compare overall survival rate and disease-free survival rate between two arms. Log-rank test was used for significance of equality of overall survival rate and disease-free survival rate between two arms. Statistical software STATA version 10.0 and SPSS Windows version 16.0 was used for statistical analysis.


 > Results Top


The pretreatment clinical characteristics are depicted in [Table 1]. All of the patients in both arms were of age more than 35 years and less than 65 years. The minimum age was 36 years and maximum age was 62 years in arm A as well as in arm B. The mean age was 50.63 ± 7.41 in arm A and 51 ± 7.71 in arm B. In each arm, 22 (73.33) were males and eight (26.66) were females. There was no statistically significant difference between the groups (P - value = 1.000, not significant (NS)). Clinical characteristics of the patients are shown in [Table 1].
Table 1: Clinical characteristics of the patients


Click here to view


Analysis of acute toxicities

Acute reactions were observed weekly in both arms. The grading was done according to the CTCAE 4.0 criteria. Nausea and vomiting was observed to be nearly the same in both arms. Grade 3 vomiting was seen in three patients (10%) of arm A and five patients (16.66%) in arm B. There was no statistically significant difference between the two arms (P - value = 0.448). Comparison of acute toxicities is shown in [Table 2].
Table 2: Comparison of acute toxicities


Click here to view


Analysis of overall tumor response

After 1 month of treatment, all the patients were called for follow-up. Post treatment ECOG performance status was recorded. There was no statistically significant difference between the two arms (P - value = 0.121). Overall tumor response compared in two arms is shown in [Table 3]. Out of 30 patients in conventional Arm A, 13 had complete response (CR; 43.33%), 9 had partial response (PR; 30%), three patients (10%) had stable disease (SD), and five patients (16.66%). In arm B out of 30 patients, 18 patients (60%) had CR, five patients (16.66%) had PR, four patients (13.33%) showed SD, and three patients (10%) had PD. There was no statistically significant difference between the two arms for CR (P - value = 0.196). Median duration of follow-up in arm A was 10.1 ± 2.59 months (range 5-16 months), while in arm B it was 9.5 ± 2.67months (range 5-15 months). There was no statistically significant difference between the two arms (P - value = 0.184).
Table 3: Overall tumor response compared in two arms


Click here to view


Analysis of overall survival at the end of 1 year of treatment

Out of 30 patients in arm A, 18 patients (60%) were alive and 12 patients (40%) dead; whereas in arm B, 21 patients (70%) were alive and nine patients were dead at the end of 1 year after completion of whole treatment. There was no statistically significant difference between the two arms (log-rank test value = 0.847, P - value = 0.357). At the time of analysis at 1 year, 18 patients were alive in arm A and 21 patients were alive in arm B, of which 10 and 13 patients had no evidence of disease, respectively. In arm A, 10 patients (33.33%) were without disease and 20 patients (66.66%) were with disease; while in arm B, 13 patients (43.33%) were without disease and 17 patients (56.66%) were with disease. There was no statistically significant difference between the two arms (log-rank test value = 0.719, P - value = 0.396). The overall survival rate was 70% in arm B, while in arm A it was 60%. There is no significant difference between two arms regarding the survival, that is, variable has no significant influence on overall survival rate (log-rank test value = 0.847, P - value = 0.357). The disease-free survival at 1-year in arm A was 33.33% and 43.33% in arm B. There was no statistically significant difference between two arms (log-rank test value = 0.719, P - value = 0.396).


 > Discussion Top


Overall tumor response as per RECIST 1.0 criteria

It was observed that CR was comparable in CBT arm with conventional arm. Out of 30 patients in conventional arm, 13 patients (43.33%) had CR, while in CBT arm 18 patients (60%) had CR. There was no statistically significant difference between the two arms for CR (P - value = 0.196). PR was seen in 10 patients (25%) in conventional arm and five patients (16.66%) in CBT arm. SD was observed in three patients (10%) in conventional arm and four (13.33%) in CBT arm. PD was observed in five patients (16.66%) in conventional arm and three patients (10%) in CBT arm.

Acute toxicities were observed weekly during the treatment in both arms. The most common acute toxicities were nausea and vomiting, mucositis, skin reaction due to radiation, xerostomia, dysphagia, and dysgeusia. The grading was done according to the CTCAE criteria version 4.0. The highest grade during the whole treatment experienced by each patient was noted as grade of toxicity for the respective patient.

In this study, nausea and vomiting was observed to be comparable in both arms. Most of the patients of both the arms experienced grade 2 vomiting. It was observed in 20 patients (66.66%) in conventional arm and 21 (70%) in CBT arm. It occurred mostly after the weekly cycle of cisplatin. These patients required IV fluid support with systemic antiemetics on daycare basis. All of them responded well to the supportive treatment and none of them required hospitalization. Grade 3 vomiting was seen in three patients (10%) of conventional arm and five (16.66%) in CBT arm (P - value = 0.448). In most of the patients, it was observed in 3 rd and 4 th week. These patients required hospitalization for IV fluid support and systemic antiemetics, aprepitants, etc., The median duration of hospitalization was 4 days. Most of the patients responded well to the treatment and did not require treatment interruption. Those who were not responding, recovered only after treatment interruption of concurrent chemotherapy cycle for 1 week.

The most common acute toxicity observed in both groups was grade 2 mucositis. Twenty-one patients (70%) in conventional arm and 15 patients (50%) in CBT arm developed grade 2 mucositis. In conventional arm, six patients (20%) developed grade 3 mucositis in the 3 rd and 4 th week and the duration of grade 3 mucositis was very small ranging from 2 to 5 days. These patients required hospitalization for administering intravenous (IV) fluids. In the CBT arm, 14 patients (46.66%) developed grade 3 mucositis. There was statistically significant difference between the two arms for grade 3 mucositis (P - value = 0.028). The maximum incidence of grade 3 mucositis was seen in the 3 rd week. These patients in CBT arm required IV fluid support because of grade 3 mucositis and were hospitalized for this purpose. Grade 3 mucositis persisted for a median duration of 4 days and subsequently subsided slowly with proper oral hygiene, systemic steroids, anti-inflammatory agents, and local analgesics. Maximum incidence of grade 3 mucositis was seen in the 3 rd week and persisted in three patients in the 4 th week. Two patients in conventional arm and six in CBT arm required treatment interruption for some fractions of radiotherapy. Most of the patient experienced grade 2 skin reaction in conventional as well as CBT arm. Twenty-one patients in conventional arm (70%) and 23 (76.66%) in CBT arm developed grade 2 skin reactions. Grade 3 skin reaction was seen in three patients (10%) in conventional arm and four (13.33%) in CBT arm (P - value = 0.688).

Seventeen patients (56.66%) in CBT arm and 13 in conventional arm (43.33%) had grade 2 × erostomia (P - value = 0.302). Only one patient (3.33%) in each arm experienced grade 3 × erostomia.

Grade 2 dysphagia was experienced by 17 patients (56.66%) in conventional arm and 12 (40%) in CBT arm. But grade 3 dysphagia was observed to be more, that is, 16 patients (53.33%) in CBT arm, while only seven (23.33%) in conventional arm. There was statistically significant difference between the two arms for grade 3 dysphagia (P - value = 0.017).

Grade 2 dysgeusia was seen in eight patients (26.66%) in conventional arm and 11 (33.33%) in CBT arm (P - value = 0.405).

Median duration of follow-up in conventional arm was 10.1 months (range 5-16 months), while in CBT arm it was 9.5 months (range 5-15 months). The overall survival rate in present study was 70% in CBT arm, while in conventional arm it was 60%. There was no significant difference between two arms regarding the survival (log-rank test value = 0.847, P - value = 0.357).

In the present study, overall survival rate at 1 year is more than the previous studies because we have considered overall survival at 1 year from completion of treatment; whereas in the previous studies, the overall survival was mentioned at 3 years. The disease-free survival rate at 1 year in the CBT arm (43.33%) was comparable with conventional arm (33.33%). There was no statistically significant difference between two arms (log-rank test value = 0.719, P value = 0.396). In the present study, disease-free survival at 1 year after treatment was less as compared to previous studies. [12],[13],[14],[15] This might be due to poor nutritional status of the patients which lead to locoregional failure.


 > Conclusions Top


CBT, an accelerated fractionation regimen, can be used as an alternative to conventional RT in advanced head and neck cancers, especially in the setting of developing country, where the total duration can be minimized and the workload can be reduced. The locoregional control after complete treatment with CBT is comparable with the response of conventional RT. Although CBT is associated with increased acute toxicities like mucositis and dysphagia than conventional RT, this fractionation regimen is tolerable in most of the patients. Severe acute toxicities with CBT can be managed with proper supportive treatment and treatment interruption is required only in few patients.

 
 > References Top

1.
Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin 2005;55:74-108.  Back to cited text no. 1
    
2.
Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010;127:2893-917.  Back to cited text no. 2
    
3.
Sankaranarayanan R, Masuyer E, Swaminathan R, Ferlay J, Whelan S. Head and neck cancer: A global perspective on epidemiology and prognosis. Anticancer Res 1998;18:4779-86.  Back to cited text no. 3
    
4.
Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin 2013;63:11-30.  Back to cited text no. 4
    
5.
Kulkarni MR. Head and neck cancer burden in India. Int J Head Neck Surg 2013;4:29-35.  Back to cited text no. 5
    
6.
National Cancer Registry Programme. Consolidated report of Hospital Based Cancer Registries (2004-2006). Indian Council of Medical Research, Bangalore, India; 2009.  Back to cited text no. 6
    
7.
Report/PreliminaryPages-PBCR2004-2005. Head and Neck Cancer in India 2013;4:29-35. Available from: http://Head and Neck Cancer Burden in India. [Last accessed on 2013].  Back to cited text no. 7
    
8.
Bonner JA, Harari PM, Giralt J, Azarnia N, Shin DM, Cohen RB, et al. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med 2006;354:567-78.  Back to cited text no. 8
    
9.
Chaukar DA, Das AK, Deshpande MS, Pai PS, Pathak KA, Chaturvedi P, et al. Quality of life of head and neck cancer patient: Validation of the European organization for research and treatment of cancer QLQ-C30 and European organization for research and treatment of cancerQLQ-H and N 35 in Indian patients. Indian J Cancer 2005;42:178-84.  Back to cited text no. 9
[PUBMED]  Medknow Journal  
10.
Bourhis J, Le Maitre A, Baujat B, Audry H, Pignon JP. Meta-Analysis of Chemotherapy in Head, Neck Cancer Collaborative Group, Meta-Analysis of Radiotherapy in Carcinoma of Head, Neck Collaborative Group, Meta-Analysis of Chemotherapy in Nasopharynx Carcinoma Collaborative Group. Individual patients' datameta-analyses in head and neck cancer. Curr Opin Oncol 2007;19:188-94.  Back to cited text no. 10
    
11.
Sanguineti G, Richetti A, Bignardi M, Corvo' R, Gabriele P, Sormani MP, et al. Accelerated versus conventional fractionated postoperative radiotherapy for advanced head and neck cancer: Results of a multicenter Phase III study. Int J Radiat Oncol Biol Phys 2005;61:762-71.  Back to cited text no. 11
    
12.
Fu KK, Pajak TF, Trotti A, Jones CU, Spencer SA, Phillips TL, et al. Radiation Therapy Oncology Group (RTOG) phase III randomized study to compare hyperfractionation and two variants of accelerated fractionation to standard fractionation therapy for head and neck squamous cell carcinomas: First report of RTOG 9003. Int J Radiat Oncol Biol Phys 2000;48:7-16.  Back to cited text no. 12
    
13.
Johnson CR, Scmidt-Ullrich RK, Wazer DE. Concomitant boost technique using accelerated superfractionated radiation therapy for advanced squamous cell carcinoma of the head and neck. Cancer 1992;69:2749-54.  Back to cited text no. 13
    
14.
Ghoshal S, Goda JS, Mallick I, Kehwar TS, Sharma SC. Concomitant boost radiotherapy compared with conventional radiotherapy in squamous cell carcinoma of the head and neck--a phase III trial from a single institution in India. Clin Oncol (R Coll Radiol) 2008;20:212-20.  Back to cited text no. 14
    
15.
Shrivastav K, Shrivastav M. Concomitant boost radiotherapy vs conventional radiotherapy in advanced oral cavity and oropharynx cancers. Indian J Radiol Imaging 2001;11:127-30.  Back to cited text no. 15
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

Top
 
 
  Search
 
Similar in PUBMED
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

  >Abstract>Introduction>Subjects and methods>Results>Discussion>Conclusions>Article Tables
  In this article
>References

 Article Access Statistics
    Viewed2039    
    Printed35    
    Emailed0    
    PDF Downloaded121    
    Comments [Add]    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]