|Year : 2014 | Volume
| Issue : 1 | Page : 10-14
Efficacy of radical radiotherapy alone for functional preservation of larynx in laryngeal carcinoma: A retrospective analysis
T Bhattacharyya, S Ghoshal, B Dhanireddy, R Kumar, SC Sharma
Department of Radiotherapy and Oncology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
|Date of Web Publication||18-Jun-2014|
Department of Radiotherapy and Oncology, Post Graduate Institute of Medical Education and Research, Chandigarh
Source of Support: None, Conflict of Interest: None
Purpose: Concurrent chemoradiation is the current standard of care in locally advanced head and neck cancer. But, in our setup, many patients of carcinoma larynx are treated with only radical radiotherapy because of poor general condition of the patients. This study was performed to assess the influence radical radiotherapy alone on functional preservation of larynx. Materials and Methods: 110 previously untreated patients with invasive squamous cell carcinoma of larynx were treated with radical radiotherapy alone between January 2006 and June 2009. Conventional one daily fraction of 2 Gy with total doses of 60-66 Gy was used. Voice preservation and local control at median follow-up period of 2 years were analyzed. Several host, tumor, and treatment parameters were also analyzed. Results: Among 110 patients, preservation of larynx was possible in 78 patients (71%). With radical radiotherapy alone, excellent preservation of larynx was achieved in stage I (88.9%) and stage II (75%) disease, while in advanced stages, results were not so encouraging. In stage III and stage IVA, larynx preservation was only 72.4% and 65.3%, respectively. Patients without any cartilage invasion had significantly better laryngeal preservation rate as compared to patients with cartilage invasion. (78.9% vs. 35.3%; P = 0.008). Conclusion: Though concurrent chemoradiation is the standard of care in preservation of voice in laryngeal cancer, definitive radiotherapy alone may also be a good option in terms of preservation of larynx in patients of laryngeal cancer in community practice in the developing world where most of the patients cannot tolerate concurrent chemoradiation.
Keywords: Carcinoma larynx, laryngeal preservation, radiotherapy
|How to cite this article:|
Bhattacharyya T, Ghoshal S, Dhanireddy B, Kumar R, Sharma S C. Efficacy of radical radiotherapy alone for functional preservation of larynx in laryngeal carcinoma: A retrospective analysis. Indian J Cancer 2014;51:10-4
|How to cite this URL:|
Bhattacharyya T, Ghoshal S, Dhanireddy B, Kumar R, Sharma S C. Efficacy of radical radiotherapy alone for functional preservation of larynx in laryngeal carcinoma: A retrospective analysis. Indian J Cancer [serial online] 2014 [cited 2020 Dec 2];51:10-4. Available from: https://www.indianjcancer.com/text.asp?2014/51/1/10/134600
| » Introduction|| |
Cancer of the larynx represents about 2% of the total cancer risk and is the most common head and neck cancer. Laryngeal cancer occurs in roughly 12,000 Americans per year, accounting for approximately one fourth to one third of all head and neck cancer cases.  Management of cancers of the larynx is a special challenge for head and neck oncologists. Laryngeal cancer even in advanced stages has a relatively high cure rate if managed appropriately. Because of this factor, it has become the paradigm for the concept of organ preservation in oncologic patient management. Curing the patient is not the only consideration in the management of this disease. Voice preservation and avoidance of tracheal stoma are important priorities.
The importance of preserving speech and swallowing function in patients of laryngeal carcinoma cannot be overstated. Organ preservation has intuitively been considered a favorable outcome of radiation and chemotherapy treatment strategies as an alternative to primary laryngectomy. The feasibility of preserving laryngeal function for patients of laryngeal carcinoma by non-surgical approaches without jeopardizing survival has been shown by different trials. , Concurrent chemoradiation (CRT) is currently thought to be the standard of care in head and neck cancer, both in terms of locoregional control as well as preserving laryngeal function.  However, these improvements have come at the cost of increased acute and late toxicities. In developing countries like ours, many a times, it is difficult to implement this optimum treatment strategy where average nutrition, built and general condition of the patients are poor. Therefore, in our set up, many patients are treated only with external beam radiotherapy. Is radical radiotherapy as sole modality very much inferior to chemoradiation for organ preservation? To find out the answer to this question, we have conducted a retrospective analysis to see the influence of radical radiotherapy (RT) alone on functional preservation of larynx in patients of laryngeal cancer.
| » Materials and Methods|| |
A retrospective review was performed of 110 patients of laryngeal carcinoma (both Ca glottis and Ca supraglottis) who had undergone radical radiotherapy alone as the sole treatment modality for stage I-IVA between January 2006 and June 2009. Patient inclusion criteria were a histologic diagnosis of infiltrative squamous cell carcinoma and no previous radiation delivered for head and neck neoplasms.
On detailed analysis of pretreatment work up, it was found that complete history was recorded and thorough physical exam including local exam of disease, neck examinations, indirect laryngoscopy, direct laryngoscopy, cytology, and biopsy were done. Baseline investigations like complete blood count, blood biochemistry were done. All patients had underwent dental checkup before radiation, and in patients who had undergone dental procedure, a minimum gap of 2 weeks was maintained between the procedure and beginning of radiotherapy. Radiographic examination including X-ray chest, X-ray soft tissue neck, and CT scan of head and neck were done. The patients were staged as per AJCC staging manual 2002.
During this period, patients were treated with external beam radiotherapy 60-66 Gy given with Co 60 beams or 4-6 Mv linac using bilateral parallel-opposed fields. Thermoplastic mask was used for immobilization in all the patients. Initially, the radiation portals encompassed primary disease, involved lymphnodes and microscopic disease around primary and in clinically uninvolved lymphnodes. Stage I and II glottis cancers were treated with small fields. Other than early-stage glottic cancers, in rest of the cases, whole neck along with primary disease was included in the radiation portals. After delivering 40 Gy in 20 fractions, the posterior neck field was reduced to spare spinal cord. Last 6 Gy boost was given to involved primary sites with primary echelon and involved lymphnodes (only gross disease).
The primary aim of our study was to assess the influence of definitive radiotherapy alone on functional preservation of larynx at a median follow up period of 2 years. We have also analyzed different prognostic factors that influence laryngeal preservation. It was an objective analysis, and disease-free larynx with grade 0 or grade I hoarseness and satisfactory swallowing function have been considered as functional preservation of larynx. Absence of CR (complete response) or more than grade I hoarseness (unsatisfactory speech) is considered as failure of laryngeal preservation.
The data were analyzed using Chi-square and t-test, and P values were calculated. For statistical analysis, data was arranged in excel format and was converted to SPSS format. 2-year laryngeal preservation and 2-year recurrence free survival were assessed. Survival curves were calculated using the method of Kaplan Meir. The results were considered statistically significant at the level of P < 0.05. In the univariate analysis, the variables analyzed include T stage, cartilage invasion, duration of symptoms, overall treatment time, site, sex, smoking status, and KPS score.
| » Results|| |
Patient characteristics [Table 1]
In this retrospective analysis, age of the patients was ranged between 31 and 80 years with median age of presentation being 59 years. There were 98 males (89%) and 12 females (11%).76 patients were of Ca supraglottis, and 34 patients were of Ca glottis with supraglottis to glottis ratio of 2.2:1. Most of the Ca glottis patients were of early stage, while Ca supraglottis presented mostly at late stage. Most of the patients were smokers (86/110).
Acute and late toxicities were analyzed according to RTOG toxicity criteria. Grade III acute skin reactions in the form of moist desquamation were seen in 12 patients (9.1%). The incidence of grade III mucositis in the form of confluent fibrinous mucositis was found in 14 patients (12.7%). Rate of radiation-related grade III laryngeal and pharyngeal toxicities were 16.3% and 20%, respectively. Late radiation-induced morbidity, mainly in the form of subcutaneous fibrosis, was seen in 8 patients.
Laryngeal preservation and analysis of prognostic factors [Table 2] and [Table 3]
At a median follow up of 2 years among 110 patients, overall laryngeal preservation was possible in 78 patients (71%). Out of 34 patients of Ca glottis, laryngeal preservation was possible in 28 patients (82.4%), whereas among 76 patients of Ca supraglottis, laryngeal preservation could be achieved only in 50 patients (65.8%). Larynx preservation of 88.9% and 75% were possible in stage I and II, respectively, but in stages III and IV, it was only 72.4% and 65.3%, respectively. Only 15 patients could not complete the treatment within 48 days. In this retrospective analysis, there was a better trend of laryngeal preservation in patients who had completed treatment within 48 days as compared to them who had completed their treatment in more than 48 days. Shorter overall treatment time could not achieve statistical significance (P = 0.239) as a prognostic factor for laryngeal preservation because of very small number of patients who had taken more than 48 days to complete their treatment.
Patients of T4 stage without any cartilage invasion had significantly better laryngeal preservation rate as compared to patients of T4 stage with cartilage invasion.(78.9% vs 35.3%; univariate analysis P = 0.008, multivariate analysis P = 0.007).
Laryngeal preservation rate was significantly higher in patients who had duration of symptoms for less than 6 months as compared to patients who had duration of symptoms for more than 6 months.(76% vs 58%; univariate analysis P = 0.044, multivariate analysis P = 0.08). Among 98 males, larynx was preserved in 67 patients, while in females out of 12 patients, larynx preservation was possible in 4 patients (P = 0.639). Among 86 smokers, larynx was preserved in 58 patients, and out of 24 non-smokers, larynx preservation was possible in 19 patients (P = 0.268). In our study, sex and smoking had no significant impact on functional preservation of larynx.
Local control and pattern of failure of preservation of Larynx [Table 4]
In early stages (stage I and II), excellent local control of around 90% was achieved. But, in advanced stage, local control was only 72.4% in stage III and 65.4% in stage IVA, respectively, we could achieve with radiotherapy alone. When we analyzed the patterns of failure of preservation of larynx, we found that there was local failure in 19 patients, local as well as nodal failure in 7 patients and only functional failure occurred in 7 patients. Only distant metastasis was seen in 5 patients. In our study, 2-year local recurrence-free survival was found to be 78% [Figure 1].
| » Discussion|| |
Larynx cancers are the most common malignancy of the upper aero digestive tract; they account for nearly 1% of all malignancies and approximately 25% of head and neck tumors. Primary glottic cancers are approximately 3 times more common than supraglottic tumors;  tumors of the subglottic larynx are exceedingly rare, accounting for approximately 1% to 2% of all larynx cancers. In Indian scenario, the situation is reverse where ca supraglottis is more common than glottic cancer.  In this retrospective analysis, the ratio of ca supraglottis and ca glottis is 2.2:1. The median age of patients presenting with larynx cancer is 65 years. Less than 4% of patients are younger than 45 years old. Laryngeal cancer remains predominantly a disease affecting men.  At diagnosis, nearly two thirds of patients with laryngeal cancer have their disease confined to the laryngeal structures and less than 10% present with distant metastases. In our study, median age of presentation is 59 years and 89% of patients were males. Most of the Ca glottis patients were of early stage, while Ca supraglottis presented mostly at advanced stage with cervical nodal involvement.
Larynx cancer is the most curable cancer of the upper aerodigestive tract and great strides, however, have been made with regard to organ preservation in the treatment of this disease, and the majority of patients are now treated with upfront organ preservation protocols.
The treatment objective for early invasive carcinoma of the larynx is to obtain cure with laryngeal preservation and optimal voice quality with minimal morbidity, expense, and inconvenience. Early stage cancers can effectively be treated with surgery or radiation. Treatment guidelines emphasize that every effort should be made to avoid combining surgery and radiation because functional outcomes may be compromised. There is no one modality that has proven superior with regard to all treatment goals. ,, Radical radiation is as effective as radical surgery in early stage with added advantage of voice preservation.
In most centers, irradiation is the initial treatment prescribed for T1 and T2 lesions, with surgery reserved for salvage after radiation therapy failure. , Although hemilaryngectomy or cordectomy produces comparable cure rates for selected T1 and T2 laryngeal cancers, irradiation is generally associated with better quality of voice. In different studies, it has been seen that the outcome of RT alone in stage I and stage II glottis ca is very high with high local control rate ranging from 85%-95% and 65%-80% respectively.  In 1974, Bataini and colleagues published an overall locoregional control rate of 76% for a relatively large series of patients with T1-2, N0-2 supraglottic carcinomas treated by RT alone.  Subsequent series reported control rates of 84% to 100% for T1 tumors.  Harrison and associates demonstrated that most of their patients irradiated for early vocal cord cancer maintained excellent voices.  In this retrospective study, rate of local control in stage I and II is found to be around 90% with functional preservation of larynx of 89% in stage I and 75% in stage II, respectively.
Locally advanced laryngeal cancers (stages III and IV) require radical surgery followed by external beam radiotherapy. Chemoradiation is an effective alternative for surgery and radiation when organ preservation is desired. The landmark trial conducted by Veterans Affairs group established the use of induction chemotherapy followed by radiotherapy as an alternative to laryngectomy for locally advanced laryngeal cancer. RTOG 91-11 study showed laryngeal preservation was best achieved with radiotherapy plus concurrent cisplatin. But, in all these trials, patients were of locally advanced stage where single modality was not efficient enough to achieve best disease control or organ preservation. , In our study, we have found that overall larynx preservation of 71% could be achieved with radiotherapy alone as the sole treatment modality in patients of stage I-IVA laryngeal cancer. In stage I and II, larynx preservation was excellent (89% and 75% respectively), but in stage III and stage IV, larynx preservation rates were not so promising (72.4% and 65.3% respectively). When compared with RTOG 91-11, our study does not show inferior results (intact larynx at 2 years with RT alone in RTOG study 70% vs. 72.4% and 65.3% in our study).
Therefore, stage is an important prognostic factor of laryngeal preservation. The other prognostic factors are site, cartilage invasion, duration of treatment, smoking etc. When analyzed according to disease sites, preservation of larynx was higher in Ca glottis (82.4%) as compared to Ca supraglottis (65.8%). Even in locally advanced Ca glottis, laryngeal preservation of 80% could be achieved, whereas we could achieve laryngeal preservation rate of only 63% in advanced supraglottic cancer. Therefore, radiation alone can be a good option for locally advanced glottis ca in terms of laryngeal preservation where combined modality cannot be considered due to different constraints.
Our study revealed that significant larynx preservation could be achieved in patients without cartilage invasion as compared to patients with laryngeal preservation (78.9% vs. 35.3%; P = 0.008). These subset of patients are candidates for total laryngectomy followed by post-operative radiotherapy. In the RTOG study also, they have not taken into consideration large volume T4 disease (defined as a tumor penetrating through the cartilage or extending more than 1 cm into the base of the tongue) in organ preservation protocol and were taken for radical surgery. 
This retrospective analysis revealed that duration of symptoms had significant impact on laryngeal preservation on univariate analysis (>6 months 77.8% vs. <6 months 57.9%; P = 0.044). But, patients who had increased duration of symptoms usually presented in late stage, which ultimately leads to poor outcome. Therefore, on multivariate analysis, it could not achieve statistical significance (P = 0.08).
In the study by Forastiere and his colleagues, both of the chemotherapy-based regimens suppressed distant metastasis and resulted in better disease-free survival than RT alone. (At 2 years, 91% were metastasis-free in NACT-RT arm, 92% were metastasis-free in CRT arm, 84% in the RT alone arm). The rates of local control were 64%, 80%, and 58% in the induction chemo followed by radiotherapy, radiotherapy with concurrent cisplatin, and radiotherapy alone arm, respectively. Locoregional control was significantly better in concurrent chemoradiation arm, but there was no significant difference between RT alone and induction chemotherapy followed by radiotherapy arm.  In our study, local control rate in stage III is around 72.4% and in advanced stages, it is found to be 65.4%, which is quite impressive when compared to western literature. When we have analyzed the pattern of failure of preservation of larynx in our patients, out of 33 patients, in which laryngeal preservation was not possible, 19 had local failure, 7 had local as well as nodal failure, and another 7 had only functional failure. 5 of our patients developed distant metastasis. 2-year local recurrence-free survival was 78%.
Regarding toxicity profile, RTOG 91-11 study  revealed that rate of high grade toxicity was greater with the chemotherapy-based regimens (81% with induction chemo followed by radiotherapy and 82% with radiotherapy and concurrent cisplatin vs 61% with radiotherapy alone). The mucosal toxicity of concurrent radiotherapy and cisplatin was nearly twice as frequent as the mucosal toxicity of other two treatments during radiotherapy. In our retrospective analysis, grade III mucositis was seen in 12.7% patients and grade III laryngeal and pharyngeal toxicity was seen in 16.3% and 20%, respectively. All these toxicities were transient and were managed conservatively. Radiation-induced late subcutaneous fibrosis was seen in only 8 patients.
It is important to remember that, in addition to showing the advantage of using chemotherapy with radiation, RTOG 91-11 trial also demonstrated that RT alone is a reasonable treatment option for patients who cannot tolerate chemotherapy. In addition, it is critical to remember that the benefits of adding chemotherapy must be tempered by the higher rates of treatment-related sequelae, some of which can be life-threatening. The benefit of concurrent chemoradiation may disappear in patients older than 70 years.  In addition, a pooled RTOG analysis showed that older age and larynx primary tumor site were associated with severe late toxicity.  Given that these patients are at greatest risk of toxicity, the use of chemotherapy in these patients needs to be further investigated. In our study, 10% of our patients were above 70 years of age where radiation alone can be a viable option for laryngeal preservation.
Our data suggest that radiotherapy alone can be sufficient in patients of Ca glottis and in early stage Ca supraglottis in terms of laryngeal preservation. For advanced stages of ca supraglottis, combined modality therapy either with chemotherapy or with altered fractionation may help to improve the outcome. T4 tumors with cartilage invasion are not suitable for organ preservation and those patients should be considered for radical surgery followed by post-operative radiotherapy for cure.
As a non-surgical means, radiotherapy alone can be an important tool for voice preservation in a large subset of patients of ca larynx, especially beneficial in a developing country like ours where general condition and performance status of the patients are very poor who are not always suitable for combined modality therapy.
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[Table 1], [Table 2], [Table 3], [Table 4]
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