Treatment Outcome of Early-stage Laryngeal Carcinoma Treated with Radical Radiotherapy Using Different Techniques: A Retrospective Study

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Introduction
Early laryngeal cancer, especially of the glottis, is primarily a local disease, and radiotherapy is the main treatment used to preserve the larynx. Early glottic cancer (T1-T2) is a highly treatable disease with excellent survival rates. Available treatment options include CO 2 transoral laser microsurgery (CO 2 TOLMS), open partial laryngectomy (OPL), or radiotherapy (RT). To date, there is no clear evidence regarding the effectiveness of surgical treatment (CO 2 TOLMS and OPL) over RT, including a recent Cochrane analysis [1][2][3][4][5][6].
Radiation is the primary nonsurgical treatment for early stage glottic tumours (i.e., T1, T2/N0). Although radiotherapy techniques and doses may vary, a standard course of radiation for glottic cancer usually consists of

Treatment Outcome of Early-stage Laryngeal Carcinoma Treated with Radical Radiotherapy Using Different Techniques: A Retrospective Study
Tavseef Ahmad Tali 1 , Fiza Amin 2 , Javaid Ahmad Dar 3 , Shahid Rashid Sofi 1 , Mushtaq Ahmad Sofi 1 , Nazir Ahmad Khan 1 , Nazir Ahmad Dar 4 a total of 60-70Gy administered in single daily fractions over 6-7 weeks. Advantages of radiotherapy include the avoidance of surgery and the subsequent hospitalization. A useful voice is preserved in 80-95% of patients who were treated with radiation for an early glottic tumor. Of these patients, 80-90% are reported to have good-to-excellent voice quality. Radiation failures can be salvaged successfully with surgery.
Five years of local control rates are 85-94% for T1 glottic cancers and 70-85% for T2 with radical RT in the literature [7][8][9][10][11][12]. Since a randomized trial from Japan demonstrated better local control rates with hypo-fractionated RT regimens, the use of such treatment modalities became more common [13]. However, the apjcc.waocp.com Tavseef Ahmad Tali, et al: Early Stage Glottic Carcinoma increase in local control rates provided by different fractionation regimens and new RT techniques has no impact on overall survival rates. The implementation of new radiotherapy techniques such as carotid-sparing treatments has led to a decrease in non-malignant deaths and is used more often in the treatment of early-stage laryngeal carcinoma patients [14]. In this study, we evaluated the treatment outcomes and the prognostic factors of patients with early-stage glottic laryngeal carcinoma.

Patients
In this study, 25 cases with T1-T2/N0 glottic laryngeal carcinoma, who underwent radical RT between January 2017 to December 2021 were evaluated retrospectively. The median age of patients was 60 years, and a clear majority of them were men (96%). The histopathological diagnosis was squamous cell carcinoma.

Diagnosis and Staging
Patients were assessed with detailed head and neck and systemic physical examination, whole blood count, and chest X-ray. The patients were staged with direct laryngoscopy and biopsy under anaesthesia. In patients with anterior commissure involvement, the cartilage involvement was evaluated by computed tomography (CT).

Radiotherapy
Radical RT was applied to patients with stage I glottic carcinoma and stage II disease (inoperable, low performance, comorbid disease, or patient preference). Patients were treated with two-dimensional (2D) conventional technique, 3DCRT (three-dimensional conformal radiotherapy and IMRT (intensity modulated radiation therapy) techniques.

Statistics
Overall survival was calculated from the first day of diagnosis to the any cause of death. The locoregional failure event/time was used to calculate disease-free survival. Disease-free survival (DFS) is defined as the time from radiotherapy start, until disease recurrence or death. Stage and anterior commissure involvement were evaluated as prognostic factors. Survival analysis was done by using SPSS software with the Kaplan-Meier method.

Follow-Up
The treatment response and side effects were assessed at least once a week during RT. Response evaluation was done by flexible and/or direct laryngoscopy and CECT at 2-4 months after treatment. Follow-up was carried out every 2-3 months for the first 2 years after RT, every 6 months between 3 and 5 years.
Early and late side effects (according to RTOG/EORTC criteria) and the response assessment were carried out together with an ENT specialist and a radiation oncology specialist. Direct laryngoscopy and biopsy was performed in case of any pathologic findings. In any case of failure, each patient was evaluated individually and salvage treatments were planned accordingly.

Results
In our study we retrospectively analysed data of 25 patients who were treated for early glottis squamous cell carcinoma (T1N0M0/T2N0M0) with definitive radiation therapy using different techniques between January 2017 to December 2021. Out of 25 patients, 24 were males and 1 was a female. Mean age of the patients was 60 years. In 24 out of 25 patients, smoking was identified as a risk factor, and hoarseness of voice was identified as the most prevalent symptom.
All of these patients received radical radiation over a period of 6 weeks and 3 days with five fractions each week at a dose of 66 Gy in 33 fractions @ 2 Gy per fraction.

Discussion
Early-stage glottic laryngeal carcinomas can be cured by radical RT or local surgical excision. The treatment decision depends on the patient's preference as well as the technical possibilities and experience of the treatment team or the disease-specific features such as tumor location, single or bilateral vocal cord, and anterior commissure involvement.
In our study, 5 years of overall survival was 80% for the whole group and 91%, 80%, 62%for T1a, T1b and T2. Diseases free survival was 78% for the whole group and 88%, 75%, 59% for T1a, T1b and T2 respectively. These results are similar to those reported in many studies. Thariat et al. evaluated 155 patients with T1 and T2 glottic carcinomas. Overall survival was 75% for the whole group, 85% for T1a, 72% for T1b, 59% for T2. Disease-free survival was 68% for the whole group, These patients had a response assessment utilising CECT and direct laryngoscopy six weeks after the radiation treatment was finished. It was discovered that 21 patients (or 84%) had a full clinico-radiological response, while 4 patients had residual disease and required a partial laryngectomy as a result. Two of the four patients who had residual disorders after finishing radiation treatment had T2 lesions, while the other two had T1 lesions that had anterior commissure involvement.
Out of 25 patients 14 (56%) were treated with the conventional technique, 6 (24%) with 3DCRT and 4 (16%) with IMRT. The overall survival rate was the same regardless of the technique used. The most frequent acute toxicities observed in the majority of individuals were Grade 1 skin toxicity and odynophagia. None of them displayed late toxicity.
The mean and median overall and disease-free survival for patients with well-differentiated glottic squamous cell carcinoma in our study were [24,20] and [21,19] months, respectively. This survival was statistically significant (p<0.001) ( Table 2). 5 year overall survival (OS) and diseases free survival (DFS) for whole group was 80% and 78% ( Figure 1) and for T1a, T1b , T2 were found to be 91%, 80%, 62% and    [10]. In our study, stage and anterior commissure involvement are evaluated as prognostic factors in univariate analyses. Stage (p < 0.001) and anterior commissure involvement (p < 0.001) were found to be significant in overall survival and disease-free survival. Patients with T2NOMO and involvement of anterior commissure were having poor survival and these results were consistent with many other studies which determined that stage and anterior commissure involvement are the prognostic factors in early stage glottic carcinoma [16][17][18][19][20][21].
In our study, using conventional or conformal radiation techniques had no effect on overall survival and toxicity profile was also same proving none beneficial over the other.
In conclusion, radical radiotherapy remains an efficient option in the treatment of early glottic carcinomas providing a high local control rate with excellent functional results in laryngectomy-free patients, regardless of treatment techniques. This strategy should be discussed according to the tumour stage, feasibility of conservative surgery and patient's preferences.

Conflict of interest Nil
Funding Nil