TREATMENT MODALITY OF EARLY LARYNGEAL CANCER

COMPARISON OF VOICE QUALITY and COST EFFECTIVENESS AFTER ENDOSCOPIC CORDECTOMY USING MICRODISSECTION ELECTRODES WITH RADIOTHERAPY AND LASER CORDECTOMYABSTRACT

Mehmet Sürmeli, Cağatay Oysu, Ayşe Aslı Şahin Yılmaz, İldem Deveci, Burak Karabulut, Ahmet Volkan Sunter, Özgür Yiğit, Beyhan Ceylaner Bıcakçı

Objective: To compare acoustic parameters and cost effectiveness after endoscopic cordectomy using radiofrequency microdissection electrodes (ECRM) with transoral laser cordectomy and radiotherapy. Methods: Disease free 81 patients treated for early larynx carcinoma (30 with ECRM, 27 with transoral laser cordectomy, 24 with primary radiotherapy) were included in the study. Post-treatment voice analysis of all patients was performed. Additionally, the cost effectiveness of all treatment procedures was calculated. Results: GRBAS scale showed a significant difference between the groups (p<0.001). The mean values for perceptive assessment score for the radiotherapy group was significantly lower than the ECRM group (p<0.05). There was no significant difference between the ECRM group and the transoral laser cordectomy group in terms of the perceptive assessment score (p>0.05 for all). Percent jitter, percent shimmer and fundamental frequency (F0) after radiotherapy was significantly different than ECRM and transoral laser cordectomy (p<0.05). Maximum phonation time (MPT) in the radiotherapy group was significantly higher than the ECRM and transoral laser cordectomy groups (p<0.001). There was no significant difference between the ECRM group and the transoral laser cordectomy group in terms of the MPT (p>0.05). The mean cost of the ECRM technique was statistically lower when compared to other treatment techniques (p<0.05). In addition, the length of hospital stay after ECRM was statistically significantly shorter than laser cordectomy (p<0.05). Conclusion: Objective and perceptive voice analysis after ECRM is similar to transoral laser cordectomy, but worse than radiotherapy. Whereas cost effectiveness of ECRM was found to be better than other treatment techniques Keywords: Early Laryngeal cancer, voice quality, radiofrequency microelectrode, cost effectiveness

MİKRODİSSEKSİYON ELEKTROT ARACILI ENDOSKOPİK KORDEKTOMİ İLE RADYOTERAPİ VE LASER KORDEKTOMİNİN SES KALİTESİ VE MALİYET ETKİNLİĞİNİN KARŞILAŞTIRILMASI

ÖZET Amaç: Radyofrekans mikrodisseksiyon elektrot aracılı transoral kordektominin (ECRM) ses kalitesi ve maliyet etkinliğinin lazer kordektomi ve radyoterapi ile karşılaştırılması. Yöntemler: Erken glottik karsinom nedeni ile tedavi edilmiş 81 hasta çalışmaya dahil edildi. (ECRM: 30, transoral lazer kordektomi: 27, primer radyoterapi: 24. Tüm hastaların tedavi sonrası ses analizi yapıldı. Ek olarak, tüm tedavi prosedürlerinin maliyet etkinliği hesaplandı. Bulgular: GRBAS skalası gruplar arasında anlamlı bir fark gösterdi (p <0.001). Radyoterapi grubu için algısal değerlendirme skoru için ortalama değerler ECRM grubundan anlamlı olarak düşüktü (p <0.05). ECRM grubu ile transoral lazer kordektomi grubu arasında algısal değerlendirme skoru açısından anlamlı fark yoktu (p> 0,05). Radyoterapi grubunda yüzde jitter, shimmer ve temel ses frekansı (F0) ECRM ve transoral lazer kordektomiye göre anlamlı olarak farklıydı (p <0.05). Radyoterapi grubundaki maksimum fonasyon süresi (MPT) ECRM ve transoral lazer kordektomi gruplarından anlamlı derecede yüksekti (p <0.001). ECRM grubu ile transoral lazer kordektomi grubu arasında MPT açısından anlamlı fark yoktu (p> 0.05). ECRM tekniğinin ortalama maliyeti diğer tedavi tekniklerine göre istatistiksel olarak daha düşüktü (p <0.05). Ek olarak, ECRM'den sonra hastanede kalış süresi lazer kordektomiden istatistiksel olarak anlamlı derecede kısaydı (p <0.05). Sonuç: ECRM sonrası objektif ve algısal ses analizi transoral lazer kordektomiye benzer, ancak radyoterapiden daha kötüdür. ECRM'nin maliyet etkinliğinin diğer tedavi tekniklerinden daha iyi olduğu tespit edildi. Anahtar Kelimeler: Erken Larinks Kanseri, Ses kalitesi, radyofrekans mikreoelektrot, maliyet etkinliği

INTRODUCTION

Laryngeal cancer is the most common head and neck cancer with 75% of cases confined to the glottic level (1). Although the definition of early glottic cancers contains differences in the literature,. the most commonly used definition is the early T stage, such as T1 and T2. (1). Laryngofissure cordectomy, transoral laser surgery and external beam radiotherapy are the treatment modalities of early glottic laryngeal cancers.

Many studies have evaluated the best approach to management of early glottic cancers. Debate continues on the advantages and disadvantages of each modality in terms of local control, laryngeal preservation, survival, functional outcome and medical costs (2).

Since radiotherapy and transoral laser surgery have become the main treatment methods for early glottic carcinoma, many reports on optimal therapy for this disease have been published. For superficial midcord T1a lesions, evidence suggest that both modalities have comparable control rates and voice outcome (3,4). The choice should be based on patient and clinician preferences, general medical condition, and in the current health economic environment, cost of treatment (1,5).

Endoscopic transoral laser surgery using CO2 laser is widely used. An alternative to CO2 laser, endoscopic cordectomy using radiofrequency microdissection electrodes (ECRM), has been defined by Basterra et al in 2006 (5). The basic principle of this surgical procedure is the application of electrical current with a hard, small and focused metal (with the tip of the micro-electrode). (6). Basterra et al, in their various publications, have shown this surgery to be a useful, inexpensive alternative to CO2 lasers with much simpler equipment for the treatment of glottic and selected supraglottic tumors (5,7). They also showed that Vocal Cord tissue damage was similar in both laser cordectomy and microdissection electrode cordectomy. (6).

In our study, we aimed to compare the functional outcomes and cost effectiveness of ECRM, transoral laser cordectomy and radiotherapy, which are different treatment modalities in early glottic cancer cases. As far as we know, no study in English literature has previously compared the outcomes of using this method with radiotherapy and transoral laser cordectomy for the treatment early glottic cancers.

MATERIAL and METHODS

Patients

For the ECRM group, records of patients with T1a glottic cancer treated at XXX Otolaryngology Clinic between January 2013 and January 2017 were reviewed. Of these patients, those with recurrent or residual disease were excluded. Forty-four (44) patients were available for inclusion into the present study. Patients were contacted and asked to participate in this study to which 30 agreed.

Between December 2013 and November 2017, patients with single midcord lesions that did not extend to the anterior commissure (early glottic cancer [T1a] ) were primarily offered transoral laser cordectomy at XXX Otolaryngology Clinic. Forty-nine (49) patients were available for inclusion into the present study. Patients were contacted and asked to participate in this study to which 27 agreed.

For the radiotherapy group, records of patients with T1a glottic cancer treated at XXX Radiation Oncology Clinic between January 2012 and January 2016 were reviewed. Patients in whom the extent of the tumor could not be retrospectively determined and those with recurrent or residual disease were excluded. 40 patients were available for inclusion into the present study. Patients were contacted and asked to participate in this study to which 24 agreed.

All patients had biopsy shown squamous cell carcinoma.

The study protocol was reviewed and approved by the Ethics Committee (reference number 7389, approval date 11.05.15).

Treatment Procedures

Endoscopic Cordectomy Using Radiofrequency Microelectrodes (ECRM): The surgical procedure was performed with direct suspension laryngoscopy. Tissue resection was performed using a 21-cm-long radiofrequency Arrowtip tungsten monopolar needle with a straight and/or 90° and 180° angled tip and “CURIS®” Radiofrequency Generator (Sutter Medizintechnik, Freiburg, Germany). The generator was adjusted to a power of 15-25 watts and the "CUT1" monopolar cutting mode, depending on the response of the electrode to the tissue. The resection was performed as described by Basterra et al 5,7 and can be described as follows. The false vocal cord on the side of the tumor is clamped with a forceps and resected with a 180°-angled microelectrode. Resection of the vocal cord is performed using either the same microelectrode or the 90° microelectrode by an anteroposterior deep section over the lateral limit of the vocal cord, followed by up-down sections , first in the anterior commissure, second one in its attachment into the vocal process of the arytenoid cartilage. Endoscopic cordectomy using radiofrequency microelectrodes surgery corresponded to type 3 cordectomy (transmuscular cordectomy) according to ELS (European laryngeal society) classification (8).

Transoral Laser Cordectomy: Patients who underwent transoral laser cordectomy were hospitalized one day before the operation in order to complete the official purchase order procedures fort he laser equipment consumables. Endoscopic cordectomies were performed under general endotracheal anesthesia with Sharplan Lumenis 40C CO2 laser (Sharplan Lasers Inc. London, UK). The Carl Zeiss Surgical OPMI Sensera optical microscope (Carl Zeiss Meditec Inc. Dublin, CA) was used to perform this procedure.

External Beam Radiotherapy: The therapy was carried out by using a 6 MV photons linear accelerator to bilateral ports and one in front, with field sizes ranging from 5 x 5 to 6 x 6 cm. The radiation dose for treatment of T1 glottic carcinoma was 65–70 Gy ( 2.0 Gy per fraction). The average duration of radiotherapy was 33 days (SD: 2).

Assessment of Voice Quality and Function:

Recordings of speech and voice analyzes were made in a soundproof room. During recording, the distance between the microphone (Dynamic Rode® NT1; Rode, Sydney, Australia) and the mouth was at least 20 cm. The speech recording for perceptual analysis consisted of a phonetically balanced Turkish text (Jale's world- [Jale's world]), which was read and recorded in normal tone in each subject. The a / a / phoneme maintained for at least 3 seconds for acoustic analysis and the longest possible time after maximum inspiration for aerodynamic voice recording was used.

Perceptual analysis (GRBAS score)

Perceptual sound analysis was performed with the GRBAS score. For each parameter, evaluation was made between 0 and 3 points. On this scale, 0 represents normal sound quality, while high scores indicate worse sound quality. Recorded sound samples were evaluated as blind by 3 independent authors.

Acoustic analysis

The mean fundamental frequencies (F0 in Hertz [Hz]), percentage of jitter and percentage shimmer were determined. Multi-dimensionalvoice and speech analysis was performed with Praat speech processing software (University of Amsterdam, The Netherlands).

Cost effective analysis

For cost effective analysis, biopsy and treatment costs applied to all patients were calculated.After the biopsy and surgical procedures of the ECRM and Transoral laser cordectomy groups, treatment costs were obtained from the hospital database. The duration of total hospitalization time for each of the two treatment approaches were calculated. In addition, after the biopsy and outpatient treatment of the patients undergoing primary radiotherapy, the treatment costs were obtained from the hospital database. All treatment costs were calculated with the dollar / tl parity at the time of treatment. The treatment costs of all groups were compared with statistical analysis methods .

Statistical analysis

Differences between groups for statistical analysis of this study were calculated by the SPSS 22.0 program (IBM Corporation, New York, NY). Descriptive statistical analyzes were performed. Data were evaluated for normal distribution with the Kolmogorow-Smirnov Test. Fischer Exact test was used for statistical analysis of categorical variables. Kruskal Wallis and Mann Whitney-U Test were used for statistical analysis of quantitative data that were not normally distributed The statistical significance was set at p<0.05.

RESULTS

Patient characteristics for three groups are listed on table 1. The groups were similar with respect to sex, age and recurrence status.

Perceptual analysis (GRBAS score)

The mean scores for the perceptive assessment of the voice quality on the basis of GRBAS scale showed a significant difference between the groups as presented in Table 2 (p<0.001). The mean values for all parameters for the radiotherapy group was significantly lower than the ECRM and transoral laser cordectomy groups (P<0.01). But, there were no significant differences between the ECRM group and the transoral laser cordectomy group in terms of any of the parameters (p>0.05 for all).

Acoustic analysis

The findings of the acoustic analysis (comparison of the mean fundamental frequencies (F0 in Hertz [Hz]), percentage of jitter and percentage of shimmer) in all groups are presented in Table 3.

When the acoustic parameters of the three groups were compared, there were statistically significant differences in all parameters between the radiotherapy group and the other treatment procedure groups(p <0.05).

Aerodynamic efficiency analysis

Maximum phonation time (MPT) obtained from all groups are shown in Table 3. MPT in the radiotherapy group was significantly higher than the ECRM and transoral laser cordectomy groups (p<0.001). There was no significant difference between the ECRM group and the transoral laser cordectomy group in terms of the MPT (p>0.05).

Cost Effectiveness

The mean cost of the procedures were as follows; 767.85 ± 308.83 $ for ECRM, 1086.95 ± 250.22 $ for transoral laser cordectomy and 1350 ± 250.22 $ for radiotherapy and (Fig.1). The mean cost of ECRM was significantly lower than radiotherapy and transoral laser cordectomy (p<0.05 for both). The length of hospital stay after ECRM was 1.46 ± 0.5 days. The length of hospital stay after transoral laser cordectomy was 2.4 ± 0.57 days. The length of hospital stay after ECRM was statistically significantly shorter than transoral laser cordectomy (p<0.05). In addition, the mean duration of treatment for radiotherapy was 32.1 ± 1.7 days.

DISCUSSION

Selection criteria of treatment modalities for early glottic cancers include the post-treatment voice quality, the cure rate, larynx preservation rate, morbidity and the treatment cost (1). In our study, which included eighty-one (81) patients with T1a glottic squamous cell carcinomas, we demonstrated that the functional outcome of ECRM is similar to the transoral laser cordectomy, but is not as good as primary radiotherapy.

We have shown in our study that perceptual voice quality of subjects that underwent radiotherapy was better that those that underwent endoscopic or transoral laser cordectomy. Possible reason for this is the fact that ECRM surgery and transoral laser cordectomy in T1a tumors corresponded to type 3 cordectomy (transmuscular cordectomy) according to ELS (European Laryngeal Society) classification. Poorer voice quality after greater resections has previously been reported by others (9,10). In a recent, and first randomized study, Aaltonen et al have shown that overall voice quality achieved by transoral laser cordectomy and radiotherapy was roughly similar after treatments, however patients treated with radiotherapy had less breathy voice (11).

When comparing parameters of aerodynamic voice analysis between the three groups in our study, we have shown that maximum phonation time was significantly longer in subjects undergoing radiotherapy. In a meta-analysis by Abdurehim et al, comparison of laser cordectomy and radiotherapy with respect to maximum phonation time was not statistically significant, but there was an obvious trend toward favoring radiotherapy (2).

In our study, there was no significant difference between patients treated with ECRM or transoral laser cordectomy and those treated with radiotherapy with respect to mean fundamental frequencies (F0 in Hertz [Hz]), percentage of jitter and percentage of shimmer. Results of a previous meta-analysis in the subgroup of F0 favored radiotherapy (2). With respect to jitter and shimmer, overall pooled effect in the same meta-analysis showed no significant difference between laser cordectomy, but there was a slight trend favoring radiotherapy (2).

In the literature, there are many studies comparing sound quality after endoscopic laser surgery or radiotherapy. In their meta-analysis, Abdurehim et al. revealed no significant differences between the acoustic analysis parameters of patients treated with both endoscopic laser surgery and radiotherapy(2), but larynx preservation rate was significantly higher in patients initially treated with endoscopic laser cordectomy. Another recent systematic review indicated that greater resections with laser obviously show poorer voice quality than those in lesser resections (12).

ECRM has been defined by Basterrra et al in 2006 for the treatment of early glottic cancers, as an alternative to CO2 laser (5). There are many advantages when ECRM technique is compared with Endoscopic Laser Cordectomy. The microelectrodes used for the ECRM technique can be reused and require no special equipment other than the microelectrodes. Laser surgery requires an experienced surgical team, safety precautions and special instruments whereas radiofrequency arrowtip electrodes do not require any of these measures . The radiofrequency tips are reusable. We have been performing ECRM at our clinic since 2012 for the treatment of T1a glottic tumors. ECRM in our experience is a useful and inexpensive alternative to laser cordectomy. As stated by Basterra et al (13), the handling of the microelectrode device is very simple and the system is familiar to the operation team. The cost of the equipment and the microelectrode is overwhelmingly low. Radiotherapy, on the other hand, has always been another treatment choice for our patients. Good local control rates and functional outcome has been obtained with this therapy, however, the dose received by the tumor free laryngeal structures has always been a matter of concern (14). Narayana A et al. performed a study in patients with successfully treated glottic cancer (stage 1a). They found that the frequency of a second primary tumor in the 5,10 and 15th year was 23%, 44% and 48.7%, respectively. (15). New techniques such as single cord irradiation have been offered for the sparing of the critical perilaryngeal tumor free structures (14,16). Another main disadvantage of radiotherapy is that the duration of treatment is longer. Type 3 cordectomy using radiofrequency microelectrodes resulted in a poorer voice quality than radiotherapy, however one should keep in mind that ECRM is a highly focused treatment for a clinical target volume, while conventional radiotherapy affects both vocal cords and other structures around it. The cost and duration of radiotherapy is also significantly higher than ECRM.

Our study has some limitations. As stated in the methods section, the choice between the three treatment modalities was not randomized and depended on the preference of the surgeon or the patient and the availability of radiofrequency electrodes. It should also be mentioned that since we were not able to evaluate the patients’ subjective and objective measurements preoperatively, a comparison between groups in terms of the amount of post treatment change in these parameters was not possible.

CONCLUSIONS

The results of our study revealed that maximum phonation time, after radiotherapy treatment is longer than ECRM and transoral laser cordectomy. Percent jitter, percent shimmer and fundamental frequency (F0) after radiotherapy was significantly different than ECRM and transoral laser cordectomy. In addition, ECRM group has lower costs and shorter hospital stay time than other treatment modalities. According to these findings, ECRM seems to be advantageous because of the lower cost of treatment and hospitalization period in patients with early stage laryngeal cancer. However, radiotherapy seems to be a more suitable treatment option in patients where sound quality is more important.

Conflict of Interest : All Authors confirm that there is no conflict of interest in this article

Funding Source: None

Sponsorships: None

REFERENCES

1. Higgins KM. What treatment for early-stage glottic carcinoma among adult patients: CO2 endolaryngeal laser excision versus standard fractionated external beam radiation is superior in terms of cost utility? Laryngoscope. 2011;121:116-34

2. Abdurehim Y, Hua Z, Yasin Y, et al. Transoral laser surgery versus radiotherapy: systematic review and meta-analysis for treatment options of T1a glottic cancer. Head Neck. 2012;34:23-33.

3. Yoo J, Lacchetti C, Hammond JA, et al. Head and Neck Cancer Disease Site Group. Role of endolaryngeal surgery (with or without laser) versus radiotherapy in the management of early (T1) glottic cancer: a systematic review. Head Neck. 2014;36:1807-19.

4. Greulich MT, Parker NP, Lee P, et al. Voice outcomes following radiation versus laser microsurgery for T1 glottic carcinoma: systematic review and meta-analysis. Otolaryngol Head Neck Surg. 2015;152:811-9.

5. Basterra J, Frías S, Alba JR, et al. A new device for treating laryngeal carcinoma using microdissection electrodes. Laryngoscope. 2006;116:2232-4.

6. Zapater E, Frías S, Pérez A, et al. Comparative study on chronic tissue damage after cordectomies using either CO2 laser or microdissection electrodes. Head Neck. 2009;31:1477-81.

7. Basterra J, Zapater E, Moreno R, et al. Electrosurgical endoscopic cordectomy with microdissection electrodes: a comparative study with CO2 laser. J Laryngol Otol. 2006;120:661-4.

8. Remacle M, Eckel HE, Antonelli A, et al. Endoscopic cordectomy. A proposal for a classification by the Working Committee, European Laryngological Society. Eur Arch Otorhinolaryngol. 2000;257:227-31.

9. Roh JL, Kim DH, Kim SY, et al. Quality of life and voice in patients after laser cordectomy for Tis and T1 glottic carcinomas. Head Neck. 2007;29:1010-6

10. Rydell R, Schalén L, Fex S, et al. Voice evaluation before and after laser excision vs. radiotherapy of T1A glottic carcinoma. Acta Otolaryngol. 1995;115:560-5.

11. Aaltonen LM, Rautiainen N, Sellman J, et al. Voice quality after treatment of early vocal cord cancer: a randomized trial comparing laser surgery with radiation therapy. Int J Radiat Oncol Biol Phys. 2014;90:255-60.

12. Van Loon Y, Sjögren EV, Langeveld TP, et al. Functional outcomes after radiotherapy or laser surgery in early glottic carcinoma: a systematic review. Head Neck. 2012;34:1179-89.

13. Basterra J, Reboll R, Zapater E. Eighty-three cases of glottic and supraglottic carcinomas (stage T1-T2-T3) treated with transoral microelectrode surgery: how we do it. Clin Otolaryngol. 2011;36:500-4.

14. Osman SO, Astreinidou E, de Boer HC, et al. IMRT for image-guided single vocal cord irradiation. Int J Radiat Oncol Biol Phys. 2012; 1;82:989-97.

15. Narayana A, Vaughan AT, Fisher SG, et al. Second primary tumors inlaryngeal cancer: results of long-term follow-up. Int J Radiat Oncol Biol Phys.1998;42:557-62.

16. Levendag PC, Teguh DN, Keskin-Cambay F, et al. Single vocal cord irradiation: a competitive treatment strategy in early glottic cancer. Radiother Oncol. 2011;101:415-9.

Table 1. Patient characteristics

Table 2. Comparison of the groups according to the auditory perceptual assessments using the GRBAS (G: Grade, R: Roughness, B: Breathiness, A: Asthenia, and S: Strain) scale

Table 3. Comparison of the groups according to the acoustic and aerodynamic efficiency analysis

Figure 1. Mean cost of treatment modalities for early glottis cancer. ECRM has a significantly lower cost than other treatment procedures (p<0.05)

ECRM: Endoscopic Cordectomy Using Radiofrequency Microelectrodes, USD: $