COMPARATIVE STUDY BETWEEN SELECTIVE NECK DISSECTION AND RADIOTHERAPY IN THE MANAGEMENT OF CLINICALLY NODE NEGATIVE NECK IN CASES OF HEAD AND NECK CANCERS

COMPARATIVE STUDY BETWEEN SELECTIVE NECK DISSECTION AND RADIOTHERAPY IN THE MANAGEMENT OF CLINICALLY NODE NEGATIVE NECK IN CASES OF HEAD AND NECK CANCERS

By

Mohammed Abd El Rahman Shams El Deen*, Eid Rizk Al Gammal**,

Said Hosny Al Bendary**, Ahmed Youssef Abdulhakeem**,

Ramadan Hassan Alfar*** and Lobna Rashed Ezz Al Arab****.

Departments of Otorhinolaryngology*, Surgical Oncology, **and General Surgery***

Al Azhar University, Radiotherapy**** – Ain shams University

ABSTRACT

Background: The management of clinically node negative neck (cN0) remains a matter of controversy. The used methods of treatment are observation and follow up and treating the neck when clinical metastasis developed, prophylactic radiotherapy, or elective neck dissection. Many surgeons prefer the elective surgical intervention because of the increasing incidence of clinically node negative neck having occult metastatic lymph nodes.

Objective: The aim of this study was to compare between the efficacy of both elective neck dissection and elective neck irradiation in the management of clinically node negative neck (cN0) of patients with squamous cell carcinoma of head and neck, and to determine which type of treatment improves the 2- year survival, disease-free survival and loco-regional control rates.

Patients and Methods: During the period from 2012-2015, this prospective study was done at Al- Azhar University hospitals (Otorhinolaryngology Department, and Surgical Oncology Unit) on 50 patients diagnosed to have clinically node negative neck (cN0) of squamous cell carcinoma of head and neck randomized into two groups, 25 of them managed by selective neck dissection (Group I) and 25 managed by elective radiotherapy (Group II).  They were followed up for a period ranged from 6 months to 24 months with a mean period of 15months. All patients were subjected for full history taking, general and local examination, (assessment of the primary site and state of nodes of the neck), neck ultrasound, computed tomography (CT) and chest X-ray. Patients of Group (I) were evaluated postoperatively for surgical complications. Patients of Group II received 50 Gy using conventional fractionation (2 Gy per fraction with 2 days rest) to a total duration of 5 weeks. The incidences of local and regional recurrences were recorded. Survival times were calculated starting from the date of the surgery.

Results: Nineteen female (38%) and 31 male patients (62%) were included in this study. 38% of patients have their primary lesion in the tongue and 30% of patients with primary laryngeal lesion. The check, lower lip, hypopharynx, alveolar margin, and nasopharynx were affected by primary lesion in 14%, 6%, 4%, 2% and 4% respectively. Moderately differentiated tumors (G2) were the most prevalent grade among the study groups. 26% of patients were presented with T1 lesion. T2, T3 and T4 were diagnosed in 50%, 14% and 12% of the studied patients respectively. Pathologically, positive nodes were observed in 4 cases of the dissected specimens ranging from 1-2 LN with the mean positive LN 1.3 nodes. Extra capsular extension was present in 3 patients (12%); positive LN without extra capsular spread was present in one patient (4%). Nine patients (18%) had a recurrence. In group I, 4 patients had recurrence, (2 local recurrences and 2 regional recurrences). In group II, 5 patients had a recurrence, (3 local recurrences, 1 regional recurrence and 1 loco-regional recurrence). The loco-regional control rate (LRC) for group I was 84% and for group II was 80%. Two years disease free survival rate in group (I) was 64% while that for group (II) was 56%. The overall survival rate (OSR) for group (I) was 80%, while that of group II was 76%. The differences between study groups as regard recurrence, loco-regional control rate, disease free survival rate, and survival time were statistically insignificant.

Conclusion: Patients with clinically node negative neck of cases of squamus cell carcinoma of head and neck, elective neck dissection and elective radiotherapy were both suitable in terms of survival and locoregional control rates. Patients receiving both modalities of therapy can get nearly the same outcome. They were nearly equally effective in controlling the cN0 neck. The choice of the type of treatment modality depended mainly on the surgical experience of the treating oncologist, how the primary site is managed, the surgeon and patient choices.

Keywords: Clinically Node Negative Neck, Squamus Cell Carcinoma of Head and Neck, Neck Dissection, Elective Neck Radiation.

INTRODUCTION

      Head and neck cancers represent the sixth most common cancer worldwide with approximately 630,000 new patients diagnosed annually, resulting in more than 350,000 deaths every year. More than 90% of head and neck cancers are squamous cell carcinomas (HNSCCs) that arise from the mucosal surfaces of the oral cavity, oropharynx hypopharynx and larynx (Vigneswaran and Williams, 2014).

     The complex process of head and neck carcinogenesis involves dynamic interactions among many factors. Chief among HNSCC-related carcinogens are tobacco and alcohol. Other important etiologic factors are viruses, genetic predisposition, occupation, and radiation exposure (Clayman et al., 2000).

     One of the most commonly used surgical interventions in treatment of clinically node negative neck is the selective neck dissection. This surgery is of increasing popularity because of its ability to accurate removal of occult metastatic nodal disease and better and accurate pathological staging.

     Radiation therapy may be used in the treatment of cervical lymph node metastases. The regional lymph nodes are considered in the treatment planning of the primary lesion. With clinically negative neck nodes, treatment planning depends on the estimated risk of subclinical disease in the nodes (Mendenhall 2008).

     Retrospective evidence suggests that external beam radiation of approximately 40–50Gy to the clinically N0 neck will control occult metastases in more than 90–95 % of cases (Bar and Chalian, 2008).

     The present study aimed to investigate the efficacy of both elective neck dissection and elective neck irradiation in the management of clinically node negative neck (cN0) of patients with squamous cell carcinoma of head and neck.

PATIENTS AND METHODS

      This prospective study was done on 50 patients proved to have clinically node negative neck (cN0) of squamous cell carcinoma of head and neck randomized into two groups, 25 of them managed by selective neck dissection and 25 managed by elective radiotherapy at Al-Azhar University hospitals (otorhinolaryngology department, and surgical oncology unit) during the period from 2012-2015, and followed up for a period ranged from 6 months to 24 months with a mean period of 15 months. All patients included in the study were with pathologically proved squamous cell carcinoma of head and neck and clinically node negative neck.

Group (I): Twenty five patients under-went selective neck dissection (removing levels I- V) as a part of their surgical management of the primary.

Group (II): Twenty five patients under-went elective radiotherapy as part of their postoperative management.

      All patients were scheduled for full history taking, general and local examination (assessment of the primary site and state of nodes of the neck), neck ultrasound, computed tomography (CT) and chest X-ray. All patients were diagnosed by tissue biopsy from the primary (whether incisional or excisional biopsy). All patients were included in the study after informed written consent.

Operative technique: The patient received an intraoperative single dose of 2 g Cefotaxime. If the pharynx was planned to be opened, or in case of oral intervention, metronidazole IV 100 mg infusion, was administrated. Schobinger incision (Y-incision) was done for most patients, hockey stick or apron incision was also used. The skin incision was deepened through the subcutaneous tissue and the platysma muscle. Flap was then raised in the subplatysmal plane. Lymphadenectomy was done by removing levels I, II, III and IV according to site of the primary tumor. Supraomohyoid neck dissection in oral squamous cell carcinoma (buccal, lower lip and alveolar margin) was done in 9 patients (36%) with removal of the contents of the submental and submandibular triangles (level I), (level II), and the lymph node-bearing tissues located anterior to the cutaneous branches of the cervical plexus and above the omohyoid muscle (levels III). Extended supraomohyoid neck dissection of levels I-IV was done in 10 patients with tongue carcinoma at the lateral aspect (40%), Bilateral supraomohyoid neck dissection was done in 3 cases with anterior tongue or floor of the mouth carcinomas (12%). Lateral neck dissection of levels II-IV was done in 3 patients with laryngeal carcinoma (12%).

Radiotherapy technique: All patients of group II received 50 Gy using conventional fractionation (2 Gy per fraction with weekend rest on Thursday and Friday) using (3D) conformal radiotherapy to a total duration of 5 weeks. In the 2 cases of nasopharyngeal carcinoma, the nasopharynx was irradiated as a primary target therapy.

     All patients of group (I) were evaluated postoperatively for medical and surgical complications. Follow up clinical examinations were done every month for the 1^st year, every 3 months thereafter. Each patient in group (II) was followed twice weekly for complications, and then the patients were followed every month for the first year, and every 3 months in the next 2^nd year. The incidences of local and regional recurrence were recorded. Survival times were calculated starting from the date of the surgery.

     The data collected including the age and gender of patients, the site of the lesion, tumor pathology, degree of differentiation, type of performed neck dissection, the complications, the recurrences, the loco-regional control, survival rate and prognostic factors for loco-regional control and survival rate; all were recorded and the data obtained were subjected for statistical analysis by computer using SPSS data editor software, version 16.0.

RESULTS

     This study was conducted in Al-Azhar University hospitals (Otorhinolaryngology Department, and Surgical Oncology Unit) on 50 patients with cancer head and neck with negative neck lymph node. There were 19 female (38%) and 31 male patients (62%). Eighteen patients of them were cigarettes smokers. They were randomized blindly into two groups, i.e. group I (25) patients underwent elective neck dissection with primary tumor control, and group II (25 patients) underwent primary tumor control and elective neck irradiation.

     In 38% of patients, the primary lesion was in the tongue (19 patients: 13 in group I and 6 in group II). In 30% of patients, the primary lesion was laryngeal (15 patients: 3 in group I and 12 in group II). In 14% of the patients, the primary lesion was in the cheek (7 patients: 5 in group I and 2 in group II). Lower lip was affected in 6% of patients (3 patients in group I), hypopharynx in 4% (2 patients in group II), alveolar margin in 2% (1 patient in group I), and 4% of the case was presented with their primary in the nasopharynx in group II (Table 1).

Table (1): Sites of the primary lesion..

       Moderately differentiated tumors (G2) were the most prevalent grade among the study groups (Table 2).

Table (2): Pathological grading of tumors for both groups.

      Post-operative complications occurred in group (I) in 12 patients (48 %). Wound infection was the most common complication occurring in 5 patients (20%). Infection was severe in one patient following excision of the primary tumor (check cancer) being associated with skin necrosis that required surgical debridement and secondary sutures and the defect was reconstructed later by radial forearm free flap (RFFF). The rest of wound infections responded to repeated daily dressings. A seroma collected in one patient without wound infection and was managed conservatively. Partial spinal accessory nerve injury occurred in one patient and responded to physiotherapy slowly. One patient suffered from a chylous fistula that was managed by conservative method. Two other patients suffered from post-operative sepsis in the form of severe chest infection (Table 3).

            Table (3): Complications to neck dissection group (I)

     In group (II), 40% of patients developed persistent xerostomia, and 44% of patients developed erythema of the skin. Loss of taste and mucosites occurred in 12 % and 36% of patients respectively.

     There were 25 neck dissection specimens resulting in this study. 10-25 with a mean of 12.4 nodes were removed per neck dissection. There were positive nodes in 4 cases in the dissected specimens ranging from 1-2 LN with the mean positive LN 1.3 nodes. Extraca-psular extension was present in 3 patients (12%), and positive LN without extraca-psular spread was present in one patient (4%).

     Nine patients (18%) had a recurrence in both groups. In group I local recurrence occurred in two patients and regional recurrence in two patients. Regarding the local recurrence, the 1^st patient was male patient with right cheek T2 ulcerative sq.c.c partially infiltrating the mandible treated by excision of the ulcer with marginal mandibulectomy and extended supraomohyoid ND (level I-IV). Ipsilateral local recurrence in the cheek infiltrating the maxilla occurred after 12 months of follow up, the patient submitted to total maxillectomy with reconstruction by rectus abdominis free flap. The other case of local recurrence was a male patient with lower lip sq.c.c, treated by local excision and ipsilateral supraomohyoid ND. Local recurrence occurred 9 months later treated by surgical excision and supraomohyoid ND of the opposite side. Regional recurrence in group (I) occurred in two case. 1^st case was T1 sq.c.c with ulcerative lesion at right lateral edge of tongue treated by excision and ipsilateral supraomohyoid ND. Regional recurrence occurred 6 months later presented by right neck abscess which drained surgically and the patient died in ICU secondary to sepsis with multi organ failure. The other patient with regional recurrence was T2 supraglottic sq.c.c of the larynx treated by total laryngectomy with ipsilateral lateral ND from level II to level V. Regional recurrence in the form of single hard fixed contralateral L.N more than 3 cm after 12 months. The patient was submitted to Rt. modified radical ND and the patient died within the first 24 post-operative suddenly (either massive MI, or Massive pulmonary embolism).

     In group II, five patients had a recurrence: three with local recurrences, one patient with regional recurrence and one patient had loco regional recurrence (Table 4). The ipsilateral side of the neck (controlled side) was affected in 50% of cases of regional recurrence in group I. in group II, the two cases of regional recurrence were in the ipsilateral side of the primary.

     The most frequently involved lymph node levels were levels II and III in most cases (N1 = 3 patients, N2 = 1 patient). The time elapsed after primary treatment either by surgery or radiotherapy to diagnosis of cervical nodal recurrence ranged from 4 months to 18 months with a median period of 8 months.

           Table (4): Incidence of recurrence among both groups.

     The loco-regional control rate (LRC), for group I was 84% (21/25), and for group II was 80% (20/25).  Two years disease free survival rate for neck dissection group was 64% (16/25), while that for radiotherapy group was 56% (14/25). The differences between study groups as regard loco-regional control rate and disease free survival rate were statistically insignificant. In group (I) two patients died within 2 weeks postopera-tively, two patients with recurrence, and one patient died disease free at 18 months. In group (II) 5 patients died with the recurrence and 1 patient died from other cause. The overall survival rate (OSR) for group (I) was 80% (20/25 patients), while that of group II was 76% (19/25). The difference between both groups regarding the survival time was not statistically insignificant (Table 5).

     Table (5):  Survival time among the 2 study groups

     The loco-regional control and overall survival has no significant statistical relation to the type of treatment (either the surgical or the radiotherapy), or even to the other variables as sex, age, smoking and tumor grades (Table 6).

Table (6): Univariate analysis of prognostic factors for LRC and OS.

LRC=loco-regional control (% of controlled patients for 2 years). OS= overall survival.    ND=neck  Dissection *= statistically non-significant G1= grade 1 (Well differentiated T) G2 = grade 2 (Moderately differentiated T.) G3= grade 3 (Poorly differentiated T)

DISCUSSION

      Head and neck squamous cell carci-nomas refers to a group of biologically similar cancers that start in the lip, oral cavity, nasal cavity, paranasal sinuses, pharynx, and larynx (Soliman and Shehata, 2015).

      Head and neck carcinoma often spread to the lymph nodes of the neck, and this is often the first (and sometimes only) sign of the disease at the time of diagnosis. They are strongly associated with certain environmental and lifestyle risk factors including tobacco smoking, alcohol consumption, ultraviolet light, particular chemicals used in certain workplaces, and certain strains of viruses such as human papillomavirus (Hosal et al.,2000).

     The aim of this study was to compare the effectiveness of either elective neck dissection or elective neck irradiation in the management of clinically node negative neck (cN0), to evaluate the effectiveness of either modality in eradication of regional disease, to compare the regional recurrence rates of both, and to determine which type of treatment improves the two year survival and disease-free survival rates.

     The current study, showed no statisti-cally significant difference as regard age, smoker’s percentage and co-morbidities percentage between the two study groups.

      In the current study the higher percen-tage of cancer of head and neck was 34% among those who were over 60 years old. Gawecki et al. (2007) showed that head and neck squamous cell carcinoma (HNSCC) develops in the sixth to seventh decade of life and significantly less frequently in patients younger than 45 years.

     The current study showed that 62% of patients were males and 38% of patients were females. Siegel et al. (2013) stated that males are affected significantly more than females with a ratio ranging from 2:1 to 4:1. Also, Jemal et al. (2008) found that HNSCC is more common in men with incidence of 66%-95%.

     This variation in the incidence, anatomic and gender distribution of HNSCC worldwide is predominately attributed to demographic differences in the habits of tobacco use and alcohol consumption which contributes to the development of most of all HNSCC diagnosed universally (Vigneswaran and Williams, 2014).

     In the current study, complications of neck dissection were as follow; 20% of patients were complicated by wound infection, 15 % by fungal oral cavity infection, 8% by neck abscess and 4% of patients by Chyle leak. Infection was severe in one patient following excision of the primary tumor (check cancer) being associated with skin necrosis that required surgical debridement and secondary sutures. The defect was reconstructed later by radial forearm free flap (RFFF), the rest of wound infections responded to repeated daily dressings.

      These results were close to that obtained by Pellini et al. (2013). In their study on 119 patients, 79.8% do not develop any complications, while 24 of them (20.2%) experience some type of wound complication. Major complications were in 14 cases (11.7%) and minor in 10 cases (8.3%).

     However, the present result differs from that of Davidson et al. (1999) where the incidence of complications was higher. This rate of increased complications could be explained by some causes as preopera-tive receive of radiotherapy, preoperative albumin level less than 38 g/L, and early neck drain removal.

     Wound complications are obviously linked to the type of neck dissection. The risk of developing major wound complica-tions is higher in the case of MRND than in the case of SND. This could be explained by the reduction of blood flow at the periphery of the skin due to the pattern of skin incision used in such type of ND. MRND and RND were performed via a tri-flapped incision which may explain the higher incidence of skin-flap necrosis or dehiscence. Also, wider surgical field resulting from the more extensive procedures carries a higher risk of morbidity.

     In group (II), 40% of patients developed xerostomia, and 44% of patients developed erythema of the skin. Loss of taste and mucosites occurred in 12 % and 36% of patients respectively.

     Xerostomia is a permanent and devastating sequela of head and neck irradiation, and its consequences are numerous (Khan and Johnstone, 2005).

     Pellini et al. (2013) explained the higher complication rate usually observed in irradiated patients by the different pattern of tissue response to radiation. Radiotherapy activates a wound-healing process different from that of normal wound healing, causing an excessive deposition of extracellular matrix and collagen that is characteristic of radiation fibrosis. Furthermore, radiation also induces vascular damage, which can lead to tissue hypoxia, perpetuating a fibro-genic response.

     The loco-regional control rate (LRC) in this study for group I was 84% (21/25) and for group II was 80% (20/25).  Disease free survival rate for 2 years for neck dissection group was 64% (16/25) while that for radiotherapy group was 56% (14/25). The differences between study groups as regard recurrence, loco-regional control rate and disease free survival rate were statistically insignifi-cant.

These results were close to that obtained by Jin (2012). His results showed that not only the 5-year LRC rate but also the 5-year OS rate were not significantly different between the surgery group and radiotherapy group. Similar results were obtained by Orús et al. (2000), and Sessions et al. (2005).

      In the current study, the overall survival rate (OSR) for two years was for neck dissection group 80% while in radiotherapy group was 78%, and the difference between both groups was statistically insignificant. Orús et al. (2000) stated that the difference between the neck dissection group and the radiotherapy treatment group regarding the overall survival was insignificant.

      Also, in this work, the loco-regional control, and overall survival were have no significant statistical relation to the type of treatment (either the surgical or the radiotherapy) or even to the other variables as sex, age, smoking and tumor grades. However, the locoregional control is improved in a retrospective study by Paleri and Watkinson (2012).

     The main limitation of the study arouse from relatively small sample size and the relatively short time of follow up (24 month). For this reason, it is recommen-ded to perform the study on a wider scale of randomized population and over a longer time of follow up in order to assign the statistical significance.

CONCLUSION

      This study concluded that, among patients with clinically node negative neck in cases of squamous cell carcinoma of head and neck, elective neck dissection and elective radiotherapy were both suitable in terms of survival and locoregional control rates. Patients receiving both modalities of therapy can get nearly the same outcome. They were nearly equally effective in controlling the cN0 neck. If the primary site was to be controlled surgically it was advised to do elective neck dissection. The choice of the type of treatment modality depended mainly on the surgical experience of the treating oncologist, how the primary site was managed, the surgeon and patient choices and the quality of life point of view.

     Neck dissection does not seem to be superior to in terms of survival and regional control of neck disease. However, it seems to be better in minimizing the complications of bilateral neck irradiation and save the neck from a heavier dose and larger field of irradiation exposure.

REFERENCES

1. Bar Ad V and Chalian A (2008): Management of clinically negative neck for the patients with head and neck squamous cell carcinomas in the modern era. Oral Oncology, 4: 817–22.

2. Clayman G., Scott M., Lippman S., Laramore G., and Hong W. (2000): Neoplasms of The Head and Neck. In: Holland-Frei Cancer Medicine, 5th edition. Editors: Robert C Bast, Donald W Kufe,  Raphael E Pollock, Ralph R Weichselbaum, James F Holland, and Emil Frei.  pbl. Hamilton (ON): BC Decker; Chap. 86, p.1173

3. Davidson BJ, Newkirk KA, Harter KW, Picken CA, Cullen KJ and Sessions RB (1999): Complications from planned, post-treatment neck dissections. Arch Otolaryngol H.N. Surg., 125(4):401-5.

4. Gawecki W, Szyfter K and  Szyfter W.( 2007): The role of exogenous and epidemiological factors in etiology of squamous cell carcinoma of the head and neck in young adults Otolaryngol Pol. ;61(1):52-7

5. Hosal A., Crrau R., Johnson T. and Myers N. (2000): Selective Neck Dissection in the Management of the Clinically Node Negative Neck. Laryngoscope, 110:2037–2040.

6. Jemal A., Siegel R., Ward E., Hao Y., Xu J., Murray T. and Thun MJ.(2008): Cancer statistics, 2008. CA Cancer J Clin; 58(2):71-96

7. Jin T (2012): Management of the clinically negative neck (N0) of T2N0M0 supraglottic laryngeal carcinoma: a retrospective study. Head Neck Oncol. 23, 4(4):79.

8. Kahn ST and Johnstone PA (2005):Management of xerostomia related to radiotherapy for head and neck cancer. Oncology. 19(14):1827-32; discussion 1832-4, 1837-9.

Mendenhall WM., Amdur RJ., Hinerman RW, Mancuso AA., Villaret DB. and Werning JW. (2008): Management of the neck including unknown primary tumour. In: Perez and Brady's Principles and Practice of Radiation Oncology 5th edition. Editors: Edward C. Halperin, Carlos A. Perez, Luther W. Brady‏  Publisher: Lippincott Williams & Wilkins. Chapter 46,  pp: 1039.

9. Orús C, León X, Vega M and Quer M (2000):Initial treatment of the early stages (I, II) of supraglottic squamous cell carcinoma: partial laryngectomy versus radiotherapy. Eur Arch Otorhinolaryngol., 257(9):512–6.

10. Paleri V. and Watkinson J. (2012):Metastatic neck disease In: Stell & Maran`S textbook of head and neck surgery and oncology, 5th edition, 661-82.

11. Pellini, R., Mercante, G., Marchese, C., Terenzi, V., Sperduti, I., Manciocco, V, Ruscito, G. Cristalli, P. Marchesi, B. Pichi and Spriano, G. (2013). Predictive factors for postoperative wound complications after neck dissection. Acta Otorhinolaryngologica Italica,33(1), 16–22.

12. Sessions DG, Lenox J, Spector GJ, Chao C and Chaudry OA(2003): Analysis of treatment results for base tongue cancer. Laryngoscope, 113:1252-61.

13. Siegel R, Naishadham D and Jemal A. (2013): Cancer Statistics, 2013. Ca Cancer J Clin., 63:11-30.

14. Soliman G. and, Shehata O. (2015): Efficacy of Cryotherapy on Oral Mucositis Prevention among Patients with Head and Neck Cancers Who Undergoing Radiotherapy. Journal of Nursing and Health Science, 4 (4):53-61.

15. Vigneswaran N and Williams M. (2014): Epidemiological Trends in Head and Neck Cancer and Aids in Diagnosis. Oral and maxillofacial surgery clinics of North America, 26(2):123-141.