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Commentary (Corry et al): The Role of Neck Dissection Following Definitive Chemoradiation

Commentary (Corry et al): The Role of Neck Dissection Following Definitive Chemoradiation

In this issue of ONCOLOGY, Kutler et al eloquently address the concept, application, and controversies of a planned neck dissection in patients with head and neck carcinoma and nodal metastasis who receive nonsurgical therapy to the primary tumor. As stated lucidly in the article, planned neck dissection arose in the historical context of low rates of complete response in patients with N2/3 neck disease treated with conventionally fractionated radiotherapy, coupled with low surgical salvage rates among patients who failed in the neck. Hence, the concept evolved that all patients with N2/3 neck disease should undergo a planned neck dissection regardless of response to radiotherapy.

Conventionally fractionated radiotherapy is, however, no longer the standard of care in locally advanced head and neck cancer, as regimens of accelerated and hyperfractionated radiation and/or concurrent radiation and chemotherapy have yielded superior complete response rates. These results have translated into better locoregional control and, in many trials, improved overall survival rates. There is a strong rationale and consensusfor a neck dissection in patients with a complete response at the primary site but a partial response in the neck, realizing, however, that many neck specimens may only show fibrosis or necrotic debris. The question that remains then is why do all patients who achieve a complete response both in the primary and neck require additional treatment in the form of a planned neck dissection? In other words, in view of improving locoregional complete response rates and the fact that only patients destined to suffer an isolated neck failure will benefit from this adjuvant therapy, has systematic planned neck dissection reached a point of diminishing return?

Study Limitations

The main argument mounted by Kutler and colleagues in support of systematic planned neck dissection is the purported high rates (> 20%) of pathologic positivity in neck specimens of patients treated with concurrent radiation and chemotherapy. However, in our view, the papers quoted in support of the case share several weaknesses.

The first is that of using physical examination alone to ascertain complete response to concurrent radiation and chemotherapy. Very few published series included documentation of a radiologic complete response prior to a planned neck dissection. McHam et al state that computed tomography (CT) scans were not routinely obtained in patients destined to undergo neck surgery and, hence, it is not clear as to why only half the patients achieving a complete response proceeded to a planned neck dissection.[1] In this day and age, physical examination alone is an inadequate assessment of a complete response, as it is associated with a significant rate of false-positives and false-negatives even in untreated papatients. Physical examination of the neck may be even less precise among patients following concurrent radiation and chemotherapy, making correlative imaging mandatory.

Second, because patients in the series cited were scheduled to have a posttreatment neck dissection regardless of treatment response, the pathologic positivity rate includes patients who had less than a complete response. The "unacceptably high" pathologically positive specimens after concurrent radiation and chemotherapy in fact include patients who have only had a partial response, thus elevating the incidence of residual microscopic disease following a complete response to concurrent radiation and chemotherapy. The exact figure cannot be ascertained, as response rates are not documented. In Lavertu's[2] and Stenson's[3] series, for example, large numbers (40%- 60%) of patients were unaccounted for, ie, patients who were to have a planned neck dissection but who, for unstated reasons, did not receive the planned treatment. Such unaccountability introduces the potential for major bias in results.

Finally, the authors correctly indicated the uncertain tumor cell viability in some of the pathologically positive neck specimens, particularly those harvested soon after completion of radiotherapy or concurrent radiation and chemotherapy.

Evidence From Nonrandomized Trials

The reason that the dispute about planned neck dissection persists is the absence of randomized studies comparing neck dissection vs no neck dissection after concurrent radiation and chemotherapy. However, many other studies have demonstrated a low incidence of isolated neck failure following a complete response to concurrent radiation and chemotherapy or radiation without planned neck dissection.

Peters et al reported on 75 patients, the majority with N2/3 disease, treated with altered fractionation radiotherapy. None of the 62 patients achieving a complete response had a planned neck dissection, and only 5% had an isolated neck failure.[4] Garden et al reported 48 node-positive patients treated with chemoradiation; 27 achieved a complete response, none of whom failed in the neck.[5] Johnson et al reported 81 patients (77% N2/3) treated with altered fractionation; 58 achieved a complete response and only 5% had a subsequent neck failure without planned neck dissection.[ 6] In the series studied by Chan et al, 80 of 121 node-positive patients treated with radiotherapy achieved a complete response and only 7.5% failed in the neck.[7] Corry et al treated 43 patients with combined radiation and chemotherapy; of the 25 node-positive patients (84% N2/3) who achieved a clinical and radiologic (CT scan) complete response, none had an isolated neck failure at a median follow-up of 3 years.[8]

In addition to a posttreatment CT scan, the 18-fluorodeoxyglucose (FDG)-positron-emission tomography (PET) scan holds promise in further refining the group of patients who do not benefit from a planned neck dissection because they have achieved a metabolic complete response to chemoradiotherapy. We fully agree with Kutler and colleagues that more thorough studies are needed to determine the real value of FDG-PET in this clinical setting.

A planned neck dissection achieves high rates of regional control, but at the expense of a 35% acute complication rate[9-11] and significant late sequelae.[12] The postchemoradiation fibrosis discussed by Kutler ismost severe in patients who have had a postchemoradiotherapy neck dissection.

Conclusions

In view of the morbidity and cost of planned neck dissections, a growing body of data demonstrating a low incidence of isolated neck failure in patients with a clinical and radiologic complete response, and the emergence of evidence suggesting that FDG-PET has an added value in ruling out the presence of viable residual disease, we believe that it is no longer appropriate to recommend systematic planned neck dissections for patients with N2/3 disease regardless of the response. It is time for head and neck oncologists to join forces to resolve this ongoing dispute through the introduction of clear work-up and reporting guidelines and the conduct of well-designed studies. Systematic imaging work-up-consisting of at least a CT scan performed 6 to 8 weeks after therapy to confirm a primary complete response and to assess nodal response-is mandatory.

As to prospective studies, a scientifically attractive option is to randomize patients with N2/3 disease who have achieved a complete response in the primary site and neck to undergo planned neck dissection or observation and compare the nodal recurrence rate. In the scenario of a complete response in the primary and a regional partial response, an additional useful study would be to assess the efficacy of regional dissection, tailoring the neck dissection to encompass the original neck disease, rather than a comprehensive neck dissection. Ideally, these types of studies can be implemented as companions to the ongoing cooperative group trials addressing various chemoradiation regimens.

Financial Disclosure: The authors have no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.

References

1. McHam SA, Adelstein J, Rybicki LA, et al: Who merits a neck dissection after definitive chemoradiotherapy for N2-N3 squamous cell? Head Neck 25:791-798, 2003.
2. Lavertu P, Adelstein DJ, Saxton JP, et al: Management of the neck in a randomized trial comparing concurrent chemotherapy and radiotherapy with radiotherapy alone in resectable stage III and IV squamous cell cancer. Head Neck 19:559-566, 1997.
3. Stenson KM, Haraf DJ, Pelzer H, et al: The role of cervical lymphadenectomy after aggressive concomitant chemoradiotherapy. Arch Otolaryngol Head Neck Surg 126:950-956, 2000.
4. Peters LJ, Weber RS, Morrison WH, et al: Neck surgery in patients with primary oropharyngeal cancer treated by radiotherapy. Head Neck 18:552-559, 1996.
5. Garden AS, Glisson BS, Ang KK, et al: Phase I/II trial of radiation with chemotherapy "boost" for advanced squamous cell carcinomas of the head and neck: Toxicities and responses: J Clin Oncol 17:2390-2395, 1999.
6. Johnson CR, Silverman LN, Clay LB, et al: Radiotherapeutic management of bulky cervical lymphadenopathy in squamous cell carcinoma of the head and neck: Is post radiotherapy neck dissection necessary? Radiat Oncol Investig 6:52-57, 1998.
7. Chan AW, Ancukiewicz M, Carballo N, et al: The role of postradiotherapy neck dissection in supraglottic carcinoma. Int J Radiat Oncol Biol Phys 50:367-375, 2001.
8. Corry J, Rischin D, Smith JG, et al: Radiation with concurrent late chemotherapy intensification ("chemoboost") for locally advanced head and neck cancer. Radiother Oncol 54:123-127, 2000.
9. Mendenhall WM, Million RR, Cassisi NJ: Squamous cell carcinoma of the Head and Neck treated with radiation therapy: The role of neck dissection for clinically positive neck nodes. Int J Radiat Oncol Biol Phys 12:733- 340, 1985.
10. Davidson BJ, Newkirk KA, Harter KW, et al: Complications from planned, posttreatment neck dissections. Arch Otolaryngol Head Neck Surg 125:401-405, 1999.
11. Lavertu P, Bonafede JP, Adelstein DJ, et al: Comparison of surgical complications after organ preservation therapy in patients with stage III or IV squamous cell Head and Neck cancer. Arch Otolaryngol Head Neck Surg 124:401-406, 1998.
12. Kuntz AL, Weymuller EA Jr: Impact of neck dissection on quality of life. Laryngoscope 109:1334-1338, 1999.
 
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