MANAGEMENT OF THE NECK IN PATIENTS WITH HEAD AND NECK CANCER TREATED BY CONCURRENT CHEMOTHERAPY AND RADIATION

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Patients with advanced head and neck squamous cell cancers have had a poor outcome when treated with conventional therapy (surgery and radiation therapy), with survival rates of 20% to 40% being generally reported for stage III and IV disease. In the 1960s and 1970s, clinical trials were conducted to determine the optimal strategies for combining surgery and radiation (XRT). Improved local-regional control compared to single modality therapy was noted. It also was found that there was no significant difference in the overall complication rate between preoperative and postoperative XRT when given in a planned fashion, with surgery performed within 3 to 6 weeks of XRT. Valuable data were obtained from these trials regarding the likelihood of complete response to XRT without intervening surgery (Table 1). Such information serves as a standard for gauging the relative efficacy of adding other treatments, such as chemotherapy, to XRT.

Unfortunately, over the last 20 years there has been little improvement in the survival of patients with advanced squamous cell carcinoma of the head and neck (SCCHN). Numerous clinical strategies have been devised to try to improve the outcome in this disease, many of which have used chemotherapy. Initially, induction chemotherapy was used as neoadjuvant treatment, most notably in the Head and Neck Contracts Program.12 This multicenter trial, and numerous subsequent trials, demonstrated no survival benefit from adding induction chemotherapy to the treatment plan.21

It was noted, however, that previously untreated patients receiving induction chemotherapy who achieved a complete response had a better outcome than those who achieved less than a complete response.21 This observation has led many investigators to search for new ways to increase the complete response rate in patients receiving chemotherapy for head and neck cancer. One strategy that has emerged in recent years is to deliver chemotherapy and radiation therapy concurrently. Such treatment schedules take advantage of the property of certain chemotherapeutic agents to act as radiation sensitizers (Table 2). Cisplatin (CP), the chemotherapeutic agent most commonly used against head and neck cancer currently, has been shown in laboratory studies to potentiate the therapeutic effects of radiation, particularly under conditions of hypoxia.9, 18 CP also has been shown experimentally to inhibit the repair of sublethal radiation damage.7 Another theoretical advantage of concurrent chemotherapy and radiation (chemoradiation) is that this approach increases the intensity of treatment by exposing tumor cells to both modalities simultaneously rather than sequentially, increasing the likelihood that resistant cells will be killed rather than repopulating the tumor.

Although the term chemoradiation has appeared in the literature in reference to treatment protocols employing either sequential or concurrent chemotherapy and XRT, currently this term is used mainly regarding concomitant use of the two modalities. Continuous course alternating chemotherapy and radiotherapy also is considered a form of concomitant treatment.15 This article focuses on concurrent chemotherapy and radiation approaches, and how this relatively new strategy may impact management of the neck in head and neck cancer patients. The evolution of concurrent chemotherapy and radiation for SCCHN will be reviewed, and the available data on the impact of this approach on the control of neck disease and surgical management of neck metastases are analyzed critically.

Section snippets

CHEMORADIATION TRIALS IN HEAD AND NECK CANCER

Formal trials of concurrent chemotherapy and radiation date to the 1970s. Early trials focused on patients with recurrent or inoperable disease. Multidrug combinations given during radiation treatment resulted in toxicity that was greater than expected.10, 11 With the emergence of CP as a single agent with major activity against squamous carcinoma, trials of this drug combined with concurrent radiation were carried out by the Radiation Therapy Oncology Group (RTOG) in the 1970s and early 1980s.

ISSUES RELATED TO CHEMORADIATION AND MANAGEMENT OF THE NECK IN HEAD AND NECK CANCER

At least two questions arise with regard to chemoradiation and its impact on management of the neck in head and neck cancer. One of these is whether chemoradiation impacts the pattern of treatment failure, particularly in the neck. In other words, is there improvement in regional control of head and neck squamous cell cancer with chemoradiation to the extent that surgical treatment philosophies should be altered? A second question is whether chemoradiation alters the complication rate of

IMPACT OF CHEMORADIATION ON REGIONAL CONTROL OF HEAD AND NECK CANCER

The concept of concurrent chemotherapy and XRT is not new, as noted above, but has been refined over the last two decades. Al-Sarraf and colleagues'4 RTOG study established the first safe and effective regimen in a controlled trial. Other than mentioning that one patient had been rendered disease-free by salvage neck dissection, the role of surgery in that trial was not discussed. Subsequent studies have focused on response rates, survival rates, and toxicities of chemotherapy. Although a

COMPLICATIONS OF NECK DISSECTION AFTER CHEMORADIATION

Although increasing numbers of patients with advanced SCCHN are treated in clinical trials and in the community with various chemoradiation protocols, there are very few reports in the medical literature addressing the rate and risk of surgical complications in patients so treated. Corey et al6 reported on a series of patients randomized prospectively to either induction chemotherapy with methotrexate and leucovorin calcium rescue before standard therapy (surgery and/or XRT), or to standard

SUMMARY

The current high level of interest in organ preservation strategies for patients with advanced SCCHN undoubtedly will result in increasing numbers of patients managed initially with chemotherapy and radiation, either sequentially or concurrently. In some protocols, surgery, and neck dissection in particular, will either be mandatory or offered based on the degree of response to treatment and initial stage of neck disease. Head and neck oncologic surgeons need to be involved and at the forefront

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  • Cited by (31)

    • Prediction of neck dissection requirement after definitive radiotherapy for head-and-neck squamous cell carcinoma

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      However, the view that nodal disease might be more radioresistant than the primary tumor (1) has led to controversy on the necessity of a planned neck dissection after radiation for patients presenting with advanced nodal disease. This controversy is best demonstrated in the design of Phase III trials during the past two decades because some organ preservation trials mandated postradiation neck dissections, whereas others left the decision of whether to surgically treat the neck at the discretion of the treating physicians (2–10). There is general agreement that patients with less than complete response (CR) should undergo neck dissection to eliminate potential residual viable tumor cells in the nodes (11, 12).

    • Incidence of isolated regional recurrence after definitive (chemo-) radiotherapy for head and neck squamous cell carcinoma

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      The overall regional control rate after three years was 80%. This is comparable to data already published [9,22,23]. A total of 11 patients had an isolated regional recurrence (2.99%).

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    Address reprint requests to Robert A. Weisman, MD, Division of Otolaryngology–Head and Neck Surgery, University of California Medical Center of San Diego, 200 W. Arbor Drive, San Diego, CA 92103–8891

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