Reirradiation for Recurrent Head and Neck Cancer

Pretesh R Patel; Joseph K Salama

Disclosures

Expert Rev Anticancer Ther. 2012;12(9):1177-1189. 

In This Article

Abstract and Introduction

Abstract

Recurrence of head and neck cancer in a previously irradiated volume presents a challenging problem and has poor prognosis. A minority of patients are eligible for the preferred therapy, surgical resection. Systemic therapy is offered to patients with unresectable disease but offers little, if any, chance of cure. Repeat irradiation with systemic therapy is a potentially curative option. One randomized trial and several cooperative group and institutional studies support its use. Long-term disease-free survival has been observed, albeit with the risk of significant, possibly life threatening, late complications. Intensity-modulated radiotherapy has been shown to reduce toxicity and improve disease control. Novel systemic therapies and radiotherapy techniques, including stereotactic body radiotherapy, are under active study.

Introduction

Radiation therapy plays a central role in the treatment of head and neck cancer (HNC) patients. Within a treatment paradigm of functional organ preservation, evidence-based guidelines recommend radiotherapy for three quarters of all patients with HNC.[1] Both organ-preserving definitive chemoradiotherapy (CRT) and selective postoperative CRT improve locoregional recurrence (LRR) and prolong overall survival (OS).[2,3] Nevertheless, despite improvements, LRR after CRT continues to be a vexing problem for 20–35% of patients.[4–8] Even patients with favorable prognosis human papillomavirus-related HNC[9] have a LRR rate of nearly 15%.[4] Locoregional recurrence is related to a number of different factors. Some tumors are inherently radioresistant. Additionally, as radiation is delivered more precisely with smaller margins, the potential for recurrences related to 'marginal misses' has increased. Ongoing exposure to carcinogens, such as cigarette smoke, leads to a 3–5% yearly risk of a second malignancy.[4,10]

Recurrent or second primary HNC in a previously irradiated field has a poor prognosis with a median survival of approximately 6 months with best supportive care.[11] Uncontrolled disease at the primary site or regional lymph nodes can cause complications including pain, disfigurement, significant difficulties with speech and swallowing, as well as the development of metastatic disease.[12] Treatment options are often limited. A small proportion of patients have resectable disease recurrence and are sufficiently fit to undergo salvage resection. However, adverse pathologic features, such as extra-capsular extension (ECE) or positive surgical margins are often seen, raising concern for postoperative disease recurrence. For unresectable disease, systemic therapy alone, the historical standard of care, results in 10–15% 1-year OS and virtually no long-term survivors.[11,13] Previously irradiated patients fare even worse.[14]

For patients with recurrent or second primary HNC within a previously irradiated area, the only potentially curative option is a second course of radiation, with or without chemotherapy, termed reirradiation (RRT). Early experiences with RRT in selected patients demonstrated OS rates (30–50%) that compared favorably to chemotherapy.[15] More recently, concomitant chemotherapy and RRT has been adopted by some as a treatment strategy of choice. Unfortunately, given the heterogeneous patient population, very limited level I evidence is available to inform decision making of physicians and patients. This manuscript will review the evidence base supporting RRT and concurrent chemotherapy with RRT (CRRT) for both resectable and unresectable, recurrent and previously irradiated HNC.

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