CLINICAL ASPECTS

AMT, vol II, nr. 3, 2011, pag. 327

THE ROLE OF CHEMOTHERAPY AND RADIATION THERAPY IN THE HYPOPHARYNGEAL CANCER

I. M. FĂGEŢAN 1

1S. C. Dinu & Fagetan S.R.L., Sibiu

Keywords: cancer, hypopharyngeal, RTOG, EORTC, chemotherapy

Abstract: Nowadays, the surgical oncology does not limit itself to eliminating (eradicating) malignant tumours and to insure a satisfactory physiognomy. It involves the recovery of the tissue dynamics, to allow the patients reinstatement into society in suitable terms. This observation involves a lot of consideration for providing a quality life for patients. In order to evaluate the quality of life, some standard questionnaires that evaluate the patient mentaly, physically, socially and physiognomically were suggested.

Cuvinte cheie: cancer, hipofaringe, RTOG, EORTC, chimioterapie

Rezumat: În prezent, chirurgia oncologică nu se mai limitează doar la eradicarea tumorii maligne şi asigurarea unei fizionomii acceptabile. Ea presupune şi refacerea funcţională a ţesuturilor, pentru a permite reintegrarea în societate în condiţii cât mai favorabile. Această constatare implică acordarea unei atenţii deosebite asigurării calităţii vieţii pacienţilor. Pentru a putea aprecia calitatea vieţii, s-au propus mai multe chestionare standardizate care evaluează pacientul din punct de vedere psihic, funcţional, social şi fizionomic.

1 Corresponding Author: I. M. Făgeţan. 6, Şerbota street, Sibiu, România; e-mail: imfagetan@yahoo.com; tel +40-0745605540 Article received on 28.12.2010 and accepted for publication on 21.04.2011 ACTA MEDICA TRANSILVANICA September 2011; 2(3)327-328

SCIENTIFICALLY ARTICLE OF BIBLIOGRAPHIC SYNTHESIS

As mentioned, definitive radiation therapy is the treatment of choice for patients with T1 and T2 hypopharyngeal cancers, although it is arguable that radiation therapy results in better function than larynx-conserving procedures. With radiation therapy, the 5-year local control rate for patients with T1 and T2 hypopharyngeal cancers ranges from 70% to 100% (32,33). In cases of T3 and T4 hypopharyngeal cancer, however, radiation therapy is used most commonly as postoperative adjuvant therapy. The use of postoperative radiation therapy results in improvement in locoregional control from approximately 28% to 43% when compared with surgery alone. Furthermore, postoperative radiation therapy produces improved locoregional control when compared with preoperativeradiation therapy (21,36). In a study by the Radiation Therapy Oncology Group (RTOG), patients with locally advanced SCC of the oral cavity, oropharynx, supraglottic larynx, and the hypopharynx were randomized to receive preoperative radiation therapy followed by surgery, postoperative radiation therapy 4 weeks following surgery, or definitive radiation therapy with salvage surgery, if necessary. Patients with hypopharyngeal cancers constituted 26% of the study group. Although subset analysis for hypopharyngeal cancer was not available, the locoregional control for all sites combined was superior for postoperative radiation therapy than for preoperative radiation therapy (37). Chemotherapy as sole therapy is not indicated in the treatment of hypopharyngeal cancer. Although no studies have yet examined the role of chemotherapy as a definitive therapy specifically in hypopharyngeal cancer, several studies have examined the role of induction chemotherapy for SCC for all sites of head and neck cancer combined (41,42). The percentage of patients with hypopharyngeal cancer in these studies ranged from 17% to 27%. These studies, however, demonstrated no improvement in survival or locoregional control with the use of

induction chemotherapy. Concurrent chemoradiotherapy, on the other hand, has

shown survival benefit in patients with advanced head and neck cancer. The Meta-Analysis of Chemotherapy in Head and Neck Cancer collaborative group performed meta-analysis of 63 trials between 1965 and 1993 involving 10,741 patients comparing the effects of neoadjuvant, concurrent, or adjuvant chemotherapy on overall survival (43). This study found a survival benefit of 8% at 2 and 5 years with concurrent chemoradiotherapy, whereas induction and adjuvant chemotherapy had no impact on survival. Supported by data such as these, the European Organization for Research and Treatment of Cancer (EORTC) performed a study of the effectiveness of chemotherapy and radiotherapy when used sequentially as an organ-preserving alternative to total laryngectomy for patients with advanced (T3 and T4) hypopharyngeal cancer (44). In this study, patients were randomized to induction chemotherapy followed by definitive radiation therapy or total laryngectomy followed by postoperative radiation therapy. No statistical differences were seen in local control rates between the two arms, although larynx conservation was possible in up to 42% of the patients. Furthermore, the median (25 vs. 44 months) and 3-year survival rates (43vs. 57 months) were higher in the larynx preservation group. Although quality of life data from this study are lacking, the study showed that larynx conservation protocols using induction chemotherapy followed by definitive radiation therapy is a legitimate option in patients with advanced hypopharyngeal cancer who desire to avoid a total laryngectomy.

Another relevant issue regarding an organ preservation approach is whether concurrent chemoradiation therapy is better than induction chemotherapy followed by radiotherapy. This issue was examined for laryngeal cancer in the intergroup R91-11 study in which patients with advanced laryngeal cancer were randomized to receive concurrent chemoradiation therapy, induction chemotherapy followed by

CLINICAL ASPECTS

AMT, vol II, nr. 3, 2011, pag. 328

radiation therapy, or radiation therapy alone (45). This study showed that concurrent chemoradiation therapy yielded superior locoregional control than did induction chemotherapy followed by radiotherapy. It remains to be studied whether concurrent chemotherapy is the next step in the evolution of organ preservation protocol for patients with hypopharyngeal cancer. A follow-up to the EORTC trial is currently in progress to answer this question.

An issue relevant to the use of concurrent chemoradiotherapy is its role in the postoperative adjuvant setting. For patients at high risk of local recurrence, the treatment of choice has been surgery combined with postoperative radiotherapy. The RTOG 9501 study and the EORTC trial 22931, however, examined the role of postoperative concurrent chemoradiotherapy in patients with head and neck cancer (46,47). In both of these studies, patients who had had surgical resection of the primary tumor and were noted to be high risk for treatment failure were randomized to receive postoperative radiotherapy or postoperative concurrent chemoradiotherapy. High risk of treatment failure was defined in the RTOG study as histologic evidence of involvement of two or more lymph nodes, extracapsular invasion, or positive margins. In addition to these features, the EORTC study extended the high-risk criteria to include vascular invasion, perineural invasion, any pT3 or pT4 disease, or tumor stage of 1 or 2 with a nodal stage of 2 or 3 and no distant metastasis. Patients with hypopharyngeal cancers constituted 20% of both the radiotherapy group and the concurrent chemoradiotherapy group in the EORTC study, whereas the hypopharynx was the primary site in 12% of the radiotherapy group and 7% of the concurrent chemoradiotherapy group in the RTOG study. Both studies showed that postoperative concurrent chemoradiotherapy increased the 2-year local and regional control compared with the postoperative radiotherapy group (increase by 10% and 11% in RTOG and EORTC studies, respectively). Only the EORTC study was able to demonstrate an increase in the survival (53% in the postoperative concurrent chemoradiotherapy group vs. 40% in the postoperative radiotherapy group). It should be noted that the incidence of severe, early side effects was higher in the combination therapy group compared with the radiotherapy alone group. Therefore, patients at high risk for treatment failure after surgical resection should benefit from adjuvant concurrent chemotherapy provided the patient is able to tolerate the intensity of the combined treatment.

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