Disclaimer: The information contained within the Grand Rounds Archive is intended for use by doctors and other health care professionals. These documents were prepared by resident physicians for presentation and discussion at a conference held at Baylor College of Medicine in Houston, Texas. No guarantees are made with respect to accuracy or timeliness of this material. This material should not be used as a basis for treatment decisions, and is not a substitute for professional consultation and/or peer-reviewed medical literature. Chemotherapy and Radiation for Advanced Head and Neck Cancer Head and neck cancer (excluding skin cancer) comprises 5% of all malignancies in the U.S. and accounted for 43,300 new cancer cases and 11,800 deaths in 1991. Approximately one half of head and neck cancer patients present with localized disease and carry a 3-year survival estimate of 70%, while the remaining half show regional or distant spread with an average 3-year survival of 45%. The majority of head and neck cancers arise in the lips and oral cavity followed by the larynx, pharynx, nose/paranasal sinuses, and salivary glands, in descending order of frequency. Squamous cell carcinoma accounts for over 90% of these cancers, except those occurring in the salivary glands. The primary goal in treating head and neck cancers is the eradication of the disease. Other important considerations include the maintenance of adequate physiologic function such as speech and swallowing, and factors of cosmesis. The mainstay of therapy has been surgery with or without post-operative radiation, with chemotherapy reserved for palliation of incurable primary tumors or recurrence. The new movement in treating head and neck cancers involves multimodality therapy using combinations of surgery, radiation, and chemotherapy. Induction or neoadjuvant chemotherapy refers to the use of chemotherapy initially to promote tumor regression, treat occult micrometastases, and identify a patient population that may benefit from post-surgical or radiation adjuvant therapy. The most common agents used for head and neck cancer are cisplatin, 5-fluorouracil, bleomycin, and methotrexate. These agents have preference of uptake in rapidly dividing cells and have various modes of tumoricidal action including inhibition of DNA synthesis, formation of free radicals which causes breaks in DNA strands, and prevention of repair of sublethal damage to DNA. Radiation therapy can be delivered by external beam (teletherapy) or interstitial (brachytherapy) methods. Brachytherapy involves the use of radium, iridium, or gold seeds implanted directly into tissues and which emit high energy photons called gamma rays that damage cellular DNA. External beam radiation consists of either electrons or x-rays (photons) delivered by machines such as the cobalt-60, betatron, microtron, and linear accelerator. Radiation causes the formation of free radicals which damage the DNA in all tissues, but its therapeutic ratio is based on the biologic difference between normal and cancer cells. Normal cells have a greater ability to repair DNA damage and are usually in a more resistant resting state of cell mitosis compared to actively dividing tumor cells. Many reports in the literature attempt to define the role of combination therapy in the treatment of head and neck cancer, and unfortunately there is very little consistency in type of study and results. Only a recent few articles have attempted to eliminate much of the subjective bias in determining treatment modalities and have enacted randomized prospective studies. Weissler and Pillsbury (1992), in a small study of 58 patients, evaluated the effects of chemotherapy on survival and time to disease progression in both a surgical and an unresectable group, both of which received radiation therapy. Their results showed no advantage in using chemotherapy in combination with surgery, but a significant increase in survival and time to disease progression was seen in unresectable (advanced CA) patients treated with combined chemotherapy and radiation therapy. Wolf and Hong et al (1991) in a VA cooperative study of 332 patients compared the results of induction chemotherapy and radiation versus surgery and radiation in resectable stage III and IV squamous cell carcinoma of the larynx. Their results demonstrated no significant difference in survival between the two groups; however, the larynx was preserved in 64% of the patients who received induction chemotherapy and radiation therapy. This data supports the idea of initial chemotherapy followed by radiation for laryngeal cancer with surgery reserved for salvage in non-responding patients. Merlano et al (1992) compared the use of combined chemotherapy plus radiation therapy to only radiation therapy in 144 patients with stage III and IV unresectable squamous cell carcinoma of the head and neck. Their data revealed a significant increase in complete clinical response rate and survival in patients treated with combined chemotherapy and radiation. The concepts and modalities of therapy for head and neck cancer are continually evolving. There is at present no general consensus except that the employment of combined therapy with surgery, radiation, and/or chemotherapy is advantageous in advanced cancer cases. Case Presentation A 60-year-old African American male presented with a 6-month complaint of odynophagia and a swelling in the left side of his neck. The swelling had increased in size over the past 2 weeks. He denied weight loss, fever, respiratory difficulty, and dysphagia. He had a 43 pack per year history of smoking, but denied the use of alcohol. There was no prior history of cancer. Physical examination was significant for 2 x 2 cm and 4 x 4 cm firm, nontender, moderately fixed lymph nodes in the left mid-jugular chain, deep to the sternocleidomastoid muscle. Indirect and fiberoptic examination revealed a large exophytic tumor of the left posterolateral hypopharyngeal wall obscuring the pyriform sinus. The tumor impaired the mobility of the left true vocal cord and involved the aryepiglottic fold and left base of tongue. CT scanning revealed a 6 cm (superior to inferior) tumor extending from the hypopharynx to the inferior aspect of the cricoid. The tumor extended into the left neck, encased the carotid artery, and crossed midline with invasion into the prevertebral musculature. The patient underwent direct laryngoscopy which confirmed the above findings, and biopsy revealed moderately differentiated squamous cell carcinoma. Esophagoscopy was negative. The tumor was staged as T4N2b. The Tumor Board recommended combined chemotherapy and radiation therapy, and the patient was begun on an alternating protocol as per Merlano et al (N Engl J Med, 1992).
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