old 40 figures

Anatomy

The posterior third of the tongue, known as the base of the tongue, lies in the oropharynx, posterior and inferior to the palatoglossal arch (anterior tonsillar pillar). It is bounded anteriorly by the circumvallate papillae, laterally by the glossopharyngeal sulci and oropharyngeal walls, and inferiorly by the glossoepiglottic fossae or valleculae and the pharyngoepiglottic fold (Fig. 40-1). [ref: 66]



Embryologically, its epithelium is derived from endoderm, unlike that of the oral tongue, which derives from ectoderm, and its body is formed by thick muscles continuous with those of the oral tongue. These muscles originate from the margins of the mandible and are attached to the hyoid bone. They are critically involved in speech and swallowing.

Epidemiology

Approximately 6400 new cases of tongue cancer were diagnosed in the United States in 1997, with about 1820 deaths occurring from this cancer. [ref: 1] These statistics include both oral tongue and base of tongue, which accounts for approximately 25% of cancers of the tongue.

A large Memorial Sloan-Kettering Cancer Center study of tongue cancers seen over a 30-year period showed that 25% to 30% arose in the base or posterior third of the organ. [ref: 25,33] These cancers more often afflict men (4:1) than women between 40 and 80 years of age, but they also can occur in the young. An analysis of tongue cancer cases over time has shown an increasing incidence in women, presumably because women smoke and drink more now than in the past. [ref: 11,81] Carcinogens contained in tobacco smoke are believed to be the leading cause of tongue cancer, and alcohol appears to act synergistically with tobacco. [ref: 13,62]

Natural History

Base of tongue cancers are usually infiltrating, with superficial ulceration. More tumor is often apparent on palpation than on inspection. By the time of diagnosis, as many as three fourths of these cancers have invaded adjacent structures, including the glossopharyngeal sulcus, pharyngeal wall, larynx, and faucial arch. [ref: 18] Tumors may infiltrate anteriorly into the oral tongue or deeply into the root because no natural anatomic barriers exist to prevent spread. An exophytic squamous cell tumor may arise as a surface mass; this presentation seems to be more common in the glossopharyngeal sulcus. [ref: 13,65]

The base of the tongue contains a rich lymphatic plexus, the branches of which terminate for the most part in the upper anterior cervical or subdigastric lymph nodes. Bilateral and contralateral lymphatic spread is common (Fig. 40-2), and retrograde spread to retropharyngeal lymph nodes has been reported. [ref: 22,44,46,66]



The deeply infiltrating nature of most cancers correlates with the high frequency of lymphatic metastases observed at presentation in as many as 80% of patients overall, with bilateral spread in 30%.

Distant metastases are not uncommon in base of tongue cancer. At Washington University, data showed a distant metastatic rate of 20% for 101 patients who were treated with preoperative radiation therapy and surgery. [ref: 73] It may be even higher in patients with advanced nodal disease. [ref: 53]

Clinical Presentation

Cancers of the base of the tongue, unlike those of the oral tongue, are rarely visualized by the patient and may grow to large size before detection. [ref: 25] The most common presenting symptom is local pain, often described as a sore throat aggravated by swallowing or coughing. The patient can usually point to the site of pain and the location of the tumor and sometimes complains of ipsilateral otalgia. Difficulty in swallowing because of pain is common, but dysphagia and impaired deglutition caused by massive infiltration of the tongue by tumor are less common. In advanced tumors that fix the root of the tongue, poor articulation is caused by impaired tongue mobility.

A common presentation, because of the great propensity for even small nonkeratinizing tumors of the base of the tongue to metastasize lymphatically, is a painless lump in the neck. This sign is more likely to occur in base of tongue, nasopharyngeal, and hypopharyngeal cancers than in cancers of other head and neck sites.

Diagnostic Workup The diagnostic evaluation of patients suspected of having cancer in the base of tongue is initially a matter of inspection and palpation (Table 40-1). Most patients present with disease limited to the oropharynx and neck that can be outlined by direct inspection, mirror examination, and palpation. Assessment of the two-dimensional tumor extent can be made relatively well by mirror examination and palpation when the patient is awake, but the third dimension of the tumor, depth of penetration, is best determined by bimanual palpation of the patient under anesthesia when the tongue is relaxed and the patient free of pain. Plain x-ray films rarely show disease that was not suspected clinically, and even benign conditions may simulate tumor radiographically; double-contrast studies have been suggested for diagnosis of base of tongue cancers. [ref: 2,29] Computed tomography (CT) scans can show retropharyngeal nodes or deep primary extension otherwise unappreciated, [ref: 48] and magnetic resonance imaging (MRI) scans with their superior soft tissue contrast may allow visualization of the depth of infiltration.

Biopsy is best performed in the primary site, leaving clinically apparent neck disease undisturbed before definitive therapy. Neck wound contamination from an incisional biopsy of neck nodes when a primary lesion is elusive may be avoided by biopsies of nonvisible but palpable lesions of the base of tongue or blind biopsies in patients suspected of having tongue cancer. Fine-needle aspiration of palpable neck nodes also may be used to make the initial diagnosis of malignancy.

Staging

The 1992 American Joint Committee (AJC) staging system (Table 40-2) depends on primary size, tongue fixation, nodal size, number, and location. [ref: 4] A criticism of this staging system is that it is largely two dimensional and does not take into account the third dimension, which determines tumor bulk and morphology (e.g., endophytic or exophytic lesions of similar size, which respond differently to similar treatment). [ref: 78] Modifications of this system, such as that of Parsons and colleagues, [ref: 53] which separate stage IV into stages IVA and IVB, may help in comparing series outcomes and choosing among various treatment modalities (Fig. 40-3). [ref: 23]





Pathologic Classification

Squamous cell carcinomas, often poorly differentiated, account for more than 90% of cancers of the base of the tongue. Other cell types include non-Hodgkin's lymphomas (1.2%), which have a more favourable prognosis, and salivary gland tumors (i.e., mucoepidermoid, adenocarcinoma, or adenoid cystic type), which appear to behave more like salivary gland tumors of similar histology in other sites rather than like squamous cell cancers of similar size. [ref: 3,16,25,69,70,73]

Prognostic Factors

Treatment decisions for patients with base of tongue cancer are best made by clinicians with a thorough understanding of the host and tumor characteristics that predict primary, nodal, or distant relapse and survival. Host and tumor factors have been correlated with survival but not with primary, nodal, and distant relapses. [ref: 11,13,14,20,25] Some prognostic information is shown from two studies of base of tongue cancers. [ref: 25,59]

Age and sex are the host characteristics that have prognostic significance. Survival declines with advancing age and is higher for women than for men, possibly because of earlier detection of tumors in women.

Tumor characteristics that have prognostic significance include tumor size and extension, presence or absence of palpable lymph nodes, and location, number, and size of involved lymph nodes. Tumor regression during radiation therapy and histologic differentiation are additional prognostic factors reported. [ref: 40] Oncogene p53 overexpression has been reported to be associated with increased survival. [ref: 60] Overall, base of tongue cancers have a worse prognosis than do their oral tongue counterparts because of greater size at diagnosis, more frequent spread to adjacent structures, and higher rates of lymphatic spread. Stage for stage, they may have prognoses similar to those of oral tongue cancers. [ref: 39] Small exophytic tumors (i.e., superficial surface lesions) have higher rates of local tumor control by surgery or irradiation and a better prognosis than infiltrating or large tumors. Patients with tumors confined to the base of the tongue survive longer than do those with tumors that extend to the faucial arch, oral cavity, or larynx and hypopharynx. [ref: 18,22,30,53,66,75] Patients with vallecular primary lesions have a slightly poorer prognosis than do those with base of tongue primary tumors. [ref: 27] The prognosis is generally better for patients without palpable lymphnodes (N0) and for those with small, ipsilateral, mobile lymph nodes rather than those with large, fixed, contralateral or bilateral nodes. [ref: 53]

General Management

The objectives of therapy are control of the primary tumor andregional lymph nodes, with preservation of anatomy and function. An understanding of the selection factors for tumors that can be controlled by surgery or irradiation alone is emerging; exophytic or surface tumors respond well to irradiation alone, whereas ulcerative, endophytic cancers that are partly or completely fixed require surgery. [ref: 8-10,12,22,53] Unfortunately, many base of tongue cancers are so large at diagnosis that total glossectomy and total laryngectomy would be required, a choice often unpalatable to patients and surgeons alike; these patients may be irradiated for palliation, [ref: 18,25,30,52,64] or if performance status permits, platinum-based chemotherapy and irradiation may be offered. [ref: 50,51]

The clinical course of patients treated by surgery or full-course irradiation alone requires a 2-year follow-up to detect 90% of primary and nodal recurrences, but select groups of patients treated by preoperative irradiation and surgery have required up to 4 years to manifest this percentage of recurrences. [ref: 9,25,59,71] Recurrence in a dissected neck is unusual, but contralateral neck failure in unilaterally irradiated patients has been a common type of neck failure (77%). [ref: 73,82] Distant metastases to lung, bone, liver, and brain may occur late in follow-up, often in patients whose primary tumor and nodes have been controlled by the original treatment. [ref: 14,73] It is likely that some patients who died of locoregional regrowth of tumor already harbored distant micrometastases that had not yet grown to detectable size. About two thirds of patients die of locoregional tumor (50%) or distant metastases (20%), and one-third die of complications of treatment, chronic illness, or second primary cancers. [ref: 41,71,73]

Control of a base of tongue tumor that has regrown after original treatment is difficult and uncommon. The patients most likely salvaged by additional treatment are those who undergo neck dissection for nodal recurrence in the contralateral neck [ref: 41,57,73]; however, some series do report successful retreatment of recurrent primaries with implants. [ref: 37,43]

Surgery Surgical resection by way of a mandibulotomy and neck dissection has been recommended for T1 and T2 cancers. Radical neck dissection yields data for determining the need for postoperative irradiation, which is recommended in patients with disease more extensive than stage N1 or with extracapsular extension. If this approach is used, almost all patients with T1 and T2 primary cancers can retain the mandible. [ref: 15] In our series at Washington University, 47% of patients treated with combined surgery and preoperative irradiation had the mandible preserved. [ref: 73] For T3 and T4 tumors, resection of mandible, partial glossectomy, and flap reconstruction may be more often required. Kraus and colleagues [ref: 42] reported an 86% rate of mandible preservation in a series of 100 patients. Weber and associates [ref: 80] reported a suprahyoid approach with neck dissection for T1 and T2 tumors, avoiding mandible splitting/resection.

Tumors of the lower base of the tongue that involve the valleculae and extend inferiorly to the supraglottic larynx and pyriform sinus may be controlled by partial glossectomy and subtotal supraglottic laryngectomy or partial laryngopharyngectomy with preservation of voice. [ref: 59,73] Conditions required for a subtotal supraglottic laryngectomy include no gross involvement of pharyngoepiglottic fold, preservation of one lingual artery, resection of less than 80% of the base of the tongue, pulmonary function suitable for supraglottic laryngectomy, and medical condition suitable for a major operation. Patients who require extensive glossectomy (i.e., more than half of the base of the tongue or both lingual arteries) or those who are elderly or have poor pulmonary function require total laryngectomy to prevent subsequent chronic aspiration. [ref: 18,25,30,52,58] A surgical technique that allows base of tongue resection with supraglottic laryngectomy and without aspiration has been described by Weisberger and Lingeman. [ref: 81] Lesions that crossed the mid-line were once considered inoperable because they demanded sacrifice of the opposite lingual artery, both hypoglossal nerves, and the superior laryngeal nerves as well as total glossectomy. [ref: 33,52,64] Total glossectomy and reconstruction allowing a reasonable degree of functional recovery may be an appropriate choice for some patients. [ref: 34,63]

Irradiation Alone Irradiation alone is advocated for small or surface tumors and exophytic lesions that do not limit protrusion of the tongue because primary and regional tumor control is quite good in these cases. [ref: 32,38] Base of tongue primary lesions fail more frequently and are less amenable to salvage surgery than anterior tonsillar pillar, tonsillar fossa, or soft palate primary tumors. [ref: 27]

Proper selection of patients for irradiation alone requires examination of the tongue with the patient awake and asleep to accurately gauge the extent of the primary tumor.

The success of radiation therapy is usually a function of tumor volume and morphology. Small T1 and T2 base of tongue tumors without significant infiltration and surface or exophytic T2 and T3 lesions of the glossopharyngeal sulcus (glossopalatine sulcus) are readily controlled by high-dose radiation therapy (Fig. 40-4). [ref: 68]



Size for size, surface and exophytic tumors of the glossopharyngeal sulcus regress more readily and are more easily controlled by irradiation than the usual infiltrating base of tongue cancer. The poor response of infiltrating or endophytic base of tongue tumors has been attributed to hypoxia. [ref: 22,68,73]

Large, unresectable base of tongue cancers that cross the midline and infiltrate and fix the tongue are often irradiated palliatively to achieve as much tumor regression as possible. Those that prove responsive may even be controlled long term by high-dose irradiation. [ref: 53,59]

Surgery and Irradiation Surgery combined with irradiation is best suited for larger tumors
that extend beyond the base of the tongue or infiltrate and partially fix the tongue. Tumors of the upper base of the tongue confined to one side may be resected with preservation of the mandible and primary closure of the pharynx. [ref: 8,66,73,82] Bulky tumors that extend anteriorly into the oral cavity and superiorly or laterally to the faucial arch or pharyngeal wall also may be resected, but hemimandibulectomy and myocutaneous flap reconstruction are often necessary to facilitate closure. [ref: 18,72]

Adjuvant irradiation should be routinely used for resectable T3 and T4 base of tongue cancers to reduce the likelihood of recurrence. [ref: 54,75] Doses of 60 Gy and bilateral fields covering the primary site and upper necks are necessary because of the significant primary tumor burden and the high rate of contralateral and bilateral lymphatic spread. Radiation therapy with these doses is better delivered postoperatively than preoperatively because higher doses can be given after pharyngeal and cutaneous suture lines have healed. [ref: 17] Reviews have demonstrated a trend to the more frequent use of radiation therapy after surgical resection. [ref: 7,75,76]

Radiation Therapy Techniques

Definitive Irradiation Irradiation portals for base of tongue cancer should encompass the primary tumor and its local and regional extensions. Portals should extend superiorly to the base of skull and the floor of the sphenoid sinus to include the retropharyngeal lymphatics, anteriorly to include the faucial arch and a portion of the oral tongue, inferiorly to include the supraglottic larynx, and posteriorly to include the posterior cervical triangle. The primary tumor and both sides of the upper neck are irradiated through opposing lateral fields. Both sides of the lower neck are irradiated through a single anteroposterior field with a mid-line block at the junction between the upper lateral and low-neck fields to prevent spinal cord injury (Fig. 40-5).




Supine patients with bite-block or thermoplastic immobilization receive daily treatment of all fields. The spinal cord is shielded after administration of 40 to 45 Gy, and the posterior cervical triangles are boosted with 9- to 12-MeV electrons to spare the underlying spinal cord. Tissue compensators are used to ensure dose homogeneity and to prevent excessive dose to the supraglottic larynx.

After 40 to 45 Gy with low-energy megavoltage beams, the remaining dose may be delivered with high-energy x-rays to concentrate the dose centrally and to reduce the dose to the parotids, the mandible, and the temporomandibular joints. After 60 Gy is delivered, the fields are reduced to encompass only the primary tumor and may be weighted to the side involved by tumor. The boost dose after 60 Gy may also be delivered by a submental electron beam or low-energy photon beam field. Doses to the primary tumor and palpable lymph nodes range from to 75 Gy delivered in 6.5 to 7.5 weeks; doses for elective irradiation of subclinical microscopic lymphatic metastases should be at least 50 Gy. Treatment plans illustrating dose distributions are shown in Fig. 40-6.




Preoperative Irradiation Preoperative irradiation is designed to reduce the size of the primary tumor and palpable lymph nodes and to eradicate microscopic local extensions and subclinical locoregional metastases. Fields and beam direction are similar to those used for full-course irradiation. Preoperative doses of 45 to 50 Gy are given in 4 to 5 weeks, and surgery is performed during a window of resolving reaction 4 to 6 weeks later.

Postoperative Irradiation To eradicate residual microscopic disease, doses of 56 to 60 Gy (66 Gy for positive margins or extracapsular nodal extension) may be delivered to the primary tumor bed and necks beginning 3 to 4 weeks after surgery.

Interstitial Implants Intraoral placement of radium needles into the base of the tongue was difficult, but skill in percutaneous placement of hollow steel needles and plastic afterloading tubes as described by Pierquin and associates [ref: 56] can be more readily acquired. With this technique, interstitial implantation of the base of the tongue for primary or recurrent tumors has become the routine procedure in several clinics. A nonlooping technique for interstitial boosts also has been described by some investigators. [ref: 6,28,57,74,77] However, Foote and associates [ref: 24] reported no improvement in local control or decrease in morbidity for patients treated with an implant boost compared with external irradiation for base of tongue cancer. In contrast, Harrison and colleagues [ref: 32] reported fewer injuries with a looping implant technique as well as high locoregional tumor control.

Dose Response When the few tumors treated with the lowest doses are excluded, there appears to be a slight dose-response correlation for T3 tumors, a moderate association for T1 and T2 base of tongue cancers, and a marked dose-response relationship for T2 and T3 glossopalatine sulcus cancers (Fig. 40-7).



Improved locoregional tumor control with increasing doses is a function of tumor volume and morphology; small base of tongue cancers and exophytic cancers of the glossopharyngeal sulcus are more radioresponsive and controllable than large infiltrating tumors (Fig. 40-8 and Fig. 40-9). [ref: 26]






Increasing dose is strongly advocated for small, surface, and exophytic lesions but less for large, infiltrating T4 lesions because there is less chance of improved tumor control but an increased risk of damage to the mandible and larynx with higher doses. Determining optimal dose is difficult in advanced cases because improved tumor control increases less rapidly than the incidence of mandibular necrosis for doses in excess of 70 Gy administered in 7 weeks. [ref: 5] Conservation surgery with preservation of the mandible and phonatory larynx and postoperative irradiation (60 Gy in 6 weeks) may achieve the same tumor control with preservation of function and fewer complications than more radical irradiation or radical surgery.

Results of Therapy

Irradiation Most information concerning treatment of base of tongue cancers comes from single-institution reports. Several investigators have reported the advantages of external irradiation plus interstitial implant for treating base of tongue lesions, particularly T1 or T2 lesions. Housset and co-workers reported a local failure rate of 20% with external irradiation plus implantation [ref: 37] but a rate of 43% with external irradiation alone. [ref: 38] Surgery plus external irradiation produced similar results, as did implantation. Because surgery was practical only for peripheral base of tongue tumors and was deemed to have rather poor functional results, external irradiation plus interstitial implant was favored for T1 and T2 lesions. Crook and colleagues [ref: 9] described their 10-year experience with external irradiation and implant for T1 and T2 base of tongue cancers. They had a 5-year local tumor control rate of 85% for T1 and 71% for T2 tumors. The overall disease-free survival rate at 5 years was 50%. Similarly, Harrison and associates [ref: 32] reported actuarial local tumor control and survival of 87.5% at 2 years with neck control in 35 of 36 patients. They also reported consistently better performance status scores and quality of life compared with primary surgery. [ref: 31]

Puthawala and associates [ref: 57] reported their 10-year experience with limited external-beam irradiation and interstitial implant in 70 patients. Eighty-three percent were stage T3 or T4 and had N2 or N3 neck disease. The primary site, vallecula, pharyngeal wall, glossopalatine sulcus, and tonsillar bed and pillars were routinely implanted to encompass the target volume. The neck nodes were separately implanted. Locoregional tumor control for a minimum of 2 years was obtained in 77% of all patients. The overall 5-year actuarial survival rate for the entire group was 35%. There was no difference in actuarial survival between patients with N0 and N1 neck disease, but patients with N2 or N3 disease had inferior survival rates.

Other investigators have advocated the use of external irradiation alone, claiming similar results as with external irradiation plus implants and superior results to surgery. Fein and colleagues, [ref: 21] in 107 patients treated with either once-daily fractionation (47 patients) or twice-daily fractionation (60 patients), observed overall local control of 90% for T1, 92% for T2, 73% for T3, and 35% for T4 disease. The probability of controlling neck disease for all patients with oropharynx cancer, including base of tongue, was 85%. This was achieved with irradiation alone in the early stages and irradiation plus neck dissection for the more advanced patients. The incidence of severe complications was 2.5%, which was reportedly lower than the operative mortality in most surgery series. Jaulerry and colleagues [ref: 40] reported on 166 patients treated with external irradiation alone, resulting in 2-year local control rates of 96% for T1, 57% for T2, 45% for T3, and 23% for T4 lesions. A significant difference in tumor control was observed if tumor regression was complete at the end of treatment compared with partial tumor regression. They also found no dose response for more than 60 Gy in 6 weeks. Nodal control was 86% at 3 years for N0, 78% for N1, and 60% for N2 and N3. They proposed evaluating the regression of tumor at 50 to 55 Gy in an effort to improve the outcome in those with incomplete response.

Other altered fractionation schedules with external irradiation alone have been reported. Mak and associates, [ref: 47] using a concomitant boost in 54 patients with base of tongue cancer treated at M.D. Anderson Cancer Center, reported a 5-year actuarial locoregional control rate of 76% for 53 patients with stage T1 to T3 disease. The concomitant boost resulted in a median dose to the primary tumor of 72 Gy in a median of 42 treatment days. The boost was given concomitantly with the large field as a second daily 1.5-Gy fraction with an interfraction interval of 4 to 6 hours. The therapeutic ratio was reported to be favorable with no persistent or severe late complications. In addition, patients with complete regression in the neck appeared not to need a planned neck dissection.

Finally, Wang [ref: 78] published a retrospective study of split-course accelerated fractionation showing improved local tumor control in carcinomas of the oropharynx, half of which arose in the base of the tongue. At 36 months, an actuarial local tumor control rate of 97% for T1 and T2 lesions and 77% for T3 and T4 lesions was obtained. For all stages, the local control rate was 77%. This compared with only 47% for patients treated with external irradiation using conventional rather than accelerated fractionation (Table 40-3).

Surgery Several series reporting the results of surgical therapy alone for base of tongue cancer illustrate the management challenge. Of 252 patients from Memorial Sloan-Kettering Cancer Center treated before 1965, 56% of patients later failed in the resection bed or neck. [ref: 33] The 5-year survival rate was also low (21%), and there was little opportunity for salvage after primary treatment failure. Results obtained by Whicker and colleagues [ref: 83] at the Mayo Clinic were considerably better but reflect a different patient population. Of 102 patients, 42% survived 5 years after surgical treatment, but only 55% of patients initially had neck node involvement, a low figure compared with most series (80%). [ref: 42] In addition, some of their patients had recurrences after primary radiation therapy for early lesions. Thirty-seven percent of their patients later experienced local or regional disease relapse. A more recent report from Mayo Clinic of 55 patients treated with surgery alone, 50% of whom had N0 and more than 50% of whom had T1 or T2 disease, yielded a 55% relapse in the dissected or undissected necks. The 5-year survival rate was 55%. [ref: 23]

Because even moderately advanced lesions of the base of the tongue have a significant propensity for bilateral neck disease, the surgical approach may be incomplete if bilateral neck exploration is not performed. This limitation is not encountered in radiation therapy of base of tongue cancers because bilateral neck treatment is routine even in N0 cases. Treating only the ipsilateral neck with preoperative radiation therapy yields an unacceptably high rate of contralateral neck recurrences (Fig. 40-10). [ref: 73]





Postoperative Radiation Therapy for Advanced-Stage Base of Tongue Cancer Zelefsky and co-workers [ref: 84] reported on 31 patients with base of tongue and 20 patients with tonsillar fossa cancer treated with surgery and postoperative irradiation. These patients were given postoperative irradiation because of advanced T stage (T3 or T4) in 34 patients, close or positive margins in 33 patients, or multiple positive neck nodes in 43 patients. Seven-year actuarial local control for base of tongue patients was 81%. Treatment interruption had a negative effect on local control, with actuarial control being 64% among those requiring an interruption compared with 93% without interruption. At 7 years, the actuarial incidence of neck failure was 21% for base of tongue patients. The likelihood of distant metastasis in this series at 7 years was 30%, and the incidence of second malignancy was 35%. It was concluded that surgery and postoperative irradiation could provide excellent long-term disease control rates; however, their current strategy was directed toward more tongue preservation without surgery as reported by Harrison and co-workers. [ref: 32]

Overall treatment results for base of tongue cancer, when all stages are considered, appear to be best for combinations of surgery and irradiation, intermediate for surgery alone, and worse for radiation therapy alone (Table 40-4). [ref: 11,33,53,59,61,76,82]

Control of the primary tumor and lymph nodes, along with prognosis, progressively declines with advancing T and N stages. [ref: 44,53,58,61,64,66] Table 40-4 compares the results of various therapeutic approaches.

Management of Recurrent Tumors

Treatment options for recurrent tumors include surgical resection, radiation implants, external-beam irradiation, cryotherapy, laser therapy, chemotherapy, and hyperthermia. Patients with recurrences in the neck can sometimes be salvaged by radical neck dissection alone, and small primary recurrences may respond well to surgery or radiation implants. Interstitial irradiation combined with interstitial hyperthermia was reported to be superior to irradiation alone in patients with recurrences in one study. [ref: 19] However, Langlois and co-workers [ref: 43] reported a 67% probability of local control in 123 patients with recurrent base of tongue cancer treated with **192Ir or with second primary lesions arising in previously irradiated areas. Housset and associates [ref: 37] reported a 48% versus 63% local control rate with continuous versus split-course implants for recurrences, which was not statistically different, but a significantly lower rate of mucosal necrosis was found with the split-course treatment.

Chemotherapy

The role of chemotherapy has been limited. A few agents produce significant regression of the primary and regional tumors. [ref: 14,20,45] In view of their limited efficacy and substantial toxicity, particularly in the elderly and in nutritionally deprived patients, it is difficult to justify the adjuvant use of drugs in this group without a carefully designed protocol study or better predictors for therapeutic response. Because the rate of distant metastasis is significant, particularly in patients with advanced nodal involvement, there is a rationale for developing a successful systemic treatment. Newer drug combinations, usually containing cisplatin, have shown high complete response rates in nonkeratinizing head and neck cancers and may improve results of treatment. They should be tested in advanced cases in prospective clinical trials. [ref: 20,50,52,55,67] Concurrent radiation therapy and weekly docetaxel in elderly patients with oropharyngeal carcinoma.

Sequelae of Treatment

High-dose irradiation for base of tongue cancer causes acute side effects, such as severe mucositis, difficulty in swallowing, loss of taste, xerostomia, and weight loss. Patients must be observed carefully, and nasogastric intubation may become necessary to ensure adequate hydration and caloric intake. Late complications of high doses of irradiation occur in one fourth of the patients and cause significant morbidity (Table 40-5). Necrosis of bone and cartilage with associated pain is a difficult management problem and can necessitate removal of the mandible. Adverse sequelae of doses of irradiation greater than 70 Gy in 7 weeks can be avoided by using compensating filters to ensure dose homogeneity, high-energy x-rays to spare the mandible, temporomandibular joints, and subcutaneous tissues, as well as by using altered fractionation schedules. Moderate doses of adjuvant irradiation of 50 to 60 Gy delivered in 5 to 6 weeks in combination with conservation surgery may reduce the incidence of late radiation complications without compromising tumor control, although producing more functional impairment. [ref: 31] Effects of swallowing therapy on oropharyngeal function in head and neck cancer patients.

Surgery for base of tongue cancer is associated with an operative mortality that ranges from 4% to 7%, which must be weighed against the possibility of improved tumor control and reduction in late radiation-induced sequelae. [ref: 23,42] Because of the proximity of pharyngeal and cutaneous suture lines to the carotid artery, formation of pharyngocutaneous fistulas with carotid artery rupture is a major concern.

Clinical Trials

Prospective clinical trials with combinations of irradiation and surgery for base of tongue cancer have been few and unilluminating. Lawrence and associates [ref: 44] studied the use of 14 Gy preoperatively in two equal fractions completed 24 hours before surgery in 69 patients with head and neck cancer, including tongue, tonsil, soft palate, and hypopharyngeal primary tumors. They compared this group with 74 patients receiving surgery alone and found no difference in local control, morbidity, or mortality.

Strong and colleagues [ref: 72] compared 100 patients with stage II and III cancers of the oropharynx treated with 20 Gy preoperatively in 5 days and surgery within 30 days with those receiving surgery alone. There was no difference in the 5-year survival rate, which was 40% for the two groups. However, both groups had unacceptably high rates (56%) of recurrence in the neck after treatment.

Despite the lack of convincing prospective randomized trials, adjuvant postoperative radiation therapy, allowing safer delivery of higher doses, has become standard treatment in moderately advanced and advanced, operable carcinoma of the base of tongue, decreasing the subsequent T and N failure. [ref: 66,75]

A prospective randomized trial by the Radiation Therapy Oncology Group (RTOG) comparing split-course radiation therapy to a dose of 60 Gy with continuous-course therapy to a dose of 66 Gy did not demonstrate any significant difference in local tumor control between the treatment arms. In this study, 89% of patients had T2 or T3 disease, 75% had N+, and 60% had N3 disease. All five T1 and seven of 10 T2 patients had initial tumor control. When both primary and regional disease were considered, however, only 38% of patients became free of locoregional tumor. Five-year survival results in this group of patients were poor, with only 15% surviving. The overall locoregional failure rates were 84% in the continuous-course group and 73% in the split-course group. These results suggest that external irradiation alone to these doses is insufficient for advanced base of tongue carcinoma. However, the adequacy of the fields and their reproducibility could be questioned because of small size and lack of external landmarks. [ref: 49]

The first prospective randomized trial to demonstrate the superiority of hyperfractionation over standard fractionation for oropharyngeal cancer was reported by Horiot and colleagues [ref: 36] for the European Organization for Research on Treatment of Cancer. They reported a significant improvement in 5-year locoregional tumor control rates for 1.15-Gy twice-daily treatment to 80.5 Gy versus 2 Gy per day irradiation to 70 Gy (57% and 37%, respectively) with no difference in late complications. However, base of tongue cancer was excluded from this trial.

A large RTOG trial (RTOG 90-03) nearing completion compares standard fractionation to hyperfractionation, accelerated hyperfractionation with a split, and standard fractionation plus a concomitant boost in patients with head and neck cancers including base of tongue. If these results confirm and extend those of Horiot, then better selection factors for treating cancers of the head and neck with altered fractionation schedules will have been established.