External Beam Radiotherapy

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The value of external beam radiotherapy (EBRT) in the management of differentiated thyroid cancer remains controversial because published data are conflicting. In many reports, results are presented with no distinction between prophylactic (adjuvant) postoperative EBRT and treatment of microscopic or macroscopic residual disease. Due to the rarity of the disease and its long natural history there are no prospective randomized controlled trials.

EBRT does not prevent simultaneous administration of radioiodine, although 131I should be given first whenever possible as uptake may be diminished after radiotherapy and, if there is good uptake by tumor, EBRT may become unnecessary. However, 20% of tumors fail to concentrate iodine. Radiotherapy is not indicated in patients with favorable prognostic features, nor in young patients with residual disease demonstrating avid iodine uptake [105]. Patients at higher risk for loco regional recurrence benefit from treatment similar to those with squamous carcinoma of the head and neck [106]. Indications include macroscopic unre-

sectable residual tumor and microscopic disease or involved excision margins. Adjuvant irradiation is required only in older patients with less differentiated cancers unlikely to concentrate radioiodine, especially those with extensive extrathyroidal spread, extracapsular lymph node extension, or recurrent disease (Table 15.2).

Farahati et al. suggest that adjuvant EBRT should be restricted to patients older than 40 years with locally advanced tumors (pT4) which are non-iodine avid [107]. Treatment improved local control in those aged over 40 years with invasive papillary cancer and lymph node involvement from 22% to 90% at 10 years (P = 0.01). A similar group of patients with follicular cancer did not show any significant benefit. Since locoregional recurrence is infrequent in patients without lymph node disease, the addition of EBRT should be discouraged.

In 1985 Tubiana et al. reported on 97 patients treated with EBRT after incomplete surgery [108]: local recurrence at 15 years was 11% in the irradiated group compared to 23% for those treated with surgery alone. More recently Tsang et al. reported on 207 patients (155 papillary, 52 follicular) with residual microscopic disease postoperatively [12]. In the subgroup of papillary cancers, those irradiated had a 10-year cause-specific survival (CSS) of 100% and a local relapse-free rate (LRFR) of 93%; in comparison, the non-irradiated group had a CSS of 95% (P = 0.038) and LRFR of 78% (P = 0.01). EBRT did not significantly affect CSS or LRFR for follicular tumors. The most plausible explanation is that patients with follicular tumors have a worse survival due to hematogenous spread and any effects of local treatment may be obscured by this biological pattern of behavior.

The presence of gross inoperable macroscopic disease is another indication for EBRT. In our retrospective study, EBRT achieved com

Table 15.2 Indications for external beam radiotherapy in differentiated thyroid cancer

Postoperative:

High dose:

3D conformal plan for phase II or intensity modulated radiotherapy (IMRT)

Known macroscopic disease:

131I + 66Gy + 131I

Known microscopic disease:

Age > 45, poor differentiation, Hurthle cell carcinoma

No known residual tumor:

Extensive pT4, extracapsular node extension, recurrent disease

Palliative irradiation:

35Gy 15# over 3 weeks or 6Gy once weekly

Figure 15.7 A and B Phase I: routine phase I comprising anterior and undercouched fields extending from hyoid to carina excluding parotid and submandibular salivary glands. Multileaf collimator protects infraclavicular portions of lungs. Chinstrap immobilization as an alternative to a Perspex shell avoids build-up to the skin and reduces skin toxicity. Occasionally, the upper deep cervical level II nodes must be treated, with the beam extending to the mastoid tips.The mandible and submandibular salivary glands still deserve protection. C Therapy CT scan for planning: large inoperable tumor displacing and compressing trachea. D and E Phase II: right anterior oblique beam encompasses residual tumor and also covers spinal cord. Left anterior oblique beam avoids spinal cord by use of multileaf collimator, limiting total dose to 46Gy.

Figure 15.7 A and B Phase I: routine phase I comprising anterior and undercouched fields extending from hyoid to carina excluding parotid and submandibular salivary glands. Multileaf collimator protects infraclavicular portions of lungs. Chinstrap immobilization as an alternative to a Perspex shell avoids build-up to the skin and reduces skin toxicity. Occasionally, the upper deep cervical level II nodes must be treated, with the beam extending to the mastoid tips.The mandible and submandibular salivary glands still deserve protection. C Therapy CT scan for planning: large inoperable tumor displacing and compressing trachea. D and E Phase II: right anterior oblique beam encompasses residual tumor and also covers spinal cord. Left anterior oblique beam avoids spinal cord by use of multileaf collimator, limiting total dose to 46Gy.

plete regression in 37.5% and partial regression in 25% [109]. Similarly, Chow et al. [110] reported the beneficial effects of EBRT in patients with gross macroscopic residual disease with an improvement in local control from 24% to 56% at 10 years (P < 0.001). EBRT is also effective for advanced and recurrent inoperable Hurthle cell carcinoma, claiming a relatively more important role because this tumor takes up iodine less frequently [111].

Despite the small study size, the 5-year local recurrence rates from Birmingham indicate a possible dose response [112]. These were 63% following a dose of less than 50Gy but only 15% and 18% for doses of 50-54Gy and more than 54 Gy.

Our policy is to use EBRT infrequently because high dose is required and side effects, especially oesophagitis, are unavoidable. The phase I target volume comprises both sides of the neck (bilateral deep cervical plus supra-clavicular nodes), thyroid bed and superior mediastinum from the level of the hyoid down to the carina, with shielding of the subapical portions of the lungs (Figure 15.7A and B). Anterior and undercouched fields ensure comprehensive coverage, with the patient su pine and neck maximally extended. Lead protection of the submandibular salivary glands is required if the treatment volume needs to extend proximally to the tips of the mastoid. A Perspex shell is then fashioned for the phase

II volume which includes sites of micro-or macroscopic tumor. We recommend three-dimensional planning and conformal beam shaping assisted by a multileaf collimator (Figure 15.7C, D, and E). The aim is to deliver 60 Gy in 30 daily fractions over 6 weeks using 4-6 MV photons. The phase I prescription should be a dose of 46 Gy in 2 Gy daily fractions (maximum spinal cord tolerance) with phase II delivering 14Gy in seven fractions. Known residual tumor in the region of the thyroid bed or neck nodes may be treated with a small phase

III volume, adding 6Gy in three fractions, provided there is no additional dose to the spinal cord. Intensity-modulated radiotherapy can improve the dose distribution by minimizing dose to the spinal cord and thus permit dose escalation [113].

A brisk cutaneous erythema is invariable with acute radiation esophagitis, which develops during the third week of radiotherapy. Liquid analgesics, liberal hydration, and ade quate dietary intake are required. Symptoms resolve within 2 weeks after completion of treatment. Acute laryngitis and dysphonia also resolve completely. Late effects include dyspha-gia, which may occur months or years later caused by stricture or motility changes as a result of muscle or nerve damage. Reduction in the length of the esophagus in the phase II volume minimizes such risks. Due to shielding of the subapical portions of the lungs, apical fibrosis may be visible on chest radiograph but is of no clinical significance.

Palliative radiotherapy is indicated for fun-gating nodes, bleeding, stridor, dysphagia, and superior vena caval obstruction due to progressive disease. Bone metastases causing pain, vertebral involvement threatening the spinal cord, long bone involvement if there is a potential for fracture, and brain metastases should also be treated with palliative radiotherapy. Tumor in the lung or mediastinum can be treated if un-resectable. Low dose treatment is inadequate; 35Gy in 15 fractions is required, or 6Gy once weekly for up to four fractions when the central nervous system is not in field.

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