The effect of external beam radiotherapy volume on locoregional control in patients with locoregionally advanced or recurrent nonanaplastic thyroid cancer

Between February 2004 and February 2008, 25 patients with locoregionally advanced or recurrent nonanaplastic thyroid cancer were treated with EBRT to the primary or recurrent site and/or regional nodal area at the National Cancer Center (NCC), Korea. Of these, two patients with medullary carcinoma were excluded. This retrospective study was performed in accordance with the guidelines of the Institutional Review Board of the NCC. The patients consisted of nineteen (83%) women and four (17%) men ranging in age from 37 to 76 years (median, 64 years) (Table 1). All patients had a histologically confirmed thyroid carcinoma; nineteen had papillary carcinoma, and four had poorly differentiated carcinoma, which were defined based on ≥ 5 mitoses/10 high power microscopic fields (400×) and/or tumor necrosis[19, 20]. The stage of all patients were determined using the American Joint Committee on Cancer (AJCC) seventh edition staging system [21] and had more than one of the high risk clinicopathologic features, such as the presence of microscopic or gross residual disease, soft tissue extension of the primary tumor (T4), or nodal metastasis (N+). Fifteen (65%) patients had locoregionally recurrent disease. Five (22%) patients had a distant metastasis which was controlled with stable disease at pre-EBRT and these patients' histologic type was all papillary.

Before surgery, a complete medical history, physical examination, routine blood counts, serum chemistry, and imaging studies including neck ultrasound (US), computed tomography (CT) and/or magnetic resonance imaging (MRI) were performed to accurately evaluate the extent of the primary or recurrent tumor and regional lymph nodes and to assess the resectability of the disease. Of the 23 patients, 19 (83%) underwent surgery before EBRT. Eighteen (78%) patients, including 4 with unresectable disease, had gross residual disease, two (9%) patients had microscopic residual disease, and three (13%) patients had no residual disease. After surgery, nineteen (93%) patients received a radioactive iodine (RAI) at a dose of 150 (n = 13) or 200 mCi (n = 6) and four patients, whose composed of three poorly differentiated and one papillary carcinoma patients, did not received a RAI. After surgery and/or RAI, all patients were treated with EBRT.

All patients underwent CT simulation for EBRT in the treatment position, which was generally supine, and they were immobilized from the head to the shoulders using a thermoplastic mask. Target volumes and the normal critical tissues, such as the spinal cord, parotid glands, larynx, and esophagus, were delineated on the treatment planning CT images. Two different EBRT target volumes, according to the patient and physician's preferences (e.g., age, history of recurrence, anxiety, and compliance for EBRT), were executed as follows: 1) In limited field group (LF, n = 11), the median total dose of 62.5 Gy (range, 62.5-67.7 Gy) was delivered to the primary (involved lobe) or recurrent tumor bed and the positive nodal area; 2) in elective field group (EF, n = 12), the median dose of 50 Gy (range, 44-54 Gy) was delivered to the initial target volume [primary (involved lobe) or recurrent tumor bed and regional nodal area in the cervical neck and upper mediastinum] and then median total dose of 62.5 Gy (range, 60-69 Gy) was delivered to boost target volume (tumor bed and positive nodal area). Radiation dose values for all patients were converted to the equivalent dose in 2 Gy fractions using a linear quadratic model, and the α/β ratio was 10 for the acute effects on normal tissues and tumors [22], because the thirteen patients received a daily fraction size of 2.5 Gy, four patients received 2 Gy and the three patients received 1.8 Gy. The planning for the EBRT was done using 3-dimensional conformal radiotherapy (3DCRT) techniques in 17 (74%) patients and intensity modulated radiotherapy (IMRT) techniques in 6 (26%) patients who were difficult to obtain the adequate target coverage within the normal tissues constraints with 3DCRT. When the 3DCRT was used for treating the initial target volume in the EF group, anterior-posterior parallel pair technique, a dominant weighting (3-4:1) to anterior beam as compared to posterior beam together with posterior midline shielding after 36-40Gy, was primarily used. During planning, the mean dose to the parotid gland was constrained to < 26 Gy, and the total doses to the spinal cord, larynx, and esophagus were constrained to < 45 Gy, < 60 Gy, and < 60 Gy, respectively.

Patient follow-up by a radiation oncologist, endocrinologist, or thyroid surgeon was performed every 3 months for the first 2 post-operative years, then every 6 months for up to 5 years, and yearly thereafter. For all patients, follow-up evaluations included a physical examination, complete blood count, liver function test, serum thyroglobulin (Tg) level, neck US and/or CT, ¹³¹I whole body scan, and other radiologic studies, if necessary. Recurrence was demonstrated pathologically by surgical resection, biopsy, or cytology, and/or radiological findings, which increased in size over time; locoregional recurrence was defined as tumor recurrence within a tumor bed or nodal areas in the cervical neck and the upper mediastinum, and distant metastasis was defined as any recurrence outside of the cervical neck and the upper mediastinum. Locoregional recurrence was subdivided into infield and outfield recurrences; infield recurrence was defined as locoregional recurrence within the RT field; and outfield recurrence was defined as locoregional recurrence outside of the RT field.