Hay, Ian

Background: Historical outcomes in anaplastic thyroid carcinoma (ATC) are poor, with a median survival of only 5 months and <20% of patients surviving 1 year from diagnosis. We hypothesized that survival in newly diagnosed patients with stages IVA and IVB locoregionally confined ATC might be improved by utilizing an aggressive therapeutic approach, prioritizing both the eradication of disease in the neck and preemptive treatment of occult metastatic disease. Methods: Between January 1, 2003, and December 31, 2007, 25 new ATC patients were evaluated at our institution. Of these 25 patients, 10 (40%) had metastatic disease at diagnosis and therefore underwent palliative treatment, whereas 5 (20%) had regionally confined disease and desired treatment at their local medical facilities. The remaining 10 consecutive patients (40%) had regionally confined ATC and elected aggressive therapy combining individualized surgery (where feasible), intensity-modulated radiation therapy (IMRT), and radiosensitizing + adjuvant chemotherapy intending four cycles of docetaxel + doxorubicin. Outcomes were assessed on an intention to treat basis. Results: There were no deaths from therapy, but hospitalization was required in two patients (20%) because of treatment-related adverse events. Five patients (50%) are alive and cancer-free, all having been followed >32 months (range: 32–89 months; median: 44 months) with a median overall Kaplan–Meier survival of 60 months. Overall survival at 1 and 2 years was 70% and 60%, respectively, compared to <20% historical survival at 1 year in analogous patients previously treated with surgery and conventional postoperative radiation at our and other institutions. Conclusions: Although based upon a small series of consecutively treated patients, an aggressive approach combining IMRT and radiosensitizing plus adjuvant chemotherapy appears to improve outcomes, including survival in stages IVA and IVB regionally confined ATC, but remains of uncertain benefit in patients with stage IVC (metastatic) disease. Also uncertain is the optimal chemotherapy regimen to use in conjunction with IMRT. Further multicenter randomized trials are required to define optimal therapy in this rare but deadly cancer.

Abstract Background Controversy exists regarding the aggressiveness of initial therapy in childhood papillary thyroid cancer (PTC). Few studies with long‐term outcome exist and second primary malignancies have rarely been analyzed. Methods We studied 215 PTC patients younger than 21 years old managed during 1940 through 2008. The patients were aged 3–20 year old (median age = 16 years); the median follow‐up was 29 years. Recurrence and mortality details were taken from a computerized database. Results Median primary tumor size was 2.2 cm. Six percent had distant metastases at presentation, 5% had incomplete tumor resection, 86% had nodes removed at initial surgery, and 78% had nodal metastases. After complete surgical resection, PTC recurred in 32% by 40 years. At 20 years, the recurrence rates at local, regional, and distant sites were 7, 21, and 5%, respectively. During 1940–1969, local and regional recurrence rates after unilateral lobectomy (UL) were significantly ( P < 0.001) higher than after bilateral lobar resection (BLR). During 1950–2008 radioiodine remnant ablation (RRA) was administered within 18 months to 32%; it did not diminish the 25‐year regional recurrence rate of 16% seen after BLR alone ( P = 0.86). Only two fatal events from PTC occurred at 28 and 30 years, for a cause‐specific mortality at 40 years of only 2%. All‐causes mortality rates did not exceed expectation through 20 years, but from 30 through 50 years, the number of deaths was significantly ( P < 0.001) higher than predicted. Fifteen of 22 deaths (68%) resulted from nonthyroid malignancy. Conclusion Survival from childhood PTC should be expected, but later death from nonthyroid malignancy is disconcerting. Seventy‐three percent of those who died from nonthyroid malignancy had received postoperative therapeutic irradiation.

AbstractBackgroundIntense disease surveillance and frequent lymph node metastases (LNMs) in papillary thyroid cancer (PTC) have resulted in increased locoregional recurrences. We examined the safety and efficacy of an optimized surgical approach including preoperative ultrasonograpy (US), bilateral thyroidectomy, routine compartment VI dissection, and lateral neck dissection for LNM.MethodsDuring 1999–2006, a total of 420 patients underwent optimized primary surgery; 291(69%) females, median age 46 years; follow‐up 98%, median 4.4 years. Patients were reviewed for tumor characteristics, pattern of LNM, staging, and outcomes.ResultsTotal or near‐total thyroidectomy was performed in 212 (51%) and 208 (49%) patients, respectively. Tumors were multicentric, 40% (average 1.7 cm); were bilateral, 30%; and showed extrathyroidal extension, 17%. Overall, 223 (53%) patients had LNMs: 213 (51%) were central and 85 (20%) were lateral jugular. pTNM staging: I, 258 (61%); II, 35 (8%); III, 88 (21%); IV, 39 (9%). AGES (age, grade, extension, and size—thyroid tumor; and MACIS (metastasis, age, completeness of resection, invasion, and size) prognostic scores were low risk in 362 (86%) and 352 (84%), respectively. Relapse developed in 57 (14%) patients: LNM in 44, soft tissue local recurrence (LR) in 5, distant metastases (DM) in 8. Hypoparathyroidism occurred in 5 (1.2%) patients and 1 had unintentional laryngeal nerve damage. Relapse with LNM occurred in previously operated fields in 19 (5%) patients, 11(3%) from disease virulence (LR or DM), preoperative false‐negative (FN) US in 12 (3%), and combination of FN‐US and recurrence in the operated field in 5 (1%) patients.ConclusionsRecurrence was limited to 5% of patients when the extent of disease was accurately defined and potentially curable. This optimized surgical strategy is relatively safe.

Background: Anaplastic thyroid carcinoma (ATC) is one of the most aggressive solid tumors in humans. The use of positron emission tomography (PET) with 18 F-fluorodeoxyglucose ( 18 F-FDG) in ATC has not been studied, and only a few case reports have been published. The objective of this study was to investigate the potential contribution of 18 F-FDG PET to the clinical management of patients with ATC. Methods: All patients with ATC studied with 18 F-FDG PET from August 2001 through March 2007 were included. The PET results were correlated with computed tomography, ultrasound, magnetic resonance imaging, bone scan, histology, and clinical follow-up. The FDG uptake was semiquantified as maximum standard uptake value. Any change in the treatment plan as a direct result of the PET findings as documented in the clinical notes was recorded. Results: Sixteen patients were included. True-positive PET findings were seen for all primary tumors, in all nine patients with lymph node metastases, in five out of eight patients with lung metastases, and in two patients with distant metastases other than lung metastases. In 8 of the 16 patients, the medical records reported a direct impact of the PET findings on the clinical management. Conclusions: ATC demonstrates intense uptake on 18 F-FDG PET images. In 8 of the 16 patients (50%), the medical records reported a direct impact of the PET findings on the management of the patient. PET may improve disease detection and have an impact on the management of patients with ATC relative to other imaging modalities.

AbstractBackgroundPatients with papillary thyroid carcinoma (PTC) may suffer recurrence despite thyroidectomy and complete radioiodine (RAI) ablation. Reoperation is vitally dependent on accurate and complete disease localization, typically utilizing cervical ultrasonography (US) and/or computed tomography. Our aim was to determine the comparative value of F18‐fluorodeoxyglucose positron emission tomography (PET) to US for localization of locoregional recurrence in patients who underwent reoperation for recurrent PTC.MethodsFrom 1999 to 2004, 30 patients who underwent re‐exploration and 100 nonoperated patients who were investigated with PET for possible recurrent PTC were reviewed. The surgical group [9 males, 21 females; mean age = 50 years (range = 18–84 years)] all had received RAI ablation. Preoperative thyroid‐stimulating hormone (TSH), thyroglobulin (Tg), and location of metastasis were recorded for each imaging study and surgical exploration. All separate sites that contained disease pathologically must have been identified by imaging for a patient to be considered true positive (TP).ResultsPET scans were TP in 43%, false positive in 7%, false negative (FN) in 50%, and had a sensitivity of 46%. Comparable US results were 86%, 10%, 3%, and 96%. Of the 15 patients with FN PET scans, 13 had lymph node metastasis less than 2 cm in diameter, 11 had Tg ≤ 10 μg/L, and the TSH < 20 in 13. In only 3 of the 30 (10%) patients was PET deemed to add value.ConclusionsAt least with suppressed TSH, PET scanning in reoperative PTC patients appears to offer modest benefit beyond high‐resolution US.

AbstractThe latest World Health Organization International Classification defines papillary thyroid carcinoma by its “follicular cell differentiation. .. as well as characteristic nuclear changes”. However the oxyphilic (Hürthle cell) papillary carcinoma have nuclei which generally resemble the nuclei seen in oxyphilic follicular carcinomas, and such oxyphilic papillary tumors may behave more aggressively than typical papillary cancers. To further characterize these rare tumors, we identified during a 32‐year period 22 patients with oxyphilic papillary cancer and compared them with 1,084 patients with typical papillary cancers and 57 patients with oxyphilic follicular cancers treated by the Mayo surgical group during the same time period. Although typical papillary and oxyphilic papillary cancers were comparable with regards to patient age, tumor size and extent, TNM stage, and prognostic score (AGES), there were significant differences. Compared to typical papillary tumors, oxyphilic papillary cancers had fewer neck nodal metastases at primary diagnosis (5% vs 40%,p<0.0001), were more often DNA non‐diploid (71% vs 21%,p<0.001), and after 10 postoperative years had higher rates of both tumor recurrence (28% vs 11%,p<0.0001) and cause‐specific mortality (1.7% vs 4%,p<0.0005). In these four important respects the oxyphilic papillary cancers more resembled the oxyphilic follicular cancers. For oxyphilic follicular cancers, the frequency of initial neck nodal metastases was 7% (cf 5%); 83% of the oxyphilic follicular tumors were non‐diploid (cf 71%), and at 10 years postoperatively the tumor recurrence and cause‐specific mortality rates were 28% and 18%, insignificantly different from 28% and 17% seen with the oxyphilic papillary cancers. These results demonstrate that oxyphilic papillary tumors are more similar to oxyphilic follicular than typical papillary cancers, and suggest that in a differentiated follicular cell‐derived carcinoma a predominance of oxyphilic cells may be a prognostically more relevant feature than the individual tumor's predominant papillary or follicular morphologic pattern. Perhaps in future Histologic Classifications the World Health Organization should group the oxyphilic papillary cancers with the oxyphilic follicular rather than the typical papillary carcinomas.