After unsuccessful surgery, medullary thyroid carcinoma (MTC) may be fatal or remain stable for decades, and precise survival predictors are needed. This study assesses the prognostic value of calcitonin and carcinoembryonic antigen (CEA) doubling-times (DT). This is a retrospective study on 65 MTC patients from 2.9-29.5 yr after surgery. Data registered in the database of the French Neuroendocrine Tumor Group were analyzed anonymously. All patients had abnormal calcitonin levels after total thyroidectomy and bilateral lymph node dissection. Calcitonin and CEA serum levels were measured during routine disease follow-up. To assess DT as prognostic factors, a patient population was extracted from the database. When calcitonin DT was less than 6 months, 5- and 10-yr survivals were three of 12 (25%) and one of 12 (8%), respectively; when between 6 months and 2 yr, 5- and 10-yr survivals were 11 of 12 (92%) and three of eight (37%), whereas all 41 patients with calcitonin DT greater than 2 yr were alive at the end of the study. Tumor-Node-Metastasis (TNM) stage, European Organization for Research and Treatment of Cancer (EORTC) score, and calcitonin DT were significant predictors of survival by univariate analysis, but only calcitonin DT remained an independent predictor of survival by multivariate analysis (P = 0.002) with a proportion of variance explained (PVE) of 37.4%. Calcitonin DT was a better predictor than CEA (PVE 63.3% and 47.0%, respectively). Calcitonin DT calculated using only the first four measurements was also an independent predictor of survival (P < 0.000001; PVE 40.4%). Calcitonin DT may be superior to initial clinical staging and among the most powerful prognostic indicators in MTC.

Posttreatment surveillance for the recurrence of head and neck squamous cell carcinoma (HNSCC) is a diagnostic challenge. Tissue distortion from radiation and surgery can obscure early detection of recurrence by conventional follow-up approaches such as physical examination, CT, and MRI. Several studies have shown that ¹⁸F-FDG PET may be an effective technique for the detection of persistent, recurrent, and distant metastatic HNSCC after treatment. The aim of this prospective study was to determine the benefits of hybrid ¹⁸F-FDG PET/CT in detecting a subclinical locoregional recurrence of HNSCC and distant metastases. The study patients were considered cured of HNSCC on the basis of 12 mo of negative findings on conventional follow-up. We also assessed the diagnostic accuracy of ¹⁸F-FDG PET/CT in these patients. Methods: Ninety-one patients cured of HNSCC without any clinical evidence of recurrence were included. Whole-body ¹⁸F-FDG PET/CT examination was performed 11.6 ± 4.4 mo after the end of the treatment. The gold standard was histopathology or 6 mo of imaging follow-up. Results: The whole-body ¹⁸F-FDG PET/CT examinations had negative results in 52 patients and positive results in 39. Nine of these patients who exhibited abnormal ¹⁸F-FDG uptake in the head and neck area did not have recurrent HNSCC (false-positive). Thirty had proven recurrence. The sensitivity and specificity of ¹⁸F-FDG PET/CT in this study for the diagnosis of HNSCC recurrence were 100% (30/30) and 85% (52/61), respectively. The positive predictive value was 77% (30/39). The negative predictive value was 100% (52/52). The overall accuracy was 90% (82/91). Conclusion: The results of our study confirm the high effectiveness of ¹⁸F-FDG PET/CT in the assessment of HNSCC recurrence and suggest that ¹⁸F-FDG PET/CT is more accurate than conventional follow-up physical examination alone in the assessment of recurrence after previous curative treatment for HNSCC and could be proposed systematically at 12 mo of the usual follow-up.

Purpose: No effective therapy is currently available for the management of patients with metastatic medullary thyroid carcinoma (MTC). The efficacy of pretargeted radioimmunotherapy (pRAIT) with bispecific monoclonal antibody (BsMAb) and a iodine-131 (¹³¹I) –labeled bivalent hapten is evaluated. Patients and Methods: Twenty-nine patients with advanced, progressive MTC, as documented by short serum calcitonin doubling times (Ct DTs), received an anti–carcinoembryonic antigen (CEA)/anti–diethylenetriamine pentaacetic acid (DTPA) –indium BsMAb, followed 4 days later by a ¹³¹I-labeled bivalent hapten. Overall survival (OS) was compared with 39 contemporaneous untreated MTC patients with comparable prognostic indicators. Results: OS was significantly longer in high-risk, treated patients (Ct DT < 2 years) than in high-risk, untreated patients (median OS, 110 v 61 months; P < .030). Forty-seven percent of patients, defined as biologic responders by a more than 100% increase in CtDT, experienced significantly longer survival than nonresponders (median OS, 159 v 109 months; P < .035) and untreated patients (median OS, 159 v 61 months; P < .010). Treated patients with bone/bone-marrow disease had a longer survival than patients without such involvement (10-year OS, 83% v 14%; P < .023). Toxicity was mainly hematologic and related to bone/bone-marrow tumor spread. Conclusion: pRAIT against CEA induced long-term disease stabilization and a significantly longer survival in high-risk patients with Ct DTs less than 2 years, compared with similarly high-risk, untreated patients. Ct DT and bone-marrow involvement appear to be prognostic indicators in MTC patients who undergo pRAIT.

Purpose: This phase I study assessed the maximum tolerated dose (MTD), dose-limiting toxicities (DLT), safety, pharmacokinetics, pharmacodynamics, and clinical activity of the first-in-class dual MEK/RAF inhibitor, RO5126766. Experimental Design: Initial dose-escalation was conducted using once daily dosing over 28 consecutive days in 4-week cycles. Further escalation was completed using 2 intermittent dosing schedules [7 days on treatment followed by 7 days off (7on/7off); 4 days on treatment followed by 3 days off (4on/3off)]. Results: Fifty-two patients received RO5126766 at doses of 0.1 to 2.7 mg once daily, 2.7 to 4.0 mg (4 on/3 off), or 2.7 to 5.0 mg (7 on/7 off). The most common DLTs were elevated creatine phosphokinase (CPK) and blurred vision. The MTD for each dosing schedule was 2.25 mg once daily, 4.0 mg (4 on/3 off), and 2.7 mg (7 on/7 off). The dose/schedule recommended for phase II (RP2D) investigation was 2.7 mg (4 on/3 off). Frequent adverse events included rash-related disorders (94.2%), elevated CPK (55.8%), and diarrhea (51.9%). Cmax occurred 1 to 2 hours after dosing and mean terminal half-life was approximately 60 hours. Pharmacodynamic changes included reduced ERK phosphorylation, an increase in apoptosis in tumor tissue, and a reduction in fluorodeoxyglucose (FDG) uptake after 15 days of dosing. Three partial responses were seen: two in BRAF-mutant melanoma tumors and one in an NRAS-mutant melanoma. Conclusion: This first-in-human study shows that oral RO5126766 has manageable toxicity, a favorable pharmacokinetic/pharmacodynamic profile, and encouraging preliminary antitumor activity in this population of heavily pretreated patients, achieving tumor shrinkage in around 40% of patients across all dose levels and all tumor types. Clin Cancer Res; 18(17); 4806–19. ©2012 AACR.

Positron emission tomography using 18F-fluorodeoxyglucose (FDG-PET) has been successfully evaluated in the management of non-Hodgkin’s lymphoma (NHL).[1][1]–[3][2] Histological transformation (HT) of indolent lymphoma is a dramatic event that occurs in 5–10% of the patients and carries a dismal prognosis.[4][3],[5][4] Previous studies prove that indolent lymphoma entities show a lower FDG uptake when compared with aggressive lymphomas.[6][5]–[8][6] We therefore postulated that FDG-PET/CT identifies aggressive transformation sites and can guide biopsies. [1]: #ref-1 [2]: #ref-3 [3]: #ref-4 [4]: #ref-5 [5]: #ref-6 [6]: #ref-8