Jean Lumbroso

Microcarcinoma of the thyroid gland

Patients with thyroid microcarcinoma (TMC) have favorable long term prognoses. However, recurrences in the neck and distant metastases have been reported. The authors investigated independent factors associated with recurrence in an effort to define therapeutic guidelines.

Prophylactic Lymph Node Dissection for Papillary Thyroid Cancer Less Than 2 cm: Implications for Radioiodine Treatment

OBJECTIVE Prophylactic neck dissection for small papillary carcinoma remains controversial. Radioiodine ablation is not recommended for tumors less than 10 mm and depends on various factors for tumors between 10 and 20 mm. The aim was to determine the effect of lymph node (LN) staging on the indication for treatment with radioiodine. PATIENTS AND METHODS We conducted a retrospective study of 115 patients presenting with papillary thyroid carcinoma less than 2 cm without ultrasonographically detectable cervical LN treated by total thyroidectomy and complete selective dissection of the central and lateral compartment. Radioiodine treatment was based on definitive pathology (tumor and LN). Follow-up was based on neck ultrasound and thyroglobulin levels. RESULTS LN were found for 41.7% of cases. Radioiodine was not used for 42% of patients with tumors less than 20 mm and no metastatic LN. Fifty-eight percent of patients were treated with radioiodine due to LN metastasis, extracapsular thyroid invasion, or unfavorable histological subtype. LN status affected the indication for radioiodine in 30.5% of cases classified as T1, 12 cases with tumors less than 10 mm but with LN metastases (who received radioiodine), and 13 cases with tumors between 10 and 20 mm but without LN metastases (who did not receive radioiodine). Definitive vocal fold paralysis and hypoparathyroidism each occurred in 0.9% of cases. At 1 yr, ultrasound was normal in all patients, and recombinant human TSH-stimulated thyroglobulin was undetectable for 97% of the patients. CONCLUSION Precise LN staging by prophylactic neck dissection for tumors initially staged T1N0 modified the indication for radioiodine ablation for 30% of patients.

Progression of medullary thyroid carcinoma: assessment with calcitonin and carcinoembryonic antigen doubling times

OBJECTIVE The progression of medullary thyroid cancer is difficult to assess with imaging modalities; we studied the interest of calcitonin and carcinoembryonic antigen (CEA) doubling times and of Ki-67 labeling and mitotic index (MI). PATIENTS AND METHODS Fifty-five consecutive medullary thyroid carcinoma (MTC) patients with elevated calcitonin levels underwent repeated imaging studies in order to assess tumor burden and progression status. We looked for relationships between tumor burden and levels of calcitonin and CEA and between progression status according to the response evaluation criteria in solid tumors (RECIST) and calcitonin and CEA doubling times, and Ki-67 labeling and MI. RESULTS The calcitonin and CEA levels were correlated with tumor burden. Ten patients with calcitonin levels below 816 pg/ml had no imaged tumor foci. Among the 45 patients with imaged tumor foci, 19 had stable disease and 26 had progressive disease, according to the RECIST. The calcitonin and CEA doubling times were strongly related to disease progression, with very few overlaps: 94% of patients with doubling times shorter than 25 months had progressive disease and 86% of patients with doubling times longer than 24 months had stable disease. Ki-67 labeling and MI were not significantly associated with disease progression. CONCLUSION For MTC patients, the doubling times of both calcitonin and CEA are efficient tools for assessing tumor progression.

Phase II Trial of Consolidation Docetaxel and Samarium-153 in Patients With Bone Metastases From Castration-Resistant Prostate Cancer

PURPOSE To assess docetaxel combined with samarium-153-ethylene diamine tetramethylene phosphonic acid (EDTMP), a radiopharmaceutical with a high affinity for bone, in patients with castration-resistant prostate cancer (CRPC). PATIENTS AND METHODS Patients with bone metastases from CRPC who achieved a response or stabilization after four cycles of docetaxel and estramustine were given consolidation docetaxel 20 mg/m(2)/wk for 6 weeks and samarium-153-EDTMP (37 MBq/kg) during week 1. Prostate-specific antigen (PSA) response was assessed by using consensus criteria, and pain was assessed by using a visual analog scale (VAS). This study used a Simon two-step design with PSA-progression-free survival (PFS) as the primary end point. RESULTS Forty-three patients were included in the trial. A PSA response was obtained in 77% (95% CI, 61% to 82%). The pain response rate was 69% (95% CI, 49% to 85%). At least five of the six planned weekly injections of docetaxel were administered to 34 patients (81%). The consolidation docetaxel-samarium-153-EDTMP regimen was well tolerated; there was no febrile neutropenia, and only two episodes (5%) of rapidly reversible grade 3 thrombocytopenia occurred. Although a serum PSA relapse eventually occurred in all patient cases, this regimen resulted in pain control in the long-term. The median PSA-PFS was 6.4 months (95% CI, 6 to 7 months). The median survival was 29 months (95% CI, 22 to 31); the 1-year survival rate was 77% (62% to 87%); and the 2-year survival rate was 56% (41% to 70%). CONCLUSION Combining docetaxel and samarium-153-EDTMP in patients with bone metastases from CRPC is well tolerated, and it yields major pain relief that persists long after treatment. Overall survival compares favorably with that expected in this population of patients, most of whom exhibit symptoms.

Malignant pheochromocytoma: Clinical, biological, histologic and therapeutic data in a series of 20 patients with distant metastases

Twenty patients, 16 males and 4 females, aged 11–76 yr, were treated for a metastatic pheochromocytoma at our institution between 1985 and 1990. A neurofibromatosis was associated in 4. Thirteen patients had a unilateral adrenal tumor, 3 had an extraadrenal retroperitoneal tumor, 2 had a bilateral adrenal pheochromocytoma, one had a unilateral tumor with a contralateral medullary hyperplasia and one an adrenal and an extraadrenal pheochromocytoma. Metastases occurred in all patients, at presentation in 11,10 to 30 months later in 7, and 9 and 28 yr later, respectively in two. Histology did not afford conclusive evidence for malignancy. Catecholamine hyperproduction was present in all, predominantly affecting norepinephrine. Neuron Specific Enolase level was elevated in 11, Neuropeptide Y level in 9 and procalcitonin level in 11/18. High dopamine, methoxytyramine and homovanilic acid excretion levels seemed to correlate with large tumors or terminal stage. MIBG uptake was found in 16 after a diagnostic dose and in 1 only after a therapeutic dose. Surgery was performed on primary tumor in 18 and on distant métastase in 10. lodine-131 MIBG therapy was performed in 11, among whom 9 were évaluable. Cumulative activity ranged from 100 to 711 mCi, in 1 to 6 courses. Symptomatic improvement occurred in 5 patients, stabilization was observed in 3 and tumor partial response in two, which lasted for 28 and 9 months, respectively terminating in a rapidly progressing disease with bone marrow involvement. Moderate myelosuppression occurred in 4 patients. Chemotherapy gave no response in 7 evaluable patients. Fourteen patients died with a median survival of 16 months from diagnosis of metastases (range 3–60). Response to therapy was poor and warrants further cooperative trials.

Staging of peritoneal carcinomatosis: enhanced CT vs. PET/CT.

PurposeTo assess and compare the performance of CT and 18F-FDG-PET/CT in the evaluation of peritoneal carcinomatosis (PC).Method and materialsThirty consecutive patients with PC and scheduled for a surgery underwent a CT of the abdomen and pelvis and a whole-body 18F-FDG PET/CT. The extent of PC was assessed precisely using the peritoneal cancer index combining the distribution of tumor throughout 11 abdominopelvic regions with a lesion size score. CT and PET/CT imaging results were compared in all patients with intraoperative findings using an interclass correlation test.ResultsThe presence of PC was correctly determined on CT and PET/CT in 23/28 and 16/28 patients, respectively. The extent of PC was understaged with CT and PET/CT in 27 patients and overstaged with CT and PET/CT in 1 and 2 patients, respectively. The interclass correlation was 0.53 (moderate) between CT and surgery and 0.12 (low) between PET/CT and surgery. The interclass correlation was higher for mucinous tumor (0.63) than for non-mucinous (0.16) on CT imaging whereas no difference was found in PET/CT.ConclusionThe intraperitoneal assessment of the extent of carcinomatosis, necessary to assess prognosis and treatment planning, is not accurate enough with CT and PET/CT imaging.

Correlation of Early Metastatic Response by123I-Metaiodobenzylguanidine Scintigraphy With Overall Response and Event-Free Survival in Stage IV Neuroblastoma

PURPOSE Metaiodobenzylguanidine (MIBG), specifically taken up in cells of sympathetic origin, provides a highly sensitive and specific indicator for the detection of metastases in neuroblastoma. The aim of this study was to correlate early response to therapy by MIBG scan, using a semiquantitative scoring method, with the end induction response and event-free survival (EFS) rate in stage IV neuroblastoma. PATIENTS AND METHODS Seventy-five children older than 1 year and with stage IV neuroblastoma had 123I-MIBG scans at diagnosis, after two and four cycles of induction therapy, and before autologous stem-cell transplantation. The scans were read by two independent observers (concordance > 95%) using a semiquantitative method. Absolute and relative (score divided by initial score) MIBG scores were then correlated with overall pretransplantation response, bone marrow response, and EFS. RESULTS The pretransplantation response rate was 81%, and the 3-year EFS rate was 32%, similar to a concomitant group of 375 stage IV patients. The median relative MIBG scores after two, four, and six cycles were 0.5, 0.24, and 0.12, respectively. The probability of having a complete response or very good partial response before transplantation was significantly higher if the relative score after two cycles was < or = 0.5, or, if after four cycles, the relative score was < or = 0.24. Patients with a relative score of < or = 0.5 after two cycles or a score of < or = 0.24 after four cycles had an improved EFS rate (P =.053 and.045, respectively). CONCLUSION Semiquantitative MIBG score early in therapy provides valuable prognostic information for overall response and EFS, which may be useful in tailoring treatment.

Histologic Results of Para-Aortic Lymphadenectomy in Patients Treated for Stage IB2/II Cervical Cancer With Negative [18F]Fluorodeoxyglucose Positron Emission Tomography Scans in the Para-Aortic Area

PURPOSE Histologic results of complete para-aortic lymphadenectomy were studied in patients treated for stage IB2/II cervical carcinoma who had no para-aortic uptake on [(18)F]fluorodeoxyglucose positron emission tomography combined with integrated computed tomography (FDG-PET/CT). PATIENTS AND METHODS Patients were treated between 2004 and 2006 for stage IB2/II cervical cancer. Magnetic resonance imaging of the abdomen and pelvis and FDG-PET/CT were initially performed. Patients with no para-aortic abnormalities were treated with external pelvic radiation therapy and concomitant chemotherapy followed by utero-vaginal brachytherapy. Para-aortic lymphadenectomy was then performed. FDG-PET/CT images were reviewed by two nuclear medicine specialists. RESULTS Thirty-eight patients were studied. Three patients had histologically proven para-aortic involvement (metastatic nodes with capsular rupture in the para-aortic area), leading to a negative predictive value of 92% for para-aortic nodal involvement. CONCLUSION In this study, three of 38 patients with no para-aortic uptake on [(18)F]FDG-PET/CT imaging had histologically proven para-aortic node involvement. PET/CT imaging without histologic examination of the para-aortic area used to determine radiation therapy fields in stage IB2/II cervical cancer would overlook 8% of patients with histologic para-aortic nodal involvement.

Do histological, immunohistochemical, and metabolic (radioiodine and fluorodeoxyglucose uptakes) patterns of metastatic thyroid cancer correlate with patient outcome?

The aim of this study is to search for relationships between histology, radioiodine ((131)I) uptake, fluorodeoxyglucose (FDG) uptake, and disease outcome in patients with metastatic thyroid cancer. Eighty patients with metastatic thyroid cancer (34 males, 46 females, mean age at the time of the diagnosis of metastases: 55 years) were retrospectively studied. All patients were treated with radioactive iodine and evaluated by FDG-positron emission tomography (PET). Primary tumor tissue sample was available in all cases. Forty-five patients (56%) had a papillary, 12 (15%) a follicular, and 23 (29%) a poorly differentiated thyroid cancer. Cellular atypias, necrosis, mitoses, thyroid capsule infiltration, and vascular invasion were frequently detected (70, 44, 52, 60, and 71% respectively). Metastases disclosed FDG uptake in 58 patients (72%) and (131)I uptake in 37 patients (45%). FDG uptake was the only significant prognostic factor for survival (P=0.02). The maximum standardized uptake value and the number of FDG avid lesions were also related to prognosis (P=0.03 and 0.009). Age at the time of the diagnosis of metastases (P=0.001) and the presence of necrosis (P=0.002) were independent predictive factors of FDG uptake. Radioiodine uptake was prognostic for stable disease (P=0.001) and necrosis for progressive disease at 1 year (P=0.001). Histological subtype was not correlated with in vivo tumor metabolism and prognosis. In conclusion, FDG uptake in metastatic thyroid cancer is highly prognostic for survival. Histological subtype alone does not correlate with (131)I/FDG uptake pattern and patient outcome. Well-differentiated thyroid cancer presenting histological features such as necrosis and FDG uptake on PET scan should be considered aggressive differentiated cancers.

Performance of 18Fluorodeoxyglucose-Positron Emission Tomography and Somatostatin Receptor Scintigraphy for High Ki67 (>10%) Well-Differentiated Endocrine Carcinoma Staging

OBJECTIVE The purpose of this prospective study was to compare the performance of (111)In-octreotide somatostatin receptor scintigraphy (SRS) and (18)fluorodesoxyglucose positron emission tomography (FDG-PET) in aggressive well-differentiated endocrine carcinoma (WDEC) defined by a high Ki67 (≥10%). METHODS Eighteen consecutive patients explored in a single hospital between November 2003 and 2008 for high Ki67 (≥10%) WDEC were prospectively included. WDEC were sporadic in 17 cases and secreting in 16 cases. FDG-PET, SRS, and computed tomography (CT) were performed within a maximum of 3 months and reviewed by two independent readers. For each patient, an analysis per organ and lesion was performed. Both the results of conventional imaging and the highest number of metastatic organs and distinct lesions visualized by all imaging methods including SRS, FDG-PET, and thoraco-abdomino-pelvic CT were considered for the determination of the standard. Correlation between tumor slope and maximum standardized uptake value, Ki67 value, and grade of uptake at SRS was evaluated. RESULTS FDG-PET, SRS, and CT showed at least one lesion in 18 (100%), 15 (83%), and 17 (94%) patients, respectively. A total of 254 lesions were diagnosed in 59 organs. FDG-PET, SRS, and CT detected 195 (77%), 109 (43%), and 195 (77%) lesions in 53 (90%), 30 (51%), and 39 (66%) organs, respectively. FDG-PET, compared to SRS, detected more, the same as, and less lesions in 14 (78%), one (6%), and three (17%) patients, respectively. A statistical trend was found between Ki67 value and tumor slope (P = 0.07). Median survival after diagnosis was 25 months (range, 6-71 months). CONCLUSION These results suggest that FDG-PET is more sensitive than the SRS for high Ki67 WDEC staging.