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Purpose To evaluate and compare diagnostic sensitivity of positron emission tomography (PET) scanning in carcinoid and islet cell tumor patients with a serotonin and a catecholamine precursor as tracers. Patients and Methods Carcinoid (n = 24) or pancreatic islet cell tumor (n = 23) patients with at least one lesion on conventional imaging including somatostatin receptor scintigraphy (SRS) and computed tomography (CT) scan underwent 11C-5-hydroxytryptophan (11C-5-HTP) PET and 6-[F-18]fluoro-L-dihydroxy-phenylalanin (18F-DOPA) PET. PET findings were compared with a composite reference standard derived from all available imaging along with clinical and cytologic/histologic information. Results In carcinoid tumor patients, per-patient analysis showed sensitivities for 11C-5-HTP PET, 18F-DOPA PET, SRS, and CT of 100%, 96%, 86%, 96%, respectively, and in islet cell tumors of 100%, 89%, 78%, 87%, respectively. In carcinoid patients, per-lesion analysis revealed sensitivities for 11C-5-HTP PET, 11C-5-HTP PET/CT, 18F-DOPA PET, 18F-DOPA PET/CT, SRS, SRS/CT, and CT alone of, respectively, 78%, 89%, 87%, 98%, 49%, 73%, and 63% and in islet cell tumors of 67%, 96%, 41%, 80%, 46%, 77%, and 68%, respectively. In all carcinoid patients 18F-DOPA PET and 11C-5-HTP PET detected more lesions than SRS (P < .001). 11C-5-HTP PET was superior to 18F-DOPA PET in islet cell tumors (P < .0001). In all cases, CT improved the sensitivity of the nuclear scans. Conclusion 18F-DOPA PET/CT is the optimal imaging modality for staging in carcinoid patients and 11C-5-HTP PET/CT in islet cell tumor patients.

Purpose To investigate the safety and clinical utility of the sentinel node procedure in early-stage vulvar cancer patients. Patients and Methods A multicenter observational study on sentinel node detection using radioactive tracer and blue dye was performed in patients with T1/2 (< 4 cm) squamous cell cancer of the vulva. When the sentinel node was found to be negative at pathologic ultrastaging, inguinofemoral lymphadenectomy was omitted, and the patient was observed with follow-up for 2 years at intervals of every 2 months. Stopping rules were defined for the occurrence of groin recurrences. Results From March 2000 until June 2006, a sentinel node procedure was performed in 623 groins of 403 assessable patients. In 259 patients with unifocal vulvar disease and a negative sentinel node (median follow-up time, 35 months), six groin recurrences were diagnosed (2.3%; 95% CI, 0.6% to 5%), and 3-year survival rate was 97% (95% CI, 91% to 99%). Short-term morbidity was decreased in patients after sentinel node dissection only when compared with patients with a positive sentinel node who underwent inguinofemoral lymphadenectomy (wound breakdown in groin: 11.7% v 34.0%, respectively; P < .0001; and cellulitis: 4.5% v 21.3%, respectively; P < .0001). Long-term morbidity also was less frequently observed after removal of only the sentinel node compared with sentinel node removal and inguinofemoral lymphadenectomy (recurrent erysipelas: 0.4% v 16.2%, respectively; P < .0001; and lymphedema of the legs: 1.9% v 25.2%, respectively; P < .0001). Conclusion In early-stage vulvar cancer patients with a negative sentinel node, the groin recurrence rate is low, survival is excellent, and treatment-related morbidity is minimal. We suggest that sentinel node dissection, performed by a quality-controlled multidisciplinary team, should be part of the standard treatment in selected patients with early-stage vulvar cancer.

Purpose The metabolic syndrome may be an important risk factor for cardiovascular disease in long-term survivors of testicular cancer (TC). We investigated the associations between hormone levels and the metabolic syndrome in these men. Patients and Methods We included TC patients cured by orchidectomy and cisplatin-based chemotherapy, stage I TC patients after orchidectomy only, and healthy men of comparable age. Presence of the metabolic syndrome was determined using guidelines from the National Cholesterol Education Program Adult Treatment Panel III. Thyroid-stimulating hormone, follicle-stimulating hormone (FSH), inhibin B, luteinizing hormone (LH), total testosterone, sex-hormone–binding globulin, free testosterone, estradiol, dehydroepiandrosterone sulfate, and insulin-like growth factor 1 were determined in blood. Cortisol metabolite excretion was measured in urine. Results Eighty-six chemotherapy patients (median follow-up, 7 years) were compared with 44 stage I patients and 47 controls. LH and FSH were higher, and inhibin B and total and free testosterone were lower in chemotherapy patients than controls. Adrenal and thyroid hormone production were unaffected. Chemotherapy patients with the metabolic syndrome (n = 22; 26%) had a higher body mass index (BMI) pretreatment, a larger BMI increase during follow-up, lower total testosterone, and higher urinary cortisol metabolite excretion than those patients without the metabolic syndrome. BMI and insulin were associated with the metabolic syndrome, while total testosterone and urinary cortisol metabolite excretion were associated with BMI. Conclusion We found gonadal dysfunction, but normal adrenal and thyroid function. Through its association with BMI, testosterone may play a role in the development of the metabolic syndrome in long-term TC survivors.

4550 Background: Four decades have passed since the introduction of cisplatin-based chemotherapy for metastatic TC, providing the opportunity to evaluate very long-term survival. Although 80-90% of the patients are cured, the effect of treatment on residual life span is unknown. Aim of the study was to investigate life expectancy after TC treatment: from prolonging survival after cancer diagnosis, focus shifts to regaining a normal residual life span. Methods: Patients with metastatic TC treated with cisplatin-based chemotherapy > 20 years ago (1977 - 1996) at the University Medical Center Groningen were included. Survival status and cause of death were obtained from medical records, Netherlands Cancer Registry and general practitioners. Events were defined as death due to any cause (overall mortality) and death due to TC or TC treatment complications (TC specific mortality). Standardized mortality ratios (SMR) were calculated as ratio between observed and expected deaths, derived from the age-matched nationwide male population (Dutch Central Office of Statistics). SMRs were calculated for overall mortality, non TC specific mortality (censoring death from TC or treatment-related complications), mortality from cardiovascular disease (censoring death from other causes than cardiovascular disease (ICD-10 I0-I99)) and mortality from secondary malignancies (censoring death from other causes than secondary malignancies (ICD-10 C0-C99 excluding C62: TC)). Results: We included 321 metastatic TC patients with a median age of 28 years (range 16 - 64) at start of chemotherapy. After a median follow-up of 25 years (range 0 - 38) 106 patients died (33%). SMR for overall mortality was 4.0 (95% CI 3.6 - 4.4) and for non TC specific mortality 1.5 (95% CI 1.1 - 1.9). SMR for secondary malignancies was 1.7 (95% CI 1.0 - 2.2) and for cardiovascular diseases 1.5 (95% CI 0.7 - 2.2). Median age at death was 5-10 years lower in TC patients than expected. Conclusions: Twenty years after cisplatin-based chemotherapy, TC patients have a 50% increased risk of dying from non TC causes compared to the general population. These findings suggest that cisplatin-based treatment for TC comes at the expense of about 7.5 life years and induces early aging.

4561 Background: Testicular cancer (TC) survivors are at risk to develop early cardiovascular morbidity. Close collaboration between oncologists and primary care physicians (PCPs) is mandatory for optimal cardiovascular risk management. We designed a simple shared survivorship care program in which TC patients regularly visit their PCP instead of their oncologist. The primary aim of this study was to test safety and feasibility of shared-care follow-up after chemotherapy for metastatic TC. Methods: TC patients with complete remission after chemotherapy and age ≥18 years were eligible. Participants received a personalized survivorship care plan with scheduled visits to the oncologist and PCP, which was available both on paper and as a mobile application. During PCP visits, signals indicating cancer recurrence, cardiovascular risk and psychosocial issues were assessed. Safety boundaries were defined for the occurrence of failed response to signals indicating cancer recurrence. Patient data were monitored real-time to check if the shared-care follow-up was carried out within these boundaries. Secondary outcomes were satisfaction among TC patients and PCPs, measured with an evaluation questionnaire, and anxiety levels, measured with the Hospital Anxiety and Depression Scale. Results: 64% of eligible TC patients and 99% of the approached PCPs were willing to participate; 162 patients were enrolled in the shared-care program and 241 primary care visits took place. No failures occurred in the detection of relapsed TC. Therefore, the safety boundary was crossed, indicating that shared-care follow-up is a safe alternative to hospital-only follow-up. Four primary care visits were deemed as failed visits because of logistic issues.Anxiety levels did not increase during shared-care follow-up (3.6 vs 3.3 (p = 0.38). Patients were satisfied with the knowledge of PCPs and appreciated this regular contact. 78% of the PCPs would like to extend their role in shared-care follow-up. Conclusions: This easy to use shared survivorship care program is safe and feasible in the follow-up of TC patients. Communication within this patient-centered follow-up program may be further supported with e-health tools. Clinical trial information: NCT01783145.

PURPOSE: To investigate the contribution to recurrence detection and survival of serum squamous cell carcinoma antigen (SCC-ag) analysis in the follow-up of early-stage cervical cancer patients. PATIENTS AND METHODS: Follow-up data were evaluated in patients with early-stage squamous cell cervical cancer treated by radical hysterectomy and pelvic lymphadenectomy with or without radiotherapy. Routine serum SCC-ag determination was performed at each follow-up visit. RESULTS: Recurrent disease occurred in 35 (16%) of 225 patients and was preceded or accompanied by serum SCC-ag elevation 26 times (sensitivity, 74%). In five (14%) of these 35 patients, elevated serum SCC-ag was the first measured clinical indicator. Desite salvage therapy, all five patients died of disease. In the other 31 patients (21 with serum SCC-ag elevation), either symptoms and/or positive signs led to recurrence detection. Median survival time after recurrence was worse (9 months; range, 2 to 112+) for patients with an elevated serum SCC-ag value at recurrence in comparison with patients with normal serum SCC-ag values (20 months; range, 4 to 96; P < .01). In 23 of the 190 patients without recurrences, serum SCC-ag values became falsely elevated. In 16 of these 23 patients, the repeat sample after 6 weeks showed a normal SCC-ag, and in seven patients benign (especially skin) disorders were found. CONCLUSION: Serum SCC-ag analysis results in earlier recurrence detection in a small proportion (14%) of patients but did not contribute to better survival. As long as treatment possibilities for recurrent cervical cancer patients are not improved, serum SCC-ag analysis should not be carried out in routine follow-up.

2009 Background: Response evaluation in glioblastoma (GBM) patients after concomitant radiotherapy and temozolomide (TMZ) is hampered by the occurrence of progressive contrast enhancing lesions on MRI that do not reflect true tumor progression. 18F-fluorothymidine (FLT) is a Positron Emission Tomography (PET) tracer that is taken up by proliferating cells. The goal of this study was to prospectively assess the value of FLT-PET in discriminating between true progression and pseudoprogression in patients with primary GBM treated with radiotherapy and TMZ (NTR3680). Methods: FLT-PET scans were performed before start and 4 weeks after radiochemotherapy. MRI scans were performed at these time points and after 3 cycles of adjuvant TMZ. Macdonald criteria were used for response evaluation on MRI. Pseudoprogression was defined as progressive disease on MRI after radiochemotherapy, with stabilization or improvement of enhancing lesions after 3 cycles of adjuvant TMZ. Changes in SUVmax and tumor to normal brain tis...

11090 Background: Patients withvon Hippel-Lindau (VHL) disease develop benign and malignant vascular tumors. Local vascular endothelial growth factor (VEGF)-A production is likely involved in the d...

10581 Background: Renal cell cancer (RCC) is characterized by high VEGF production leading to excessive angiogenesis. To visualize VEGF, we performed serial 89Zr-bevacizumab-PET scans before and during antiangiogenic treatment in RCC patients. Methods: Metastatic (m) RCC patients who received sunitinib (50 mg once daily, 4 out of 6 weeks) or bevacizumab (10 mg/kg every 2 weeks) plus interferon (IFN 3-9 MU 3x/week), underwent 89Zr-bevacizumab-PET scans at baseline and after 2 and 6 weeks, and CT scans at baseline and every 3 months. Tracer uptake in tumor lesions was quantified with maximum Standardized Uptake Value (SUVmax). Relationship between baseline and Δ SUVmax and time to progression (TTP) was analyzed. Wilcoxon test was used to compare scans, Kaplan-Meier method for survival analysis. Results: 22 out of 26 patients were evaluable, 11 per treatment. On 89Zr-bevacizumab-PET, 131 out of 231 lesions ≥ 10 mm (detection limit) were visible and 125 quantifiable. Mean SUVmax at baseline was 10.1 (SD 8.4; range 2.3 - 46.9). During bevacizumab/IFN treatment, SUVmax consistently decreased (mean decrease 47.0% 95% CI 39.1-54.9, P 11.1 (highest normal tissue uptake) in the 3 most intense lesions than in those with a lower value (median 89.7 vs 22.8 weeks, HR 0.16, 95% CI 0.04 - 0.70). TTP was longer in patients (n=11) with an absolute Δ SUVmax >6.00 in the most intense lesion at 2 weeks (HR 0.25, 95% CI 0.06-0.98). Conclusions: 89Zr-bevacizumab-PET visualizes tumor lesions in mRCC patients. Different changes in tumor tracer uptake after start of bevacizumab/IFN versus sunitinib indicate that these drugs induce different angiogenic responses. High baseline SUVmax and large change in SUVmax corresponded with longer TTP, suggesting that 89Zr-bevacizumab-PET may help to identify patients who benefit the most from antiangiogenic treatment.