Thyroid cancer has a small impact on patient-partner relationships and their frequency of sexual activity.

ABSTRACTObjective:This cross-sectional survey examined changes in perceived relationships and sexual activity in a sample of thyroid cancer patients and their partners, taking into account sociodemographic and disease-related variables, as well as such outcome measures as anxiety, depression, fatigue, and quality of life (QoL). METHOD: A total of 38 patients with thyroid cancer who were being treated at the department of nuclear medicine in Zürich or Lucerne over the preceding seven years, as well as their partners, completed questionnaires about the quality of their relationships (RQ), about perceptions of changes in their relationships, and about their frequency of sexual activity. They also filled out prevalidated questionnaires related to anxiety, depression, fatigue, and QoL. RESULTS: Some 17 patients (44.7%) and 16 partners (42.1 %) reported that the cancer diagnosis had changed their relationships. Of these, 10 (26.3%) patients and 9 (23.7%) partners reported positive changes only, while 7 patients (18.4%) and 7 partners (18.4%) reported mixed or negative changes. A perceived mixed/negative relationship change was associated with increased depression and lower RQ in patients and partners, as well as with increased anxiety in patients. While the frequency of sexual activity only changed in roughly half of patients and partners (16 patients [42.1%] and 20 partners [52.6%]), increased sexual activity was associated with lower physical QoL scores and a higher depression score than in counterparts who reported no change. SIGNIFICANCE OF RESULTS: Compared to other cancer sites, in our sample thyroid cancer had a relatively small impact on patient-partner relationships and levels of intimacy. We found that screening patients and their partners with a simple question-"Did the diagnosis of cancer change your relationship?"-can lead to early detection of couples who are potentially at risk for perceived negative relationship changes and can facilitate timely psychosocial referral for couple's therapy.

Early Timing of Thyroidectomy for Hyperthyroidism in Graves' Disease Improves Biochemical Recovery.

BACKGROUND: The role of thyroidectomy as an early treatment for hyperthyroidism has been poorly investigated. Our aim was to examine its success rates, particularly focusing on thyroidectomy as an early treatment. METHODS: Patients with thyroidectomy for hyperthyroidism between February 2008 and October 2014 were included. They were divided into two groups (early and delayed thyroidectomy), and patient characteristics, treatment indications, complications and time to biochemical recovery were analyzed. RESULTS: Ninety-nine patients met the inclusion criteria, of whom 65 (66%) suffered from Graves' disease, 25 (25%) from toxic goiters and 9 (9%) from amiodarone-induced hyperthyroidism. Structural abnormalities of the thyroid (39 patients, 39%) represented the most frequent indications for thyroidectomy. Forty-six patients (46%) underwent an early and 53 (54%) a delayed surgical approach. Patients with Graves' disease undergoing early thyroidectomy did not suffer more often from complications but had a significantly faster biochemical recovery after surgery than those with a delayed thyroidectomy, as judged by a shorter time to reach TSH (121 ± 24 vs. 240 ± 31 days, p = 0.007) and fT4 (91 ± 29 vs. 183 ± 31 days p = 0.015) levels in the normal range. As expected, there were no recurrences of hyperthyroidism. CONCLUSIONS: Early thyroidectomy was neither associated with permanent complications nor thyroid storm, but with a significantly improved biochemical recovery and therefore has to be recommended early in patients with Graves' disease.

Perception of treatment burden, psychological distress, and fatigue in thyroid cancer patients and their partners - effects of gender, role, and time since diagnosis.

OBJECTIVES: The aim of this study was to examine diagnosis and treatment burden as well as psychological distress (anxiety and depression) and fatigue in thyroid cancer patients and their partners, focusing on the effects of gender, role, and time since diagnosis. METHODS: Seventy-one patients diagnosed and treated for differentiated thyroid cancer within the past 7 years, participated in this online study, as well as 40 partners. Standardized questionnaires were used rating anxiety, depression, fatigue, and quality of life. Suffering in the context of diagnosis and treatment was evaluated using numeric analog scales. Patients' most recent hormone status was integrated into analysis. RESULTS: Male and female patients but not their partners had significantly higher mean anxiety scores (p < 0.001) than the norm. Severe fatigue that warrants observation and treatment was reported by two of 21 male patients (9.5%), 12 of 50 female patients (24%), two of 28 male partners (7.1%), and no female partners. With respect to diagnosis and treatment burden, female partners expressed the highest burden, while male patients expressed the lowest. This burden was associated with current fatigue levels in male patients and with current anxiety, depression, and fatigue levels in female patients. CONCLUSIONS: Although both patients and partners suffer from the diagnosis and treatment of differentiated thyroid cancer, only patients are at risk of developing anxiety symptoms or fatigue. A simple question like 'How did being told you have thyroid cancer affect you?' might successfully screen for patients who are at risk.

Diagnostic and prognostic implications of the PAX8-PPARγ translocation in thyroid carcinomas-a TMA-based study of 226 cases.

AIMS: Follicular thyroid carcinoma (FTC) has been a diagnostic challenge for decades. The PAX8-PPARγ rearrangement has been detected in FTC and classic papillary thyroid carcinomas (PTCs). The aims of this study were to assess the presence of PAX8-PPARγ by using tissue microarrays in a large cohort of different thyroid neoplasms, and to assess its diagnostic and prognostic implications. METHODS AND RESULTS: Fluorescence in-situ hybridization (FISH) analysis for PAX8-PPARγ was performed on 226 thyroid tumours, comprising FTCs (n = 59), PTCs (n = 126), poorly differentiated thyroid carcinomas (PDs; n = 34), follicular thyroid adenomas (FTAs; n = 5), and follicular tumours of unknown malignant potential (FTUMPs; n = 2). PAX8-PPARγ was detected in 12% of FTCs, 1% of PTCs, 7% of PDs, and in both cases of FTUMP. There was no correlation between the extent of capsular or vascular invasion and PAX8-PPARγ, or between lymph node or haematogenous metastasis and PAX8-PPARγ. Overall survival (OS), tumour-specific survival (TSS) and relapse-free-survival (RFS) were not influenced by PAX8-PPARγ. CONCLUSIONS: In this study, we demonstrate for the first time the presence of PAX8-PPARγ in PDs and FTUMPs, whereas in FTCs and PTCs the prevalence of PAX8-PPARγ is lower than previously reported. PAX8-PPARγ did not correlate with invasiveness or affect prognosis in any tumour type.

Poorly differentiated oncocytic thyroid carcinoma--diagnostic implications and outcome.

AIMS: Poorly differentiated thyroid carcinomas (PDTC) are an ongoing diagnostic challenge. Although the Turin consensus criteria for PDTC excluded consideration of oncocytic tumours, the World Health Organization (WHO) classification does recognise an oncocytic variant of conventional PDTC. The aims of this study were to establish whether the Turin criteria can be applied to oncocytic PDTC, and to determine if there are prognostic differences between conventional and oncocytic PDTC. METHODS AND RESULTS: We applied the Turin criteria to 129 thyroid carcinomas. We identified 18 oncocytic PDTC and 16 conventional PDTC. Kaplan-Meier analysis revealed a significantly worse outcome for oncocytic PDTC with regard to overall and tumour-specific survival but no difference for relapse-free survival, all of which were confirmed by multivariate analysis. There was no association of survival with gender, age or tumour stage. CONCLUSIONS: The Turin criteria can be applied to oncocytic PDTC and patients with this variant have a decreased survival using conventional radioiodine treatment compared to conventional PDTC and might therefore be candidates for novel treatment modalities.

Limited value of 18F-FDG PET/CT and S-100B tumour marker in the detection of liver metastases from uveal melanoma compared to liver metastases from cutaneous melanoma.

PURPOSE: The objective of this study was to evaluate the value of (18)F-FDG PET/CT and S-100B tumour marker for the detection of liver metastases from uveal melanoma in comparison to liver metastases from cutaneous melanoma. METHODS: A retrospective evaluation was conducted of 27 liver metastases in 13 patients with uveal melanoma (UM) (mean age: 56.8, range: 30-77) and 43 liver metastases in 14 patients (mean age: 57.9, range: 40-82) with cutaneous melanoma (CM) regarding size and FDG uptake by measuring the maximum standardized uptake value (SUV(max)). S-100B serum tumour markers were available in 20 patients. Cytology, histology, additional morphological imaging and follow-up served as reference standard. In nine patients liver metastases were further evaluated histologically regarding GLUT-1 and S-100 receptor expression and regarding epithelial or spindle cell growth pattern. RESULTS: Of 27 liver metastases in 6 of 13 patients (46%) with UM, 16 (59%) were FDG negative, whereas all liver metastases from CM were positive. Liver metastases from UM showed significantly (p < 0.001) lower SUV(max) (mean: 3.5, range: 1.5-13.4) compared with liver metastases from CM (mean: 6.6, range: 2.3-15.3). In four of six (66.7%) patients with UM and liver metastases S-100B was normal and in two (33.3%) increased. All PET-negative liver metastases were detectable by morphological imaging (CT or MRI). S-100B was abnormal in 13 of 14 patients with liver metastases from CM. S-100B values were significantly higher (p = 0.007) in the CM patient group (mean S-100B: 10.9 microg/l, range: 0.1-115 microg/l) compared with the UM patients (mean: 0.2 microg/l, range: 0.0-0.5 microg/l). Histological work-up of the liver metastases showed no obvious difference in GLUT-1 or S-100 expression between UM and CM liver metastases. The minority (36%) of patients with UM had extrahepatic metastases and the majority (86%) of patients with CM had extrahepatic metastases, respectively. There was a close to significant trend to better survival of UM patients compared with CM patients (p = 0.06). CONCLUSION: FDG PET/CT and serum S-100B are not sensitive enough for the detection of liver metastases from UM, whereas liver metastases from cutaneous melanoma are reliably FDG positive and lead regularly to increased S-100B tumour markers. The reason for the lower FDG uptake in UM liver metastases remains unclear. We recommend to perform combined contrast-enhanced PET/CT in order to detect FDG-negative liver metastases from UM.

Baseline staging of melanoma with unknown primary site: the value of serum s100 protein and positron emission tomography.

BACKGROUND: Baseline staging is important in all melanoma types, including melanoma with unknown primary site (MUP). Staging includes different examination strategies, each with different accuracy. OBJECTIVE: To determine the value of serum S100 protein levels and positron emission tomography (PET) in the baseline staging of MUP. METHODS: Twenty patients with MUP were evaluable for the analysis between 1996 and 2007 with both S100 assessment and PET performed for baseline staging. RESULTS: Serum S100 was elevated in 7 patients (35%). The PET scan detected the metastases in 6 of 7 patients with elevated serum S100 protein showing a strong correlation (p = 0.005). Patients with metastases had significantly higher serum S100 levels (p = 0.01) than the ones without. Serum S100 protein was shown to be discriminative between patients with and without metastases (receiver-operating characteristic, p = 0.012) with 75% sensitivity and 92% specificity. CONCLUSION: Serum S100 protein appears to be a sensitive as well as specific marker to detect metastases. We therefore might recommend serum S100 assessment to be included in the baseline staging of MUP.

Staging of non-small-cell lung cancer with integrated positron-emission tomography and computed tomography.

BACKGROUND: We compared the diagnostic accuracy of integrated positron-emission tomography (PET) and computed tomography (CT) with that of CT alone, that of PET alone, and that of conventional visual correlation of PET and CT in determining the stage of disease in non-small-cell lung cancer. METHODS: In a prospective study, integrated PET-CT was performed in 50 patients with proven or suspected non-small-cell lung cancer. CT and PET alone, visually correlated PET and CT, and integrated PET-CT were evaluated separately, and a tumor-node-metastasis (TNM) stage was assigned on the basis of image analysis. Nodal stations were identified according to the mapping system of the American Thoracic Society. The standard of reference was histopathological assessment of tumor stage and node stage. Extrathoracic metastases were confirmed histopathologically or by at least one other imaging method. A paired sign test was used to compare integrated PET-CT with the other imaging methods. RESULTS: Integrated PET-CT provided additional information in 20 of 49 patients (41 percent), beyond that provided by conventional visual correlation of PET and CT. Integrated PET-CT had better diagnostic accuracy than the other imaging methods. Tumor staging was significantly more accurate with integrated PET-CT than with CT alone (P=0.001), PET alone (P<0.001), or visual correlation of PET and CT (P=0.013); node staging was also significantly more accurate with integrated PET-CT than with PET alone (P=0.013). In metastasis staging, integrated PET-CT increased the diagnostic certainty in two of eight patients. CONCLUSIONS: Integrated PET-CT improves the diagnostic accuracy of the staging of non-small-cell lung cancer.

Single-photon emission computed tomography/computed tomographyfor sentinel node mapping in breast cancer.

Accurate lymph node staging is essential for the prognosis and treatment in patients with cancer. The sentinel lymph node is the first node to which lymphatic drainage and metastasis from the primary tumor occurs. In malignant melanoma and breast cancer, the sentinel lymph node detection and biopsy already have been implemented into clinical practice. Currently, 2 techniques are used to identify the sentinel lymph nodes: technetium-99m-labeled colloid and blue dye. After peritumoral injection, the material migrates through the lymphatics to the first lymph nodes draining the tumor. The precise anatomic localization of the sentinel lymph nodes is important for minimal invasive surgery and to avoid incomplete removal of the sentinel lymph nodes. All sentinel lymph nodes should be resected to achieve a complete nodal staging. In the inguinal or low-axillary nodal stations, planar scintigraphic images mostly are adequate for the localization of the sentinel lymph nodes. However, in the regions of the head and neck, the chest, and the pelvis, an imaging method for the more precise anatomic localization of the sentinel lymph nodes preoperatively is highly desired. Recently, integrated single-photon emission computed tomography and computed tomography (SPECT/CT) scanners have become available. Initial reports suggest that integrated SPECT/CT might have an additional value in sentinel lymph node scintigraphy in head and neck tumors and tumors draining to the pelvic lymph nodes. We evaluated the clinical use of integrated SPECT/CT in the identification of the sentinel lymph nodes in patients with operable breast cancer. In our experience, localization and identification of sentinel lymph nodes was more accurate by integrated SPECT/CT imaging in comparison with planar images and SPECT images, respectively. In this report, the experiences of sentinel lymph node imaging with SPECT/CT are summarized.

Diagnosis, treatment and long-term outcome of solitary fibrous tumours of the pleura.

OBJECTIVE: Solitary fibrous tumours of the pleura (SFTP) are rare and can histologically be differentiated into benign and malignant forms. The aim of this study is to present new cases, and discuss up-to-date preoperative examinations, the role of video-assisted thoracic surgery and long-term outcome. METHODS: Between 1993 and 2006, 27 SFTPs were diagnosed (14 females, mean age+/-SD, 62.3+/-9.6 years) at our institution. Medical records were reviewed, and follow-up was obtained by repeated examinations or contact with general practitioners. RESULTS: SFTPs were associated with symptoms in 63% of all cases. In the six patients in which positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) was performed preoperatively, malignant lesions were all found to be positive. Complete resection was achieved by video-assisted thoracic surgery in 15 and anterolateral thoracotomy in 12 patients. Mean hospital stay was shorter for patients operated by video-assisted thoracic surgery compared to thoracotomy, 4.5 (range 3-6) versus 7.5 (range 4-25) days, respectively (p<0.01). Histology revealed 17 benign and 10 malignant SFTP. Mean+/-SD tumour diameter of malignant SFTPs was larger than in benign forms, 11.9+/-7.1 versus 6.1+/-3.5 cm, respectively (p<0.01). Tumour recurrence was recognised in four patients with malignant SFTPs at a median time interval after surgery of 38 (range 6-122) months, two late deaths occurred resulting from tumour recurrences. CONCLUSIONS: SFTPs can be treated minimally invasively by video-assisted thoracic surgery with short hospital stay. Large SFTPs with increased FDG-uptake have a high likelihood for malignancy. Long-term follow-up is mandatory in malignant SFTPs because of late recurrences associated with death.

S-100B and FDG-PET/CT in therapy response assessment of melanoma patients.

OBJECTIVE: To compare the value of the tumor marker S-100B protein and fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) in patients treated for melanoma metastases. METHODS: In 41 patients with proven melanoma metastases, S-100B measurements and FDG-PET/CT were performed before and after therapy. The change of S-100B levels (DeltaS-100B) was assessed. In all patients, therapy response was assessed with PET/CT using visual criteria and change of maximal standard uptake value (DeltaSUV(max.)) or total lesion glycolysis (DeltaTLG). RESULTS: In 15 of 41 patients (37%), S-100B values were not suitable because they were normal before and after therapy. In 26 patients, S-100B was suitable for therapy response assessment. PET/CT was suitable for response assessment in all patients. Correlations between DeltaS-100B and DeltaTLG (r = 0.850, p < 0.001) and between DeltaS-100B and DeltaSUV(max.) (r = 0.818, p < 0.001) were both excellent. A complete agreement between S-100B and PET/CT response assessment was achieved in 22 of 26 patients. In 4 patients, therapy response differed between the S-100B and PET/CT findings, but subsequent S-100B measurements realigned the S-100B results with the later PET/CT findings. CONCLUSION: In a third of our patients with metastases, the S-100B tumor marker was not suitable for therapy assessment. In these patients, imaging techniques remain necessary, and FDG-PET/CT can be used for response assessment.

Etiology of solitary extrapulmonary positron emission tomography and computed tomography findings in patients with lung cancer.

PURPOSE: The aim of this prospective study was to assess the incidence and the nature of solitary extrapulmonary [18F] fluorodeoxyglucose (FDG) accumulations in patients with non-small-cell lung cancer (NSCLC) staged with integrated positron emission tomography and computed tomography (PET/CT) and to evaluate the impact on management. PATIENTS AND METHODS: A total of 350 patients with NSCLC underwent whole-body PET/CT imaging. All solitary extrapulmonary FDG accumulations were evaluated by histopathology, further imaging, or clinical follow-up. RESULTS: PET/CT imaging revealed extrapulmonary lesions in 110 patients. In 72 patients (21%), solitary lesions were present. A diagnosis was obtained in 69 of these patients, including 37 (54%) with solitary metastases and 32 (46%) with lesions unrelated to the lung primary. Histopathologic examinations of these 32 lesions revealed a second clinically unsuspected malignancy or a recurrence of a previous diagnosed carcinoma in six patients (19%) and a benign tumor or inflammatory lesion in 26 patients (81%). The six malignancies consisted of carcinoma of the breast in two patients, and carcinoma of the orbit, esophagus, prostate, and non-Hodgkin's lymphoma in one patient each. Benign tumors and inflammatory lesions included eight colon adenomas, four Warthin's tumors, one granuloma of the lower jaw, one adenoma of the thyroid gland, one compensatory muscle activity due to vocal chord palsy, two occurrences of arthritis, three occurrences of reflux esophagitis, two occurrences of pancreatitis, two occurrences of diverticulitis, one hemorrhoidal inflammation, and one rib fracture. CONCLUSION: Solitary extrapulmonary FDG accumulations in patients with newly diagnosed lung cancer should be analyzed critically for correct staging and optimal therapy, given that up to half of the lesions may represent unrelated malignancies or benign disease.

Visualization of Parathyroid Hyperplasia Using 18F-Fluorocholine PET/MR in a Patient With Secondary Hyperparathyroidism.

Several imaging modalities exist for the detection of parathyroid adenomas in patients with primary hyperparathyroidism. Unlike solitary parathyroid adenoma, parathyroid hyperplasia in patients with secondary hyperparathyroidism hitherto is difficult to assess with any imaging modality. Our case of a young patient with chronic kidney failure illustrates that F-fluorocholine PET/MR might be an imaging tool suitable for the diagnosis and presurgical assessment of parathyroid hyperplasia.

[CME: Radioactive iodine therapy in thyroid cancer]. / CME: Radiojodbehandlung des Schilddrüsenkarzinoms.

Differentiated thyroid carcinomas represent about 90% of all thyroid tumors and are divided in papillary and follicular carcinomas. Their prognosis is good, however, recurrences are not rare. Their ability to accumulate iodine is used for the radioactive iodine treatment. The aim of the postoperative radioactive iodine ablation therapy is the complete elimination of remnant thyroid cells and sensitive staging (Fig. 1). The recurrence rate decreases after a complete thyroid ablation. Furthermore, thyroglobulin can be used as a sensitive tumor marker. Radioactive iodine treatment by itself describes the therapy of metastases. An exception is the papillary microcarcinoma, which in general is treated by a lobectomy alone.

Tall cell papillary thyroid carcinoma: new diagnostic criteria and mutations in BRAF and TERT.

The tall cell (TC) variant of papillary thyroid carcinoma (PTC) has an unfavorable prognosis. The diagnostic criteria remain inconsistent, and the role of a minor TC component is unclear. Molecular diagnostic markers are not available; however, there are two potential candidates: BRAF V600E and telomerase reverse transcriptase (TERT) promoter mutations. Using a novel approach, we enriched a collective with PTCs that harbored an adverse outcome, which overcame the limited statistical power of most studies. This enabled us to review 125 PTC patients, 57 of which had an adverse outcome. The proportion of TCs that constituted a poor prognosis was assessed. All of the tumors underwent sequencing for TERT promoter and BRAF V600E mutational status and were stained with an antibody to detect the BRAF V600E mutation. A 10% cutoff for TCs was significantly associated with advanced tumor stage and lymph node metastasis. Multivariate analysis showed that TCs above 10% were the only significant factor for overall, tumor-specific, and relapse-free survival. Seven percent of the cases had a TERT promoter mutation, whereas 61% demonstrated a BRAF mutation. The presence of TC was significantly associated with TERT promoter and BRAF mutations. TERT predicted highly significant tumor relapse (P<0.001). PTCs comprised of at least 10% TCs are associated with an adverse clinical outcome and should be reported accordingly. BRAF did not influence patient outcome. Nevertheless, a positive status should encourage the search for TCs. TERT promoter mutations are a strong predictor of tumor relapse, but their role as a surrogate marker for TCs is limited.

Sensitivity and Specificity of Dual-Isotope 99mTc-Tetrofosmin and 123I Sodium Iodide Single Photon Emission Computed Tomography (SPECT) in Hyperparathyroidism.

PURPOSE: Despite recommendations for 99mTc-tetrofosmin dual tracer imaging for hyperparathyroidism in current guidelines, no report was published on dual-isotope 99mTc-tetrofosmin and 123I sodium iodide single-photon-emission-computed-tomography (SPECT). We evaluated diagnostic accuracy and the impact of preoperative SPECT on the surgical procedures and disease outcomes. METHODS: Analysis of 70 consecutive patients with primary hyperparathyroidism and 20 consecutive patients with tertiary hyperparathyroidism. Imaging findings were correlated with surgical results. Concomitant thyroid disease, pre- and postoperative laboratory measurements, histopathological results, type and duration of surgery were assessed. RESULTS: In primary hyperparathyroidism, SPECT had a sensitivity of 80% and a positive predictive value of 93% in patient-based analysis. Specificity was 99% in lesion-based analysis. Patients with positive SPECT elicit higher levels of parathyroid hormone and higher weight of resected parathyroids than SPECT-negative patients. Duration of parathyroid surgery was on average, approximately 40 minutes shorter in SPECT-positive than in SPECT-negative patients (89 ± 46 vs. 129 ± 41 minutes, p = 0.006); 86% of SPECT-positive and 50% of SPECT-negative patients had minimal invasive surgery (p = 0.021). SPECT had lower sensitivity (60%) in patients with tertiary hyperparathyroidism; however, 90% of these patients had multiple lesions and all of these patients had bilateral lesions. CONCLUSION: Dual-isotope SPECT with 99mTc-tetrofosmin and 123I sodium iodide has a high diagnostic value in patients with primary hyperparathyroidism and allows for saving of operation time. Higher levels of parathyroid hormone and higher glandular weight facilitated detection of parathyroid lesion. Diagnostic accuracy of preoperative imaging was lower in patients with tertiary hyperparathyroidism.

In vivo profiling reveals immunomodulatory effects of sorafenib and dacarbazine on melanoma.

Sorafenib is a multi-kinase inhibitor used alone or in combination with dacarbazine to treat metastasized melanoma. Our study investigated the relationship between metabolic response assessed by PET-CT and global transcriptome changes during sorafenib and dacarbazine therapy in patients with advanced melanoma. We conducted an open-label, investigator-initiated study that enrolled 13 sorafenib-naïve Stage IV melanoma patients, whose metastases were accessible for repeated biopsies. Treatment regimen included orally administered sorafenib and intravenous dacarbazine. Biopsies of skin or superficial lymph node metastases were taken before treatment (baseline), during sorafenib and after dacarbazine therapy and used for transcriptional profiling and validation experiments. Serum samples were evaluated for cytokine production. Metabolic response to therapy was observed in 45.5% of patients. The study drugs were well tolerated. We observed a clear upregulation of interferon (IFN)-stimulated immune response genes in profiled metastases. The IFNγ-induced gene signature seemed to be enhanced after addition of dacarbazine to sorafenib. Serum IFNγ also increased during therapy, particularly after addition of dacarbazine. Induction of IFNγ stimulated genes correlating with increased serum IFNγ was predictive of better clinical outcome and responders who had significantly higher serum IFNγ levels lived longer. Our data reveal in situ changes in melanoma metastases during treatment with sorafenib and dacarbazine and suggest an additional mechanism of action through immunomodulation.

Radiation treatment planning with an integrated positron emission and computer tomography (PET/CT): a feasibility study.

PURPOSE: To investigate the usefulness of hardware coregistered PET/CT images for target volume definition. METHODS AND MATERIALS: Thirty-nine patients presenting with various solid tumors were investigated. CT and a FDG-PET were obtained in treatment position in an integrated PET/CT scanner, and coregistered images were used for treatment planning. First, volume delineation was performed on the CT data. In a second step, the corresponding PET data were used as an overlay to the CT data to define the target volume. Delineation was done independently by two investigators. RESULTS: Coregistered PET/CT showed good fusion accuracy. The GTV increased by 25% or more because of PET in 17% of cases with head-and-neck (2/12) and lung cancer (1/6), and in 33% (7/21) in cancer of the pelvis. The GTV was reduced > or =25% in 33% of patients with head-and-neck cancer (4/12), in 67% with lung cancer (4/6), and 19% with cancer of the pelvis (4/21). Overall, in 56% (22/39) of cases, GTV delineation was changed significantly if information from metabolic imaging was used in the planning process. The modification of the GTV translated into altered PTV changes exceeding >20% in 46% (18/39) of cases. With PET, volume delineation variability between two independent oncologists decreased from a mean volume difference of 25.7 cm(3) to 9.2 cm(3) associated with a reduction of the standard deviation from 38.3 cm(3) to 13.3 cm(3) (p = 0.02). In 16% of cases, PET/CT revealed distant metastasies, changing the treatment strategy from curative to palliative. CONCLUSION: Integrated PET/CT for treatment planning for three-dimensional conformal radiation therapy improves the standardization of volume delineation compared with that of CT alone. PET/CT has the potential for reducing the risk for geographic misses, to minimize the dose of ionizing radiation applied to non-target organs, and to change the current practice to three-dimensional conformal radiation therapy planning by taking into account the metabolic and biologic features of cancer. The impact on treatment outcome remains to be demonstrated.

Why most PET of lung and head-and-neck cancer will be PET/CT.

Experience in our and other institutions with PET/CT imaging of lung and head and neck cancers has shown that this new modality has higher specificity and sensitivity than PET alone and in certain settings even when compared to PET and CT viewed side by side. The largest experience exists with non-small cell lung cancer (NSCLC), in which it has been demonstrated that PET/CT is superior to PET and CT in T and in N staging. Superiority in M staging has yet to be demonstrated. CT contrast media enhancement is probably only necessary when a substantial mediastinal tumor component is present. In such cases, delineation of tumor from vascular structures is relevant. In ENT tumors, PET/CT also appears to be superior to PET, and probably also to PET and CT viewed side by side. Early information suggests that contrast media enhancement for staging may not be required, but the data available is still limited. In both settings, it is interesting to note that in a number of patients, second metachronous tumors are discovered with PET/CT, mainly localized in the GI tract.