Interobserver variability in target volume delineation of hepatocellular carcinoma : An analysis of the working group "Stereotactic Radiotherapy" of the German Society for Radiation Oncology (DEGRO).

BACKGROUND: Definition of gross tumor volume (GTV) in hepatocellular carcinoma (HCC) requires dedicated imaging in multiple contrast medium phases. The aim of this study was to evaluate the interobserver agreement (IOA) in gross tumor delineation of HCC in a multicenter panel. METHODS: The analysis was performed within the "Stereotactic Radiotherapy" working group of the German Society for Radiation Oncology (DEGRO). The GTVs of three anonymized HCC cases were delineated by 16 physicians from nine centers using multiphasic CT scans. In the first case the tumor was well defined. The second patient had multifocal HCC (one conglomerate and one peripheral tumor) and was previously treated with transarterial chemoembolization (TACE). The peripheral lesion was adjacent to the previous TACE site. The last patient had an extensive HCC with a portal vein thrombosis (PVT) and an inhomogeneous liver parenchyma due to cirrhosis. The IOA was evaluated according to Landis and Koch. RESULTS: The IOA for the first case was excellent (kappa: 0.85); for the second case moderate (kappa: 0.48) for the peripheral tumor and substantial (kappa: 0.73) for the conglomerate. In the case of the peripheral tumor the inconsistency is most likely explained by the necrotic tumor cavity after TACE caudal to the viable tumor. In the last case the IOA was fair, with a kappa of 0.34, with significant heterogeneity concerning the borders of the tumor and the PVT. CONCLUSION: The IOA was very good among the cases were the tumor was well defined. In complex cases, where the tumor did not show the typical characteristics, or in cases with Lipiodol (Guerbet, Paris, France) deposits, IOA agreement was compromised.

[Fusion of Continuously Moving Table MRI and PET Improves Lesion Detection in Recurrent Rectal Cancer]. / Kombination von MRT und PET erlaubt genauere Rezidivdiagnostik des Rektumkarzinoms durch Bildfusion.

PURPOSE: It was the aim of this study to investigate the complementary diagnostic performance of a combined pelvic and thoracoabdominal magnetic resonance imaging (MRI) examination and positron emission tomography (PET) enhanced by image fusion in patients with suspected rectal cancer recurrence. PATIENTS AND METHODS: Thirty-one patients with clinically suspected recurrence from rectal cancer were retrospectively included, who had received MRI (high resolution pelvic MRI combined with thoracoabdominal MRI performed during continuous table translation) and (18)F-FDG-PET within 30 days. MRI alone, PET alone, and MRI and PET combined including fusion images were analysed by two observers in consensus. The likelihood of malignancy of all detectable lesions was rated on a 5-point Likert scale. The standard of reference consisted of histopathology and follow-up imaging. Confidence ratings were analysed with a jackknife free response receiver-operator characteristic paradigm (JAFROC). Further test characteristics were derived by considering "probably malignant" and "definitely malignant" lesions as positive test results. RESULTS: The reference standard comprised 150 malignant lesions (48 local, 102 distant). JAFROC analysis revealed overall figures-of-merit of 0.73 for MRI, 0.63 for PET, and 0.83 for the combined approach (differences significant). The sensitivities of MRI, PET and the combined approach were 85.4, 52.1, and 95.8 % for local recurrence and 61.8, 47.1, and 81.4 % for distant recurrence, respectively. CONCLUSION: The combination of local high-resolution MRI, thoracoabdominal continuously moving table MRI and FDG-PET supported by image fusion improves lesion detection in recurrent rectal cancer.

Salvage lymph node dissection with adjuvant radiotherapy for nodal recurrence of prostate cancer.

PURPOSE: We evaluated the impact of salvage lymph node dissection with adjuvant radiotherapy in patients with nodal recurrence of prostate cancer. By default, nodal recurrence of prostate cancer is treated with palliative antihormonal therapy, which causes serious side effects and invariably leads to the development of hormone refractory disease. MATERIALS AND METHODS: A total of 47 patients with nodal recurrence of prostate cancer based on evidence of (11)C-choline/(18)F-choline ((18)F-fluorethylcholine) positron emission tomography-computerized tomography underwent primary (2 of 52), secondary (45 of 52), tertiary (4 of 52) and quaternary (1 of 52) salvage lymph node dissection with histological confirmation. Of 52 salvage lymph node dissections 27 were followed by radiotherapy. Biochemical response was defined as a prostate specific antigen less than 0.2 ng/ml after salvage therapy. The Kaplan-Meier method, binary logistic regression and Cox regression were used to analyze survival as well as predictors of biochemical response and clinical progression. RESULTS: Mean prostate specific antigen at salvage lymph node dissection was 11.1 ng/ml. A mean of 23.3 lymph nodes were removed per salvage lymph node dissection. Median followup was 35.5 months. Of 52 salvage lymph node dissections 24 resulted in complete biochemical response followed by 1-year biochemical recurrence-free survival of 71.8%. Gleason 6 or less (OR 7.58, p = 0.026), Gleason 7a/b (OR 5.91, p = 0.042) and N0 status at primary therapy (OR 8.01, p = 0.011) were identified as independent predictors of biochemical response. Gleason 8-10 (HR 3.5, p = 0.039) as a preoperative variable, retroperitoneal positive lymph nodes (HR 3.76, p = 0.021) and incomplete biochemical response (HR 4.0, p = 0.031) were identified as postoperative predictors of clinical progression. Clinical progression-free survival was 25.6% and cancer specific survival was 77.7% at 5 years. CONCLUSIONS: Based on (11)C/(18)F-choline positron emission tomography-computerized tomography as a diagnostic tool, salvage lymph node dissection is feasible for the treatment of nodal recurrence of prostate cancer. Most patients experience biochemical recurrence after salvage lymph node dissection. However, a specific population has a lasting complete prostate specific antigen response.

Treatment of recurrent prostate cancer following radical prostatectomy: the radiation-oncologists point of view.

Recurrence of prostate cancer after radical prostatectomy is a common event. Salvage radiation therapy (RT) is the mainstay of treatment in cases with recurrence defined as PSA failure, offering the chance of cure. Multiple studies showed that the lower the PSA level at the beginning of salvage RT, the better the treatment outcome. There is evidence that higher radiation doses are associated with improved PSA relapse free rates. Four different recurrence patterns exist: 1) local recurrence in the prostatectomy bed only; 2) loco-regional metastases in the pelvic lymph nodes; 3) distant metastases (most commonly nodal or osseous); 4) a combination of local and distant recurrence. Modern functional imaging modalities like magnetic resonance imaging (MRI) and choline-PET/CT offer additional information to clinical and therapeutic variables and provide high accuracy depending on the level of PSA recurrence and PSA kinetics. These image modalities are valuable tools that can be used for gross tumor volume (GTV) definition in the RT-planning process in the salvage RT setting and guide interdisciplinary salvage therapy strategies in case of locoregional relapse. We discuss the impact of MRI and choline-PET/CT in the salvage setting from the radiation-oncologist point of view.

[Genetics of pheochromocytoma]. / Genetik der Phäochromozytome.

About one third of all patients with a pheochromocytoma are carriers of germ line mutations of 1 of the 10 susceptibility genes. Thus, these patients can be diagnosed and classified with specific tumor syndromes. This group is composed of the entities of multiple endocrine neoplasia type 2 (MEN2) due to mutations in the RET gene, von Hippel-Lindau disease (VHL, VHL gene), the paraganglioma syndromes types 1-4 (PGL1-4) due to mutations of the genes SDHD, SDHAF2, SDHC, SDHB, neurofibromatosis type 1 (NF1) due to mutations of the NF1 gene and familial pheochromocytoma syndromes due to mutations of the SDHA, TMEM127 and MAX genes. Patients with hereditary pheochromocytomas run a lifelong risk of relapse of pheochromocytoma. In addition extraparaganglial tumors are frequent and include medullary thyroid carcinoma in MEN2 or renal cancer or neuroendocrine pancreatic cancer as well as hemangioblastomas of the retina and the central nervous system in VHL. Furthermore, renal cancer may be associated with PGL4 and PGL3. In conclusion, molecular genetic screening is essential for the diagnosis of pheochromocytoma-associated cancer syndromes and is thus the cornerstone for successful lifelong preventive medicine of such patients and their relatives.

Relapsing high grade mucoepidermoid carcinoma. Long-lasting complete response following reirradiation and EGFR blockade.

BACKGROUND AND PURPOSE: The treatment strategy for inoperable recurrent mucoepidermoid carcinoma (MEC) is not well established. Here, we present a case of a relapsed high grade MEC of the salivary glands of the hard palate that was successfully treated with a reirradiation (re-RT) and cetuximab, an antibody against epidermal growth factor receptor (EGFR). CASE REPORT: Twelve years after resection and adjuvant radiotherapy for high grade MEC of the salivary glands, a patient presented with inoperable recurrent disease. She received another 59.4 Gy. In addition, 400 mg/m(2) cetuximab was administered in the first week, followed by six additional weekly courses at 250 mg/m(2). RESULTS: Treatment was well tolerated. The patient is doing well and continuous radiological complete response (CR) is documented for 25 months after completion of the combined treatment. CONCLUSION: Combined re-RT and targeted inhibition of EGFR with cetuximab may be a valuable therapeutic strategy in patients with recurrent localized high grade MEC who are not candidates for radical surgery.

[Metastatic breast carcinoma with neuroendocrine differentiation--its combined therapy with tamoxifen and the somatostatin analog octreotide]. / Metastasiertes Mamma-Karzinom neuroendokriner Differenzierung--kombinierte Therapie mit Tamoxifen und dem Somatostatin-Analogon Octreotid.

HISTORY AND ADMISSION FINDINGS: A 75-year-old woman with histologically confirmed liver metastases from an undiagnosed primary tumor was admitted for further diagnosis and treatment. She had no symptoms and was in a very good general condition. The physical examination was unremarkable. INVESTIGATIONS: The liver enzymes GOT and GPT were slightly elevated. The carcinoembryonic antigen (CEA) and the erythrocyte sedimentation rate (ESR) were markedly raised. Repeat analysis of the liver biopsies revealed a carcinoma with neuroendocrine differentiation (carcinoid). TREATMENT AND COURSE: Chemoembolization of the advanced liver metastases was undertaken. Subsequently the breast tumor was resected. Histological analysis revealed a mammary carcinoma with neuroendocrine differentiation. Postoperative radiotherapy to the breast was instituted and she was started on tamoxifen (30 mg daily). But despite repeat chemoembolization the liver metastases continued to grow. Administration of octreotide, a somatostatin analogue, was begun (200 micrograms twice daily). There were no side effects; the tumor markers showed definite reduction and scintigraphy demonstrated almost complete regression. Computed tomography indicated a dissociated response of the liver metastases to the treatment (some got smaller, one had grown and several new ones had appeared). CONCLUSION: Combined tamoxifen and octreotide treatment of a metastasizing carcinoma of the breast with neuroendocrine differentiation may give effective palliation.