Purpose: The clinical impact of positron emission tomography (PET) evaluation performed early during first-line therapy in patients with advanced-stage Hodgkin lymphoma, in terms of providing a rationale to shift patients who respond poorly onto a more intensive regimen (PET response-adapted therapy), remains to be confirmed. Patients and Methods: The phase II part of the multicenter HD0801 study involved 519 patients with advanced-stage de novo Hodgkin lymphoma who received an initial treatment with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and who underwent an early ifosfamide-containing salvage treatment followed by stem-cell transplantation if they showed a positive PET evaluation after two cycles of chemotherapy (PET2). The primary end point was 2-year progression-free survival calculated for both PET2-negative patients (who completed a full six cycles of ABVD treatment) and PET2-positive patients. Overall survival was a secondary end point. Results: In all, 103 of the 512 evaluable patients were PET2 positive. Among them, 81 received the scheduled salvage regimen with transplantation, 15 remained on ABVD (physician’s decision, mostly because of minimally positive PET2), five received an alternative treatment, and two were excluded because of diagnostic error. On intention-to-treat analysis, the 2-year progression-free survival was 76% for PET2-positive patients (regardless of the salvage treatment they received) and 81% for PET2-negative patients. Conclusion: Patients with advanced-stage Hodgkin lymphoma for whom treatment was at high risk of failing appear to benefit from early treatment intensification with autologous transplantation, as indicated by the possibility of successful salvage treatment in more than 70% of PET2-positive patients through obtaining the same 2-year progression-free survival as the PET2-negative subgroup.

Purpose: To compare the accuracy of magnetic resonance (MR) imaging and combined fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT), alone and in combination, in detection and restaging treated nasopharyngeal carcinoma (NPC). Materials and Methods: This retrospective study was performed after institutional review board approval and informed consent were obtained. Sixty-three consecutive patients treated for NPC underwent follow-up with both MR imaging and FDG PET/CT. Findings were evaluated according to the TNM classification. Final diagnosis was confirmed at biopsy or imaging follow-up for at least 6 months. Proportions and their 95% confidence intervals were computed; for comparison of data obtained separately from MR imaging and FDG PET/CT and those obtained from their combined use, the McNemar test was used. P < .05 was considered to indicate a statistically significant difference. Results: There was a trend toward greater overall accuracy of MR over PET/C...

Introduction: The increased bone degradation in osteolytic metastases depends on stimulation of mature osteoclasts and on continuous differentiation of new pre-osteoclasts. Metalloproteinases (MMP)-13 is expressed in a broad range of primary malignant tumours and it is emerging as a novel biomarker. Recent data suggest a direct role of MMP-13 in dissolving bone matrix complementing the activity of MMP-9 and other enzymes. Tumour-microenvironment interactions alter gene expression in malignant breast tumour cells promoting osteolytic bone metastasis. Gene expression profiles revealed that MMP-13 was among the up-regulated genes in tumour-bone interface and its abrogation reduced bone erosion. The precise mechanism remained not fully understood. Our purpose was to further investigate the mechanistic role of MMP-13 in bone osteolytic lesions. Methods: MDA-MB-231 breast cancer cells that express MMP-13 were used as a model for in vitro and in vivo experiments. Conditioned media from MDA-MB-231 cells were added to peripheral blood mononuclear cultures to monitor pre-osteoclast differentiation and activation. Bone erosion was evaluated after injection of MMP-13-silenced MDA-MB-231 cells into nude mice femurs. Results: MMP-13 was co-expressed by human breast tumour bone metastases with its activator MT1-MMP. MMP-13 was up-regulated in breast cancer cells after in vitro stimulation with IL-8 and was responsible for increased bone resorption and osteoclastogenesis, both of which were reduced by MMP inhibitors. We hypothesized that MMP-13 might be directly involved in the loop promoting pre-osteoclast differentiation and activity. We obtained further evidence for a direct role of MMP-13 in bone metastasis by a silencing approach: conditioned media from MDA-MB-231 after MMP-13 abrogation or co-cultivation of silenced cells with pre-osteoclast were unable to increase pre-osteoclast differentiation and resorption activity. MMP-13 activated pre-MMP-9 and promoted the cleavage of galectin-3, a suppressor of osteoclastogenesis, thus contributing to pre-osteoclast differentiation. Accordingly, MMP-13 abrogation in tumour cells injected into the femurs of nude mice reduced the differentiation of TRAP positive cells in bone marrow and within the tumour mass as well as bone erosion. Conclusions: These results indicate that within the inflammatory bone microenvironment MMP-13 production was up-regulated in breast tumour cells leading to increased pre-osteoclast differentiation and their subsequent activation.

The objective of this study was to explore the ability of the initial Gleason score (GS) to predict the rate of detection of recurrent prostate cancer (PCa) with (18)F-choline PET/CT in a large cohort of patients. Data from 1,000 patients who had undergone (18)F-choline PET/CT because of biochemical evidence of relapse of PCa between 2004 and 2013 were retrieved from databases at 4 centers. Continuous data were compared by the Student t test or ANOVA, and categoric variables were compared by the χ(2) test. Univariable and multivariable analyses were performed by logistic regression. The GS at diagnosis was less than or equal to 6 in 257 patients, 7 in 347 patients, and greater than 7 in 396 patients. The results of 645 PET/CT scans were positive for PCa recurrence. Eighty-one percent of the positive PET/CT results were found in patients with a PSA level of greater than or equal to 2 ng/mL, 43% were found in patients with a PSA level of 1-2 ng/mL, and 31% were found in patients with a PSA level of less than or equal to 1 ng/mL; 78.8% of patients with positive PET/CT results had a GS of greater than 7. The results of (18)F-choline PET/CT scans were negative in 300 patients; 44% had a GS of less than or equal to 6, 35% had a GS of 7, and 17% had a GS of greater than 7. PET/CT results were rated as doubtful in only 5.5% of patients (median PSA, 1.8 ng/mL). When the GS was greater than 7, the rates of detection of (18)F-choline PET/CT were 51%, 65%, and 91% for a PSA level of less than 1 ng/mL, 1-2 ng/mL, and greater than 2 ng/mL, respectively. In univariable and multivariable analyses, both a GS of 7 and a GS of greater than 7 were independent predictors for positive (18)F-choline PET/CT results (odds ratios, 0.226 and 0.330, respectively; P values for both, <0.001). A high GS at diagnosis is a strong predictive factor for positive (18)F-choline PET/CT scan results for recurrent PCa, even when the PSA level is low (i.e., ≤1 ng/mL).

Background: Current diagnosis and staging of neuroendocrine tumors (NETs) are significantly improved by the introduction of the chromogranin A (CgA) assay in plasma or serum as a tumor marker, and by the use of somatostatin receptor scintigraphy (SRS) for tumor localization. However, the clinical role of CgA assay compared with SRS in the management of NETs has not been well elucidated. Patients and methods: Sixty-three consecutive patients with a histological diagnosis of NET underwent plasma CgA assay and SRS for tumor staging (23 cases), evaluation of tumor response (18 cases) and evaluation of tumor recurrence on follow-up (22 cases). Twenty-one patients had well-differentiated neuroendocrine tumors (WDNETs: 18 gastroenteropancreatic tumors and three lung NETs); 22 patients had well-differentiated neuroendocrine carcinomas (WDNECs: 17 gastroenteropancreatic carcinomas, two lung neuroendocrine carcinomas and three neuroendocrine carcinomas of unknown origin) and 20 patients had poorly differentiated neuroendocrine carcinomas (PDNECs: 14 extra-pulmonary small-cell carcinomas and six Merkel cell carcinomas). Almost all (58 of 63) NETs were non-functioning. The quantitative determination of CgA was performed in plasma using an enzyme immunoassay with a cut-off value fixed at 34 U/l. Scintigraphies with indium 111‐DTPA-octreotide (¹¹¹In-pentetreotide) included whole-body images and single photon emission computed tomography (SPECT) scans of the chest and abdomen. Results: SRS results were compared with CgA findings and final clinical data. The overall sensitivity of SRS and CgA, based on the final clinical data, was 77% and 55%, respectively, whereas the specificity of both SRS and CgA was 94%. Concerning tumor type, SRS accuracy was 95% for WDNETs, 86% for WDNECs and 60% for PDNECs; CgA accuracy was 76% for WDNETs, 68% for WDNECs and 50% for PDNECs. With regard to disease extent, SRS sensitivity was 100% for limited disease and 72% for advanced disease; CgA sensitivity was 43% for limited disease and 57% for advanced disease. Conclusions: In our NET series, SRS proved to be more sensitive than CgA, with equivalent specificity. Tumor differentiation influences the sensitivity of SRS and CgA analysis. In addition, the plasma CgA level is related to tumor secretory activity. Nevertheless both SRS and CgA should be considered useful tools in the diagnostic work-up of NET patients.