(18)F-FLT-PET for Response Evaluation of MEK Inhibitor Selumetinib (AZD6244, ARRY-142886) in Patients with Solid Tumors.

Selumetinib (AZD6244, ARRY-142886) is a potent, selective, uncompetitive inhibitor of MEK 1 / 2, part of the RAF/MEK/ERK protein kinase signal cascade, which is responsible for tumor. This pilot study was used to explore if (18)F-fluoro-l-thymidine (FLT), a thymidine analogue positron emission tomography (PET) tracer and a surrogate marker for proliferation, can be used as an early predictor of response for patients with solid cancers treated with Selumetinib. FLT-PET scans were performed in four patients at baseline and after 2 weeks of treatment with Selumetinib.

Expression and clinical relevance of MET and ALK in Ewing sarcomas.

Because novel therapeutic options are limited in Ewing sarcomas (ES), we investigated the expression, genetic aberrations and clinical relevance of MET and anaplastic lymphoma kinase (ALK) in ES and determined the relevance of targeting these receptors. MET and ALK protein expression was determined immunohistochemically in 31 (50 samples) and 36 (59 samples) ES patients, respectively. Samples included primary tumors, postchemotherapy resections, metastases and relapses.

Bevacizumab reduces tumor targeting of antiepidermal growth factor and anti-insulin-like growth factor 1 receptor antibodies.

Bevacizumab (antivascular endothelial growth factor [anti-VEGF]) and cetuximab (antiepidermal growth factor receptor [anti-EGFR]) are approved antibodies for treatment of cancer. However, in advanced colorectal cancer, the combination fails to improve survival. As the reason for the lack of activity is unknown, our study aims to determine the effect of bevacizumab on targeting of anti-EGFR and insulin-like growth factor 1 receptor (IGF-1R) antibodies in tumors with single-photon emission computed tomography (SPECT)/CT imaging.

Pheochromocytoma and gastrointestinal stromal tumors in patients with neurofibromatosis type I.

Background: Neurofibromatosis I may rarely predispose to pheochromocytoma and gastrointestinal stromal tumors.

Methods: A 59-year-old woman with neurofibromatosis I presented with pheochromocytoma of the left adrenal gland. During surgery, 3 gastrointestinal stromal tumors adjacent to the stomach and small intestine were removed.

Quantitative immuno-SPECT monitoring of pretargeted radioimmunotherapy with a bispecific antibody in an intraperitoneal nude mouse model of human colon cancer.

Unlabelled: The prospects for using pretargeted immuno-SPECT to monitor the response to pretargeted radioimmunotherapy were examined. In this study, a bispecific anticarcinoembryonic antigen (CEACAM5; CD66e) × antihapten monoclonal antibody, TF2, was used in combination with a small (1.5 kD) peptide, IMP288, labeled with (111)In and (177)Lu.

3'-Deoxy-3'-18F-fluorothymidine PET-derived proliferative volume predicts overall survival in high-grade glioma patients.

Unlabelled: 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) is a radiopharmaceutical depicting tumor cell proliferation with PET. In malignancies of the lung, breast, head and neck, digestive tract, brain, and other organs, quantitative assessment of (18)F-FLT targeting has been shown to correlate with the proliferation marker Ki-67 and with clinical outcome measures such as time to progression and overall survival (OS). The aim of this study was to assess various PET segmentation methods to estimate the proliferative volume (PV) and their prognostic value for OS in patients with suspected high-grade glioma.

The impact of age on outcome of embryonal and alveolar rhabdomyosarcoma patients. A multicenter study.

Background: The prognosis of rhabdomyosarcoma (RMS) in children and adolescents has improved since the introduction of multi-agent chemotherapy. However, outcome data of adults with RMS are scarce. This multicenter retrospective study investigated the effect of age on outcome of RMS.

Aggressive fibromatosis in the head and neck region: Benign tumor with often mutilating effects.

Background: Aggressive fibromatosis (AF) or desmoid tumor of the head and neck region is a rare, usually unresectable, benign soft tissue tumor with locally aggressive behavior.

Methods And Results: A 31-year-old woman presented with a progressive trismus, a swelling in the retromandibular area, as well as loss of sensibility of the maxillary and mandibular branch of the trigeminal nerve. MRI of the head and neck revealed an infiltrative mass involving the masticator, parapharyngeal, and prevertebral and paravertebral space on the left with intracranial extension through the orbital fissure.

A long-term prospective population pharmacokinetic study on imatinib plasma concentrations in GIST patients.

Purpose: Imatinib minimal (trough) plasma concentrations after one month of treatment have shown a significant association with clinical benefit in patients with gastrointestinal stromal tumors (GIST). Considering that a retrospective pharmacokinetic analysis has also suggested that imatinib clearance increases over time in patients with soft tissue sarcoma and GIST, the primary aim of this study was to assess systemic exposure to imatinib at multiple time points in a long-term prospective population pharmacokinetic study. As imatinib is mainly metabolized in the liver, our secondary aim was to elucidate the potential effects of the volume of liver metastases on exposure to imatinib.

Surgical management of rectal gastrointestinal stromal tumors.

Background: Five percent of gastrointestinal stromal tumors (GISTs) are primarily localized in the rectum. We analyzed the outcome of multimodality treatment for rectal GIST in a multicenter retrospective series.

Methods: All surgically treated patients with a rectal GIST were identified from four specialized centers in the Netherlands.

Optimization of IGF-1R SPECT/CT imaging using 111In-labeled F(ab')2 and Fab fragments of the monoclonal antibody R1507.

The insulin-like growth factor 1 receptor (IGF-1R) is a potential new target for the treatment of breast cancer. Patients with breast cancer lesions that express IGF-1R may benefit from treatment with anti-IGF-1R antibodies. IGF-1R expression can be visualized using radiolabeled R1507, a monoclonal antibody directed against IGF-1R.

New systemic therapy options for advanced sarcomas.

The outcome of patients with advanced soft tissue sarcomas (STS) has not improved much during the last decade. Apart from non-pleomorphic rhabdomyosarcoma, adjuvant chemotherapy has no standard role in high risk STS. In metastatic disease little progress has been made, but during recent years much effort has been put into the development of better clinical study protocols, with stratification of patients to at least the most common histological subtypes, preventing the dilution of potential treatment efficacy when measuring results over the total heterogeneous group of STS.

'Big'-insulin-like growth factor-II signaling is an autocrine survival pathway in gastrointestinal stromal tumors.

New treatment targets need to be identified in gastrointestinal stromal tumors (GISTs) to extend the treatment options for patients experiencing failure with small-molecule tyrosine kinase inhibitors, such as imatinib. Insulin-like growth factor (IGF)-II acts as an autocrine factor in several tumor types by binding to IGF receptor type 1 (IGF-1R) and/or the insulin receptor (IR) isoform A. The aim of the present study was to investigate the putative role of unprocessed pro-IGF-II, called 'big'-IGF-II, in GISTs.

Pazopanib for metastatic soft-tissue sarcoma (PALETTE): a randomised, double-blind, placebo-controlled phase 3 trial.

Background: Pazopanib, a multitargeted tyrosine kinase inhibitor, has single-agent activity in patients with advanced non-adipocytic soft-tissue sarcoma. We investigated the effect of pazopanib on progression-free survival in patients with metastatic non-adipocytic soft-tissue sarcoma after failure of standard chemotherapy.

Methods: This phase 3 study was done in 72 institutions, across 13 countries.

Anaplastic lymphoma kinase aberrations in rhabdomyosarcoma: clinical and prognostic implications.

Purpose: The aim of this study is to investigate anaplastic lymphoma kinase (ALK) protein expression and underlying genetic aberrations in rhabdomyosarcoma (RMS), with special attention to clinical and prognostic implications.

Patients And Methods: A total of 189 paraffin-embedded RMS tumor specimens from 145 patients were collected on tissue microarray. ALK protein expression was evaluated by immunohistochemistry.

Imaging of human epidermal growth factor receptor type 2 expression with 18F-labeled affibody molecule ZHER2:2395 in a mouse model for ovarian cancer.

Unlabelled: Affibody molecules are small (7 kDa) proteins with subnanomolar targeting affinity. Previous SPECT studies in xenografts have shown that the Affibody molecule (111)In-DOTA-Z(HER2)(:2395) can discriminate between high and low human epidermal growth factor receptor type 2 (HER2)-expressing tumors, indicating that radiolabeled Affibody molecules have potential for patient selection for HER2-targeted therapy. Compared with SPECT, PET with positron-emitting radionuclides, such as (18)F, may improve imaging of HER2 expression because of higher sensitivity and improved quantification of PET.

Predicting IGF-1R therapy response in bone sarcomas: immuno-SPECT imaging with radiolabeled R1507.

Purpose: To investigate whether indium-111-labeled R1507 ((111)In-R1507) immuno-SPECT (single-photon emission computed tomography), a novel noninvasive, in vivo screening method to visualize membranous insulin-like growth factor 1 receptor (IGF-1R) expression and accessibility, can be used to predict IGF-1R treatment (R1507) response in bone sarcomas.

Experimental Design: BALB/c nude mice were subcutaneously implanted with IGF-1R-expressing human bone sarcoma xenografts (OS-1, EW-5, and EW-8) which showed high, modest, or no response, respectively, to R1507, a monoclonal antibody targeting the extracellular domain of IGF-1R. An IGF-1R-negative tumor (OS-33), unresponsive to IGF-1R inhibitors, was examined as well.

Age as prognostic factor in patients with osteosarcoma.

Age at diagnosis is a well known prognostic factor in many different malignancies; its significance for patients with osteosarcoma is however controversial. To gain more insight in the prognostic role of age, we performed a retrospective study at our institute. We included 102 patients with de-novo osteosarcoma and formed three age groups to evaluate age specific survival rates: ≤ 14 years, 15-19 years and 20-40 years.

Weight loss induced by tyrosine kinase inhibitors of the vascular endothelial growth factor pathway.

Weight loss, cachexia and sarcopenia are profound problems in the frail oncologic patients. With the development and increasing use of angiogenesis inhibitors in metastatic cancer patients, the question arises as to their influence on body weight and composition. Angiogenesis is not only important for the growth, development and metastatic potential of tumors but also for physiological processes in adipogenesis.

Building the bridge between rhabdomyosarcoma in children, adolescents and young adults: the road ahead.

Rhabdomyosarcoma (RMS) is a rare type of soft tissue sarcoma that mainly affects children, but also occurs in adolescents and (young) adults (AYA). Despite dramatic survival improvements reported by international study groups in children over the past decades, the awareness of a dismal outcome for older patients with RMS has grown. In contrast to the world-wide organization of care for children with RMS, standard care in adults lags behind.

Nuclear medicine imaging of infection in cancer patients (with emphasis on FDG-PET).

Infections are a common cause of death and an even more common cause of morbidity in cancer patients. Timely and adequate diagnosis of infection is very important. This article provides clinicians as well as nuclear medicine specialists with a concise summary of the most important and widely available nuclear medicine imaging techniques for infectious and inflammatory diseases in cancer patients with an emphasis on fluorodeoxyglucose positron emission tomography (FDG-PET).

When hope is all there is left.

One particular patient who was facing the fact that she would die from cancer reveals an important lesson for the oncologist about listening and caring. Medical oncologists have a role beyond offering new treatments to patients with incurable disease: the role of supporter, and of witness, supporting a patient, especially in the last stages of illness, when hope is all there is left.

Efficacy and safety of palliative chemotherapy for patients with advanced breast cancer pretreated with anthracyclines and taxanes: a systematic review.

No standard monotherapy or combination palliative chemotherapy currently exists for patients with advanced breast cancer pretreated with anthracyclines and taxanes. In this systematic review we assess the current knowledge on the efficacy and safety of palliative single-agent chemotherapy drugs--capecitabine, vinorelbine, gemcitabine, and liposomal doxorubicin--commonly used in daily clinical practice. We identified 22 studies, of which ten investigated capecitabine, nine investigated vinorelbine, three investigated gemcitabine, and one investigated liposomal doxorubicin.

Clinical applications of positron emission tomography in sarcoma management.

Positron emission tomography (PET) with the fluorine-18-labeled glucose analog FDG is a technique that noninvasively visualizes glucose metabolism in the human body. In oncology, the addition of FDG-PET to the conventional anatomical imaging techniques provides very useful clinical information in diagnosis, staging, treatment response monitoring and follow-up. In the heterogeneous group of patients with sarcoma, FDG-PET has been shown to be of great value in improving patient care.