B and T cell prolymphocytic leukaemia.

Prolymphocytic leukaemias B-PLL and T-PLL are rare disorders, typically with an aggressive clinical course and poor prognosis. Combining morphology, immunophenotyping, cytogenetic and molecular diagnostics reliably separates B-PLL and T-PLL from one another and other disorders. In T-PLL discovery of frequent mutations in the JAK-STAT pathway have increased understanding of disease pathogenesis.

Radiotherapy in the Management of Childhood Rhabdomyosarcoma.

Rhabdomyosarcoma is the most common soft-tissue sarcoma of childhood, comprising over 50% of cases. It is considered to be an embryonal tumour of skeletal muscle cell origin, frequently occurring at genitourinary and head and neck sites, although it can arise throughout the body and at sites where there is no skeletal muscle. For most cases, multimodality therapy is required to achieve the best results, incorporating induction ifosfamide, vincristine and actinomycin D-based chemotherapy and local therapy (radiotherapy and/or surgery).

Surveillance of HPV-Positive Head and Neck Squamous Cell Carcinoma with Circulating and Salivary DNA Biomarkers.

Head and neck squamous cell carcinoma (HNSCC) manifests in the mucosal epithelial lining of the oral cavity, oropharynx, hypopharynx, nasopharynx or larynx and has a tremendous disease burden worldwide. Smoking and alcohol consumption were once major risk factors, but HPV-associated infection has emerged as the major contributor to HNSCC occurrence in developed countries. Circulating biomarker evaluations in biofluids, also known as liquid biopsy, are an attractive alternative for cancer screening as they are minimally invasive, potentially low cost, and easily repeatable on a serial basis.

Surgical management of metastatic gastrointestinal stromal tumour.

Background: Gastrointestinal stomal tumours (GISTs) are the most frequently diagnosed mesenchymal tumour of the gastrointestinal tract. The response of most GISTs to tyrosine kinase inhibitor (TKIs) treatment is spectacular; however progression and/or secondary resistance inevitably occurs with long-term treatment of recurrent or metastatic disease. Randomised studies investigating the potential additive benefit of metastasectomy in addition to TKI treatment unfortunately failed to accrue sufficient patients.

Managing Nonmetastatic Castration-resistant Prostate Cancer.

Context: Patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) have rising prostate-specific antigen (PSA) and castrate testosterone levels, with no radiological findings of metastatic disease on computed tomography and bone scan. Given recent drug approvals for nmCRPC, with many other therapeutics and imaging modalities being developed, management of nmCRPC is a rapidly evolving field that merits detailed investigation.

Objective: To review current nmCRPC management practices and identify opportunities for improving care of nmCRPC patients.

Detection of circulating tumour cell clusters in human glioblastoma.

Human glioblastoma (GBM) is a highly aggressive, invasive and hypervascularised malignant brain cancer. Individual circulating tumour cells (CTCs) are sporadically found in GBM patients, yet it is unclear whether multicellular CTC clusters are generated in this disease and whether they can bypass the physical hurdle of the blood-brain barrier.  Here, we assessed CTC presence and composition at multiple time points in 13 patients with progressing GBM during an open-label phase 1/2a study with the microtubule inhibitor BAL101553.

Perioperative Management of Extremity Soft Tissue Sarcomas.

Surgery is potentially curative for primary nonmetastatic extremity soft tissue sarcomas. After surgery alone, patients may remain at risk for local recurrences and/or metastatic disease. To reduce the likelihood of a local relapse, the addition of radiotherapy (RT) to limb-sparing surgery may result in higher local control rates of at least 85%.

Long-Term Responders on Olaparib Maintenance in High-Grade Serous Ovarian Cancer: Clinical and Molecular Characterization.

Maintenance therapy with olaparib has improved progression-free survival in women with high-grade serous ovarian cancer (HGSOC), particularly those harboring mutations. The objective of this study was to characterize long-term (LT) versus short-term (ST) responders to olaparib. A comparative molecular analysis of Study 19 (NCT00753545), a randomized phase II trial assessing olaparib maintenance after response to platinum-based chemotherapy in HGSOC, was conducted.

Primary retroperitoneal soft tissue sarcoma: Imaging appearances, pitfalls and diagnostic algorithm.

Although retroperitoneal sarcomas are rare tumours, they can be encountered by a wide variety of clinicians as they can be incidental findings on imaging or present with non specific symptoms and signs. Surgical resection can offer hope of cure and patient outcomes are improved when patients are managed in high-volume specialist centers. Failure to recognize retroperitoneal sarcomas on imaging can lead to inappropriate management in inexperienced centers.

Biomarker Associations with Efficacy of Abiraterone Acetate and Exemestane in Postmenopausal Patients with Estrogen Receptor-Positive Metastatic Breast Cancer.

Purpose: Abiraterone may suppress androgens that stimulate breast cancer growth. We conducted a biomarker analysis of circulating tumor cells (CTCs), formalin-fixed paraffin-embedded tissues (FFPETs), and serum samples from postmenopausal estrogen receptor (ER) breast cancer patients to identify subgroups with differential abiraterone sensitivity.

Methods: Patients (randomized 1:1:1) were treated with 1,000 mg/d abiraterone acetate + 5 mg/d prednisone (AA), AA + 25 mg/d exemestane (AAE), or exemestane.

Abiraterone acetate, exemestane or the combination in postmenopausal patients with estrogen receptor-positive metastatic breast cancer.

Background: Androgen receptor (AR) signaling and incomplete inhibition of estrogen signaling may contribute to metastatic breast cancer (MBC) resistance to a nonsteroidal aromatase inhibitor (NSAI; letrozole or anastrozole). We assessed whether combined inhibition of androgen biosynthesis with abiraterone acetate plus prednisone and estradiol synthesis with exemestane (E) may be of clinical benefit to postmenopausal patients with NSAI-pretreated estrogen receptor-positive (ER+) MBC.

Patients And Methods: Patients (N = 297) were stratified by the number of prior therapies for metastatic disease (0-1 versus 2) and by prior NSAI use (adjuvant versus metastatic), and randomized (1 : 1 : 1) to receive oral once daily 1000 mg abiraterone acetate plus 5 mg prednisone (AA) versus AA with 25 mg E (AAE) versus 25 mg E alone (E).

B- and T-cell prolymphocytic leukemia: antibody approaches.

B- and T-cell subtypes of prolymphocytic leukemia (PLL) are rare, aggressive lymphoid malignancies with characteristic morphologic, immunophenotypic, cytogenetic, and molecular features. Prognosis for these patients remains poor, with short survival times and no curative therapy. The advent of mAbs has improved treatment options.

A randomized phase II study evaluating the combination of carboplatin-based chemotherapy with pertuzumab versus carboplatin-based therapy alone in patients with relapsed, platinum-sensitive ovarian cancer.

Background: Pertuzumab, a humanized monoclonal antibody targeting human epidermal growth factor receptor (HER)-mediated signalling, has shown activity in ovarian cancer in preclinical models and in the clinic. This randomized phase II study evaluated efficacy and safety of pertuzumab in combination with carboplatin-based chemotherapy in patients with platinum-sensitive, recurrent advanced ovarian cancer.

Patients And Methods: Patients were randomized to receive six cycles of chemotherapy (carboplatin and either paclitaxel (Taxol) or gemcitabine) with or without pertuzumab.

A comparison of the efficacy and safety of oral and intravenous fludarabine in chronic lymphocytic leukemia in the LRF CLL4 trial.

Background: An oral formulation of fludarabine was introduced for use in chronic lymphocytic leukemia in 2001 following studies demonstrating the bioequivalence of a 40 mg/m(2) oral dose with a 25 mg/m(2) intravenous dose. We assessed retrospectively the efficacy of these two routes of administration in the LRF CLL4 trial.

Methods: A total of 777 patients were randomized from 1999-2004 to receive fludarabine, alone or with cyclophosphamide, or chlorambucil.

Fluorescence in situ hybridization methods and troubleshooting applied to fixed cell suspensions.

A robust procedure for performing fluorescence in situ hybridization (FISH) is described, with tips for troubleshooting. FISH probes are now more reliable and there is a greater range commercially available. FISH is an essential part of the cytogeneticist's repertoire.

Horizon scanning for novel therapeutics for the treatment of prostate cancer.

Treatment options for patients with advanced prostate cancer (PCa) remain limited. Improved understanding of the underlying molecular drivers of PCa pathogenesis, progression and resistance development has provided the fundamental basis for rational targeted drug design. Key findings in recent years include the identification of ETS gene rearrangements, the dissection of PCa molecular heterogeneity and the discovery that castration-resistant prostate cancer (CRPC) remains androgen driven despite the androgen-depleted milieu, thus making androgen receptor (AR) signaling a continued focus of molecularly targeted treatments.

Weekly paclitaxel in the treatment of recurrent ovarian cancer.

Weekly paclitaxel is a highly active and well tolerated regimen that is increasingly being adopted for the treatment of relapsed ovarian cancer. This regimen is usually administered at 80-90 mg/m(2)/week, and the use of a 1 h infusion helps minimize myelosuppression. When compared with the 3-weekly schedule, weekly paclitaxel is better tolerated, with a reduced frequency of grade 3-4 toxic effects.