Prophylactic cranial irradiation for small-cell lung cancer: how, when and for whom?

Prophylactic cranial irradiation (PCI) reduces the incidence of brain metastases and improves overall survival in both limited disease (LD) and extensive disease (ED) small-cell lung cancer (SCLC), in complete and good responders to initial chemo(radio)therapy. In LD-SCLC, a standard dose of 25 Gy given in ten fractions is recommended, whereas in ED-SCLC a shorter schedule of 20 Gy in five fractions could be used. The issues of acute neurotoxicity (NT) and the potential impact of PCI on quality of life are of particular concern in ED-SCLC patients, as their expected survival is short. In LD-SCLC late neurologic sequelae may worsen quality-adjusted life expectancy for long-term survivors, as the pronounced effect of NT becomes apparent after several years. Some novel potential approaches to reduce the PCI-related late NT have recently been investigated. Despite the growing incidence of lung cancer in elderly people, there are no established standards of treatment for this subset of the population.     

Prostate biopsy techniques and indications: when, where, and how?

Transrectal ultrasound (TRUS) and prostate biopsy have become one of the most common office-based procedures for the practicing urologist. During the past 50 years, the techniques, indications, and pathologic interpretation of prostate biopsies have evolved. The abandonment of blind finger-guided needle biopsies in favor of systematic TRUS-guided biopsies epitomizes much of this change. Similarly, the indications for prostate biopsy have become more refined. In the past, the presence of a prostatic nodule on digital rectal examination (DRE) was the primary indication for biopsy until the introduction of prostatic-specific antigen (PSA) in the 1980s and its widespread use for prostate cancer screening. Abnormalities of PSA or its derivatives now represent the most common indication for prostate biopsy. Although TRUS initially began as a tool to direct needles into various locations within the prostate, today a great deal of information can be obtained from prostate ultrasound for the discerning clinician. As such, TRUS-guided biopsy of the prostate has become an important staging and diagnostic tool for the practicing urologist. Here we review the current techniques and indications as well as pertinent pathologic and staging data obtained through TRUS and prostate biopsy.     

TPF sequential therapy: when and for whom?

Concurrent chemoradiation is a standard approach for the treatment of locally advanced squamous cell carcinoma of the head and neck. However, sequentially administered chemotherapy and radiotherapy/chemoradiation may be an effective alternative for some patients. Although chemoradiation is a highly effective treatment approach, it is associated with high incidences of severe acute toxicities, including mucositis. In addition, late toxicities can cause long-term morbidity in a substantial proportion of patients. In a retrospective analysis of three Radiation Therapy Oncology Group trials, pharyngeal dysfunction was seen in 27% of patients and feeding tube dependence and laryngeal dysfunction were each seen in approximately 12% of patients. Sequential administration of chemotherapy and radiotherapy, with a doublet cisplatin and 5-fluorouracil (PF) induction chemotherapy regimen, is associated with less acute severe mucositis than concomitantly administered cisplatin and radiotherapy. The addition of the taxane docetaxel to PF has resulted in the highly active triplet induction regimen TPF. Data from randomized trials indicate that TPF sequential therapy may be an effective alternative to concurrent chemoradiation for some patients. TPF is well tolerated, although it is associated with a higher incidence of hematologic adverse events than with PF, including neutropenia and neutropenia-related complications. This may be managed by the use of prophylactic G-CSF and/or antibiotics. Patients suitable for treatment with a TPF-based sequential administration approach include those with a good performance status, no contraindication to cisplatin or taxanes, and locally advanced oropharyngeal, hypopharyngeal, or laryngeal cancer with a high tumor load.     

Assessment of HER2 status in breast cancer: why, when and how?

Human epidermal growth factor receptor 2 (HER2) is overexpressed, usually as a result of HER2 proto-oncogene amplification, in 20-30% of breast cancers. A HER2-positive status is generally associated with more aggressive disease and a worse prognosis. Furthermore, a positive HER2 status may predict the likelihood of resistance to some conventional therapies, as well as probably being predictive of sensitivity to anthracycline dose intensification. In addition to this prognostic/predictive value, HER2 is a target for specific therapy, with anti-HER2 monoclonal antibody therapy available in the USA. This article reviews the different assays used to determine HER2 status, discussing their relative advantages/disadvantages and the need for their standardisation before integration alongside other pathological indices into the clinical management of breast cancer.     

Pharmacotherapy of epileptic seizures in glioma patients: who, when, why and how long?

BACKGROUND: The risk for patients with primary brain tumors of experiencing an epileptic seizure at least once in the course of disease probably exceeds 50%, depending on tumor location and tumor type. Several aspects regarding the role of anticonvulsants in the treatment of brain tumor patients have remained controversial. PATIENTS AND METHODS: We reviewed the seizure history in 107 patients undergoing a surgical procedure for glioma at our institution. RESULTS: The overall seizure incidence was 68%. Pre-operative seizures did not predict the occurrence of post-operative seizures. After surgery, postoperative chemo- or radiotherapy and anticonvulsive therapy one third of patients was seizure-free whereas one third showed frequent seizures despite this treatment. Seizure frequency increased regardless of anticonvulsive treatment with progressive or recurrent tumor growth. CONCLUSIONS: Based on a literature review and our institutional experience, we delineate some recommendations for the management of seizures in patients with brain tumors.     

Locoregional radiological treatment for hepatocellular carcinoma; Which, when and how?

Hepatocellular carcinoma (HCC) is one of the most frequent and deadliest cancers worldwide. Liver transplantation, surgical resection or local ablation offer the best survival advantages but most patients either present when the tumor is in an advanced stage or the degree of underlying liver disease precludes these options. Several therapies have been proposed for these patients with proven survival benefits. These therapies comprise the locoregional treatment for HCC, and include percutaneous ethanol injection (PEI), radiofrequency ablation (RFA), transarterial chemoembolization (TACE), transarterial radioembolization (TARE), and drug-eluting bead (DEB). PEI and RFA are considered curative treatments for early stage HCC; whereas TACE is a standard of care for intermediate stages. Additionally, evaluation of response to locoregional treatment in HCC is important, as objective response may become a surrogate marker for improved survival. Currently, there are several criteria for response assessment, including the World Health Organization (WHO), the Response Evaluation Criteria in Solid Tumors (RECIST), the European Association for the Study of the Liver Criteria (EASL), and the modified RECIST (mRECIST); however, there has been poor correlation between the clinical benefit provided by locoregional interventional therapies and conventional methods of response assessment.The aim of our study was to review and analyze the current evidence for radiological interventions in HCC, and to propose evidence based recommendations to improve the management of these patients.     

Single-nucleotide polymorphism array karyotyping in clinical practice: where, when, and how?

Single-nucleotide polymorphism array (SNP-A) karyotyping is a new technology that has enabled genome-wide detection of genetic lesions in human cancers, including hematopoietic neoplasms. Taking advantage of very large numbers of allele-specific probes synthesized on microarrays at high density, copy number alterations as well as allelic imbalances can be sensitively detected in a genome-wide manner at unprecedented resolutions. Most importantly, SNP-A karyotyping represents the only platform currently available for genome-scale detection of copy neutral loss of heterozygosity (CN-LOH) or uniparental disomy (UPD), which is widely observed in cancer genomes. Although not applicable to detection of balanced translocations, which are commonly found in hematopoietic malignancies, SNP-A karyotyping technology complements and even outperforms conventional metaphase karyotyping, potentially allowing for more accurate genetic diagnosis of hematopoietic neoplasms in clinical practice. Here, we review the current status of SNP-A karyotyping and its application to hematopoietic neoplasms.     

Hemopoietic stem cell transplantation in T-cell malignancies: Who, when, and how?

Only in recent years has there been a specific focus on the treatment of T-cell lymphomas in general and peripheral T-cell lymphomas (PTCLs) in particular. An increasing number of PTCL-specific retrospective analyses have been reported, and the first data from PTCL-restricted prospective clinical trials have appeared more recently. In this context, the role of hemopoietic stem cell transplantation—primarily autologous but also allogeneic—has been investigated. High-dose therapy with autologous stem cell transplantation (HDT/ASCT) proved feasible in both relapsed/refractory and previously untreated PTCL. Overall results show a more favorable impact when HDT/ASCT is part of first-line therapy rather than salvage treatment. Reported outcomes have varied, often depending on the number of anaplastic large-cell lymphomas in the cohort. In addition, retrospective results usually focus on patients undergoing transplantation, whereas the fraction of patients with primary refractory or early relapsing disease is best described in the intention-to-treat analysis of prospective trials. This article reviews the most recent results of upfront HDT/ASCT consolidation in different subtypes of systemic PTCL. The data on allogeneic stem cell transplantation are more limited, but promising results have recently been reported in the setting of relapsed or primary refractory disease.     

Metastasectomy for stage IV melanoma: for whom and how much?

Although the conventional paradigm for treating metastatic melanoma relies on systemic therapies, a surgical approach should be strongly considered in selected patients. A surgical approach may not be appropriate for all patients, but it can offer a rapid clearance of disease without the toxicity of systemic therapy. Patient selection is of paramount importance for surgery to be effective. The rationale for surgical intervention in the management of metastatic melanoma, selection factors to be considered, published results, and future directions are discussed in this article.     

Mechanism of cell adaptation: when and how do cancer cells develop chemoresistance?

Chemotherapy treatments are considered essential tools to defeat cancer progression and dissemination to improve patients' quality of life and survival. Although most malignancies initially respond to chemotherapeutic treatments, after an unpredictable period, tumor cells develop mechanisms of resistance to the treatment. Different cell compartments are involved in the mechanism of chemoresistance, and multiple mechanisms can be activated by single cells at different times of the cancer progression. Alteration of drug metabolism, derangement of intracellular pathways' signaling, cross-talk between different membrane receptors, and modification of apoptotic signaling and interference with cell replication are all mechanisms that the cell uses to overcome the effect of pharmacological compounds.In this review, we describe different adaptation, mostly at the level of the proteome, which cancer cells use to develop resistance to cancer treatment.     

Intraperitoneal drug delivery for ovarian cancer: why, how, who, what, and when?

In 1996, intraperitoneal (IP) administration of cisplatin plus intravenous (i.v.) cyclophosphamide proved superior to both drugs given intravenously at the same doses--which, at the time, was the standard treatment in the United States. The IP 'option' was not adopted, however, because the standard treatment had shifted to i.v. cisplatin plus paclitaxel.Two additional phase III trials by the Gynecologic Oncology Group (GOG) comparing IP versus i.v. cisplatin, but including other variables, have shown similar superior effects of the IP route on outcome, but with toxicities-particularly local tolerance and neuropathy--increased. An ongoing trial by the GOG is again looking into an IP versus i.v. comparison, and introducing in one of the IP arms the substitution of IP carboplatin for IP cisplatin. All three arms of this trial contain bevacizumab (Avastin). Two other trials comparing i.v. versus IP administration of platinums or platinums and paclitaxel have just been launched, led by Japanese and Canadian investigators, respectively. While awaiting additional data on the ongoing debate over IP versus i.v. therapy, it is important that we consider issues concerning why the IP route may be relevant, how can one increase the safety of this route, and who should be treated and with what drugs, particularly when faced with a patient outside the clinical trials setting. The underlying hypothesis for use of IP therapy is based on the existence of a dose-effect relationship for platinum drugs in ovarian cancer. We review the known data on this relationship, and explore why interest in platinum drugs has become the central focus of ovarian cancer treatment.