Should there be a standard therapy for mantle cell lymphoma?

Mantle cell lymphoma (MCL) is an uncommon subtype of B-cell lymphoma that is characterized by monoclonal B cells that express CD5 on their surface, but not CD23, and harbor the t(11:14) chromosomal translocation that leads to dysregulated expression of cyclin D1. MCL is a biologically and clinically heterogeneous disease. It has the unfavorable characteristics of both aggressive and indolent lymphoma in that MCL is not curable with current standard therapy, yet patients have a shorter survival compared with other indolent histology. MCL is incurable, yet more intensive therapy does lead to longer disease-free intervals; therefore, treatment must be designed to optimize survival while maintaining quality of life. Thus, therapy should be individualized based on both the clinical behavior of the lymphoma and the patient's status. While there is no clear standard therapy that can be recommended for all patients, there may be an optimal choice for each patient. Knowledge of the expected clinical benefits and toxicities of various approaches will allow the physician and patient to appropriately select the therapy.     

Could BEACOPP be the new standard for the treatment of advanced Hodgkin's lymphoma?

In 1992, the German Hodgkin Study Group (GHSG) developed the BEACOPP regimen for further improving the outcome of patients with advanced Hodgkin's lymphoma (HL). Since then, BEACOPP has been introduced in 3 different prospective randomized clinical trials of the GHSG to find an equilibrium between maximal efficacy and least toxicity with the BEACOPP principle for the treatment of advanced stage HL. In the HD9 trial of the GHSG, with 1,186 patients, after a median observation time of 7 years, the rates for FFTF are 85 percent and for overall survival 90 percent for dose-escalated BEACOPP, and for COPP/ABVD (C/ABVD comparable to ABVD) the rate for FFTF is 67 percent and for overall survival it is 79 percent. These superior BEACOPP results are obtained inspite of a higher rate of secondary AML/MDS in the escalated BEACOPP arm. The number of toxic deaths during treatment, however, was lower for escalated BEACOPP (1.6 percent) than for C/ABVD (1.8 percent). The majority of patients were treated in an outpatient setting, in a multicenter study with more than 400 centers, including 120 private doctors, located in Germany and 9 other European countries. To reduce acute and long-term toxicity, the GHSG started in the consecutive studies HD12 and HD15 for advanced stage HL to de-escalate BEACOPP by reducing the number of escalated BEACOPP cycles and by applying the baseline dose BEACOPP, a time dense regimen, called BEACOPP-14. The excellent results obtained with the BEACOPP principle challenge the seemingly global consensus that ABVD is the gold standard treatment strategy for advanced stage HL.     

Do the results of the new trials change the standard treatment of metastatic renal cell cancer?

With the emergence of novel angiogenesis inhibitors, we are moving to a new era for patients with metastasized renal cell carcinoma. Since the results achieved reflect more a modification of the natural course of the disease than a cure, past achievements should not be neglected. Low-risk patients with clear cell histology, especially those with pulmonary metastasis only, should still be offered cytokine therapy. For intermediate-risk patients sunitinib is the treatment of choice. For high-risk patients, temsirolimus has to date provided the most convincing data, its availability is however limited. Data with sorafenib and sunitinib in the high-risk group are still anecdotal. The toxicity profiles of these 2 drugs are different and might particularly relate to patients with known cardiovascular co-morbidity. No sufficient data are available regarding sequential use. After cytokine failure, sorafinib is the treatment of choice. Patients should preferably be treated within clinical trials to answer unaddressed questions. It is well known that the strict entry criteria used within the clinical studies were applied very flexibly when drugs have been approved. These aspects require a careful follow-up to ascertain optimal use and to prevent misuse. Finally, the costs of prolonged treatment will be enormous, and only meaningful survival advantages will convince the health authorities to make these new treatments available for all patients.     

Is axillary clearance the standard of care for breast cancer patients with sentinel node involvement?

Sentinel node biopsy (SNB) has become accepted for staging the axilla in early breast cancer with avoidance of axillary lymph node dissection (ALND) in patients with negative SNB. For those with positive SNB, the standard surgical management is ALND; however, this approach is increasingly being challenged. The central problem is that it is not possible to preoperatively predict whether the SNB will be positive, and it is even more difficult to determine the likelihood of nonsentinel node positivity. Various histopathological features indicate increased risk of nonsentinel node metastasis, including size of SNB metastasis, presence of lymphovascular invasion, multifocality, number of involved sentinel nodes and, conversely, the number of negative sentinel nodes. These features have been combined to produce predictive nomograms but, understandably, these still lack precision. Presently, the decision to avoid ALND will depend upon both the clinician and the patient's impression of risk, but if either requires assurance that no residual axillary disease remains, a completion clearance will be required.     

Will focal therapy become a standard of care for men with localized prostate cancer?

The current treatment choice for men with localized prostate cancer lies between active surveillance and radical therapy. The difference between these two extremes of care is 5% in terms of cancer-related absolute mortality at 8 years. It is generally accepted that this small difference will decrease for men diagnosed in the prostate-specific-antigen era. Radical therapy is associated with considerable adverse effects (e.g. incontinence, impotence, rectal problems) because it treats the whole gland, and damages surrounding structures in up to half of men. Men are being diagnosed at a younger age with lower-risk disease, and many have unifocal or unilateral disease. We propose a new concept whereby only the tumor focus and a margin of normal tissue are treated. This paradigm might decrease adverse effects whilst, at the same time, retaining effective cancer control. The arguments for and against active surveillance and radical therapy are reviewed in this article, with focal therapy presented as a means for bridging these two approaches.     

Is mantle cell lymphoma a sex-related disease?

Mantle cell lymphomas are characterized by a male predominance with a range between 55 and 65 years (sex ratio M/F of 6.5). When the sex ratio of patients having mantle cell lymphoma was compared to that of each of the subtypes of non-Hodgkin's lymphomas, it was significantly higher in all cases except Burkitt's and lymphoblastic T-cell lymphomas. These observations suggest a possible relation between the chromosome X and mantle cell lymphomas which has to be explored.     

Intraperitoneal chemotherapy: standard of care for patients with minimal residual stage III ovarian cancer?

Epithelial ovarian cancer is the leading cause of death from gynecological cancer in most of the Western world, and long-term survival remains poor despite good initial response to systemic therapy after debulking surgery. Even after complete pathological response, the risk of recurrence in the first few years is substantial. The peritoneum is the predominant site of failure and the disease remains confined to the peritoneal cavity for much of its course. Efforts to improve clinical outcomes in this group of patients included investigation of intraperitoneal administration of active agents to expose the low-volume postoperative residual disease in the peritoneum to high concentrations of these drugs. In spite of three National Cancer Institute-sponsored randomized trials demonstrating clinical benefit with intraperitoneal therapy in patients with advanced ovarian cancer, the fact remains that it is not uniformly accepted by the gynecologic oncology community in the USA and is rarely used by clinicians in Europe. Intraperitoneal regimens are perceived to be too toxic for administration, although most of the toxicity is reversible. In this article we discuss the available evidence for intraperitoneal chemotherapy, challenges facing the gynecologic oncology community to make this modality more widely acceptable, the selection of patients most likely to tolerate intraperitoneal therapy and ongoing research in this field.     

Short-term androgen deprivation therapy for patients with intermediate-risk prostate cancer undergoing dose-escalated radiotherapy: the standard of care?

What is the best way to manage patients with intermediate-risk prostate cancer? One of the most controversial aspects of treatment is the role of short-term androgen deprivation therapy in combination with definitive radiotherapy. In two randomised trials of patients with mostly intermediate-risk prostate cancer, increased overall survival was reported when short-term androgen deprivation therapy was added to radiotherapy. However, radiation doses in these studies were far below the current standard of care. This limitation, in combination with the heterogeneous nature of the cancers classified as intermediate risk, has complicated the application of these trial results to modern clinical practice. In this Review, we discuss clinical evidence for and against use of short-term androgen deprivation therapy with dose-escalated radiotherapy for patients with intermediate-risk prostate cancer.     

Intraperitoneal chemotherapy: standard of care for patients with minimal residual stage III ovarian cancer?

Epithelial ovarian cancer is the leading cause of death from gynecological cancer in most of the Western world, and long-term survival remains poor despite good initial response to systemic therapy after debulking surgery. Even after complete pathological response, the risk of recurrence in the first few years is substantial. The peritoneum is the predominant site of failure and the disease remains confined to the peritoneal cavity for much of its course. Efforts to improve clinical outcomes in this group of patients included investigation of intraperitoneal administration of active agents to expose the low-volume postoperative residual disease in the peritoneum to high concentrations of these drugs. In spite of three National Cancer Institute-sponsored randomized trials demonstrating clinical benefit with intraperitoneal therapy in patients with advanced ovarian cancer, the fact remains that it is not uniformly accepted by the gynecologic oncology community in the USA and is rarely used by clinicians in Europe. Intraperitoneal regimens are perceived to be too toxic for administration, although most of the toxicity is reversible. In this article we discuss the available evidence for intraperitoneal chemotherapy, challenges facing the gynecologic oncology community to make this modality more widely acceptable, the selection of patients most likely to tolerate intraperitoneal therapy and ongoing research in this field.