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The overall survival rate for primary central nervous system lymphoma (PCNSL) has improved significantly. This prolongation in survival is related mainly to advances in chemotherapy regimens and radiotherapy. In contrast, the role of surgery in PCNSL has been limited because tumors are frequently not amenable to resection and because most studies have failed to show that resection is beneficial. A recent analysis of the German Primary CNS Lymphoma Study Group 1 (G-PCNSL-SG-1) trial has challenged this convention by showing that the survival of patients with PCNSL may actually be prolonged if tumors are resected. While there are a number of weaknesses in the analysis, many authorities now feel that an attempt at gross total resection is reasonable for patients with solitary lesions that can be removed without morbidity. However, even if resection does benefit some patients, the diagnosis of lymphoma is almost always made in retrospect, and there are few occasions when a neurosurgeon will actually need to make a decision whether or not to resect a known PCNSL., Primary diffuse large B-cell lymphoma of the central nervous system (CNS) is recognized as a distinct entity in the World Health Organization (WHO) classification of lymphoma. On occasion, primary CNS [...]

Primary central nervous system (CNS) lymphoma (PCNSL) is an aggressive intracranial malignant neoplasm in adults whose incidence in the United States is about 15% of that of glioblastoma. [1] Tumor [...]

In acute myeloid leukemia, the karyotype of the leukemic cell is the most powerful predictor of treatment outcome. Approximately 30% of cases of AML have an unfavorable karyotype, and if treated with conventional chemotherapy, a complete response rate of about 50% and a 5-year overall survival of 10% to 20% are expected. Of those in the unfavorable group, almost half will have a complex karyotype, which is associated with a poorer outcome, and 40% of those will have a monosomal karyotype, which carries an even worse prognosis. The best chance for cure for patients with an unfavorable karyotype is seen in those who achieve a complete response and proceed to allogeneic transplant. For patients who are not candidates for aggressive therapy, preliminary data suggest that outcomes at least equivalent to those seen with standard chemotherapy can be obtained using azacitidine or decitabine., Introduction The karyotype of the leukemic cell is the strongest prognostic factor for response to induction therapy and survival in acute myeloid leukemia (AML). Three cytogenetic risk groups based on [...]

Breast cancer brain metastases (BCBMs) are the second most frequent secondary central nervous system metastases following those associated with non-small-cell lung cancer. It is increasingly evident that BCBM arises as a function of the biology of the primary tumor and the metastatic niche, which combine to create a unique microenvironment in the brain impacting both metastatic colonization and therapeutic response. Clinical outcomes are improving for BCBM patients as a result of modern combinatorial therapies, challenging the traditionally nihilistic approach to this patient subgroup. This review will focus on the breast cancer subtypes with the highest incidence of BCBM--human epidermal growth factor receptor 2 (HER2)-positive breast cancer, and triple-negative (estrogen receptor [ER]-negative, progesterone receptor [PR]-negative, and HER2negative) breast cancer (TNBC)--and will characterize differences in the clinical behavior of brain metastases that arise from these different subtypes. We will also highlight some of the recent preclinical studies that may shed light on the biological mechanisms and mediators underlying brain metastases. Finally, we will review published and current prospective trials of systemic therapies specifically for BCBM, including novel pathway-specific therapies., The Changing Landscape of Breast Cancer Brain Metastases The diagnosis of central nervous system (CNS) recurrence is a much dreaded outcome among breast cancer patients, and its incidence varies with [...]

The article by Drs. Stein and Tallman is an excellent summary indicating that several different approaches may lead to the cure of acute promyelocytic leukemia (APL). The goal then becomes [...]

Diffuse large B-cell lymphoma (DLBCL) is the most commonly occurring lymphoid malignancy. While a series of trials support R-CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone, plus rituximab)-21 as the standard of care for all patients, DLBCL has substantial biological and clinical heterogeneity, leading to marked differences in outcomes for disease subgroups. We examine clinical, biological, and functional imaging techniques for risk-stratifying patients, and we review approaches for dose intensification in the rituximab era that are aimed at improving outcomes for poor-risk patients. Together, the results achieved with these measures indicate no particular benefit for administering R-CHOP-14 vs R-CHOP-21 in older or younger patients with DLBCL, highlight opportunities for future studies of young patients with high-risk DLBCL, and suggest the promise of biologic risk stratification. Such approaches will provide key opportunities for further advances in the treatment of DLBCL, given that chemotherapy intensification appears to provide limited additional benefits over the current standard of care., Introduction Diffuse large B-cell lymphoma (DLBCL) is the most commonly occurring lymphoid malignancy and accounts for one-third of adult cases of non-Hodgkin lymphoma (NHL). It is regarded as an aggressive [...]

Significant advances have been made in the treatment of metastatic colorectal cancer (mCRC). Development of the targeted biologic agents and their integration with cytotoxic chemotherapy regimens has led to improvements in clinical efficacy. Despite these gains, the overall impact of these combination regimens in mCRC therapy has been relatively modest. While 2-year survival has improved, substantive gains have yet to be made in 5-year survival. However, a small subset of patients can be cured of their metastatic disease, with prolonged 5- and 10-year overall survival. This select group of patients includes those with metastatic disease limited to the liver or other organ-specific sites, as these patients are able to undergo surgical resection at the time of diagnosis or following conversion therapy with the appropriate integration of chemotherapy. A multimodality team-based approach involving medical oncologists, surgical oncologists, radiologists, and other healthcare providers is absolutely critical for the success of this therapeutic approach. This article reviews the main issues that must be considered from the surgical oncology and medical oncology perspectives, respectively., Introduction In 2012, colorectal cancer (CRC) continues to be a major public health problem. In the United States this year, there will be an estimated 147,000 new cases diagnosed and [...]

It is sometimes easy to forget what the field of cancer therapy used to look like. In an early report on the natural history of 125 patients with isolated metastases [...]

In their article in this issue of ONCOLOGY, authors Bartlett and Chu discuss a very provocative suggestion that the possibility exists to cure patients with advanced colorectal cancer. Before we [...]

Lymphedema is a feared complication of cancer treatment and one that negatively impacts survivorship. The incidence of breast cancer-related lymphedema ranges from 6% to 70%, but lymphedema may be a common and under-reported morbidity. No standard guidelines for its diagnosis and assessment exist. Although the true etiology of lymphedema remains unknown, radiation, chemotherapy, type of breast surgery, and extent of axillary surgery are commonly cited risk factors. However, the relationship between the number of nodes removed and the risk of lymphedema is not clearly correlated. Clinical trials are focusing on ways to reduce the need for axillary dissection even in the setting of a positive sentinel node, to help minimize axillary morbidity. Riskreduction practices, including avoidance of skin puncture and blood pressures in the ipsilateral upper extremity, and precautionary behaviors such as wearing compression garments during air travel continue to be advocated by the medical and survivor communities, despite a lack of rigorous evidence supporting their benefit. Emerging data support exercise in at-risk and affected women with lymphedema when started gradually and increased cautiously., Introduction The most recent survivorship data from the Surveillance, Epidemiology, and End Results (SEER) database demonstrate a significant increase in the number of US cancer survivors over the last 30 [...]

The etiology and risk factors of breast cancer-related lymphedema (BCRL) are multifactorial and not fully understood. BCRL risk factors are divided into three main categories. There are treatment-related factors, including [...]

In the current issue of ONCOLOGY, Gertz and Dispenzieri provide a scholarly review of the early recognition, diagnosis, and treatment of immunoglobulin light-chain (AL) amyloidosis. Since the first reports of [...]

The treatment strategy of poly(ADP-ribose) polymerase (PARP) inhibition capitalizes on the inherent defect in homologous recombination that occurs in BRCA-deficient tumors by inhibiting the alternative DNA repair pathway involving base excision repair. Although PARP inhibitors were initially considered a potential treatment specifically for tumors with germline BRCA mutations, evidence of frequent somatic deficiency in the BRCA pathway has caused reconsideration of that approach. PARP inhibitors have been shown to have activity in epithelial ovarian, fallopian tube, and primary peritoneal cancer in phase I and II clinical trials. Responses have been seen in both BRCA-deficient and sporadic tumors, and they do not appear to require platinum sensitivity. Although PARP inhibitors are well tolerated as monotherapy, additional study is required to determine their efficacy and toxicity in combination with chemotherapy and other targeted agents. Many hurdles remain along the pathway to drug registration, but the motivation of the community of ovarian cancer patients, researchers, and clinicians to find new treatments may speed the process., The identification of BRCA1 and BRCA2 in the early 1990s as genes that, when mutated, are associated with an increased risk of breast, epithelial ovarian, fallopian tube, primary peritoneal, and [...]

In this issue of ONCOLOGY, von Minckwitz and colleagues review the current standards for neoadjuvant therapy for HER2-positive breast cancer. Until recently, neoadjuvant therapy was primarily used to treat larger, [...]

Women with high-grade serous ovarian cancer who harbor a BRCA2, but not a BRCAi mutation tend to have a better chemotherapy response and overall survival compared with patients who are [...]

Isolated pulmonary metastases (PM) represent a unique manifestation of the myriad presentations of systemic spread from a primary neoplasm. Selected patients with metastases isolated within an organ system that has [...]

Radium-223, an alpha particle given intravenously, has been shown to improve overall survival in men with castrate-resistant prostate cancer (CRPC), with a 30% reduction in the risk of death (HR [...]

This phase I/II trial assessed the efficacy of mFOLFOX6 with either BIBF 1120, an oral anti-angiogenesis agent, or with bevacizumab, an anti-angiogenesis antibody, in chemotherapy-naive patients with metastatic colorectal cancer [...]

Dr. Josep Tabernero of the Vall D'Hebron University Hospital in Barcelona presented the positive results of the VELOUR study on Sunday September 25, including the newly presented pre-specified subgroup analysis. [...]

Historically, liver-related metastases associated with melanoma or breast cancer have portended a poor prognosis. Many affected patients are not considered for surgical resection based on the extent and multifocal nature of their disease. For this patient population, treatment includes systemic and/or regional therapy, local destruction (ablation/radiation), and embolization. Despite the best therapeutic regimens, prognosis remains poor. Advances in surgical technique and postoperative care have led to a resurgence in the use of metastasectomy, most notably seen in patients with colorectal-related liver metastases. With the potential for therapeutic durability and a small chance of cure, surgical resection may offer improved survival compared to other therapeutic modalities. This review summarizes the existing literature that addresses the topic of metastasectomy in patients with melanoma and breast cancer., Introduction Advances in perioperative planning, surgical technique, and postoperative care over the past two decades have allowed the indications for hepatic resection to be potentially broadened to include histologies and/or [...]

DNA repair is essential for the survival of both normal and cancer cells. An elaborate set of signaling pathways detect single-strand and double-strand DNA breaks and mediate either DNA repair or apoptosis if the damage is too great to repair. Poly(adenosine diphosphate [ADP]-ribose) polymerases (PARPs) play a key role in the repair of base damage via the base excision repair pathway. Pharmacological inhibition of PARP induces cell death in tumors with mutations in certain DNA repair pathways--such as the BRCA pathways of double-strand break repair--and when combined with chemotherapies that cause DNA damage. PARP inhibitors are being investigated as a monotherapy for the treatment of patients with BRCA1/2 mutations; in the treatment of triple-negative breast cancer, because of its molecular similarities to BRCA7-mutated malignancies; and as a strategy to potentiate the DNA-damaging effects of chemotherapy and radiation. The aim of this article is to review the preclinical data and rationale for PARP inhibitor use in the aforementioned settings, as well as the current status of the clinical development of these agents in the treatment of breast cancer, along with future directions for research in this field. Trials have been identified via searches of PubMed, clinicaltrials.gov, and the Proceedings of the American Society of Clinical Oncology Annual Meeting and the San Antonio Breast Cancer Symposium., DNA Repair and PARP Function DNA repair is critical for the survival of cells. Estimations of the number of DNA damage events that occur on a daily basis are in [...]

The change to less-morbid local therapy for operable breast cancer continues. Systemic induction therapy, whether hormonal therapy or chemotherapy, increases the eligibility for breast-conserving surgery. Sentinel lymph node biopsy (SLNB) has greatly reduced the requirement for axillary dissection, and recent data show that, in addition, whole-breast irradiation can obviate the need for dissection in most patients with clinically node-negative, SLN-positive disease. Although resection margins must be negative for best results, there is no clear evidence that margins exceeding 'no ink on tumor' for invasive cancer, or 2 mm for ductal carcinoma in situ, are significantly better. The role of radiation has been clarified, with a clear survival advantage for patients with nodepositive disease; however, hypofractionation, which permits a briefer period of treatment, and accelerated partial breast irradiation (APBI) show promise of even further reductions in treatment--although late results for APBI are still needed. Elderly patients (> 70 years) with node-negative disease and estrogen receptor-positive tumors who have been treated with hormonal therapy can avoid primary breast irradiation without significant risk of ultimate breast loss or inferior survival., Since 1990, death rates from breast cancer have decreased, mainly in women younger than 50 years of age (3.3% per year) vs women aged 50 years or older (2% per [...]

Our paper, 'Darbepoetin Alfa Administered Every 2 Weeks Alleviates Anemia in Cancer Patients Receiving Chemotherapy,' at the time of its publication almost a decade ago, was impactful and frequently cited [...]

In 2004, Dr. Leisha Emens and I reviewed the use of trastuzumab (Herceptin), the monoclonal antibody directed against the HER2 protein, in the treatment of breast cancer. At that time, [...]

I began practice as a medical oncologist in 1986, and like the journal ONCOLOGY, I am celebrating my 25th year in the field. Much has changed over the past two [...]

Locally advanced non-small-cell lung cancer is a heterogeneous group of diseases encompassing both stage IIIA and IIIB disease. The treatment options vary, including surgery, chemotherapy, neoadjuvant concurrent chemoradiation, definitive chemoradiation, radiation, and various combinations of the above. Optimal therapy for each patient group is controversial; however, previous trials have shown efficacy of various treatments for different stages. Surgery as initial therapy is beneficial for patients with stage T3, N1 or T3-4, N0-1 disease due to satellite lesions within the same lung. Chemotherapy should be used for diseases minimally involving the mediastinal lymph nodes, whereas concurrent induction chemoradiation is a good option for bulky nodal disease prior to planning a resection. Concurrent definitive chemoradiation or definitive radiation should be reserved for patients who are not candidates for a surgical resection. Most importantly, the treatment strategy for stage IIIA/IIIB disease should involve a multimodality approach individualized to the patient's disease stage, age, underlying medical conditions, and performance status., Despite recent therapeutic advances, lung cancer continues to be one of the leading causes of cancer-related mortality. Of the various histologic subtypes, non-small-cell lung cancer (NSCLC) is the most common--accounting [...]