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This review describes the anatomy of the blood-brain barrier and currently available methods to quantify the entry of therapeutic compounds into the brain. It also summarizes data from a variety of approaches designed to improve drug delivery to the central nervous system.

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In light of recent clinical trial data, key opinion leaders reflect on the appropriate selection of transplant for patients with newly diagnosed multiple myeloma.

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Mantle cell lymphoma (MCL) accounts for approximately 6% of non-Hodgkin’s lymphomas. Patients usually present with advanced disease, with a tendency for extranodal involvement. MCL is an aggressive lymphoma with moderate chemosensitivity, but it remains one of the most difficult therapeutic challenges. Complete response rates to chemotherapy range from 20% to 40%, with median survivals of 2½ to 3 years. Anthracycline-containing regimens do not prolong survival compared with nonanthracycline regimens. Single-agent rituximab (Rituxan) has produced response rates of about 30%, and when combined with an anthracycline-containing regimen, response rates increase to above 90%; however, an impact on survival has not yet been demonstrated. More intensive regimens such as hyperCVAD (hyperfractionated cyclophosphamide [Cytoxan, Neosar], vincristine, doxorubicin [Adriamycin], dexamethasone, methotrexate, cytarabine) with either stem cell transplant or rituximab have been associated with promising results.

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Recent studies have elucidated some of the molecular and cellular mechanisms that determine the sensitivity or resistance to ionizing radiation. These findings ultimately may be useful in devising new strategies to improve the

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This video examines a study that looked at whether aromatase inhibitors are associated with higher myocardial infarction risk in breast cancer patients.

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Influenza infection is a potential cause of additional morbidity and mortality in patients who are immunocompromised because of cancer or its treatment. Of particular note, influenza infection may delay or interrupt chemotherapy and necessitate hospitalization. Successful immunization depends on an intact immune system that can produce antibodies in response to antigen exposure. Patients with cancer often have a suppressed immune system, resulting from their disease and/or immunosuppressive therapies, and as a consequence they may have a suboptimal serologic response to influenza vaccination. Since vaccination is the only proven method for preventing influenza infection, the Advisory Committee on Immunization Practices recommends seasonal influenza vaccination for adults without contraindications who have disease- or medication-related immunosuppression. Patients with cancer should be given the trivalent inactivated vaccine. Preliminary data suggest that administering the vaccine between cycles of chemotherapy may yield the best results.

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The article “Adjuvant Hormonal Therapy in Premenopausal Women With Operable Breast Cancer: Not-So-Peripheral Perspectives” by Richard Love, published in this issue of ONCOLOGY,

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Pancreatic cancer is a disease seen predominantly in elderly patients. Compared to younger patients, older patients are more likely to present with early-stage disease and, therefore, may be candidates for aggressive local

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The treatment of advanced non–small-cell lung cancer (NSCLC)has evolved rapidly over the past few years. Systemic chemotherapy isassociated with both quality of life and modest survival benefit for patientswith advanced NSCLC. Platinum-based doublet combinationsare the “standard of care.” The US Food and Drug Administration(FDA) has approved gemcitabine (Gemzar), a pyrimidine analog, to beused in combination with cisplatin for the treatment of advanced NSCLCin the first-line setting. Randomized clinical trials have established comparableefficacy with improved therapeutic index for the carboplatin/gemcitabine regimen when compared with cisplatin/gemcitabine andother platinum doublets. Nonhematologic toxicities occur at a lowerfrequency with carboplatin/gemcitabine combinations compared withother “standard” platinum-based doublets, whereas dose-limitingthrombocytopenia, the most common toxicity, rarely requires therapeuticintervention. Both the 3- and 4-week schedules of carboplatin/gemcitabine result in similar efficacy and toxicity profiles, but the3-week regimen is preferred. The combination of carboplatin andgemcitabine is an effective regimen with an acceptable toxicity profilefor the treatment of advanced NSCLC. This regimen can also be usedas a foundation for the development of innovative combinations withmolecularly targeted agents.

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Chemotherapy-induced peripheral neuropathy is a serious yet common side effect of cancer treatment. This devastating complication, which typically manifests as tingling and numbness in the hands and feet, has an enormous influence on patients’ quality of life.

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Cytokines have been used in the treatment of patients with cutaneousmelanoma. Granulocyte-macrophage colony-stimulating factor(GM-CSF, sargramostim [Leukine]) leads to dendritic cell/macrophagepriming and activation, and also increases interleukin-2 (IL-2)receptor expression on T lymphocytes. IL-2 creates lymphokineactivatedkiller cells and tumor-infiltrating lymphocyte cells. In thisopen-label, single-arm study of 16 high-risk patients, we combined thesetwo agents to take advantage of their different but complementary functions.All patients underwent potentially curative surgery. Postoperatively,each patient received GM-CSF at 125 μg/m2/d subcutaneously(SC) for 14 days; this was followed by IL-2 at 9 million IU/m2/d SC for4 days, and then 10 to 12 days of no treatment. In addition, patientswho had large tumors that could yield over 100 million live tumor cellsreceived autologous melanoma vaccines. The duration of follow-upranged from 21 to 42 months (median: 27 months). During follow-up,five patients developed metastases. This program was carried out on anoutpatient basis, and no hospitalization was required. It was well toleratedwith minimal side effects. The combination treatment regimen ofGM-CSF and IL-2 with or without autologous vaccine used adjuvantlyappears to benefit high-risk melanoma patients; further clinical testingof this regimen is warranted.

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In this helpful review, the authors catalog a number of the novel molecular agents now being examined for treatment of radioiodine-resistant, metastatic differentiated thyroid cancer. They also call for increased systematic study of outcomes through recruitment of patients into large-scale trials.

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We applaud Ghobrial andWitzig for their comprehensiveand balanced article on"Radioimmunotherapy: A New TreatmentModality for B-cell Non-Hodgkin's Lymphoma." Theseauthors have provided a review thatwill serve the oncologist and oncologypatient well. They have not engagedin arcane and tedious discussionof which anti-CD20 monoclonal antibody(ibritumomab tiuxetan [Zevalin]or tositumomab/iodine-131[I-131] tositumomab [Bexxar]), or radionuclide(yttrium-90 [Y-90] orI-131), or dosing method is better.Wisely, Ghobrial and Witzig have providedaccurate distillates of the manypublications on these exciting drugs.Because no rigorous body of dataclearly indicates that one drug is betterthan the other, these debates onlyconfuse the oncologist and are betterleft to the "technocrat."

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For years, chemotherapy-associated myelosuppression has represented a major limitation to a patient's tolerance of anticancer therapy. In addition, the clinical consequences of chemotherapy-induced myelosuppression (such as febrile neutropenia, dose reductions, or lengthy dose delays) may have had significant negative effects on quality of life or even response to treatment.

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CancerNetwork® sat down with Salma Jabbour, MD, of Rutgers Cancer Institute, at 2021 ASCO to talk about what she believed was the most interesting and impactful study to come out of the meeting.

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In 2008, more than 184,000 new patients were diagnosed with breast cancer, the most commonly diagnosed malignancy in women in the United States. Despite great advances over the past few years in screening, detection, and treatment, more than 40,000 women died from the disease in 2008.[1] Early breast cancer is considered a curable disease, but the curative potential of patients with locally advanced or metastatic disease is limited.

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Drs. Dutcher, Mourad, and Ennis have provided an excellent review of current and potential future treatments of renal cell carcinoma (RCC); we would like to highlight some salient points from a urologic perspective.

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In this Stump the Professor video, two fellows test Dr. Marshall's diagnostic skills with a unique case study involving an 80-year-old patient who presents with abdominal pain, bilateral edema, weight loss, and dark, tarry stools.

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We review here the state of the art of diagnosis and treatment of AML and provide insights into the emerging novel biomarkers and therapeutic agents that are anticipated to be useful for the implementation of personalized medicine in AML.

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Lung cancer is a global problem fueled by the continuous use of tobacco in most countries, despite efforts at expanding smoking cessation programs. Several advances in the diagnosis and treatment of lung cancer were achieved in the past decade. This progress notwithstanding, most lung cancer patients succumb to their illness, and few enjoy long-term survival.

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Quan and colleagues have providedan important and timelyreview on the treatment ofbrain metastases in patients with smallcell lung cancer (SCLC). We certainlyagree with the comments and viewsof the authors, but wish to emphasizeseveral aspects of central nervoussystem (CNS) metastases in SCLCpatients.

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Much excitement has beengenerated in the past fewyears around the potential of“omics technologies” to produce advancesin medicine. For example, globalprofiling using DNA microarrayshas uncovered patterns of gene expressionthat may have clinical utility. However,it has become clear that numerousobstacles must be overcome beforefindings from these studies have a substantialimpact on clinical practice.

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Lung cancer is the leading cause of cancer mortality in the United States. A significant number of patients present with disease involving mediastinal lymph nodes. As survival after surgery alone for stage III disease is poor, radiation therapy and chemotherapy have been evaluated in the neoadjuvant and adjuvant settings to improve outcomes. The benefit of adjuvant chemotherapy in the subgroup of patients with N2 disease is uncertain. Small randomized trials enrolling patients with stage III disease have shown a benefit of neoadjuvant chemotherapy over surgery alone. Whether neoadjuvant chemotherapy is superior to adjuvant chemotherapy is under investigation. Furthermore, whether neoadjuvant chemoradiotherapy is superior to neoadjuvant chemotherapy is controversial, and few randomized studies comparing these approaches have been reported. Nevertheless, neoadjuvant chemoradiotherapy appears to be associated with higher rates of resection, higher rates of clearance of mediastinal nodal disease, and better local/regional control. The use of postoperative radiation therapy (PORT) has declined since the publication of the 1998 meta-analysis suggested a detriment in survival with this strategy. However, radiation techniques are improving and emerging data support the use of carefully delivered PORT. Finally, it remains unclear whether surgical resection offers an advantage over definitive chemoradiotherapy alone for stage III disease. In summary, locally advanced NSCLC remains a formidable challenge with few cures, and optimal treatment requires the careful use of surgery, chemotherapy, and radiation therapy.

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Our aims in this article are to describe the various imaging sequences that comprise the multiparametric MRI exam, as well as to review current literature on the strengths/weaknesses of these sequences; to delineate strategies for standardizing interpretation and reporting of MRI results; and to expound on the role of prostate MRI in clinical practice.

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A 37-year-old Lebanese male with no significant past medical history initially presented with an increase in abdominal girth over a few weeks with worsening shortness of breath, nausea, and intermittent vomiting.

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In this paper, we review the use of serum tumor markers in risk assignment and response evaluation; the treatment of previously untreated and relapsing patients; the role of surgical resection of residual disease, including retroperitoneal node dissection; and the importance of clinical trials for addressing unanswered questions and testing new therapies.

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In 1970, Ansfield and colleagues published the results of a randomized trial in head and neck cancer, which showed that giving fluorouracil (5-FU) concomitantly with radiation decreased regional recurrences and improved overall survival over radiation alone.[1] Publication of these results came 6 years before those of an Italian trial showing similar findings with adjuvant cyclophosphamide, methotrexate, and 5-FU (CMF) in breast cancer.[2] Yet, while adjuvant chemotherapy has rapidly become the norm in the management of early breast cancer, concomitant chemotherapy is still considered undefined in the treatment of head and neck cancer. This situation is elegantly described by Dr. Karen Fu, one of the most respected investigators in this area.

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Michael H. Levy, MD: This 38-year-old white male first came to his physician in January of 1993 complaining of epigastric and low back pain. In March of 1993, he was diagnosed with pancreatic cancer that was metastatic to his

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Unresectable pancreatic cancer has few therapeutic options and adismal prognosis. Cyclooxygenase-2 (COX-2) expression is increasedat the RNA and protein levels in most human pancreatic cancers. Thepurpose of this trial was to determine whether the addition of a COX-2inhibitor to chemotherapy was beneficial. To date, 11 patients with inoperablepancreatic cancer have been treated with the combination ofgemcitabine (Gemzar), irinotecan (Camptosar), and celecoxib(Celebrex) at 400 mg orally twice daily. Encouraging pain relief, improvementin performance status, and decreases in CA 19-9 andcarcinoembryonic antigen levels have been observed.