This special series on cancer and genetics is compiled and edited by Henry T. Lynch, MD, director of the Hereditary Cancer Institute and professor of medicine and chairman of the Department of Preventive Medicine and Public
Methods for detecting breast cancer are evolving as new technology provides a wider range of options for screening and definitive diagnosis. In addition to mammography and physical examination, screening techniques now include ultrasonography, technetium-99m sestamibi nuclear scanning, and magnetic resonance imaging.
Authors Winkfield and Harris kindly submit to the reader an article that reemphasizes the link between local control (LC) and overall survival (OS).
This video examines the safety and efficacy of definitive stereotactic body radiation therapy in patients 80 and older with inoperable, early-stage lung cancer.
High-dose myeloablative therapy with allogeneic hematopoietictransplantation is an effective treatment for hematologic malignancies,but this approach is associated with a high risk of complications.The use of relatively nontoxic, nonmyeloablative, or reduced-intensitypreparative regimens still allows engraftment and the generation ofgraft-vs-malignancy effects, is potentially curative for susceptiblemalignancies, and reduces the risk of treatment-related morbidity.Two general strategies along these lines have emerged, based on theuse of (1) immunosuppressive chemotherapeutic drugs, usually apurine analog in combination with an alkylating agent, and (2) lowdosetotal body irradiation, alone or in combination with fludarabine(Fludara).
The majority of patients with ovarian cancer, especially those whopresent with stages IIIC and IV, will relapse soon after completion ofplatinum-based induction treatment. It is imperative to find ways to improveand/or enhance the efficacy of induction and to prolong the durationof the first remission. The epidermal growth factor receptor (EGFR)family has been exploited, and currently, three agents that directly targetthis group of receptors are in use in the treatment of colorectal,non–small-cell lung and breast cancers. EGFR and HER2/neu areoverexpressed in a significant percentage of epithelial ovarian cancers.Thus, it would be reasonable to explore directly targeted therapyin ovarian cancer. Numerous investigational trials involving a varietyof EGFR inhibitors in ovarian cancer are ongoing. Our institution hasan active phase II clinical study that seeks to define the role of erlotinib(Tarceva) in potentiating first-line chemotherapy, and to determinewhether the drug offers a significant contribution as maintenancetherapy. It is hoped that data from these and other studies will helpinvestigators to understand more clearly the biology of ovarian cancerand to delineate the role of EGFR inhibitors in the management ofovarian cancer.
The author gives a comprehensive review of the literature on the treatment of brain metastasis by radiation therapy. His emphasis is on randomized trials, the most extensive and comprehensive of which are those conducted by the Radiation Therapy Oncology Group (RTOG). This commentary will provide some amplification of the data presented in the review.
In this article, we review the role of baseline tumor size in response and survival on traditional and contemporary therapies for the treatment of locoregional and distant melanoma recurrences.
Fenretinide (N-4-hydroxyphenyl-retinamide, or 4-HPR) is a semisynthetic retinoid that was initially developed as a low-dose chemopreventative agent.[1-3] Unlike other naturally occurring retinoids such as all-trans, 13-cis, and 9-cis retinoic acids, fenretinide does not induce systemic catabolism that interferes with the maintenance of effective plasma levels during long-term use. This characteristic, combined with the agent’s low toxicity and its ability to block aspects of carcinogenesis, provided the rationale for the development of fenretinide in lower doses as a chemoprevention agent for breast, prostate, and bladder cancer.
High-dose chemotherapy (HDCT) with autologous stem-cell is effective against a wide range of malignant diseases. This approach is increasingly used for treating hematologic malignancies and selected solid tumors. Since 1990, the number of autologous transplantations has exceeded the number of allogeneic transplantations.
Transurethral resection remains the standard for first-line treatment of transitional cell carcinoma of the bladder. This technique clearly defines the pathologic grade and is essential in determining the clinical stage of
Dr. Severin's article is a valuable asset for the practitioner--legal or medical--or academician concerned with the burgeoning of civil lawsuits over failure to comply with new approaches to the management and control of cancer. The article identifies two types of such suits and explores the history of medical malpractice litigation relating to cancer care. The focus is the physician who either misses or fails to make a timely diagnosis of hereditable cancer.
The surgical management of cutaneousmelanoma remainscontroversial in part becausethere is no consensus regarding themargins of excision for the primarytumor or the therapeutic benefit ofremoving clinically normal appearingregional lymph nodes (electivelymph node dissection).[1] Intraoperativelymphatic mapping with sentinellymph node dissection hasrevolutionized the management of regionallymph nodes by allowing thesurgeon to perform a minimally invasiveprocedure instead of electivelymph node dissection, and by allowingthe pathologist to focus on one ortwo lymph nodes rather than all thenodes in a complete lymph node dissectionspecimen.[2]
A dramatic spike in the incidence of Kaposi’s sarcoma (KS) in never-married men in New York and California in 1981 was one of the first indications of a new disease now known as acquired immunodeficiency syndrome (AIDS). We now appreciate a number of mechanisms by which human immunodeficiency virus (HIV) infection contributes to the pathogenesis of these tumors. The article by Drs. Gates and Kaplan provides an excellent review of changes in the epidemiology, presentation, and treatment of these tumors since the development of potent combination anti-HIV therapy.
While the future is bright for the development and investigation of novel chemotherapeutics for treatment of soft-tissue sarcoma, investigators will need to gain better insight into the molecular drivers of pathogenesis, and give continued thoughtful consideration to clinical trial design.
Although testicular cancer is a rare disease accounting for only 1% of all male neoplasms, it represents a paradigm for cancer curability. Overall, more than 95% of patients can expect to be cured of their disease with minimal long-term toxicity. Given these expectations, it is critical that cancer care providers are familiar with the diagnostic and therapeutic challenges encountered in these rare patients. In particular, clinicians managing these patients should be aware of some of the pitfalls encountered when determining relapse. In a series of case presentations, we review the evaluation and management of patients with persistent elevation of serum tumor markers and postchemotherapy residual radiographic abnormalities.
In this video we discuss the results of the NSABP B-35 trial of anastrozole vs tamoxifen in postmenopausal women with DCIS who had undergone lumpectomy plus radiation therapy.
Dr. Beyer has done a good jobof summarizing the issuesconcerning the use of brachytherapyas a salvage modality to treatradiation therapy failures. This willbecome an issue of greater importanceas we continue to diagnose andtreat younger and younger patientswith prostate cancer. This trend canbe primarily attributed to the successof prostate-specific antigen (PSA)screening. With younger patients optingfor radiation treatment, the numberof patients at potential risk forfailure and hence potential candidatesfor salvage brachytherapy will increase.This, coupled with the stagemigration toward early-stage, lower-PSA disease, may result in an increasingpopulation of patients with perhapsmore curable recurrent disease.
Bill, 53 years old and a 3-year survivor of non-Hodgkin’s lymphoma, reflects on his ongoing journey as a cancer survivor: “I was very sick and treatment was very rough, complete with a severe allergic reaction that was difficult to diagnose for a long time. But I made it through to the other shore…remission. Since then, I’ve been trying to rebuild a new life…Living with an 18-year-old [son], I can see how in some ways I’m in a parallel universe…Both of us are looking out at the world before us, at all the many possible options...trying to figure out what we want tomorrow to look like.
Tositumomab/iodine-131 tositumomab (Bexxar) and ibritumomab tiuxetan (Zevalin) are radioimmunoconjugates targeting the CD20 antigen. Both agents are approved in the United States for use in relapsed or refractory, indolent or transformed, B-cell lymphoma. These agents are well tolerated and have the highest levels of single-agent activity observed in these histologies. This review will summarize the key trials that led to approval of both I-131 tositumomab and ibritumomab tiuxetan, and then focus on four novel therapeutic concepts in radioimmunotherapy: retreatment, therapy of de novo indolent lymphoma, therapy of aggressive histologies, and incorporation in high-dose therapy programs utilizing autologous stem cell support.
I was pleased to read the timely update on prostate-specific antigen (PSA) by Drs. Jürgen Pannek and Alan W. Partin in the September 1997 issue of oncology (pp 1273-1278) and the accompanying review by Dr. Steven J. Jacobsen (pp 1281-
Soft-tissue sarcomas comprise approximately 7% of all pediatric malignancies. Surgery, chemotherapy, and radiation therapy have significantly improved survival.
Increasing experience with magnetic resonance imaging (MRI) has raised important questions about how it should be used in breast cancer screening, and for presurgical evaluation and posttherapy follow-up of women with this disease. Overall, the availability of MRI as an adjunct to mammography and ultrasound offers clear clinical benefit to women at increased risk of breast cancer development due to BRCA1 and BRCA2 mutations, and to women presenting with axillary adenopathy and an occult primary breast tumor. In contrast, its benefit for routine selection of breast conservation or further assessment of lobular carcinoma in women of average risk has not been demonstrated.This article reviews the use of MRI in these settings, with an emphasis on the clinical outcomes that have been observed to date.
The current ONCOLOGY articleby Drs. Merrick, Wallner,and Butler is a valuable additionto the literature. An estimated189,000 American men were diagnosedwith prostate cancer in 2002,and 30,200 died of the disease, makingit the most common cancer amongmen, and the second most commoncause of cancer death.[1] The treatmentshave led to a high rate of cure,but the results of treatment oftencause a reduction in quality of life.
Dr. Hoppe and colleagues present a strong case supporting the use of proton therapy (PT) for the treatment of patients with Hodgkin lymphoma (HL).
Docetaxel (Taxotere) isa semisynthetic taxoid that possesses significant activity as a single
The patient is a 5-month-old Caucasian boy with no developmental abnormalities who presented Christmas Eve 2004 to his pediatrician with increasing fussiness, emesis, and inability to tolerate oral intake. He had a temperature of 100.2°F but otherwise normal vital signs. Physical exam at that time revealed a distended abdomen. He was sent home with a diagnosis of viral gastroenteritis.
Bcl-2 functions as a key survival factor for lymphocytes and is highlyexpressed in a majority of non-Hodgkin's lymphomas. The ability ofoblimersen sodium (Genasense, previously known as G3139) to targetbcl-2 messenger RNA and decrease Bcl-2 protein levels has the potentialto enhance the activity of cytotoxic chemotherapy. Pretreatmentwith oblimersen followed by cyclophosphamide (Cytoxan, Neosar)markedly improved survival relative to single-agent cyclophosphamidein a murine xenograft model. Oblimersen has also enhanced the cytotoxicityof a variety of other agents against non-Hodgkin's lymphoma,including etoposide, rituximab (Rituxan), and alemtuzumab (Campath).An initial phase I study of oblimersen in non-Hodgkin's lymphomademonstrated modest single-agent activity. Recent reports suggest thatoblimersen may add to the activity of R-CHOP (rituximab-cyclophosphamide/doxorubicin/vincristine/prednisone) in previously untreatedmantle cell lymphoma and to rituximab alone in a variety of subtypesof relapsed non-Hodgkin's lymphoma. Additional studies in both treatment-naive and relapsed patients will define the role of oblimersen inthe treatment of non-Hodgkin's lymphoma.
In this article we review the scientific rationale, preclinical evidence, and most recent clinical data for the use of checkpoint inhibitor therapy in patients with relapsed Hodgkin lymphoma.