Authors

Honing Therapy for Rectal Cancer

Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) are often overexpressed in colorectal cancer and are associated with inferior outcomes. Based on successful randomized phase III trials, anti-EGFR and anti-VEGF therapeutics have entered clinical practice. Cetuximab (Erbitux), an EGFR-specific antibody, is currently approved in the United States in combination with irinotecan (Camptosar) for patients with metastatic colorectal cancer refractory to irinotecan or as a single agent for patients unable to tolerate irinotecan-based therapy. In retrospective analyses, patients with EGFR-expressing rectal cancer undergoing neoadjuvant radiation therapy had a significantly inferior disease-free survival and lower rates of achieving pathologic complete response. Based on the positive data in metastatic colorectal cancer and synergy with radiation therapy seen in preclinical models, there is a strong rationale to combine cetuximab with neoadjuvant radiation therapy and chemotherapy in rectal cancer. Bevacizumab (Avastin), a VEGF-specific antibody, was the first antiangiogenic agent to be approved in the United States for use in combination with standard chemotherapy in the first- and second-line of treatment in metastatic colorectal cancer. VEGF-targeted therapy may lead to indirect killing of cancer cells by damaging tumor blood vessels, and may increase the radiosensitivity of tumor-associated endothelial cells. VEGF blockade can also "normalize" tumor vasculature, thereby leading to greater tumor oxygenation and drug penetration. This review will address completed and ongoing trials that have established and continue to clarify the effects of these agents in rectal cancer.

Cardiovascular Toxicity of Newer Chemotherapeutic Agents: The Heart of the Matter

Standard heart failure regimens remain the mainstay of therapy for chemotherapy-related cardiac dysfunction until newer randomized trials suggest otherwise, and earlier detection of toxicity through judicious surveillance with biomarkers and noninvasive imaging remains the cornerstone of management for the foreseeable future.

Induction Chemotherapy for Resectable Non–Small-Cell Lung Cancer

Lung cancer remains the leading cause of cancer death in Americanmen and women. Non–small-cell lung cancer (NSCLC) accountsfor 85% of these cases. Although surgery is the best curative approachfor resectable NSCLC, long-term survival for patients with operabledisease remains poor. More than half of patients who initially presentwith stage I to IIIA disease experience relapse of metastatic disease.Postoperative adjuvant therapy has been evaluated in several randomizedtrials, and provides a survival benefit. It appears reasonable tolook to induction chemotherapy, or preoperative chemotherapy, to providea similar improvement in survival with early treatment ofmicrometastatic disease. Multiple trials of induction therapy have beencarried out with encouraging results. The use of various induction regimenswith chemotherapy alone or chemotherapy combined with radiotherapyfor stage IIIA NSCLC is under investigation. Randomized trialsare under way to better define the role of induction therapy in themultimodality treatment of NSCLC.

Bone Sarcomas

Multidisciplinary Management of Breast Cancer Brain Metastases

This review summarizes the most up-to-date approach to the multidisciplinary management of patients with breast cancer brain metastases.

A 63-Year-Old Patient Presents With Significant Dyspnea

Palliative Radiotherapy for Prostate Cancer

This review will include discussion of the role of radiation therapy for osseous metastases and metastatic spinal cord compression, as well as the use of radiopharmaceuticals for painful osseous metastases.

The Cancer Genome Atlas: Clinical Applications for Breast Cancer

This article aims to provide an overview of The Cancer Genome Atlas findings, with a particular focus on their potential biological relevance and therapeutic implications.

Problem-Related Distress in Cancer Patients Drives Requests for Help: A Prospective Study

The Moores UCSD Cancer Center has implemented the use of an innovative instrument for screening cancer patients at first visit to assist them with distress due to cancer-related problems. This 36-question screening instrument addresses physical, practical, social, psychological and spiritual problems. Patients are asked to rate the severity of each problem on a scale of 1 to 5, and to circle "Yes" if they would like staff assistance. Data from a prospective study of the first 2,071 patients to complete this questionnaire has been entered into a database and analyzed to identify common patient problems, demographics, and trends. The five most common causes of problem-related distress were fatigue, sleeping, finances, pain, and controlling my fear and worry about the future. The five most common problems for which patients circled "Yes" to ask for assistance were understanding my treatment options, fatigue, sleeping, pain, and finances. Compared to the entire population, patients who circled "Yes" on a particular problem, demonstrated a robust increase in problem-related distress.

Diagnostic Dilemma: GI Disease

An 85-year-old woman presented to the emergency department with epigastric pain and nausea for 2 days. She denied vomiting, fever, or early satiety. The patient stated she had lost 10 pounds over the past 3 months. A CT scan of the abdomen revealed a 1 cm low attenuation lesion in the second portion of the duodenum.

Management of Barrett's Esophagus

Barrett's esophagus represents replacement of normal distal esophageal squamous epithelium with specialized columnar epithelium containing goblet cells. Typically arising in the setting of chronic gastroesophageal reflux disease, the presence of Barrett's esophagus carries a 50- to 100-fold increased risk of developing esophageal cancer. Risk factors include male sex, smoking history, obesity, Caucasian ethnicity, age > 50 and > 5-year history of reflux symptoms. Aggressive medical or surgical antireflux therapy may ameliorate symptoms, but have not yet been proven to affect the risk of developing esophageal adenocarcinoma in randomized trials. Although dysplasia is an imperfect biomarker for the development of subsequent malignancy, random sampling of esophageal tissue for dysplasia remains the clinical standard. There have been no studies to establish that endoscopic screening/surveillance programs decrease the rates of death from cancer. Fit patients with Barrett's esophagus and high-grade dysplasia should undergo esophagectomy to prevent the risk of developing esophageal adenocarcinoma. For non–operative candidates, endoscopic ablative approaches may represent a reasonable therapeutic alternative.

Hereditary Cancer Litigation: A Status Report

During the past few decades, cancer patients have sued their physicians for negligence in diagnosing or managing their disease, based on the charge that the clinician failed to consider the patient's genealogy when trying to arrive at a diagnosis. Other suits have charged that the clinician is liable for failing to investigate other members of the cancer patient's family, regardless of whether they were his or her patients.

Diagnosing and Treating Chronic Lymphocytic Leukemia in 2009

Chronic lymphocytic leukemia (CLL) is the most common form of adult leukemia in the Western hemisphere. Both the Rai and Binet staging systems have been important clinical tools for predicting outcomes of this heterogeneous disease.

Neuroendocrine Tumors: Answers-and Questions

The relative abundance of new data on the biological underpinnings of neuroendocrine tumors, combined with clinical trial data supporting new treatment options, is a clear sign of progress. Yet, as is so often the case, these recent studies have generated a multitude of new and different questions.

Endocrine Therapy in 2009: Consideration of the Tumor and the Host

Breast cancer is the most common female malignancy in the Western world. Two-thirds of all breast cancers are estrogen receptor (ER)-positive, a phenotypic characteristic that is prognostic of disease-free survival and predictive of response to endocrine therapy.

Early Engagement in Physical Activity and Exercise Is Key in Managing Cancer Cachexia

Despite consensus on the diagnosis and staging of cancer anorexia/cachexia syndrome, there is currently no accepted standard of care, and affected patients remain widely undertreated.

Prostate Cancer and African-American Men

Dr. Powell has written a comprehensive review of factors believed to contribute to the racial differences observed for prostate cancer incidence and mortality. Prostate cancer has a greater negative impact on African-Americans than on any other racial or ethnic group. However, the etiology of the striking racial variation in prostate cancer incidence and mortality remains enigmatic.

The Management of Early Ovarian Cancer

Approximately one third of patients with epithelial ovarian cancer present with localized or early-stage disease. Prognostic features identify certain subsets of patients with good risk characteristics who do not require adjuvant

TPS 83 ELAINE 3: Open-Label, Randomized, Multicenter, Phase 3 Study of the Efficacy and Safety of Lasofoxifene Plus Abemaciclib for Treating Locally Advanced or Metastatic, ER+/HER2–, Breast Cancer With an ESR1 Mutation

Percutaneous Ablation: Safe, Effective Treatment of Bone Tumors

Percutaneous radiofrequency ablation (RFA) of osteoid osteomashas replaced surgical excision as the preferred method for treatment ofthese benign lesions, due to high effectiveness and low morbidity. BothRFA and cryoablation are safe and effective for palliation of pain dueto metastatic disease in patients who have failed conventional therapies.These image-guided treatments can be performed precisely, allowingsafe treatment of complex metastatic tumors. A single ablationtreatment is effective in most patients, is well tolerated, and provides along duration of pain relief.

Prostate Cancer 2004: Insights From National Disease Registries

In 2004, the large majority of prostate cancers are detected via prostate-specific antigen (PSA) screening. Most are diagnosed at an earlystage and are amenable to aggressive local treatment. However, thenatural history of the disease may be prolonged, and all available activetreatments exert a potential negative effect on patients’ HRQOL.Management options for localized prostate cancer have become increasinglycomplex in recent years, and rigorous trials are frequently difficultto perform due to the extended follow-up required to reach meaningfuloutcomes. In this context, the advent of the national prostatecancer disease registries-Prostate Cancer Outcomes Study (PCOS),Center for Prostate Disease Research (CPDR), Cancer of the ProstateStrategic Urologic Research Endeavor (CaPSURE), and Shared EqualAccess Regional Cancer Hospital (SEARCH)-has greatly facilitatedclinical research in prostate cancer. This review summarizes key findingsfrom the registries in the areas of risk migration, practice patterns,outcome prediction, and quality-of-life outcomes. The availabilityof these large databases of patients will be a tremendous asset asprostate cancer management continues to evolve in the coming years.

Complications of Androgen Deprivation Therapy: Prevention and Treatment

Androgen deprivation therapy(ADT) with a gonadotropinreleasinghormone agonist isthe cornerstone of treatment for metastaticprostate cancer. Patterns of carehave changed dramatically over thepast decade, and gonadotropin-releasinghormone agonists are now routinelyadministered to men withoutradiographic evidence of metastases.These agents account for about onethirdof Medicare expenditures for thetreatment of prostate cancer[1]; in1999, that portion exceeded $800 million.The routine use of gonadotropin-releasing hormone agonists in menwith nonmetastatic prostate cancer increasesthe importance of understandingand preventing treatment-relatedadverse effects. In this issue ofONCOLOGY, Dr. Holzbeierlein andcolleagues provide a timely summaryof the adverse effects of ADT.

Radiotherapy for Cutaneous Malignant Melanoma: Rationale and Indications

The use of radiation as adjuvant therapy for patients with cutaneousmalignant melanoma has been hindered by the unsubstantiatedbelief that melanoma cells are radioresistant. An abundance of literaturehas now demonstrated that locoregional relapse of melanoma iscommon after surgery alone when certain clinicopathologic featuresare present. Features associated with a high risk of primary tumor recurrenceinclude desmoplastic subtype, positive microscopic margins,recurrent disease, and thick primary lesions with ulceration or satellitosis.Features associated with a high risk of nodal relapse include extracapsularextension, involvement of four or more lymph nodes, lymphnodes measuring at least 3 cm, cervical lymph node location, and recurrentdisease. Numerous studies support the efficacy of adjuvant irradiationin these clinical situations. Although data in the literatureremain sparse, evidence also indicates that elective irradiation is effectivein eradicating subclinical nodal metastases after removal of theprimary melanoma. Consequently, there may be an opportunity to integrateradiotherapy into the multimodality treatment of patients at highrisk of subclinical nodal disease, particularly those with an involvedsentinel lymph node. Such patients are known to have a low rate ofadditional lymph node involvement, and thus in this group, a shortcourse of radiotherapy may be an adequate substitute for regional lymphnode dissection. This will be the topic of future research.

Bone Disease in Multiple Myeloma

Despite the significant progress that has occurred in recent decades in the treatment of many advanced malignancies, skeletal morbidity remains a major problem for patients affected by cancers that metastasize to or grow primarily within bone.[1] Thus as patients with a variety of malignancies survive longer, therapies to limit cancer-associated as well as treatment-associated skeletal complications have become increasingly important for the provision of optimal patient care.

Pegylated Liposomal Doxorubicin: Antitumor Activity in Epithelial Ovarian Cancer or Cancers of Peritoneal Origin

After pegylated liposomal doxorubicin (PEG-LD) (Doxil) was shown to be active in ovarian tumors, several trials were developed at the University of Southern California to determine its safety and efficacy in a variety of gynecologic and peritoneal malignancies. Completed phase I and phase II trials have found PEG-LD to be safe and effective in the treatment of platinum- and paclitaxel-refractory epithelial ovarian carcinoma. A new phase II trial is currently underway in similarly refractory patients with ovarian and other related cancers and various degrees of pretreatment. In addition, the efficacy of PEG-LD is being explored in combination with paclitaxel (Taxol), with cisplatin, and with hyperthermia. [ONCOLOGY 11(Suppl 11):38-44, 1997]

Nonsteroidal and Steroidal Aromatase Inhibitors in Breast Cancer

Anastrozole (Arimidex), letrozole (Femara), and exemestane (Aromasin) are members of the third generation of aromatase inhibitors that has now replaced aminoglutethimide (Cytadren), the progestins, and tamoxifen

Checkpoint Inhibitors and Urothelial Carcinoma: The Translational Paradigm

The emergence of immune checkpoint inhibitors as effective cancer immunotherapy has effectively built a new “highway” connecting the promise of oncologic translational research to progress in treating advanced malignancies.

Chemotherapy for Treatment of Grade II Gliomas

In this article, we provide a brief overview of the management of grade II astrocytomas, oligodendrogliomas, and mixed oligoastrocytomas-the three most heavily encountered and studied of the low-grade gliomas.

Pharmacology of Antineoplastic Agents in Older Cancer Patients

Drs. Lichtman and Skirvin have written an excellent review on the pharmacology of antineoplastic agents in older cancer patients. However, as in any text (often due to space limitations), one can find shortcomings, some of which will be covered in this commentary.

Evolution of the Concept of Focal Therapy for Prostate Cancer

In this review we focus on the recent evolution of the concept of focal therapy and the potential applications of this management approach within an array of options currently available for patients with localized prostate cancer.