Upper gastrointestinal (GI) tract cancers originating in the esophagus, gastroesophageal (GE) junctions, and stomach constitute a major health problem worldwide; esophageal cancer is the eighth most common cancer worldwide. An estimated 16,470 new cases of and 14,280 deaths from esophageal cancer will occur in the United States in 2008. A dramatic shift in the location of upper GI tumors has occurred in the United States, while changes in histology and location of upper GI tumors have also been observed in some parts of Europe. In many other parts of the world, particularly among developing nations, esophageal cancer is endemic. Risk factors associated with development of esophageal cancer include age, male gender, Caucasian race, body mass index, Barrett’s esophagus, and history of gastroesophageal reflux disease. Important updates for the 2009guidelines include a new page on “Principles of Best Supportive Care” that gives specific recommendations for esophageal cancer best supportive care throughout the guidelines.

Myelodysplastic Syndromes

Myelodysplastic syndromes (MDS) represent myeloid clonal hemopathies with relatively heterogeneous spectrums of presentation. The major clinical problems in these disorders are morbidities caused by patients’ cytopenias and the potential for MDS to evolve into acute myeloid leukemia (AML). In the general population, MDS occur in 5 per 100,000 people. However, among individuals older than age 70, the incidence increases between 22 and 45 per 100,000 and increases further with age. Managing MDS is complicated by the generally advanced age of patients, attendant non‑hematologic comorbidities, and older patients' relative inability to tolerate some therapies. In addition, when the illness progresses into AML, these patients experience lower response rates to standard therapy than patients with de novo AML. Important changes from the 2008 version of the guidelines include the addition of lenalidomide as a possible treatment for symptomatically anemic non-del(5q) patients whose anemia does not respond to initial therapy.

Featured Articles

Combined Modality Therapy of Esophageal Cancer
Rosalyn A. Juergens, MD, and Arlene Forastiere, MD

Esophageal cancer is a deadly disease; only a third of patients with localized disease experience long-term survival. To improve survival rates for these patients, treatment must focus on increasing response in patients with localized disease. Over the past 20 years, investigators have evaluated neoadjuvant strategies to improve the outcomes of surgical management. Chemotherapy and radiation have been evaluated individually and in combination for preoperative management of patients with localized esophageal cancer. Currently, controversy exists worldwide regarding the optimal treatment approach. This article provides a critical review of the data on multimodality approaches to the management of esophageal cancer.

Modern Staging and Utility of PET Imaging in Esophageal Cancer Management
Kwang-Yu Chang, MD; Jang-Yang Chang, MD; Joseph Chao, MD; and Yun Yen, MD, PhD

Esophageal cancer is the eighth most common cancer worldwide and one of the most fatal diseases despite modern medical treatment. Because correct staging and surveillance of neoadjuvant therapy is mandatory for further treatment planning, choosing an imaging system is important. The development of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) has provided alternate means of tumor detection distinct from more conventional methods. This modality has extraordinary performance in detecting locoregional lymph node involvement and distant metastatic disease, and has been introduced as a powerful tool in many guidelines. However, some factors still lead to false-negative or -positive results, raising questions of its accuracy. This article discusses the clinical efficacy of PET in staging and surveillance of neoadjuvant therapy in esophageal cancer, comparing its accuracy with conventional imaging modalities.

Principles and Techniques of Radiation Therapy for Esophageal and Gastroesophageal Junction Cancers
Lisa Hazard, MD; Gary Yang, MD; Mary Frances McAleer, MD; James Hayman, MD, MBA; and Christopher Willett, MD

Radiation therapy serves an integral role in the primary and adjuvant treatment of esophagus cancer. Potentially curative treatment options for medically fit patients with esophageal carcinoma without distant metastases include surgery alone, chemoradiation alone, or chemoradiation followed by surgery. Because radiation therapy serves an important definitive and adjuvant role in the treatment of esophagus carcinoma, radiation techniques to maximize tumor control and minimize morbidity are of importance. As such, radiation techniques continue to improve, providing more accurate localization of the tumor while limiting dose to normal structures. This article reviews current practices and recommendations for radiation therapy techniques for esophageal and gastroesophageal malignancies.

Minimally Invasive Surgery for Esophageal Cancer
Alfredo A. Santillan, MD, MPH; Jeffrey M. Farma, MD; Kenneth L. Meredith, MD; Nilay R. Shah, MD; and Scott T. Kelley, MD

Esophageal cancer represents a major public health problem worldwide. Several minimally invasive esophagectomy (MIE) techniques have been described and represent a safe alternative for the surgical management of esophageal cancer in selected centers with high volume and expertise in minimally invasive procedures. Recent larger series have shown MIE to be equivalent in postoperative morbidity and mortality rates to conventional surgery. MIE has been associated with less blood loss, less postoperative pain, and a decreased length of hospital stay compared with conventional surgery. Despite limited data, conventional surgery and MIE have shown no significant difference in survival, stage for stage. The myriad of MIE techniques complicates the debate of defining the optimal surgical approach for treating esophageal cancer. Randomized controlled trials comparing MIE with conventional open esophagectomy are needed to clarify the ideal procedure with the lowest postoperative morbidity, best quality of life after surgery, and long-term survival.

Modern Surgical Considerations for Gastric Cancer
Quan P. Ly, MD, and Aaron R. Sasson, MD

Surgical resection remains the mainstay of treatment of localized gastric adenocarcinoma. The type and extent of resection depends on tumor location. Although the incidence of gastric cancer has been declining, a shift has occurred to more tumors involving the proximal compared with distal stomach. Appropriate treatment depends on a thorough staging process to exclude the presence of distant metastatic disease. Current staging modalities include high-quality CT scan, endoscopic ultrasound, PET, and laparoscopy. The value of peritoneal lavage to detect occult peritoneal disease is under investigation. The principles of surgical resection have always included negative resection margins and adequate lymph node examination. Controversial topics requiring further study include laparoscopic resections and hepatic metastectomy. This review highlights the salient points of current surgical management of gastric adenocarcinoma.

An Update on Biochemotherapy of Advanced Gastric and Gastroesophageal Adenocarcinoma
Peyman Haghighat, MD, MS, and Tanios Bekaii-Saab MD

Gastric and gastroesophageal adenocarcinoma (GGA) are significant worldwide health problems. With most patients presenting with advanced disease, palliative chemotherapy plays a significant role in treatment. Results from recent phase III studies of cytotoxic agents in combination therapy, such as docetaxel, oxaliplatin, irinotecan, capecitabine, and S-1, have been encouraging and provide patients with additional therapeutic options. Although these forthcoming regimens have allowed for more flexible patient-tailored therapy, survival continues to be suboptimal. Although still in its infancy, targeted biotherapy, including inhibitors of the vascular endothelial and epidermal growth factor receptors, seems to be promising and its incorporation into the next generation of clinical trials will hopefully improve outcome and help advance future treatments. This article reviews current active chemotherapeutic regimens and explores the role of novel targeted therapies in advanced GGA.

Impact of Age and Comorbidity in Myelodysplastic Syndromes
Reinhard Stauder, MD; Thomas Nösslinger, MD; Michael Pfeilstöcker, MD; Wolfgang R. Sperr, MD; Friedrich Wimazal, MD; Otto Krieger, MD; and Peter Valent, MD

Myelodysplastic syndromes (MDS) represent a heterogeneous group of myeloid neoplasms that are preferentially diagnosed in the elderly. With an increase in MDS among older patients and the availability of more treatment options, new strategies and algorithms for optimal management and treatment must be developed. Although age has been recognized as an important adverse variable affecting survival in MDS, most scoring systems have not included age in score-risk calculations. Comorbidity is of particular importance and a frequent co-variable in elderly patients with MDS. However, comorbidity scores have only just begun to be applied to elderly patients, with relevant results. Advanced age should not exclude a patient from appropriate treatment, and age alone should not be considered a surrogate marker for functional decline or comorbidities. This article discusses the need to improve scoring systems, individualized risk-assessment, and treatment algorithms for older patients with MDS.

The Role of Flow Cytometry in Myelodysplastic Syndromes
Michael R. Loken, PhD, and Denise A. Wells, MD

Flow cytometry quantifies the gene product expression on hematopoietic cells, permitting the identification of all cells within a bone marrow aspirate and classifying them according to lineage and maturational stage. The relationships in expression of multiple markers on myeloblasts, maturing monocytes, and myeloid cells suggest that development of these cells is a stepwise process in which genes are not only turned on or off, but are up- and down-regulated at the junctions between stages. A loss of coordination of these steps in neoplastic processes result in the abnormal relationships identified by flow cytometry. In myelodysplastic syndromes, the abnormal patterns can be identified on both the immature myeloblasts as well as on the maturing myeloid cells and monocytes. The detection of these abnormalities is useful in the diagnosis of myelodysplasia, but requires a detailed understanding of the expression of these gene products to discriminate neoplastic transformation from a stressed marrow. Therefore, scoring systems in which the abnormalities are counted provide a means of determining the extent of dysregulation at all the maturational steps. Thereby a “distance from normal” can be determined for patients at specific times in the disease course. This is useful, not only to facilitate diagnosis, but to provide prognostic information that may complement the conventional classification schemes and scoring systems.

The Costs of Drugs Used to Treat Myelodyplastic Syndromes Following National Comprehensive Cancer Network Guidelines
Peter L. Greenberg, MD; Leon E. Cosler, RPh, PhD; Salvatore A. Ferro; and Gary H. Lyman, MD, MPH, FRCP(Edin)

Because myelodysplastic syndromes (MDS) are a heterogeneous spectrum of disorders, patients with MDS have been categorized into prognostic subgroups, predominantly using the International Prognostic Scoring System (IPSS). Several drugs have been used to treat these patients, and their selection and sequential recommended use by the NCCN MDS Guidelines Panel depend on disease characteristics and responses to treatment. Recombinant erythropoietin alfa and darbepoetin alfa have been the mainstay of therapy for treating anemia associated with MDS. The FDA recently approved several other drugs for treating MDS, including azacytidine and decitabine, lenalidomide, and deferasirox. Treatment with immunosuppressive therapy has been therapeutically beneficial for a subset of younger patients with MDS. Because the economic impact of these therapies are substantial and have received only limited attention, this article evaluates the costs of specific drugs and their sequential use in the lower-risk IPSS (low and intermediate-1) subgroups based on the NCCN guidelines. Results estimate an average annual cost for potentially anemia-altering drugs to be $63,577 per patient, ranging from $26,000 to $95,000, depending on the specific therapies. In patients for whom the therapies fail, annual costs for iron chelation plus red blood cell transfusions are estimated to average $41,412. This article suggests that the economic impact of drug therapy should be weighed against the patient’s potential for improvement in clinical outcomes, quality of life, and transfusion requirements.

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