Gastrointestinal Cancer

The minimally invasive procedure of radiofrequency ablation (RFA) appears to be as effective as surgical resection for the treatment of patients with a small hepatocellular carcinoma (HCC) and offers similar survival, according to a study presented at the 31st Annual Meeting of the Society of Interventional Radiology (abstract 1021). "Radiofrequency ablation can offer the same life expectancy as surgical resection to patients with solitary, small HCC, most of whom cannot tolerate a resection," said Riccardo Lencioni, MD, University of Pisa, Italy.

Carcinoembryonic antigen (CEA) monitoring in patients with stage I-IV colorectal cancer has been, and remains, a controversial issue in oncology practice. Recommendations vary from bimonthly monitoring to no monitoring in the surveillance setting (for stage I-III disease). In the metastatic setting, there are no clear guidelines for CEA follow-up, although continued monitoring in such patients is common in the oncology community. This manuscript reviews the accuracy of CEA testing, its value as a prognostic indicator, and its role in surveillance and response assessment. The limitations of the test in the adjuvant and metastatic settings are illustrated through several case reports from the Colorectal Oncology Clinic at Roswell Park Cancer Institute. Guidelines for CEA monitoring are provided, based on a detailed literature review and institutional experience.

Carcinoembryonic antigen (CEA) monitoring in patients with stage I-IV colorectal cancer has been, and remains, a controversial issue in oncology practice. Recommendations vary from bimonthly monitoring to no monitoring in the surveillance setting (for stage I-III disease). In the metastatic setting, there are no clear guidelines for CEA follow-up, although continued monitoring in such patients is common in the oncology community. This manuscript reviews the accuracy of CEA testing, its value as a prognostic indicator, and its role in surveillance and response assessment. The limitations of the test in the adjuvant and metastatic settings are illustrated through several case reports from the Colorectal Oncology Clinic at Roswell Park Cancer Institute. Guidelines for CEA monitoring are provided, based on a detailed literature review and institutional experience.

Carcinoembryonic antigen (CEA) monitoring in patients with stage I-IV colorectal cancer has been, and remains, a controversial issue in oncology practice. Recommendations vary from bimonthly monitoring to no monitoring in the surveillance setting (for stage I-III disease). In the metastatic setting, there are no clear guidelines for CEA follow-up, although continued monitoring in such patients is common in the oncology community. This manuscript reviews the accuracy of CEA testing, its value as a prognostic indicator, and its role in surveillance and response assessment. The limitations of the test in the adjuvant and metastatic settings are illustrated through several case reports from the Colorectal Oncology Clinic at Roswell Park Cancer Institute. Guidelines for CEA monitoring are provided, based on a detailed literature review and institutional experience.

Sanofi-Aventis announced that following a priority review of the supplemental new drug application (sNDA), the US Food and Drug Administration (FDA) has approved docetaxel (Taxotere) in combination with cisplatin and fluorouracil (5-FU) for the treatment of patients with advanced stomach (gastric) cancer, including cancer of the gastro-esophageal junction, who have not received prior chemotherapy for advanced disease.

During the 1980s, the only drug routinely used to treat colorectal carcinoma was single-agent fluorouracil (5-FU), a drug that had shown no proven benefit in the adjuvant setting. Since then, significant improvements in the overall management of colorectal cancer have been made. This review will compare today's standard of care for adjuvant colorectal carcinoma to that practiced 20 years ago. The authors examine key questions asked about adjuvant therapy and the answers that ultimately changed clinical practice standards and improved overall survival for patients diagnosed with this disease. In addition, this review explores whether 5-FU should be given as part of a multidrug regimen and which route of administration is best when this drug is given. Further, the authors delve into both the use of locally directed therapies to the liver or peritoneum to improve outcomes and the selection of patients to receive adjuvant chemotherapy. Finally, a look to the future shows monoclonal antibodies to be an avenue of great promise in fighting colorectal cancer.

Colon cancer remains one of the most common human malignancies, with an annual global incidence of slightly less than 1 million patients per year.

During the 1980s, the only drug routinely used to treat colorectal carcinoma was single-agent fluorouracil (5-FU), a drug that had shown no proven benefit in the adjuvant setting. Since then, significant improvements in the overall management of colorectal cancer have been made. This review will compare today's standard of care for adjuvant colorectal carcinoma to that practiced 20 years ago. The authors examine key questions asked about adjuvant therapy and the answers that ultimately changed clinical practice standards and improved overall survival for patients diagnosed with this disease. In addition, this review explores whether 5-FU should be given as part of a multidrug regimen and which route of administration is best when this drug is given. Further, the authors delve into both the use of locally directed therapies to the liver or peritoneum to improve outcomes and the selection of patients to receive adjuvant chemotherapy. Finally, a look to the future shows monoclonal antibodies to be an avenue of great promise in fighting colorectal cancer.

The FDA has approved the use of Taxotere (docetaxel, Sanofi-Aventis) in combination with cisplatin and fluorouracil (5-FU) for the treatment of advanced gastric cancer, including cancer of the gastroesophageal junction, in patients who have not received prior chemotherapy for their advanced disease.

Liver transplantation is lifesaving in patients with localized hepatocellular carcinoma, with some 75% of transplant recipients still alive 5 years later, compared with only 12% of other patients, finds the first large population-based study of this treatment for this disease.

The first comprehensive assessment of cancer care quality in the United States indicates adherence to recommended care for patients with breast or colorectal cancer is excellent overall, but specific areas need improvement. Overall, breast cancer patients received 86% of generally recommended care, based on 36 quality-care measures. Patients with colorectal cancer received 78% of generally recommended care, based on 25 quality-care measures.

March 2006 marks the seventh annual National Colorectal Cancer Awareness Month. The national nonprofit Cancer Research and Prevention Foundation (CRPF) and its partners have activities planned to increase general knowledge in the United States about colorectal cancer, to advocate screening, and to encourage potentially life-saving lifestyle changes.

The US Food and Drug Administration (FDA) recently approved sunitinib malate (Sutent) capsules for two types of cancer: advanced renal cell carcinoma and malignant gastrointestinal stromal tumor (GIST), after disease progression on or intolerance to the frontline drug imatinib mesylate (Gleevec).

Approximately 6% of colorectal cancers can be attributed to recognizable heritable germline mutations. Familial adenomatous polyposis is an autosomal dominant syndrome classically presenting with hundreds to thousands of adenomatous colorectal polyps that are caused by mutations in the APC gene.

Approximately 6% of colorectal cancers can be attributed to recognizable heritable germline mutations. Familial adenomatous polyposis is an autosomal dominant syndrome classically presenting with hundreds to thousands of adenomatous colorectal polyps that are caused by mutations in the APC gene.

Approximately 6% of colorectal cancers can be attributed to recognizable heritable germline mutations. Familial adenomatous polyposis is an autosomal dominant syndrome classically presenting with hundreds to thousands of adenomatous colorectal polyps that are caused by mutations in the APC gene.

Colon cancer is a major public health problem. The primary treatment is resection. For patients with early-stage disease, surgery results in excellent survival rates. In contrast, patients with locally advanced tumors arising in "anatomically immobile" segments of large bowel have a less satisfactory outcome, in part secondary to compromised surgical clearance. Patterns-of-failure analyses suggest that for tumors that invade adjacent organs, exhibit perforation or fistula, or are subtotally resected, local failure rates exceed 30%. Multiple single-institution retrospective studies have shown improved local control and possibly survival with the addition of external irradiation and/or intraoperative radiation. In contrast, a recent Intergroup trial failed to show any benefit by the addition of adjuvant radiation therapy combined with chemotherapy. Interpretation of this trial's results is handicapped by low patient accrual. With the advent of novel and more effective systemic therapies for metastatic colon cancer, current and future clinical research will address the efficacy of these agents in the adjuvant setting. Adjuvant radiation therapy should be considered in patients with colon cancer at high risk for local failure.

Colon cancer is a major public health problem. The primary treatment is resection. For patients with early-stage disease, surgery results in excellent survival rates. In contrast, patients with locally advanced tumors arising in "anatomically immobile" segments of large bowel have a less satisfactory outcome, in part secondary to compromised surgical clearance. Patterns-of-failure analyses suggest that for tumors that invade adjacent organs, exhibit perforation or fistula, or are subtotally resected, local failure rates exceed 30%. Multiple single-institution retrospective studies have shown improved local control and possibly survival with the addition of external irradiation and/or intraoperative radiation. In contrast, a recent Intergroup trial failed to show any benefit by the addition of adjuvant radiation therapy combined with chemotherapy. Interpretation of this trial's results is handicapped by low patient accrual. With the advent of novel and more effective systemic therapies for metastatic colon cancer, current and future clinical research will address the efficacy of these agents in the adjuvant setting. Adjuvant radiation therapy should be considered in patients with colon cancer at high risk for local failure.

Treatment with sunitinib (Sutent), an oral, multitargeted tyrosine kinase inhibitor, improves clinical outcomes in patients with gastrointestinal stromal tumor (GIST) that has become resistant to imatinib (Gleevec), George D. Demetri, MD, director of the Center for Bone Oncology, Dana-Farber Cancer Institute, reported at the 2006 Gastrointestinal Cancers Symposium (abstract 8).

For the first time, the US Food and Drug Administration (FDA) has granted a new oncologic drug product approval for indications for two different cancers simultaneously. The agency approved Sutent (suniti-nib, Pfizer) for the treatment of patients with gastrointestinal stromal tumors (GIST) whose disease has progressed on imatinib (Gleevec) or who are unable to tolerate imatinib. It also granted Sutent accelerated approval for treating advanced renal cell carcinoma (RCC).

Colon cancer is a major public health problem. The primary treatment is resection. For patients with early-stage disease, surgery results in excellent survival rates. In contrast, patients with locally advanced tumors arising in "anatomically immobile" segments of large bowel have a less satisfactory outcome, in part secondary to compromised surgical clearance. Patterns-of-failure analyses suggest that for tumors that invade adjacent organs, exhibit perforation or fistula, or are subtotally resected, local failure rates exceed 30%. Multiple single-institution retrospective studies have shown improved local control and possibly survival with the addition of external irradiation and/or intraoperative radiation. In contrast, a recent Intergroup trial failed to show any benefit by the addition of adjuvant radiation therapy combined with chemotherapy. Interpretation of this trial's results is handicapped by low patient accrual. With the advent of novel and more effective systemic therapies for metastatic colon cancer, current and future clinical research will address the efficacy of these agents in the adjuvant setting. Adjuvant radiation therapy should be considered in patients with colon cancer at high risk for local failure.

Traditionally, most hereditarynonpolyposis colorectal cancer(HNPCC) syndrome patientshave been identified and cared for bygastroenterologists, colorectal surgeons,and gastrointestinal medicaloncologists. Hence, the realization thatgynecologic tumors actually play amajor role in HNPCC has come relativelylate. Consequently, much of theclinical and basic science focus ofresearch in HNPCC has concentratedon colorectal cancer.

Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomaldominant cancer susceptibility syndrome associated with inheriteddefects in the DNA mismatch repair system. HNPCC family membersare at high risk for developing colorectal, endometrial, and ovariancancers. Studies of HNPCC families have helped define the importantrole that mismatch repair genes play in the molecular pathogenesis ofendometrial and ovarian cancers. This review will describe some of theimportant clinical and molecular features of HNPCC-related endometrialand ovarian cancer and describe how genetic susceptibility can beidentified in patients with sporadic endometrial and ovarian cancers. Itis important to identify patients with HNPCC, as families of mutationcarriers may benefit from genetic counseling, testing, and intensifiedcancer surveillance.

In their article, Taylor and Mutchbring attention to the gynecologiccancer risks associated with hereditarynonpolyposis colorectal cancer(HNPCC).[1] The identificationof individuals and families at risk forHNPCC has often focused on the coloncancer phenotype, but the diagnosisof endometrial or ovarian cancershould also be considered.

In the past several years, the impact of the new biologic therapies oncolorectal cancer has been dramatic. The focus of this article is to summarizesome of the key advances of incorporating biologically targetedtherapies into the routine management of patients with colorectal cancer.We will review important data presented at the 2005 American Society ofClinical Oncology annual meeting and discuss the incorporation of thesedata into the most optimal management of our patients, including howbest to manage side effects and keep quality of life as high as possible.

Several developments in the past few years have incrementally progressedthe field and provided additional insights into the managementof advanced colorectal cancer. This review discusses the componentsof current cytotoxic chemotherapy regimens for advanced colorectalcancer: fluorouracil (5-FU), capecitabine (Xeloda), irinotecan(Camptosar), and oxaliplatin (Eloxatin). The equivalence of severalfront-line regimens has provided opportunities for increased tailoringof therapies for individual patients. Preliminary data onpharmacogenomics provides hope that we will be able to better matchpatients with regimens and doses on the basis of individualized predictionsof toxicity and response. The importance of second-line therapyin overall survival has again been highlighted; the best outcomes haveoccurred in patients treated with 5-FU, oxaliplatin, and irinotecan incombination with targeted therapies during the course of their disease.Elderly patients are no exception to this finding. Combination regimensand second-line therapy should be offered to elderly patients whohave adequate performance status and no contraindicated comorbidconditions, without regard for their chronological age.

Colorectal cancer is a worldwide public health problem, with nearly 800,000new cases diagnosed each year resulting in approximately 500,000deaths. In the United States, it is the second leading cause of cancer mortality,and nearly 60,000 deaths will be attributed to this disease in 2005. Whendiagnosed as advanced, metastatic disease, colorectal cancer is traditionally associatedwith a poor prognosis, with 5-year survival rates in the range of 5% to 8%. Thissurvival rate has remained unchanged over the past 35 to 40 years. However, duringthe past 5 years, significant advances have been made in treatment options so thatimprovements in 2-year survival are now being reported, with median survival ratesin the 21- to 24-month range in patients with metastatic disease.

Continuing advances in immunology and molecular biology duringthe past several decades have provided optimism that immunomodulatorystrategies may be clinically useful in patients with cancer.Key advances have included: (1) recognition of the critical role of theantigen-presenting cell and greatly improved understanding of antigenprocessing and presentation, including the molecular interactionsbetween HLA molecules and antigenic epitopes on the antigen-processingcell and the receptors on T cells, and (2) the roles ofcostimulatory molecules such as B7.1, ICAM-1, and LFA-3 in the inductionand maintenance of an immune response. In addition, newtechniques have allowed us to identify immunogenic antigenic determinants,alter their binding affinities, and evaluate the overall successof the intervention through both in vivo and in vitro assays.Carcinoembryonic antigen (CEA) is overexpressed in a large numberof gastrointestinal, lung, and breast cancers. Clinical trials have establishedtreatment protocols using viral vectors to immunize patients toCEA without producing deleterious autoimmune phenomena. By combiningvarious vectors to include MUC-1 and/or CEA plus costimulatorymolecules in a prime-and-boost regimen, we are beginning to see signsthat this intervention can not only produce changes in immune functionbut also potentially improve clinical outcomes. Phase III studies totest these hypotheses are under way.

Kauh and colleagues nicely outlinethe major problems facingclinicians who treat humanimmunodeficiency virus (HIV)-positivepatients with squamous cell carcinomaof the anus. This is a highly curabledisease with combined-modality therapy,though the HIV-positive populationpresents unique challenges. Weagree with the approaches outlined bythe authors and would also like to emphasizeseveral principles in the managementof anal cancer.

Squamous cell anal cancer remains an uncommon entity; however,the incidence appears to be increasing in at-risk populations, especiallythose infected with human papillomavirus (HPV) and human immunodeficiencyvirus (HIV). Given the ability to cure this cancer using synchronouschemoradiotherapy, management practices of this disease arecritical. This article considers treatment strategies for HIV-positive patientswith anal cancer, including the impact on chemoradiation-inducedtoxicities and the role of highly active antiretroviral therapy in the treatmentof this patient population. The standard treatment has beenfluorouracil (5-FU) and mitomycin (or cisplatin) as chemotherapy agentsplus radiation. Consideration to modifying the standard treatment regimeis based on the fact that patients with HIV tend to experience greatertoxicity, especially when CD4 counts are below 200; these patients alsorequire longer treatment breaks. Additional changes to the chemotherapydosing, such as giving 5-FU continuously and decreasing mitomycin dose,are evaluated and considered in relation to radiation field sizes in an effortto reduce toxicity, maintain local tumor control, and limit need forcolostomy. The opportunity for decreasing the radiation field size andusing intensity-modulated radiation therapy (IMRT) is also considered,particularly in light of the fact that IMRT provides dose-sparing whilemaximizing target volume dose to involved areas. The impact of the immunesystem in patients with HIV and squamous cell carcinoma of theanus and the associated response to therapy remains unknown. Continuedstudies and phase III trials will be needed to test new treatment strategiesin HIV-infected patients with squamous cell cancer of the anus todetermine which treatment protocols provide the greatest benefits.