Search

This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Colon Cancer focuses on systemic therapy options for the treatment of metastatic colorectal cancer (mCRC), because important updates have recently been made to this section. These updates include recommendations for first-line use of checkpoint inhibitors for mCRC, that is deficient mismatch repair/microsatellite instability-high, recommendations related to the use of biosimilars, and expanded recommendations for biomarker testing. The systemic therapy recommendations now include targeted therapy options for patients with mCRC that is HER2-amplified, or BRAF V600E mutation–positive. Treatment and management of nonmetastatic or resectable/ablatable metastatic disease are discussed in the complete version of the NCCN Guidelines for Colon Cancer available at NCCN.org. Additional topics covered in the complete version include risk assessment, staging, pathology, posttreatment surveillance, and survivorship.

Small bowel adenocarcinoma (SBA) is a rare malignancy of the gastrointestinal tract that has increased in incidence across recent years. Often diagnosed at an advanced stage, outcomes for SBA are worse on average than for other related malignancies, including colorectal cancer. Due to the rarity of this disease, few studies have been done to direct optimal treatment, although recent data have shown that SBA responds to treatment differently than colorectal cancer, necessitating a separate approach to treatment. The NCCN Guidelines for Small Bowel Adenocarcinoma were created to establish an evidence-based standard of care for patients with SBA. These guidelines provide recommendations on the workup of suspected SBA, primary treatment options, adjuvant treatment, surveillance, and systemic therapy for metastatic disease. Additionally, principles of imaging and endoscopy, pathologic review, surgery, radiation therapy, and survivorship are described.

The NCCN Guidelines for Colon Cancer provide recommendations regarding diagnosis, pathologic staging, surgical management, perioperative treatment, surveillance, management of recurrent and metastatic disease, and survivorship. These NCCN Guidelines Insights summarize the NCCN Colon Cancer Panel discussions for the 2018 update of the guidelines regarding risk stratification and adjuvant treatment for patients with stage III colon cancer, and treatment of BRAF V600E mutation-positive metastatic colorectal cancer with regimens containing vemurafenib.

Neuroendocrine tumors (NETs) comprise a broad family of tumors that may or may not be associated with symptoms attributable to hormonal hypersecretion. The NCCN Clinical Practice Guidelines in Oncology for Neuroendocrine Tumors discuss the diagnosis and management of both sporadic and hereditary NETs. This selection from the guidelines focuses on sporadic NETs of the pancreas, gastrointestinal tract, lung, and thymus.

The NCCN Guidelines for Occult Primary tumors provide recommendations for the evaluation, workup, management, and follow-up of patients with occult primary tumors (cancers of unknown primary). These NCCN Guidelines Insights summarize major discussion points of the 2014 NCCN Occult Primary panel meeting. The panel discussed gene expression profiling (GEP) for the identification of the tissue of origin and concluded that, although GEP has a diagnostic benefit, a clinical benefit has not been demonstrated. The panel recommends against GEP as standard management, although 20% of the panel believes the diagnostic benefit of GEP warrants its routine use. In addition, the panel discussed testing for actionable mutations (eg, ALK) to help guide choice of therapy, but declined to add this recommendation.

The NCCN Guidelines for Colon Cancer address diagnosis, pathologic staging, surgical management, perioperative treatment, posttreatment surveillance, management of recurrent and metastatic disease,and survivorship. This portion of the guidelines focuses on the use of systemic therapy in metastatic disease. The management of metastatic colorectal cancer involves a continuum of care in which patients are exposed sequentially to a variety of active agents, either in combinations or as single agents. Choice of therapy is based on the goals of treatment, the type and timing of prior therapy, the different efficacy and toxicity profiles of the drugs, the mutational status of the tumor, and patient preference.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Colon Cancer begin with the clinical presentation of the patient to the primary care physician or gastroenterologist and address diagnosis, pathologic staging, surgical management, perioperative treatment, patient surveillance, management of recurrent and metastatic disease, and survivorship. The NCCN Colon Cancer Panel meets annually to review comments from reviewers within their institutions and to reevaluate and update their recommendations. In addition, the panel has interim conferences as new data necessitate. These NCCN Guidelines Insights summarize the NCCN Colon Cancer Panel's discussions surrounding metastatic colorectal cancer for the 2013 update of the guidelines. Importantly, changes were made to the continuum of care for patients with advanced or metastatic disease, including new drugs and an additional line of therapy.

The workup and management of squamous cell anal carcinoma, which represents the most common histologic form of the disease, are addressed in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Anal Carcinoma. These NCCN Guidelines Insights provide a summary of major discussion points of the 2012 NCCN Anal Carcinoma Panel meeting. In summary, the panel made 4 significant changes to the 2012 NCCN Guidelines for Anal Carcinoma: 1) local radiation therapy was added as an option for the treatment of patients with metastatic disease; 2) multifield technique is now preferred over anteroposterior-posteroanterior (AP-PA) technique for radiation delivery and the AP-PA technique is no longer recommended as the standard of care; 3) PET/CT should now be considered for radiation therapy planning; and 4) a section on risk reduction was added to the discussion section. In addition, the panel discussed the use of PET/CT for the workup of anal canal cancer and decided to maintain the recommendation that it can be considered in this setting. They also discussed the use of PET/CT for the workup of anal margin cancer and for the assessment of treatment response. They reaffirmed their recommendation that PET/CT is not appropriate in these settings.

Advances in the understanding of tumor biology have led to the identification of important cellular processes involved in the pathogenesis of colon cancer. Drugs that interfere with these critical pathways are known as targeted agents. The goal of these therapies is to selectively interrupt the signal transduction pathways responsible for tumor growth and survival. Some of these targeted agents have made important, albeit modest, contributions to the treatment of patients with metastatic colorectal cancer. However, the activity levels with the currently available targeted therapies are far lower than experts had hoped, and toxicities are often nontrivial. This article reviews the available therapies, the data that justify their use, and the challenges of optimizing targeted therapies through combinations with cytotoxic chemotherapies and other targeted agents. Finally, some newer drugs and strategies currently being tested in clinical trials are discussed.

It has long been appreciated that the clinical entity we call colorectal cancer is a phenotype which is made up of numerous different genotypes, accounting for the wide variation in clinical course and responses to therapies experienced by different individuals. Observations reported by Khambata-Ford et al and subsequently confirmed by Amato et al have made the practicing community aware that activating mutations in exon 2 of the gene encoding for KRAS, a key signal transduction protein, result in primary resistance to anti-epidermal growth factor receptor (EGFR) agents by leading to EGFR-independent activation of mitogen-activated protein kinase (MAPK) signaling.1,2 BRAF is a signal transduction protein which is downstream of KRAS in the MAP-Kinase pathway. Approximately 5–10 percent of colorectal cancers harbor mutations in BRAF, the most common of these being the V600E mutation. The occurrence of these mutations in colorectal cancers raises two important questions: what are the clinical characteristics of a colorectal cancer with a V600E BRAF mutation, and can that mutation be targeted for therapeutic advantage?

This NCCN Task Force Report describes the management of dermatologic and ocular toxicities that occur in patients treated with epidermal growth factor receptor (EGFR) inhibitors. Task force members are from NCCN member institutions and include oncologists, dermatologists, an ophthalmologist, and a mid-level oncology provider. This report describes commonly used therapies that the task force agreed are appropriate standards of care for dermatologic and ophthalmologic toxicities associated with EGFR inhibitors, which generally are supported only by anecdotal evidence. Few recommendations are evidence based; however, some commonly used therapies have data supporting their use. Conclusions from completed clinical trials are generally limited by the small numbers of patients enrolled. The information in this report is based on available published data on treating toxicities associated with EGFR inhibitors, data from treatment of clinically similar toxicities from different etiologies, and expert opinion among the NCCN Task Force members.

Oral chemotherapy is emerging as a new option for well-selected patients who can manage potentially complex oral regimens and self-monitor for potential complications. If a choice between oral and parenteral therapy is available, patients may opt for oral chemotherapy because it is more convenient to administer, allows them to avoid multiple office visits, and gives them a sense of control over their own cancer care. Whether these potential advantages are maintained in regimens that combine oral and parenteral drugs is less clear. The use of oral chemotherapeutic agents profoundly affects all aspects of oncology, including creating significant safety and adherence issues, shifting some traditional roles and responsibilities of oncologists, nurses, and pharmacists to patients and caregivers. The financing of chemotherapy is also affected. To address these issues, the NCCN convened a multidisciplinary task force consisting of oncologists, nurses, pharmacists, and payor representatives to discuss the impact of the increasing use of oral chemotherapy. (JNCCN 2008;6[Suppl 3]:S1–S14)

An estimated 3,990 new cases of anal cancer will occur in 2005, accounting for approximately 1.6% of digestive system cancers in the United States. Prognosis directly depends on the size of the primary tumor and the likelihood of lymphatic spread, with tumors 2 cm or smaller cured in 80% of cases. The NCCN guidelines recommend a thorough evaluation for any patient with a suspicious lesion in the anal canal and include additional recommendations for diagnosis, treatment, and follow up for anal canal cancer. For the most recent version of the guidelines, please visit NCCN.org