The National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology™ are among the most widely used guidelines in oncology practice. The Guidelines cover 97% of all patients with cancer and are continually updated by expert panels. The following is a synopsis of the 2011 updates and key points made by panel representatives at the NCCN 16th Annual Conference, held March 10–11 in Hollywood, Florida.

“The Panel, in reviewing the data from a single randomized trial, decided to add a footnote to the guidelines that there was no improvement observed in overall survival or local recurrence rates with completion axillary lymph node dissection in women with 1 to 3 involved sentinel lymph nodes and who were treated with breast-conserving surgery and whole breast radiation.”

• Eribulin (Halaven) was added as a new chemotherapeutic option for treating metastatic disease.
• Denosumab (Xgeva) was added as an option for preventing skeletal-related events in patients with bone metastases.
• Bevacizumab (Avastin), in combination with paclitaxel, was reaffirmed as an option for metastatic disease.
• Hormonal status and HER2 status should be determined in metastatic disease patients.

“There is an increase in myelodysplastic syndrome and acute leukemia, but the all-cause mortality analysis shows a significant reduction in risk with growth factors….There clearly is an overall net benefit.”

• Granulocyte colony-stimulating factors (G-CSF) can prevent febrile neutropenia and its complications and improve survival in patients at increased risk for these complications.
• Outcomes with pegfilgrastim (Neulasta) and filgrastim (Neupogen) are similar.
• Prior to beginning chemotherapy, patients should be assessed for risk, and those with > 20% febrile neutropenia risk should receive G-CSF starting at the first cycle.
• Risk of myelodysplasia and acute myeloid leukemia is real, but it is small, and is confounded by the increase in chemotherapy dose delivery and offset by a  reduction in all-cause mortality in appropriate patients treated with G-CSF.

“Mitotic index is the single most important predictor of survival in the patient with a thin melanoma.”

• Mitotic index replaces Clark level in defining clinical stage IB melanoma.
• The presence of any mitosis (mitotic rate ≥ 1 mm2) in a thin melanoma (≤ 1 mm) upstages the patient to stage IB and has implications for sentinel lymph node biopsy (SLNB).
• SLNB should be discussed and offered to patients with stage IA, IB, or II melanomas; the threshold for considering SLNB is a risk of recurrence of approximately 7%.
• For follow-up of patients with ≤ stage IIA disease, there is less emphasis on routine bloodwork and cross-sectional imaging.
• Newer targeted agents and immunotherapy strategies are yielding dramatic, and sometimes durable, responses and will change the treatment paradigm.
• Radiotherapy and genetic analysis have a growing role.

“Patients with resectable desmoid tumors can be considered for observation.”

• The major change to the guidelines for the treatment of sarcoma pertains to the management of desmoid tumors.
• Patients with desmoid tumors can be followed carefully if the tumors are small and not located on the trunk and if surgery would lead to excessive morbidity.
• Several changes in staging were made; lymph node involvement was reclassified as stage III, rather than IV.
• Molecular profiles will become increasingly evident in sarcoma, and markers will aid in diagnosis, prognosis, and treatment.

“Oncologists can start new patients on a second-generation tyrosine kinsase inhibitor or stick with imatinib (400 mg), reserving the newer agents for sequential use after imatinib failure since salvage rates are excellent.”

• Second-generation tyrosine kinase inhibitors nilotinib (Tasigna) and dasatinib (Sprycel) were added as front-line treatment options.
• Nilotinib and dasatinib exerted similar improvements in short-term endpoints, as compared with imatinib, in randomized trials; with short follow-up, their impact on event-free and overall survival has not yet been established.
• Cytogenetic complete response remains the gold standard for response; molecular responses do not define treatment failure.
• New agents now in clinical trials show promising activity.

“Histology matters in non–small cell lung cancer [NSCLC], and NSCLC ‘not otherwise specified’ [NOS] is unacceptable in 2011.”

• Testing for the epidermal growth factor receptor (EGFR) is a category 1 recommendation for adenocarcinoma, large cell disease, and NSCLC NOS but is not recommended for squamous cell carcinoma.
• Mutational status, particularly EGFR, KRAS, and EML4/ALK, is now affecting the choice of effective treatment options.
• Platinum doublets, chemotherapy with bevacizumab, and newer targeted agents are improving outcomes in advanced NSCLC.
• New pages were added to the 2011 guidelines to discuss the debate surrounding the use of surgery after induction therapy for patients with stage IIIA (N2) disease; the benefit of surgery in this heterogeneous group remains unclear.
• Patients with a single lymph node < 3 cm can be considered for a multimodality approach that includes surgical resection.

“Post-transplant lymphoproliferative disorder has emerged as a significant complication of solid organ and allogeneic bone marrow transplantation.”

• A significant change to the guidelines is the addition of a new guideline for post-transplant lymphoproliferative disorder.
• Recommended treatment options for post-transplant lymphoproliferative disorder include reduction of immunosuppression, single-agent rituximab (Rituxan), and chemoimmunotherapy.
• Category 1 recommended treatments for follicular lymphoma now include bendamustine (Treanda)/rituximab for first-line treatment, rituximab maintenance, and radioimmunotherapy for treatment after first remission.
• Patients with mantle cell lymphoma who have a low proliferation fraction and are treated aggressively are potentially curable.

“The addition of sipuleucel-T and cabazitaxel into the Guidelines represents a significant advancement in the case of men with advanced prostate cancer.”

• The Guidelines establish a new “very low risk” category that incorporates the strictest Epstein criteria from all definitions for clinically insignificant prostate cancer.
• Active surveillance is recommended as the sole initial treatment for men meeting the criteria for very low-risk disease who have a life expectancy of > 20 years.
• Active surveillance monitoring was made more rigorous for men in the very low-risk category: For men with a life expectancy < 20 years, prostate-specific antigen must be measured at least every 6 months, a prostate exam must be performed at least every 12 months, and repeat prostate biopsies should be considered as often as every 12 months.
• Men with low-risk prostate cancer and a life expectancy < 10 years should also be recommended for active surveillance.
• Sipuleucel-T (Provenge) was added as an immunotherapy option for asymptomatic or minimally symptomatic castrate-resistant metastatic disease and a life expectancy ≥ 6 months.
• Cabazitaxel (Jevtana) was added as a new second-line option for castrate-resistant metastatic disease after progression on docetaxel.
• Denosumab was added as an alternative to zoledronic acid for the prevention of skeletal-related events.

 “The guidelines now include a suggestion that the workup for cancer of the oropharynx include testing for human papillomavirus.”

• An algorithm for  mucosal melanoma was added to the guidelines for malignant melanoma.
• Human papillomavirus is a growing concern in certain head and neck cancers and is associated with a better prognosis. Testing for the virus is now suggested for oropharynx cancers, as well as occult primary cancers with a squamous cell or undifferentiated  histology.
• The therapeutic benefits associated with the integration of chemotherapy with radiation compared with radiation alone continues to be upheld in several disease settings.
• The concomitant integration of chemotherapy with radiation therapy is backed by a large body of data.

“Regardless of the type of cancer, the guidelines reflect the importance of stage and grade of disease on prognosis and treatment recommendations.”

• Borderline epithelial ovarian cancer of low malignant potential should be primarily managed surgically.
• For women with borderline epithelial ovarian cancer wishing to maintain fertility, surgery should be limited to unilateral salpingo-oophorectomy; standard debulking surgery is recommended for those not concerned about fertility preservation.
• Stage II, III, or IV epithelial ovarian cancer should be considered for intraperitoneal chemotherapy first-line; updated recommendations include intravenous dose-dense paclitaxel as a possible treatment option, though this may be more toxic.
• New language details the Panel’s view that it is premature to recommend the addition of bevacizumab to carboplatin/paclitaxel upfront; participation in clinical trials is encouraged.
• New language supports the discussion of the pros and cons of CA-125 monitoring, based on data showing a lack of survival benefit when treatment for relapse was initiated based on a rising CA-125 level.
• Specific recommendations were added on managing infusion drug reactions.

“There has been a very rapid bench-to-bedside translation with the targeted agents in multiple myeloma.”

• Bortezomib (Velcade)/cyclophosphamide/dexamethasone is now a category 2A option for induction therapy in the transplant setting, and lenalidomide (Revlimid)/bortezomib/dexamethasone is a promising category 2B alternative.
• Lenalidomide maintenance, which has nearly doubled progression-free survival, has been added as a new option after autologous stem cell transplant.
• Melphalan/prednisone/lenalidomide and bortezomib/dexamethasone are now category 2A options in the nontransplant setting.
• Cyclophosphamide/bortezomib/dexamethasone and cyclophosphamide/lenalidomide/dexamethasone have been added as category 2A salvage treatment options.
• Carfilzomib, pomalidomide, and panobinostat are promising novel investigational agents for relapsed/refractory disease.

“One-third of the world has been exposed to hepatitis B, making it an enormous problem…Depending on how it’s defined, 5% to 40% of people who have an acute reactivation will die of liver failure.”

• Many patients are unaware that they have been exposed to or have active hepatitis B infection.
• Many patients being treated for cancer with immunosuppressive therapies are at risk of hepatitis B virus (HBV) reactivation.
• Limited data suggest that antiviral prophylaxis is 100% effective in preventing chemotherapy-related HBV reactivation.
• Many medical groups recommend universal screening for HBV, although ASCO is not one of them.
• The optimal antiviral agent and duration of prophylaxis remain unresolved issues.

“Many facilities throughout the country are using stereotactic body radiation therapy [SBRT] for tumors in the pancreas, head and neck, prostate, and spinal cord; however, until further data are available, use of SBRT outside the lungs and liver should be limited to cooperative trials.”

• Inoperable lung and liver tumors are the only two NCCN-approved indications for SBRT.
• Used to treat pediatric tumors, proton therapy can deliver an increased dose to the target volume while decreasing the dose to normal tissue, thereby reducing morbidity.
• Intensity-modulated radiation therapy has proven benefit in reducing dry mouth in patients with head and neck cancer and in improving associated quality of life. ■

Financial Disclosures: Comprehensive disclosure information relevant to the complete NCCN Clinical Practice Guidelines is available at nccn.org. The following NCCN panel members reported no potential conflicts of interest with the manufacturer(s) of product(s), mentioned in this report: Kenneth C. Anderson; Robert W. Carlson; Daniel G. Coit; Michael Kuettel; Emmy Ludwig; James L. Mohler; Robert J. Morgan; Susan O’Brien; and David G. Pfister.  Other NCCN panel members reported potential conflicts of interest as follows: Jeffrey Crawford has received research funding from Amgen and has served on the advisory board at Amgen. David S. Ettinger has indicated serving on an advisory board, speakers bureau, as an expert witness, or consultant for  Boehringer Ingelheim GmbH, Daiichi-Sankyo Co., Eli Lilly and Company, Genentech, Inc., Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Biodesix, Inc., Poniard Pharmaceuticals, Inc., Prometheus, Shin Nippon Biomedical Labs, and Telik, Inc.  Margaret von Mehren disclosed that she has served as a scientific advisor/consultant to Novartis, scientific advisor to Merck, and consultant to Pfizer and Pharma Mar. In addition, she has received research support from Novartis and Merck. Andrew Zelenetz reported receiving clinical research support from Cephalon, Inc., Genentech, Inc., GlaxoSmithKline, Millennium Pharmaceuticals, Inc., Onyx Pharmaceuticals, Inc., Allos Pharm., Calistoga, Pharmacyclics, Plexxikon, Roche, and Seattle Genetics. He reported serving on an advisory board, speakers bureau, as an expert witness, or consultant for  Abbott Laboratories, Cephalon, Inc., Genentech, Inc. GlaxoSmithKline, Allos Pharm, Cancer Genetics, Seattle Genetics, Roche Laboratories, Inc., and sanofi-aventis U.S.