NCCN Panelists Relay ‘What’s Hot’ in Their Fields


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AT THE NATIONAL Comprehensive Cancer Network® (NCCN®) 22nd Annual Conference, experts from several fields met with journalists to highlight “what’s hot” in their specialties. The ASCO Post captured that conversation. 

Myeloproliferative Neoplasms Guidelines 

NCCN HAS LAUNCHED new NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) specifically geared to treating myeloproliferative neoplasms. The first set was developed for myelofibrosis. Future NCCN Guidelines will be issued for polycythemia vera, essential thrombocytopenia, and atypical myeloproliferative neoplasms, according to Ruben Mesa, MD, Chair of the Division of Hematology and Medical Oncology at the Mayo Clinic in Arizona.

Ruben Mesa, MD

Ruben Mesa, MD

Although myeloproliferative neoplasms are not particularly common, Dr. Mesa acknowledged, they are part of every hematology/ oncology practice. “We all have some of these patients, and unlike many other types of cancer, these are chronic malignancies,” he said. 

The Guidelines provide algorithms for treating myelofibrosis according to risk status and for using the only approved agent, ruxolitinib (Jakafi). They are also informative regarding transplantation, which is expected to become a more active component of treatment with the publication of these Guidelines, predicted Dr. Mesa. 

“The Centers for Medicare and Medicaid (CMS) put a moratorium on stem cell transplant for myelofibrosis, and for myeloma and sickle cell anemia, CMS is asking for more data,” he revealed. The new Guidelines will help to validate transplant as an important approach. In the absence of national guidance, Dr. Mesa added, the CMS made coverage decisions “we felt were incorrect.” 

New Tool for Immune-Related Toxicities 

NCCN HAS DEVISED a teaching and monitoring tool for toxicities related to immunotherapy, according to Stephanie Andrews, MS, ANP-BC, of Moffitt Cancer Center, Tampa. Noting that the efficacy of immunotherapy must be balanced with “a healthy respect for the power of T-cell activation,” toxicities can be brutal. Education of patients and staff is key for prompt identification of immune-related adverse effects, which can affect virtually all organ systems. Symptoms should be regularly assessed and education about them reinforced, she urged. 

Stephanie Andrews, MS, ANP-BC

Stephanie Andrews, MS, ANP-BC

The tool provides information on monoclonal antibodies, including checkpoint inhbitors. Separate sections of the tool are directed at clinicians and patients, with drug-related adverse events described as well. It also includes a checklist of symptoms unique to each drug in the form of a questionnaire to patients. 

Furthermore, clinicians can find guidance for managing immune-related toxicities under the NCCN Guidelines for Melanoma, where the most experience with checkpoint inhibitors has been gained. But with immunotherapies now used in many tumor types, clinicians need tumor-specific information. Through a collaboration between NCCN and ASCO, more specific practice guidelines (for the management of immunotherapy-related toxicity) will be published later this year. 

“We would like a more regimented way of dealing with these toxicities, and we will be working on that to produce uniform recommendations,” Ms. Andrews said. 

Patient Distress Guidelines—for Patients Themselves 


“A lot of cancer patients don’t want to be whiners, therefore they may tend to underreport symptoms….”
— Teresa DeShields, PhD

NCCN HAS ALSO DEBUTED Guidelines on patient distress—for patients themselves. The NCCN Guidelines for Patients®: Distress includes the NCCN Distress Thermometer and Problem List for Patients, a process for identifying stressors and facilitating the patient-provider conversation. The tool spans issues ranging from physical concerns to emotional problems and onto the practical challenges of housing, finance, and child care. The guide for patients also outlines risk factors for high distress, such as living alone or having a coexisting illness, and recognizes vulnerable periods of distress, such as learning one’s treatment has been ineffective. It provides questions that patients can ask their providers and lists helpful resources. 

“The value of the patient version of the distress guidelines is to validate the patient’s experience and encourage patient reporting,” said Teresa Deshields, PhD, Manager of Counseling Services at the Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine, St. Louis. “A lot of cancer patients want to be ‘good patients,’ which can mean they don’t want to be whiners or give providers a reason to pull back on treatment; therefore, they may underreport symptoms…. We depend on patients to speak up about their challenges, so we can help them.” 

The guide is available directly to patients on NCCN.org/patients as a booklet or the NCCN Patient Guides for Cancer mobile app. Providers can order them as well and distribute them to their patients. 

HPV Gains Status in Head and Neck Cancer 


“There is careful evolution in how to therapeutically adapt to the reality that head and neck cancer is increasingly becoming two diseases.”
— David Pfister, MD

HUMAN PAPILLOMAVIRUS (HPV) in recurrent and metastatic head and neck cancer is emerging as an important component of prognostication and therefore treatment, according to David Pfister, MD, Chief of the Head and Neck Oncology Service at Memorial Sloan Kettering Cancer Center, New York. Although the incidence of this malignancy related to alcohol and tobacco use is declining, HPV-positive cancers are increasing. It has become widely appreciated that the prognosis for these two types of tumors is very different, both for newly diagnosed and recurrent/metastatic disease, he said. “There is careful evolution in how to therapeutically adapt to the reality that head and neck cancer is increasingly becoming two diseases,” said Dr. Pfister. 

Although the NCCN Guidelines do not yet formally stratify patients by HPV status, they soon will, he predicted. For example, some studies suggest treatment can often be de-escalated in selected HPV-positive cases. The caveat is, he noted, “the vast majority of patients are cured with treatment that’s been around for a while, so as much as we want to decrease morbidity in this good-risk group, we have to be cautious about compromising this excellent cure rate.” 

It may also be important to customize survivorship plans. HPV-positive patients tend to have better survival and therefore will be living with treatment-related toxicities longer, he noted. 

“Right now, management recommendations are the same for both groups,” Dr. Pfister commented. This stems mostly from the fact that clinical trials upon which NCCN algorithms were based did not subdivide patients according to HPV status. “But we see inklings that we are starting to customize treatment,” he said. “We are cautiously moving forward in this regard.” 

Neoadjuvant Chemotherapy in Pancreatic Cancer 

MARGARET A. TEMPERO, MD, Professor of Medicine and Director of the University of California, San Francisco, Pancreas Center, told journalists the current emphasis in her field is optimizing the resection of localized pancreatic cancer. “Pancreatic cancer is still the emperor of all cancer maladies, and immunotherapy does not work in this tumor, according to what we know now, but there are some very important things happening in this field,” she said. 


“Pancreatic cancer is still the emperor of all cancer maladies, and immuno-therapy does not work in this tumor, … but there are some very important things happening in this field.”
— Margaret A. Tempero, MD

One, she said, is the recognition that chemotherapy can deliver “a pretty profound impact” in patients with borderline-resectable tumors. “There is a trend to give these patients neoadjuvant chemotherapy, because this can dramatically increase the number of patients we take to surgery,” Dr. Tempero explained. Although this approach is not always curative, the hope is that it does increase the chance of that, she said. “And in those we cannot cure, it may help us reduce the primary tumor that is causing pain and local complications, which will greatly improve the quality of the survival that we can give patients,” Dr. Tempero noted. 

Clinical trials are aiming to document the efficacy of neoadjuvant chemotherapy and determine the rates of pathologic complete response and negative surgical margins. “We want to be able to benchmark these outcomes, especially using new agents that combine well with chemotherapy,” she said. 

Preferred neoadjuvant regimens include FOLFIRINOX (fluorouracil, irinotecan, leucovorin, oxaliplatin) and gemcitabine plus albumin-bound paclitaxel (Abraxane), the latter serving as the best backbone for trials of new agents. Three novel additions are eliciting excitement: (1) the Bruton’s tyrosine kinase inhibitor ibrutinib (Imbruvica); (2) the cyclin-dependent kinase (CDK4/6) inhibitor palbociclib (Ibrance); and (3) PEGPH20 (pegylated recombinant human hyaluronidase), which degrades the hyaluronan matrix that makes pancreatic tumors difficult to penetrate. 

Finally, Dr. Tempero lauded the new collaboration between the National Institute of Diabetes and Digestive and Kidney Diseases and the National Cancer Institute, formed partly in response to the “Recalcitrant Cancer Act” of 2013. The Act calls on the National Cancer Institute to develop scientific frameworks, similar to strategic plans, for pancreatic and other cancers with 5-year survival rates below 50%. The group is pushing for funding for pancreatic cancer research. One initiative is the creation of a network of institutions, which will identify individuals at high risk for developing pancreatic cancer (such as some individuals with new-onset diabetes), for whom screening strategies can be tested. 

AJCC’s New Staging System: More Biologic Factors 

STEPHEN EDGE, MD, Vice President of Healthcare Outcomes and Policy and Professor of Oncology at Roswell Park Cancer Institute, Buffalo, described key changes to the American Joint Committee on Cancer (AJCC) staging system. “In cancer staging, we group patients with similar prognoses to help understand their potential outcomes. Among other things, this is used as a basis for defining treatment in the NCCN Guidelines, which start with clinical stage,” he said. “The AJCC staging system has primarily been anatomically based, accounting for the extent of the cancer.” 


“Anatomic staging alone is decreasingly relevant in understanding cancer.”
— Stephen Edge, MD

“But in point of fact, there are many other critical factors in understanding the biology of the cancer and its potential response to treatment. For example, there are HPV in head and neck cancer and various biomarkers in breast cancer,” stated Dr. Edge. “Anatomic staging alone without other information about the cancer is decreasingly relevant in understanding cancer.” 

In step with greater understanding of tumors, the 8th edition of the AJCC staging manual incorporates more biologic factors. For example, in head and neck cancer, HPV status has become a critical component, and in breast cancer, the status of estrogen receptor, progesterone receptor, and HER2 has been incorporated into tumor grade. Mutations deemed clinically relevant, such as KRAS and the epidermal growth factor receptor (EGFR), are also considered. 

In short, the new staging system is more granular, he noted. For example, for breast cancer it no longer simply divides breast cancer into “four bins” (stages). Since the potential survival of patients with stage II disease, for example, ranges from 55% to 95%, “these broad classifications did not serve patients and physicians well,” pointed out Dr. Edge. 

Under the new AJCC staging system, the tables for defining breast cancer stage are “huge,” he revealed. There are now 422 lines in the staging table to account for the various combinations of tumor grade and size; nodal and metastasis status; estrogen receptor, progesterone receptor, and HER2 status; and the 21-gene Recurrence Score. “Breast cancer staging has changed dramatically to incorporate biologic factors. This is increasingly complicated, but it’s what is relevant to doctors and patients,” he added. 

The next challenge will be to “take this from the cancer registry into the clinical world,” added Dr. Edge. Ultimately, clinicians need to be able to enter the patient’s information into the electronic health record and have stage and prognosis automatically generated. He also anticipates that the periodic updates to staging will be “more rapid” as new evidence emerges. 

The 8th edition has been published, but due to the “overwhelming culture change,” the “live” date for use of this staging system was extended to January 1, 2018, noted Dr. Edge. ■

DISCLOSURE: Dr. Mesa has been a consultant for Novartis, ARIAD, and Galena and has received research support from Incyte, Gilead, CTI, Promedior, and Celgene. Ms. Andrews is on the speakers bureau for Genentech. Dr. Deshields is on the speakers bureau for Lilly Oncology and Genentech. Dr. Pfister reported no conflicts of interest. Dr. Tempero has received grant funding from Halozyme, Pharmacyclics, and Celgene. Dr. Edge reported no conflicts of interest. 



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