Mike Hennessy, Chairman

The word &ldquo;marker&rdquo; is defined, in medical terms, as &ldquo;something that serves to identify, predict, or characterize.&rdquo; A variation on this word, known as a biological marker, or biomarker, (defined as a measurable indicator of a biological condition) takes this concept one step further.

And that&rsquo;s exactly what we are doing in this issue of

, which has a special focus on biomarkers within our section of peer-reviewed articlestaking the exploration of biomarkers as they are applied in cancer research and treatments one step further (actually, many steps further).

This issue&rsquo;s first peer-reviewed article, &ldquo;Integrating Immunotherapy With Chemoradiation in the Treatment of Head and Neck Cancer,&rdquo; looks at the potential benefits of combining chemotherapeutics, radiotherapy, and immunotherapy as a treatment for squamous cell carcinoma of the head and neck (SCCHN). The authors contend that gaining better understanding of the synergy between these approaches in treating SCCHN will result in more rational and improved clinical trials, and could improve outcomes in SCCHN patients in the definitive treatment setting.

The first of the two peer-reviewed biomarkers articles in this issue, &ldquo;The Importance of Biomarkers for Cancer Immunotherapy,&rdquo; examines the benefits and limitations of immunotherapy as a cancer treatment strategy. The use of checkpoint blockade with cytotoxic T-lymphocyte-associated protein 4 and programmed death-1 (PD-1) antibodies, and other recently approved biologic drugs, has shown encouraging results in patients. But, there are still toxicities associated with such immunotherapies. Response is not durable in most patients. For this reason, the author feels, there is an urgent need for standardized, validated biomarkers to measure immunotherapy efficacy. Biomarkers that could potentially meet this goal are discussed with great insight in this piece.

Our next biomarkers article, &ldquo;Next Generation Diagnostics for Immuno-Oncology,&rdquo; reviews current immuno-oncology therapies, which, the authors attest, are only effective for a small portion of patients. They feel current biomarkers to measure immune response are less than optimal. The use of programmed death ligand 1 (PD-L1) to guide the administration of PD-1 inhibitors, in their view, has low accuracy and analytic challenges. As an alternative, the authors propose the features of an ideal immuno-oncology diagnostic, summarize PD-L1 measurement by immunohistochemistry, and document different biomarkers under development that could revolutionize the practice of immuno-oncology in years to come.

These articles all have the mark of excellence. We hope you enjoy and benefit from them, and from all of the valuable content contained in this issue.

Articles

The word &quot;marker&quot; is defined, in medical terms, as &quot;something that serves to identify, predict, or characterize.&quot; A variation on this word, known as a biological marker, or biomarker (defined as a measurable indicator of a biological condition) takes this concept one step further.

Markers of Excellence

It is impossible to traverse life without a friend or family member experiencing cancer. For many in the United States, this experience manifests as breast cancer, since 1 in 8 women are diagnosed with this disease at some point in their lifetime. As the most common cancer worldwide, screening for breast cancer is of the utmost importance.

Despite the prevalence, the US Preventive Service Task Force (USPSTF) kicked off 2016 with a controversial recommendation against screening for women under the age of 50 who are at average risk. This change, which was preceded by half a decade of debate, joined other guidelines suggesting a similar starting age, including those from the American Cancer Society (ACS).

Across guidelines, the term "average" is used to describe a woman's risk; however, many women are not unaware of their level of risk, which adds to the confusion. The group Bright Prink emphasized this point, after the ACS announced the new guidelines. To help provide important information, Bright Pink provides a helpful tool that helps women gauge their risk (

), and the group continues to recommend annual screening starting at age 40.

The success of earlier screening was showcased during the keynote address delivered by Amy Robach at the

. Robach shared her story about the importance of beginning screening at age 40, which was her age when she was diagnosed with stage II breast cancer after receiving a mammogram on live TV. Had she followed the new guidelines, her cancer may still be growing undetected today (see more, on page 24).

Each year, even in the wake of these guidelines, we are reminded prior to the month of April about the importance of cancer screening. Like clockwork a Presidential Proclamation is issued in March declaring April &ldquo;Cancer Control Month.&rdquo; This tradition was established in March 1938 and has been repeated every year since, with the latest proclamation made on March 31, 2016.

During Cancer Control Month the question that begs to be asked is, &ldquo;Why is screening being cut in the same breath that diet, exercise, and lifestyle choices are heralded as keystones in controlling cancer?&rdquo; Following the USPSTF guidelines, a joint statement from the American College of Radiology and the Society of Breast Imaging said the decision could be lethal for thousands of women. If this is truly the case, these guidelines are a step in the wrong direction toward controlling cancer.

The breast cancer guidelines in the United States need to be fixed, which can only be accomplished by those on the frontlines. We need oncologists to chime into the discussion. To contact the USPSTF, visit

The breast cancer guidelines in the United States need to be fixed, which can only be accomplished by those on the frontlines. We need oncologists to chime into the discussion.

New Mammography Guidelines Are Flawed

The ASCO Annual Meeting is always packed with the latest and greatest advances in the field of oncology, and this year was no exception! The 2015 meeting had posted record-breaking numbers for abstract submissions and attendance, with over 37,000 individuals crowding the halls of the McCormick Place in Chicago.

One of the most popular presentations at the meeting focused on the impressive activity of immuno-oncology in hepatocellular carcinoma (HCC). This important study found that the PD-1 inhibitor nivolumab (Opdivo) could effectively shrink tumors for patients with pretreated HCC without inducing substantial side effects.

In this phase I/II study, the 19% prolonged objective response rate (ORR) with nivolumab is encouraging, and offers the potential of a novel treatment modality for HCC. Importantly, nivolumab was effective in patients with viral hepatitis and those with underlying liver cirrhosis, marking an important advance that is desperately needed for patients with limited options.

Exciting data for other novel agents were also presented at the Meeting. Another checkpoint inhibitor, tremelimumab, showed an ORR of 40% in combination with chemoembolization or radiofrequency ablation in pretreated HCC. Additionally, the antibody TRC105 plus sorafenib and axitinib with chemoembolization showed high responses in two separate early phase clinical trials.

While these findings are exciting for patients with advanced disease, the focus remains on early detection and improvements to curative surgical strategies. Additionally, HCC prevention remains an important factor, especially with novel therapies that are revolutionizing the treatment of hepatitis C, according to Michael P. Manns, MD (

Click here, to see more from this interview

With the host of evolving therapies, potential prevention strategies, growing curative options, and improved surveillance modalities, the future for HCC looks bright. I look forward to larger investigations and validation studies as we move closer to eradicating this disease.

Mike Hennessy, Chairman | Authors

Articles

Markers of Excellence

New Mammography Guidelines Are Flawed

Immuno-Oncology Arrives in HCC