On May 12, Dr. Ezra Cohen joined us on GRACE for a webinar. Dr.Cohen is an associate professor at the University of Chicago where he specializes in medical oncology for patients with lung cancer and head and neck cancer. Dr. Cohen’s talk came the day after Dr. Lin explained the role of radiation after surgery for head and neck cancer. Dr. Lin explained to us why some patients benefit from radiation after surgery to reduce recurrence risk. In this webinar, Dr.Cohen expanded on this subject, explaining that some patients who benefit from radiation after surgery will have even lower recurrence rates when chemotherapy is given together with the radiation.

Here are the links to the audio and video podcasts, the transcript, and the figures for the program

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Here is the question and answer session that followed the excellent presentation by Dr. Alex Lin offering some general history, basic concepts, and specifics about radiation in the setting of head/neck cancer. We cover management of radiation-associated side effects, some emerging techniques, and how radiation oncologists make decisions about what treatment to recommend for a particular patient.

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Lymph node stations in the neck

Combined chemoradiotherapy is a standard therapy for the treatment of locally advanced squamous cell carcinoma of the head and neck (SCCHN) (webinar on both curative radiation and curative chemoradiotherapy to come within the next few months). Response rates are high, and cure rates surpass 50%, even for stage III and IV disease. Head and neck cancer tends to spread to the lymph nodes in the neck, and the neck is typically covered in the radiation field. Those patients with cancer remaining in the neck after chemoradiotherapy clearly need these nodes removed surgically to elicit a cure. But what about those who have a complete response, as judged by CT imaging? Are outcomes improved by elective lymph node dissection after successful chemoradiotherapy (as judged by CT) or is this just unnecessary surgery?

I think that the majority opinion right now leans towards neck dissection for most patients with N2 or N3 disease at presentation. Those who feel this way argue that neck dissection can improve local control and point to series showing that neck dissections find residual disease in about a quarter of patients. Older data showed advantages both in local control and disease-free survival for neck dissection and ASCO guidelines for larynx cancer endorse this perspective.

But have things changed with better chemoradiotherapy? In more modern series, the disease control advantage is less clear. Isolated neck recurrence has become rare in patients with complete response to chemoradiotherapy-it’s now under 5%. A JCO paper in 2006 showed a lack of survival advantage for elective lymph node dissection for patients with complete response on CT. Investigators at the University of Florida looked back at 550 patients with node positive SCCHN treated with radiation therapy (76%) or chemoradiotherapy (24%); 62% also had elective lymph node dissection. All patients had CT imaging a month after the completion of therapy. Of those patients who had neck dissection, the negative predictive value of being NED on CT imaging was 94%. Of 32 patients with radiographic complete response and no elective lymph node dissection, the five year neck-control rate was 100% and cause-specific survival was not different from patients with neck dissection. NCCN guidelines follow this perspective, listing active observation as a treatment option.

Why am I blogging about this now? A new study presented this week (6/4/10) at ASCO studied this question in a very large series from MD Anderson Cancer Center. They looked back at their experience over a decade from 1994 to 2004. During this period, the institutional policy was to not perform elective neck dissection for patients with a complete nodal response to irradiation. They looked back at 935 patients and found that half had a complete nodal response in the neck as judged by CT. The key finding was that among patients with complete nodal response and no elective neck dissection, there was only a 4% incidence of neck-only recurrence. This suggests that those patients with complete nodal response on CT from chemoradiotherapy can safely forgo elective neck dissection. One subgroup was notable-hypopharynx patients with big nodes at presentation had high failure rates, even when they had a complete nodal response, suggesting that this group may benefit from additional therapy, such as elective nodal dissection. One final finding was of note from this study, and it is consistent with previous literature. Among patients who did have a nodal dissection, prognosis was better when there was a pathologic complete response (no residual living cancer cells in the nodes taken out). This makes common sense-if the main therapy kills all your cancer cells, you do better! What’s harder is to know what to do with those patients with residual cancer on elective node dissection. Should they be given additional therapy to try to improve their cure rates? Or, has their cancer demonstrated that it is not sensitive to our therapies, meaning that this extra therapy would only cause toxicity without added cancer control?

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On May 11, Dr. Alex Lin, a radiation oncologist from the University of Pennsylvania, joined us on GRACE to give a webinar. Dr. Lin’s practice and research focus on radiation therapy for lung cancer and cancers of the head and neck. His talk focuses on the use of adjuvant radiation therapy in the treatment of head and neck cancer. Patients with head and neck cancer are treated with either surgery or radiation as curative therapy. Many patients who are treated with surgery can be treated with additional radiation therapy to increase their cure rate after the surgery (adjuvant therapy). Dr. Lin provides here an excellent introduction to what radiation is, how it is given, and who should get it in the adjuvant setting.

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The origin of head and neck cancer (HNC) has been linked to smoking and alcohol consumption, and more recently to infection by human papillomavirus family viruses (HPV). But an area that was obscure and where recent research is being unveiled is the actual cell of origin of HNC.

Ask any cancer survivor what his or her greatest fear is, and chances are he or she’ll reply: “The cancer coming back.” Recurrence rates from different cancers can vary widely, from 5 to 95 percent depending on how far the original tumor had spread, its particular molecular characteristics and other clinical factors. But what makes cancer come back?

A possible answer may get to the root of the cancer problem: cancer stem cells (CSCs).

CSCs can be thought of as generals in a war. There aren’t very many of them, they are located at the rear, and organize the battles and send in the troops to invade. They build the armies. Many scientists believe that CSCs originate and keep tumors growing, invading and spreading into new places. They also may make up less than 0.1 percent, or one in 1,000 cells, of a solid tumor’s bulk. They are not related to embryonic stem cells, other than their name who indicates that they are at the root of an event; in the case of embryonic stem cells it means that they give rise to an embryo, in the case of CSC it implies that they give rise to cancer.

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Most of the abstracts are now available online at http://abstract.asco.org/abst_files/HeadNeck_5500-5601.pdf for those with interest. Below, you will find a summary of the three clinical science symposium abstracts and the poster discussion abstracts. There’s a lot to cover…

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I enjoyed Dr. West’s summary of upcoming ASCO highlights for lung cancer and so decided to copy him for the oral head and neck session, where the most important abstracts are broken:

#5503-Vandetanib (VAN) in locally advanced or metastatic medullarythyroid cancer (MTC): A randomized, double-blind phase III trial (ZETA).

-Medullary thyroid cancer, once incurable, is hard to treat. Results with chemotherapy (doxorubicin) have been unimpressive, with <40% response rate, short duration of response, and toxicity. The phase II results with vandetanib, a pill tyrosine kinase inhibitor to VEGF, RET, and EGFR were promising and so I await anxiously the results of this 331 patient trial.

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The incidence of head and neck cancer (HNC) has been gradually increasing over the last 3 decades. Although certain subsets of HNC (such as larynx cancer) have decreased in incidence in parallel with the reduction in smoking, rates of oral cavity tumors (including tongue and tonsil) have risen among young (<45 years old) men and women. In addition to the classic risk factors of tobacco and alcohol use (that used to be responsible for the majority of HNC) recent data have linked infection with a virus to cases of HNC especially from the oral cavity and related sites. The virus strains responsible belong to the human papillomavirus family (HPV). HPV is the main cause for cervix cancers in women, and the HPV subtypes associated with HNC are rather similar with those causing cervical cancer. Subtype HPV16 accounts for the majority of HPV-positive cases (> 65% of oral tumors, >80% of oropharynx cancers, and 70% of laryngeal cases), with HPV18 having a far second place (around 5-8% of HPV-positive cases). Epidemiological data seem to suggest that sexual transmission is important but other transmission routes are under investigation.

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Is this patient really incurable?

The first question to ask when addressing incurable SCCHN is to be sure that the cancer really is incurable. When SCCHN recurs, it often recurs locally, at or near the site of the original cancer. For this reason, local salvage therapies such as surgery, radiation, chemoradiation or even repeat chemoradiation can sometimes elicit a cure for the patient with a local or local-regional recurrence. These topics are important and will likely be the subject of future posts on GRACE. The rest of this post will assume that the patient truly is incurable, either because local maneuvers are no longer possible, the cancer has spread to distant sites, or the patient has made a choice to not receive further surgeries or radiation.

Why Chemotherapy for Incurable Disease?

Every cancer therapy has two purposes: to improve duration of life, and to improve quality of life. Every other measure of chemotherapy success, such as response rate or progression-free-survival, is a surrogate to these two true goals.

For the patient with metastatic disease, chemotherapy is the most important treatment for achieving these two goals. “Incurable” is not the same as “untreatable.” Cure means eliminating every last cancer cell. Treatment means providing real benefit, in the form of achieving these two goals.

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