INTERNATIONAL SOCIETY FOR ORAL ONCOLOGY ISOO January 2007

Newsletter 2006-2007 Editor: Andrei Barasch Associate Editor: Rajesh V. Lalla

Volume

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Toronto borrowed a sweet page from Egyptian pharaonic history and was inundated by frogs in late June. Those who did not participate in the writing of guidelines were passed over and thus escaped the onslaught of calories. Other important moments from the MASCC/ISOO Annual Meeting can be found throughout the Newsletter.

Table of Contents Views from Toronto i

We live and learn

Editorial: Is working with drug makers

selling your soul to the devil?

A. Barasch 2

ISOO News Items 4

Treasurer’s report

M Brenan 6

Bisphosphonate-related osteonecrosis:

more than science

S. Elad 7

President’s report for ISOO newsletter

Deborah McGuire 10

Head and neck cancer: evolving science

Andrei Barasch 11

Your letters 14

I S O O N E W S L E T T E R

. Views from Toronto: ISOO Continuing Education session, with some soporific effects

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We live and learn Andrei Barasch, Editor

Judging by the resounding success of last year’s Newsletter, the Editorial Committee voted overwhelmingly (2 for, 0 against) to continue with the current format. We would like you, our readership, to know that your opinions count and we read all your comments carefully. Here is a brief synopsis of the correspondence the Editorial Office received last year:

So we implemented all the suggestions and responded to all your concerns. We are looking forward to your finger’s continued presence on the pulse of the organization.

Note

Please send all your communications electronically to Andrei Barasch at abarasch@uab.edu

Editorial: Is working with drug makers selling your soul to the devil? Andrei Barasch, DMD, MDSc, Associate Professor, University of Alabama at Birmingham

A flurry of scandals have rocked Washington, DC last year, mostly centered around

gifts and payments made by lobbyists and deep pocket industrial interests to

legislators. Some of these activities were illegal and brought about resignations and

jail time, while others were merely ... odd, and led to more people preserving their

cash savings hidden among ice cubes. (Aware of the opportunity, President Bush

presses on with his plan to start exploration in Alaska.)

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A similar crisis is facing the medical community: To accept or to not accept

pharmaceutical industry money? Evidently there are multiple layers to this question,

which does not lend itself to an easy answer. Nevertheless, I believe that a thorough

soul search is in order.

The drug industry has brought about numerous scientific advances, both through

their own research and through sponsorship of scientific efforts elsewhere.

Nevertheless, as the economic laws of capitalism go, the big pharma companies are

motivated primarily by financial profit. And profit they have: this industry has the

highest return on investment. In other words, man, they’ve got a lot of cash! As a

champion rationalizer, I often use this fact to drown my guilt whenever I indulge in

the little perks and pleasures magnanimously offered to us. But the main question

remains: is my indulgence resulting in a bias? To take it further from the trivial, is my

accepting salary support and consulting jobs from a drug maker influencing my

opinion as a scientist and a clinician? Experience from my brief existence in the

citadel of Academia pushes in a clear YES answer. This doesn’t make me feel good,

so I must go on: bias is as human as sweaty armpits and buying it is as American as

Tom DeLay. So why fight it? At a time when the funds at NIH are chasing the Dodo

bird and more academic positions (including mine) require full extramural support,

why not take from where the funds are available? As my Chinese grandmother used

to say, bias-shmias, it’s the science that matters. Everybody knows that! But what

about the patients who will inevitably be the ultimate target of my bias? And how

biased am I in estimation my own bias? Looks like I’m losing this battle, so I’d better

quit.

In a nut shell, this is the dilemma. Naturally, the problem is much larger and more

complex than can be even hinted at in the space of an editorial. There are no laws

governing this issue and the ethics seem to be in the eye of the beholder. Meanwhile,

we must remain pragmatic and thank our generous sponsor for the unrestricted grant

that made this Newsletter possible.

(We welcome your editorial comments, whether in answer to a previous editorial or on any topic related to ISOO).

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ISOO News AMGEN sponsors study for burden of illness of cancer therapy-induced mucositis

A multicenter study that aims to quantify the burden of illness of mucositis was initiated in 2006 with participation of many ISOO members. The principal investigators are Steve Sonis, Linda Elting and Dorothy Keefe. In addition to gathering incidence and severity data, the study will also analyze treatment-related and patient-related risk factors for development of aerodigestive tract mucositis. A second study from AMGEN will test the effects of palifermin on chemoradiation mucositis in head and neck cancer patients and is scheduled to start in early 2007.

Change in Leadership

At the 22 June ISOO Board meeting in Toronto, Judith Raber-Durlacher officially passed the presidency baton to Deborah McGuire. Joel Epstein and Cesar Migliorati also relinquished their positions as immediate past president and vice-president for communications, respectively. Our sincerest thanks go to these looong-serving officers for their devotion and successful leadership. The other members of the Board are:

Inger von Bultzingslowen—vice-president

Monique Stokman—vice-president for communications

Sharon Elad—secretary

Mike Brennan--treasurer

Doug Peterson—liaison to MASCC

We warmly welcome the new Board members and are looking forward to continued prosperity and increased impact of our organization under their able leadership.

MASCC/ISOO session at the meeting of the International Academy of Oral Oncology MASCC/ISOO has been invited to organize a session on oral supportive care during the First World Congress of the International Academy of Oral Oncology (IAOO). This meeting will be held May 17-20, 2007 in Amsterdam. This will be an important opportunity for MASCC/ISOO to reach out to colleagues who are mainly involved in research and management of head and neck cancers. The session will be chaired by Steve Sonis, and Judith Raber-Durlacher will be the moderator. Dorothy Keefe will present on the MASCC/ISOO mucositis guidelines, including the recent updates. Ourania Nicolatou-Galitis will discuss management issues of fungal infections in head and neck cancer patients. Joel Epstein will talk about pain in

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cancer patients, whereas Fred Spijkervet will review a number of clinical cases of bisphosphonate-associated osteonecrosis of the jaws. More detailed information can be found at www.iaoo2007.com MASCC/ISOO CE course for Swiss oncology nurses in St Gallen, Switzerland MASCC/ISOO is preparing a half day pre-conference workshop on June 27, 2007 in St Gallen. This interactive workshop will be on oral care in cancer patients (“Mundpflege bei onkologischen Patienten; Die Rolle der Onkologie-Pflegefachperson”) and is primarily aimed at Swiss oncology nurses. For this reason the course will be held in German. The President of the Nurses Group of the European Bone and Marrow Transplantation, Monica Fliedner, will co-chair the course together with Judith Raber-Durlacher. Monica, who is affiliated to the Inselspital in Berne, Switzerland has extensive knowledge and experience in the field of oral complications in cancer patients and we are very happy to have her on board with MASCC/ISOO. The workshop will be based on a number of clinical cases presented by Cesar Migliorati, Dominik Ettlin and Monique Stokman and will be followed by a multi-professional panel discussion. Agnes Glaus is actively involved in the organization, and ISOO’s President Debbie McGuire has an advisory role. ISOO Continuing Education—A Great Success-Again

Our CE course in Toronto was very well attended and received unanimous accolades. Eva Greyzel, a cancer survivor presented Head and Neck Cancer from a Patient Perspective. She is a professional storyteller and fascinated the audience with her account of the grueling road through surgery and chemoradiation. Mark Katz talked about Facial Disfigurement and the Multiple Psychosocial Needs of the Head and Neck Cancer Patients with special emphasis on the social stigma associated with post-surgical facial deformities. The Implementation of Oral Care for the Oncology Patient was discussed by Debbie McGuire who presented evidence of the lack of standardization in this arena. Mike Brennan presented data on the Incidence and Prevalence of Oral Complications in the Cancer Patient, emphasizing the heterogeneity of the literature and the need for an organized effort to examine and improve on the current evidence. Next, the microphone went to Monique Stokman for a presentation on Oral care for the Chemotherapy Patient. She reviewed the oral complications from cytotoxic treatments and the current approaches to their management. Deborah Saunders picked up the topic and addressed Oral Care for the Head and Neck Cancer Treatment, presenting information and data necessary for the safe dental treatment of radiation therapy cancer patients. The relatively new entity of Jaw Necrosis in Patients Receiving Bisphosphonate Therapy was addressed by Cesar Migliorati. The inconstantly increasing number of cases creates legitimate concerns for use of bisphosphonates, particularly in cancer patients (see Sharon Elad’s article below).

This eclectic group of presenters captivated a rapt audience for over four hours.

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ISOO—Treasurer’s Report Michael Brenan, DDS, MHS, Director of Oral Medicine, Carolinas Medical Center,

Charlotte, NC, co-chair of the Oral Care Study Group

The current year has been very interesting for the ISOO budget. The costs for the 2005 Geneva meeting, 2006 Toronto meeting and all other expenses for 2006 have thus far totaled $23,361.88. The good news is that our income for 2006 is currently $28,546.34 and sufficient to cover these expenses. Our much needed increase in income in 2006 is credited to the generous support of Laclede, Inc., MGI Pharma, and Zila Pharmaceuticals, Inc. A small amount of income also came from interest of CD accounts (approximately $700) and registration fees for the CE course ($2300). Our current balance in our CD accounts and checking account is $36,504.96.

Considering the long term financial viability of ISOO, the key will be continued partnerships with industry. This will allow for the continuation of our high quality CE courses and other exciting future activities spearheaded by ISOO. I look forward to seeing an expansion of our ISOO funds!

Joel Epstein and Mike Brennan sharing the stage in Toronto

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Bisphosphonate-Related Osteonecrosis – More than Science

Sharon Elad, DMD, MSc, Head of Hospital Oral Medicine Service, Hadassah University Medical Center and Hebrew University-Hadassah School of Dental Medicine, Jerusalem and Chairperson of the Israeli Society of Oral Medicine.

Bisphosphonate-related osteonecrosis (ON) emerged as a medical entity in late 2003. Since then, numerous cases have been described in the literature. Many of these patients have cancer, as bisphosphonates are indicated in the treatment of metastatic bone disease, multiple-myeloma and hypercalcemia of malignancy. Clinically the ON patients suffer from pain, swelling, exposed bone, and oral dysfunction such as difficulty eating, swallowing and speaking. There is intensive world-wide research to reveal the pathogenesis of this condition and identify a treatment. At present typical management is not effective and management of ON focuses on prevention of local trauma to the jaws.

The Israeli Society of Oral Medicine (ISOM) has been active in this arena during the last year. Three target audiences were addressed: The dental community, the medical community and the general public.

The dental care providers were addressed through the Journal of the Israeli Dental Association in an invited editorial authored by Dr. Noam Yarom. His article referred to the current knowledge and to the recommendations of the American Dental Association as published in the Position Paper of the American Academy of Oral Medicine. In addition, a joint lecture about bisphosphonate-related osteonecrosis was presented in the 81st annual meeting of the Israeli Dental Association by Drs. Sharon Elad, Rizan Nashef and Benjamin Shlomi (November 2nd, 2006, Tel-Aviv).

The ISOM contacted the chairmen of the Israeli medical societies in the fields of oncology, hematology, internal medicine and family practice, endocrinology, and otolaryngology. Members of these medical societies were informed about the new entity and were invited to participate in the scientific meeting of the ISOM on this topic. This scientific meeting encompassed various aspects of bisphosphonate-related osteonecrosis, including the mechanisms of action of bisphosphonates, clinical dilemmas in patients treated with bisphosphonates, risk management in the dental office and recent Israeli studies on the topic. Prof. Cesar Migliorati, a leading clinician in this field and a past board member of the International Society of Oral Oncology was our guest speaker at this event.

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Finally, an article about the risk for osteonecrosis in patients treated with bisphosphonates was published in the most popular evening newspaper in Israel (Maariv, October 4th, 2006). The journalist interviewed Dr. Noam Yarom who tried to raise the awareness of the general public to this possible complication of bisphosphonate treatment.

We hope that the continuous efforts of the ISOM board members will achieve the goal of minimizing the occurrence of bisphosphonate-related osteonecrosis. I would like to take this opportunity to thank the members of the ISOM who consistently contribute to the national effort – Drs. Noam Yarom, Esti Scheuer and. Sharon D. Robinson.

For additional information about the ISOM activity please visit the ISOM English homepage (www.ida.org.il/oralmedicine under the English link.

Joel and Debbie McGuire—all between presidents

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President’s Report for ISOO Newsletter By Deborah B. McGuire, PhD, RN, FAAN The ISOO Board has been working hard over the past few months to address three issues of importance to the organization and its members. In addition to meeting twice while in

Toronto this past June, the Board met by telephone in October, in the first of its newly instituted plan for quarterly telephone conferences. We all agreed that ‘meeting’ in this way would help us stay on track with our work, and more efficiently accomplish our goals. Thanks to the assistance and support of Cindy Rittenberg in the MASCC office, we were able to conduct our first international telephone conference meeting with great ease. I might add that this support is one of the benefits of our current alliance with MASCC!

The first major issue the Board is working on is the alliance with MASCC. The current agreement expires in August 2007, so a subgroup of the Board has drafted a new alliance document and circulated it to all Board members for their input. Among the key issues we are including in this document are the financial aspects of the alliance, and the provision of MASCC support for our continuing education workshops at the annual MASCC scientific meetings. Input from ISOO members at our General Business Meeting in Toronto was quite helpful to us in this effort. We are now in the process of revising the alliance document to incorporate Board input, and will then move it forward for more review and consideration before sending it to MASCC. A second major issue, related to the one above, is a substantive revision of our bylaws. These bylaws have not been updated in any significant way for quite some time, and no longer fit how we do our business (for example, they do not cover electronic election of Board members). Ably led by Dianna Weikel, the BARC has completed a revision of the bylaws, using the MASCC bylaws as a model. This draft is currently undergoing review and scrutiny by the full Board, with comments due back in early December. The third issue we are working on is the legal ‘home’ of ISOO. The organization is currently chartered in the State of Washington, USA, because of its origin and historical development (early charter members were in that state, etc.). We have learned that it may be quite easy to move the organization to Louisiana, where MASCC is located, and cheaper in terms of annual fees that must be paid to the state by corporations such as ISOO. The Board has recently authorized a full exploration of the financial and other ramifications of

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moving the organizations, so we should be able to give you an update on this issue in the near future. Lastly, the Board has been involved in several other activities. First, the Nominating Committee, led by Past President Judi Raber-Durlacher, is working to prepare a slate of candidates for the upcoming Board election. Positions that will be open include President, Secretary, and Treasurer. Please look for a call for nominees for these positions in the near future. Second, Judi Raber-Durlacher has also been working closely with the MASCC Program Planning Committee for the St. Gallen meeting to plan and implement our annual continuing education workshop. Details of that important even are elsewhere in this newsletter. Third, various members of the Board are working with the MASCC Professional Liaison Committee, Cindy Rittenberg, Judi Johnson, and others, to ensure an ISOO presence in oncology and/or dental related conferences around the world. As always, the Board values the input of all ISOO members, and encourages correspondence on any issue, any time! Let us hear from you! You can reach Debbie McGuire electronically at dmcguire@son.umaryland.edu

Stage corner property: Rene-Jean Bensadoun and Doug Peterson, members of the discussion panel

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Head and Neck Cancer: Evolving Science If you ever thought that number 7 is lucky, place it as a hierarchic cause of cancer deaths for the Head and Neck category. Only six other cancers rank higher on this macabre list and the incidence of head and neck in general, and oral cancer in particular, is increasing at a rapid pace in developing countries (1). A superficial look may lead to the conclusion that not much is changing in this arena. Nothing could be farther from the truth. Careful assessment of the literature reveals significant qualitative and quantitative advances in head and neck cancer therapy. We will highlight some of these below: Combined therapy: A meta-analysis (2) of concomitant chemoradiation in naive patients with stage III-IV disease demonstrated an 8% improvement in survival at 5 years. Among the trials included in this analysis, the more recent ones reported even higher survival. Post-operative chemoradiation has also increased survival when compared to radiation alone (3). The bad news is an almost doubling of acute grade 3-4 mucositis and dermatitis. Targeted therapy: The new century has brought to fruition some of the promises of the “magic bullet.” The use of novel biologic agents in the fight against cancer has moved to the mainstream of therapy. Current drugs include epidermal growth factor receptor inhibitors (EGFRI), proteasome inhibitors, cell cycle kinase inhibitors and antiangiogenic agents. EGFR is present in >90% of head and neck tumors, but the amount expressed varies considerably (4). Overexpression of EGFR is associated with more aggressive tumors and worse overall outcomes (5). Tyrosine kinase inhibitors and anti-EGFR monoclonal antibodies are categories of agents that target the EGFR and have shown efficacy as treatments for a variety of tumor types. To date, the US Food and Drug Administration has approved gefitinib and erlotinib (kinase inhibitors) for treatment of non-small cell lung cancer, and cetuximab (anti EGFR antibody) for colorectal cancer. Gefitinib and erlotinib were both tested as single agents in head and neck cancer (5,6) and both showed promising results. Addition of gefitinib to chemoradiation showed an 88% complete remission rate in earlier stage disease. Of note, this protocol was no more toxic than chemoradiation alone (7). A new tyrosine kinase inhibitor, lapatinib, is currently undergoing phase II studies at the University of Chicago. Possibly the most exciting news came from studies of cetuximab, which is a murine monoclonal antibody that binds to EGFR. Phase III trials (8) demonstrated that addition of the drug to high-dose radiation therapy increased survival by 13% at two years and 7% at three years when compared to radiation alone. Both were highly significant. While a significant acneiform rash was reported in cetuximab patients, radiation-induced mucositis was not increased. Current phase III studies are examining the effect of cetuximab added to chemoradiation in advanced stage or recurrent head and neck cancer. References 1. Shibuya K, Mathers CD, Boschi-Pinto C, et al. Global and regional estimates of cancer mortality and

incidence by site: II. Results for the global burden of disease 2000. BMC Cancer, 2002; 2:37.

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2. Pignon JP, Baujat B, Bourhis J. [Individual patient data meta-analysis in head and neck carcinoma: what have we learnt?] Cancer Radiother 2005; 9:31-36.

3. Bernier J, Domenge C, Ozsahin M, et al. Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. N Engl J Med 2004; 350:1945-52.

4. Albanell J, Codony-Servat J, Rojo F et al. Activated extracellular signal-regulated kinases: association with epidermal growth factor receptor/transforming growth factor alpha expression in head and neck squamous carcinoma and inhibition by anti-epidermal growth factor receptor treatments. Cancer Res 2001; 61:6500-10.

5. Ang KK, Berkey BA, Tu X, et al. Impact of epidermal growth factor receptor expression on survival and pattern of relapse in patients with advanced head and neck carcinoma. Cancer Res 2002; 62:7350-6.

6. Cohen EE, Rosen F, Stadler WM, et al. Phase II trial of ZD1839 in recurrent or metastatic squamous cell carcinoma of the head and neck. J Clin Oncol 2003, 21:1980-7.

7. Cohen EE, Lingen MW, Martin LE, et al. Response of some head and neck cancers to epidermal growth factor receptor tyrosine kinase inhibitors may be linked to mutation of ERBB2 rather than EGFR. Clin Cancer Res 2005, 11:8105-8.

8. Bonner J, Giralt J, Harari P et al. Cetuximab prolongs survival in patients with locoregionally advanced squamous cell carcinoma of the head and neck : a phase III study of high dose radiation therapy with or without cetuximab. Proc AM Soc Clin Oncol 2004, abstract.

Toronto: some had time for games and had a good time despite disagreements between French and American styles

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The ISOO leadership making sure the financial situation is stable. The table is full with the goods we could afford. Save the date: MASCC/ISOO 20th annual meeting will convene in St. Gallen, Switzerland 27-30 June 2007. Additional information and registration on line at MASCC/ISOO site (www.mascc.org)

Happy holidays and a prosperous and successful new year

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