Abstract
The 2010 Multidisciplinary Head and Neck Cancer Symposium was held in Arizona on February 25–27, 2010 and sponsored by the American Head and Neck Society, American Society of Clinical Oncology, American Society for Therapeutic Radiology and Oncology, and Society of Nuclear Medicine. Expertise from various fields spanned topics that included diagnosis and management of skull-base malignancies; discovery and integration of biomarkers in clinical trials; organ preservation and functional outcomes; patient-centered care initiatives; functional imaging for head and neck cancer; and the treatment of recurrent disease. This meeting was informative and provocative in reporting the latest advances in the management of head and neck cancer. It provided the opportunity to gather expertise for interdisciplinary discussion and especially illustrated the challenges in managing these complex and heterogeneous diseases.
This Multidisciplinary Head and Neck Cancer Symposium was held on February 25–27, 2010 under cosponsorship of the American Head and Neck Society, American Society of Clinical Oncology, American Society for Therapeutic Radiology and Oncology and Society of Nuclear Medicine (SNM). It attracted more than 500 attendees, including clinicians, medical imaging, basic-translational research and other health professionals who care for head and neck cancer (HNC) patients. The goal was to promote interdisciplinary discussion on the latest research and state-of-the-art care in HNC. In total, 16 plenary papers, two late breaking abstracts and 85 posters were presented.
Sinonasal & skull-base malignancies
Sinonasal and skull-base malignancies are challenging owing to their rarity and histological heterogeneity, as well as treatment complexity. The anatomy of the region often lends itself to relatively late presentations owing to lack of patient and healthcare provider awareness, the ability for significant growth within the sinus cavities and the infrequent warning sign of a mass in the neck due to relatively uncommon regional lymph node metastases. Advances in endoscopy, high-resolution imaging and better histopathological classification have improved diagnostic accuracy. Innovations include developments in craniofacial surgery, conformal photon and proton radiotherapy (RT), and neoadjuvant and adjuvant chemotherapy. Laurie Loevner from the University of Pennsylvania (PA, USA) described CT-guided fine-needle aspiration procedures for skull base malignancies that appear expeditious and safe with an accuracy of greater than 90% in selected cases. Annie Chan of the Massachusetts General Hospital (MA, USA) reported encouraging outcomes of proton-beam therapy for 99 patients with advanced sinonasal malignancies treated between 1991 and 2003. Local control at 5 and 8 years was 87 and 83%, respectively, and the overall survival (OS) for these time points were 57 and 46%. Merrill Kies from MD Anderson Cancer Center (MDACC; TX, USA) described an institutional experience of induction chemotherapy for sinonasal undifferentiated carcinoma. Docetaxel–CDDP induction chemotherapy followed by primary RT (8), chemo–RT (7), and Sx (15) yielded a 3-year disease-specific survival of 55%. Response to chemotherapy subdivides the population according to survival but he emphasized this observation did not necessarily indicate that the treatment itself was the cause of improved outcome in responding cases. While sequential chemo-RT is feasible with this protocol, prospective studies are desirable to establish optimal approaches.
Biomarkers & head & neck cancer
A keynote by Maura Gillison of Ohio State University (OH, USA) and several presentations addressed biomarkers with emphasis on discovery, validation, implementation into clinical trial design, and outcome prediction. Unfortunately, despite extensive research that includes evidence of adverse prognosis related to molecular dysfunction and expression in several pathways, the search continues for elusive targets for which specific agents can be employed selectively in HNC.
Human papillomavirus (HPV)-positive oropharyngeal carcinoma (OPC) is exhibiting a meteoric rise in the 50–59-year age group and is associated with superior response and survival outcome. Therefore, HPV is widely considered a prognostic biomarker for OPC, or alternatively could be considered a different disease from conventional HNC arising in the same location. There is also an emerging awareness that a subset of HPV-positive patients fare less well. The underlying mechanism appears multifactoral. Potential modifiers for outcome include tobacco use, Bcl2 and EGF receptor expression. Gillison illustrated the interaction between tobacco use and HPV status on OS in the recently presented RTOG 0129 trial Citation[1]. HPV-positive OPC patients with a 20 and above pack-year smoking history had reduced OS compared with those with below 20 pack-year of tobacco use. A pressing issue is whether HPV-positive OPC should be managed differently and especially whether de-escalation of treatment intensity might be safe for these patients with such a favorable prognosis compared with traditional tobacco-related cancers in the same region. Designing a noninferior clinical trial to answer this question is proving a statistical challenge as was eloquently discussed by Tom Pajak from the RTOG (PA, USA). He suggested that the paucity of events in trials involving relatively younger and fitter patients could theoretically require 20 years for data to mature sufficiently to confirm noninferiority for a deintensified treatment regimen in favorable ‘never smoker’ HPV-positive OPC; indeed by that time the disease could potentially disappear with progress in vaccination and behavior modification. A proposal for the early release of outcome data from a carefully specified subset of noninferior trials may help to resolve the dilemma Citation[2].
Organ preservation & functional outcome
Various organ preservation strategies and outcomes for HNC were outlined. Gilles Calais of the GORTEC (France) reported a retrospective analysis of functional results of 213 patients enrolled in the GORTEC 2000–2001 randomized trial (comparing docetaxel plus cisplatin and fluorouracil [TPF] versus cisplatin plus fluorouracil [PF] induction for laryngeal preservation) using two new end points: 5-year laryngo–esophageal dysfunction and disease-free survival rate (LEDD-FS) and 5-year freedom from laryngo–esophageal dysfunction (FF-LED). The 5-year LEDD-FS was 36% and FF-LED was 6% in the TPF arm. Gregory Chronowski from MDACC presented the result of ipsilateral RT in 102 patients with T1–2 N0–N2b squamous cell carcinoma of the tonsil treated between 1970 and 2007; 5-year disease-free survival was 96%. Only two patients developed contralateral lymph node recurrence. However, HPV status was not available for those patients and caution was raised concerning selection of HPV-positive OPC for the approach as they may present with multicentric lesions and HPV-positive early tonsil squamous cell carcinoma may also be more likely to have contralateral lymph node spread (shown in two posters). Arlene Forastiere from Johns Hopkins University (MD, USA) and co-chair of the NCI Head and Neck Steering Committee summarized several induction chemotherapy trials for locally advanced laryngeal cancer Citation[3–5]. Efficacy compared with concurrent chemo–RT remains controversial as toxicity/tolerance remains an unresolved concern. Induction TPF followed by RT with biological agents, such as cetuximab, was a logical next step. Felix Nguyen-Tan of the RTOG also reported the outcome of 721 HNC patients enrolled in the RTOG 0129 trial comparing accelerated (AFX-C) versus standard fractionation radiation with concurrent cisplatin. AFX-C did not improve outcome or increase late toxicity, the treatment effect was similar for HPV-positive and HPV-negative HNC and the benefit of the third chemotherapy cycle chemotherapy appeared minimal. This result presents a dilemma in choosing the control arm for future clinical trials, especially since the long-term toxicity profile remains unknown.
Patient-centered care initiatives
Innovation and initiatives to improve quality and provide greater support for patients with HNC were discussed. Brian O’Sullivan from the Princess Margaret Hospital (PMH; ON, Canada) described the PMH Bioclinical Head and Neck Anthology System to improve efficiency in a busy head and neck clinic environment and to track outcome and compile data elements at the point-of-care. Peggy Wiederholt from the University of Wisconsin outlined the role of the nurse coordinator in facilitating HNC patient navigation through a complex healthcare system. Jonathan Irish showed initiatives he developed at Cancer Care Ontario (ON, Canada) in improving surgical quality throughout the largest province in Canada via data information, knowledge development and transfer, and performance management. Andy Trotti from the Moffitt Cancer Center (FL, USA) and co-chair of the NCI Head and Neck Steering Committee presented an overview of measurement, management and approaches to amelioration of the late effects in HNC. Improved RT targeting, reduced RT dose in favorable-risk HPV-positive OPC and development of additional medical mitigators may facilitate reduction of late toxicity. Barbara Murphy of the Vanderbilt–Ingram Cancer Center (TN, USA) reported increasing evidence of neurocognitive alterations in HNC probably due to direct toxic effects of chemotherapy/RT on the brain and various ways of assessing them. Erich Sturgis described the concept and implementation of the HNC survivorship program at the MDACC to monitor the late effects and recurrence as well as providing general preventive healthcare and personal health behavior recommendations.
Functional imaging for head & neck cancers
A keynote and several presentations addressed the important implementation of metabolic and functional imaging for HNC. For example, Michael M Graham, President of SNM (VA, USA), comprehensively reviewed the role of metabolic imaging in diagnosis, staging and assessing treatment response. This field will acquire even greater importance as molecular probes are developed to permit imaging of metabolic signaling and may support chemotherapy and RT adaptation in the future.
Treatment of recurrent head & neck cancers
Management of recurrent HNC is daunting, but a subset of selected patients may enjoy long-term cure if management is based on sound principles. Surgery, whenever possible, should be the cornerstone of treatment in patients who have undergone previous radiation. Randal Weber from the MDACC and conference chair addressed key elements needed in selection including patient fitness, anticipated functional outcome and feasibility. The surgical focus should be on oncologic resection rather than debulking procedures as well as the type of reconstruction, which must be tailored to the anatomic setting. Additional important aspects are tumor site and bulk, and the dose and interval since prior RT. Promising advances in systemic treatment are also exemplified from several sources, including the presentation by Jan Vermorken of the EORTC (Brussels, Belgium) who discussed the EXTREME trial (Erbitux in First-Line Treatment of Recurrent or Metastatic HNC), which showed the potentiation of 5-fluorouracil–platinum effect in the presence of targeted treatments Citation[6].
Summary
This meeting was informative and provocative in reporting the latest advances in the management of HNC. It provided the opportunity to gather expertise for interdisciplinary discussion and especially illustrated the challenges in managing these complex and heterogeneous diseases. This was particularly evident through the unusual and urgent need to develop less intense treatments for a rapidly emerging population of younger patients with exceptionally favorable prognosis and identified by their association with HPV.
Acknowledgement
The authors would like to acknowledge the Bartley-Smith/Wharton Foundation at the Princess Margaret Hospital for supporting the authors’ academic activities in head and neck cancer.
Financial & competing interests disclosure
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.
References
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- Forastiere AA, Goepfert H, Maor M et al. Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer. N. Engl. J. Med.349(22), 2091–2098 (2003).
- Pointreau Y, Garaud P, Chapet S et al. Randomized trial of induction chemotherapy with cisplatin and 5-fluorouracil with or without docetaxel for larynx preservation. J. Natl Cancer Inst.101(7), 498–506 (2009).
- Posner MR, Norris CM, Wirth LJ et al. Sequential therapy for the locally advanced larynx and hypopharynx cancer subgroup in TAX 324: survival, surgery, and organ preservation. Ann. Oncol.20(5), 921–927 (2009).
- Vermorken JB, Mesia R, Rivera F et al. Platinum-based chemotherapy plus cetuximab in head and neck cancer. N. Engl. J. Med.359(11), 1116–1127 (2008).