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Contributors Numbers in parentheses indicate the pages on which the Janet Dancy (535) Cancer Treatment Evaluation Program, authors' contributions begin. National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892 David J. Adelstein (461) Department of Hematology and Medical Oncology, Cleveland Clinic Foundation, R. Kim Davis (359) Division of Otolaryngology--Head Cleveland, Ohio 44195 and Neck Surgery, University of Utah School of Medicine, Salt Lake City, Utah 84132 Muhyi AI Sarraf (491) Department of Radiation Oncology, Eastern Virginia Medical School, Norfolk, Virginia 23507 John .F Ensley ,3( ,9 167) Department of Medicine, Oncology, and OtolaryngologymHead and Neck Panomwat Amornphimoltham (509) Oral and Pharyngeal Surgery, Karmanos Cancer Institute, Wayne State Cancer Branch, National Institute of Dental and University, Detroit, Michigan 48201 Craniofacial Research, National Institutes of Health, J. K. Field (117) Molecular Genetics and Oncology Group, Bethesda, Maryland 20892 Clinical Dental Sciences, University of Liverpool and K. Klan Ang (445) Department of Radiation Oncology, Roy Castle International Centre for Lung Cancer The University of Texas M.D. Anderson Cancer Center, Research, Liverpool L69 3BX, United Kingdom Houston, Texas 77030 Arlene A. Forstiere (475) Department of Oncology, Johns William B. Armstrong (339) Department of Hopkins University School of Medicine, Baltimore, Otolaryngology--Head and Neck Surgery, University of Maryland 21231 California, Irvine, College of Medicine and Craniofacial/ Maura Gillison (475) Department of Oncology, Johns Skull Base Surgery Center, University of California, Hopkins University School of Medicine, Baltimore, Irvine, Medical Center, Orange, California 92868 Maryland 21231 Thomas H. Bugge (137) Oral and Pharyngeal Cancer .P G. Shankir Giri (491) Department of Radiation Branch, National Institute of Dental and Craniofacial Oncology, Eastern Virginia Medical School, Norfolk, Research, National Institutes of Health, Bethesda, Virginia 23507 Maryland 20892 J. Silvio Gutkind (509) Oral and Pharyngeal Cancer Brenda Cartmel (261) Department of Epidemiology and Branch, National Institute of Dental and Craniofacial Public Health,Yale University School of Medicine, New Research, National Institutes of Health, Bethesda, Haven, Connecticut 06520 Maryland 20892 Gary Clayman (555) Department of Surgery, The Walter N. Hittelman (227) Department of Experimental University of Texas M.D. Anderson Cancer Center, Therapeutics, The University of Texas M.D. Anderson Houston, Texas 77030 Cancer Center, Houston, Texas 77030 Barbara Conley (535) Cancer Treatment Evaluation John R. Jacobs (329) Department of Otolaryngology-- Program, National Cancer Institute, National Institutes of Head and Neck Surgery, Karmanos Cancer Institute, Health, Bethesda, Maryland 20892 Wayne State University, Detroit, Michigan 48201 xiii xiv srotubirtnoC Fadlo R. Khuri (271) Department of Thoracic/Head and Douglas E. Morse (261) New York University College of Neck Medical Oncology, The University of Texas M.D. Dentistry, New York, New York 10010 Anderson Cancer Center, Houston, Texas 77030 Jose E. Otero-Garcia (329) Department of Otolaryngologym Edward S. Kim (271) Department of Thoracic/Head and Head and Neck Surgery, Karmanos Cancer Institute, Neck Medical Oncology, The University of Texas M.D. Wayne State University, Detroit, Michigan 48201 Anderson Cancer Center, Houston, Texas 77030 Urjeet Patel (433) Department of Otolaryngology, Harold Kim (9) Department of Radiation Oncology, Washington University, .tS Louis, Missouri 63110 Karmanos Cancer Institute, Wayne State University, Vyomesh Patel (509) Oral and Pharyngeal Cancer Branch, Detroit, Michigan 48201 National Institute of Dental and Craniofacial Research, S. Kim (151) Department of Otolaryngology and National Institutes of Health, Bethesda, Maryland 20892 Communication Sciences, SUNY Upstate Medical Tomasz Pawlowski (569) Department of Pathology, University, Syracuse, New York 13210 University of California, Irvine, College of Medicine, Wayne M. Koch (305,523) Department of Otolaryngologym Orange, California 92868 Head and Neck Surgery, Johns Hopkins University Jay PiceirUlo (433) Department of Otolaryngology, School of Medicine, Baltimore, Maryland 21286 Washington University, .tS Louis, Missouri 63110 Randall H. Kramer (65) Oral Cancer CentermDepartment Catherine Poh (245) School of Kinesiology, Simon Fraser of Stomatology, School of Dentistry, University of University, Burnaby, British Columbia, Canada V5A 6S1 California, San Francisco, San Francisco, California and Faculty of Dentistry, University of British Columbia, 94143 Vancouver, British Columbia, Canada V6T 3Z1 Omer Kucuk (201) Karmanos Cancer Institute, Wayne Ananda Prasad (201) Karmanos Cancer Institute, Wayne State University, Detroit, Michigan 48201 State University, Detroit, Michigan 48201 Stephen .Y Lai (405) Department of Otolaryngology~ K. Thomas Robbins (393) Department of Otolaryngologym Head and Neck Surgery, University of Pennsylvania Head and Neck Surgery, University of Florida, Medical Center, Philadelphia, Pennsylvania 19104 Gainesville, Florida J. Jack Lee (287) Department of Biostatistics, The Miriam R. Rosin (245) British Columbia Cancer University of Texas M.D. Anderson Cancer Center, Agency/Cancer Research Centre, Vancouver, British Houston, Tesax 77030 Columbia, Canada V5Z 4E6 and School of Kinesiology, Simon Fraser University, Burnaby, British Columbia, Chidchanok Leethanakul (509) Oral and Pharyngeal Canada V5A 1 $6 Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, A. Rustgi (57) Laboratory of Molecular Pathology, Harvard Bethesda, Maryland 20892 University, School of Dental Medicine, Boston, Massachusetts 02115 Caryn Lerman (185) University of Pennsylvania Health Sciences, Philadelphia, Pennsylvania 19104 .W Sakr (35) Department of Pathology, Wayne State University, School of Medicine, Detroit, Michigan 48201 .F Lonardo (35) Department of Pathology, Wayne State University, School of Medicine, Detroit, Michigan 48201 Naomi R. Schechter (445) Department of Radiation Oncology, The University of Texas M.D. Anderson Val J. Lowe (23) Department of Radiology, Mayo Clinic Cancer Center, Houston, Texas 77030 and Foundation, Rochester, Minnesota 55905 Robert A. Schnoll (185) Fox Chase Cancer Center, Lawrence G. Lum (569) Roger Williams Cancer Center, Cheltenham, Pennsylvania 19012 Providence, Rhode Island 02908 Crispian Scully (117) Eastman Dental Institute for Oral Z. Maciorowski (167) Institut Curie, Paris 75005, France Health Care Sciences, University College London, Susan .T Mayne (261) Department of Epidemiology and University of London, London WC1X 8LD, United Public Health,Yale University School of Medicine, New Kingdom Haven, Connecticut 06520 Adrian M. Senderowicz (535) Molecular Therapeutics Jesus E. Medina (317) Department of Otorhinolaryngology, Unit, Oral and Pharyngeal Cancer Branch, National The University of Oklahoma Health Sciences Center, Institute of Dental and Craniofacial Research, National Oklahoma City, Oklahoma 43190 Institutes of Health, Bethesda, Maryland 20892 srotubirtnoC VX Terry Y. Shibuya (339, 569) Department of Carter Van Waes (535) National Institute of Deafness and Otolaryngology--Head and Neck Surgery and the Chao Communication Disorders, National Institutes of Health, Family Comprehensive Cancer Center, University of Bethesda, Maryland 20892 California, Irvine, College of Medicine and Robert E. Watson, Jr. (23) Department of Radiology, Mayo Craniofacial/Skull Base Surgery Center, University of Clinic and Foundation, Rochester, Minnesota 55905 California, Irvine, Medical Center, Orange, California 92868 Randal S. Weber (405) Department of Otolaryngology~ Head and Neck Surgery, University of Pennsylvania Peter Shields (213) Cancer Genetics and Epidemiology Medical Center, Philadelphia, Pennsylvania 19104 Program, Lombardi Cancer Center, Georgetown University Medical Center, Washington, DC 2007 Qingyi Wei (213) Department of Epidemiology, The University of Texas M.D. Anderson Cancer Center, E.J. Shillitoe (151) Department of Microbiology and Houston, Texas 77030 Immunology, SUNY Upstate Medical University, Syracuse, New York 13210 Gregory S. Weinstein (375) Department of Otolaryngology~ Head and Neck Surgery, The Center of Head and Neck G. Shklar (57) Laboratory of Molecular Pathology, Harvard Cancer, The University of Pennsylvania Medical Center, University, School of Dental Medicine, Boston, Philadelphia, Pennsylvania 19104 Massachusetts 02115 Jack Shohet (339) Department of OtolaryngologymHead Anton Wellstein (81) Lombardi Cancer Center, Georgetown University, Washington, DC 20007 and Neck Surgery, University of California, Irvine, College of Medicine and Craniofacial/Skull Base Surgery Theresa L. Whiteside (569) Departments of Center, University of California, Irvine, Medical Center, OtolaryngologymHead and Neck Surgery and Pathology, Orange, California 92868 Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania 31251 David Sidransky (305) Department of Otolaryngology~ D. .T Wong (57) Laboratory of Molecular Pathology, Head and Neck Surgery, Johns Hopkins University Harvard University, School of Dental Medicine, Boston, School of Medicine, Baltimore, Maryland 21286 Massachusetts 02115 Margaret R. Spitz (213) Department of Epidemiology, The Katharine H. Wrighton (101) Molecular Carcinogenesis University of Texas M.D. Anderson Cancer Center, Group, Head and Neck Cancer Program, Guy's King's and Houston, Texas 77030 .tS Thomas' Schools of Medicine and Dentistry, King's Brendan C. Stack, Jr. (23) Department of College London, London 1ES 9RT, United Kingdom OtolaryngologymHead and Neck Cancer, Pennsylvania .W Andrew Yeudall (101) Molecular Carcinogenesis Group, State University, College of Medicine, Hershey, Head and Neck Cancer Program, Guy's King's and Pennsylvania .tS Thomas' Schools of Medicine and Dentistry, King's Erich M. Sturgis (213) Department of Epidemiology, The College London, London 1ES 9RT, United Kingdom University of Texas M.D. Anderson Cancer Center, George H. ooY (329, 555) Department of Otolaryngology-- Houston, Texas 77030 Head and Neck Surgery, Karmanos Cancer Institute, Hideki Tanzawa (117) Department of Oral Surgery, Chiba Wayne State University, Detroit, Michigan 48201 University, Chiba 260-8670, Japan Lewei Zhang (245) Faculty of Dentistry, University of Elena Tassi (81) Lombardi Cancer Center, Georgetown British Columbia, Vancouver, British Columbia, Canada University, Washington, DC 20007 V6T 3Z1 R. Todd (57) Laboratory of Molecular Pathology, Harvard Barry L. Ziober (65) Department of Otorhinolaryngology-- University, School of Dental Medicine, Boston, Head and Neck Surgery, University of Pennsylvania, Massachusetts 02115 Philadelphia, Pennsylvania 19104 Foreword You hold in your hands an important new volume detailing You will find here a highly comprehensive review of the the most advanced, cutting-edge research that is changing state-of-the-art clinical, basic, and translational research in the way we diagnose, treat, and prevent head and neck this area, with contributions from some of today's most cancer. These cancers are among the leading cause of death esteemed head and neck cancer scientists. I recommend that from cancer worldwide, and the survival rate has stubbornly it is worthwhile to purchase it, read it, and keep it on your refused to change to any significant degree. However, new bookshelf for frequent reference. It's a guide to the most approaches are finally beginning to offer realistic hope for effective, cutting-edge treatments available today, and a map improvement in these patients' survival rates and in their to the future of head and neck cancermto the prevention, early quality of life. detection, diagnosis, treatment, and survival of our patients. Waun Ki Hong, M.D. Head, Division of Cancer Medicine Chair, Department of Thoracic/Head and Neck Medical Oncology M. D. Anderson Cancer Center llVX ~176 C H A P T E R 1 Clinical Perspectives in Head and Neck Cancer JOHN F. ENSLEY Department of Medicine, Oncology, and Otolaryngology--Head and Neck Surgery Karmanos Cancer Institute Wayne State University Detroit, Michigan 48201 I. Clinical Patterns in Head and Neck Cancer molecular genetic mechanisms involved. The potential value .A TNM Differences 3 of these clinical observations for translational and basic can- .B Histopathology Differences 4 cer research is underappreciated and clearly underutilized. In .C Treatment Outcome Differences 4 the past, justified limitations on experimental research in .D Correlative Parameters and Outcome 5 humans may have precluded such a direct study of these dis- II. Human Cancer Surrogates and Models 5 eases 2. However, with today's sophisticated, relatively non- III. Translational or Correlative Cancer Research invasive sampling procedures and a patient population that is IV. Conclusion 6 usually willing to participate, cancer research can and should References 7 move closer to the direct study of these diseases rather than using nonrepresentative surrogates and nonvalidated models. The following are a few illustrative examples, many of which will be addressed more thoroughly in the chapters in this text. At first glance, head and neck cancers appear to be a heterogeneous group of tumors consisting of multiple histopathologies, primary sites, TNM stages, natural histo- I. CLINICAL PATTERNS IN ries, and treatment outcomes 1. However, as one gains clin- HEAD AND NECK CANCER ical experience with these cancers, predictable and stable groupings, with recognizable patterns of tumor/host behavior, A. TNM Differences emerge. For example, approximately 70% of patients with stage T2N0 squamous cell carcinomas (SCC) of the endolar- What factors determine the TNM stage of a patient's ynx are cured when treated with full course, conventionally tumor when they present with their head and neck cancers? administered, radiation therapy and 30% are not. Such obser- Certainly time can be implicated in accounting for such vations suggest that there are fundamental differences in the differences. Patient delay in seeking treatment and their dif- mechanisms that control the phenotypic expression of these ferences in tolerance thresholds for noxious symptoms are tumor subgroups and that these differences are not evident at clearly important in this respect. Moreover, certain primary the time the disease is diagnosed. Because these variations in sites, such as the endolarynx, tend to be detected earlier due the natural history and treatment outcome certainly result to their anatomy and the subsequent early disruption of func- from differences in underlying pathophysiological mecha- tion, whereas tumors such as pyriform sinus, supraglottic lar- nisms, they provide a unique and identifiable opportunity for ynx, and base of tongue tend to present at a later stage. Time experimental investigation. Unfortunately, such clinical alone, however, does not adequately account for the spectrum observations rarely become the basis for experimental study, of TNM stages observed at presentation. The inexperienced and when they do, they are rarely performed with the rigor clinician is often skeptical when confronted with a patient and thoroughness required to shed light on the underlying who claims that their N3 neck mass was not present a few Copyright 2003, Elsevier Science (USA). daeH dna kceN recnaC All rights reserved. 4 .i Introduction weeks ago, but such skepticism dissipates rapidly when an predictive of the natural or treatment outcome for patients N1 neck node is actually observed to progress to the N3 stage with SCCHN 9. However, local tumor-host features, such as in a week following diagnosis. The degree and rate at which tumor-stromal borders, pattern of invasion, degree of stromal a tumor progresses are determined mainly by molecular- or inflammatory response, access to microvasculature, or vas- genetic factors that control the (1) rate of local growth and cularity (angiogenesis) and extracapsular lymph node involve- invasion, which involves the induction of angiogenesis and ment 10,11, have been shown to have a marked effect on the adequate stromal substructure formation; (2) ability of the ability to achieve and determine negative margins at surgery cancer cells to migrate to and access local vasculature (motil- and the subsequent rates of local relapse and cure. The subse- ity and diapedesis); and (3) ability of cancer cells to survive quent local recurrence rates are two to three times higher in and exit the vasculature and implant at distant sites, which for patients in surgical series who present with histological also involves the successful induction of angiogenesis and "high-risk" histological phenotypes, and the survival is only adequate stromal substructure formation at the distant site. one-third to one-half as good as those that do not have such During this process, to be successful, tumors must deploy features 12,13. However, conventional grading is extremely or develop mechanisms to suppress the local and systemic significant for salivary gland tumors, such as adenocarcino- host immune systems. At one end of this spectrum are the mas and mucoepidermoid carcinomas, where high-grade or unresectable, massive "T4" cancers that invade through mul- poorly differentiated lesions commonly recur very often with tiple local tissue and bony barriers, including complex vas- distant metastases 14-16. Perhaps the most intriguing tumor culature, but do not, or cannot, develop regional or distant among all human cancers is the subset of salivary gland metastatic disease 1 . At the other end are patients with SCC tumors with adenoidcystic histopathology 17. It is common of unknown primary. In these instances, cells, which, by def- for these tumors to either present with or later evolve distant inition, do not or cannot propagate or invade sufficiently lung, bone, and liver metastases. Distant metastases may to be detected at their site of origin, can and do access local remain undetected clinically for years or even decades. vasculature, disseminate, implant, and often progress vigor- Occasionally, these metastases, once documented, may persist ously at regional and distant sites 3. Implications for the for decades, with minimal morbidity to the host. How these inherent biological differences between these two well- cancers and their host remain in such a symbiosis for decades recognized tumor groups, and the potential they provide for is unclear and unique in cancer. The unique biological aspects studying cancer mechanisms, are extraordinary. of these tumors and their host-tumor relationships have not Other examples, illustrative of observations that raise been the subjects of adequate scientific investigation. similar opportunities for investigation, include the difference in the rate of distant metastases, which are a feature at pres- C. Treatment Outcome Differences entation or recurrence in SCC of the nasopharynx, as opposed to other squamous cell carcinomas of the head and neck Why do subsets of patients with tumors in seemingly (SCCHN) 4, the relatively high distant metastatic rate for homogeneous clinical subgroups behave so differently fol- paranasal sinus carcinomas 5, and, most recently, the site- lowing treatment? This is true regardless of which modality specific difference in the rate and type of the secondary upper is chosen as the initial therapy. The ability to achieve micro- aerodigestive tract, which can be associated with the site of the scopically negative surgical margins is possible in nearly original primary tumor 6. Finally, the clinical implications, 100% of early staged SCCHN and the majority of patients particularly the risk of distant metastases, for local/regional with advanced, resectable tumors 7. Although microscopi- lymph node involvement in SCCHN are substantially different cally negative surgical margins remain the hallmark of suc- when compared with other carcinomas, such as breast, lung, cessful surgery, when achieved, substantial percentages of prostate, melanoma, and colon. Even with advanced N2C and patients still fail locally with increasing frequency as the N3 lymph node status, a substantial proportion of these TNM stage increases 1,7. Although this observation has patients can still be cured with local modalities alone 7. Are been made repeatedly for decades, it is only recently that these lymph nodes in this region more efficient as "traps" or is studies have demonstrated that negative histological margins it that the biology of SCCHN itself is different? Does this are not negative "molecular margins" and that histologically explain the relatively good outcome for patients with SCCHN normal-appearing tissue may be molecularly/genetically of unknown primary as compared to other types of unknown fated to become malignant or may be malignantly trans- primaries, such as adenocarcinomas or nonhead and neck formed already 18. SCC of unknown primary 8? Similar examples can be provided for patients treated initially with radiation therapy. Clearly, tumor oxygenation and whether there is an intact mechanism for programmed .B Histopathology Differences cell death following lethal radiation are keys to the suc- The microscopic appearance of the tumor, as described cess or failure when radiotherapy is employed 19,20. by the conventional morphological grade, is not particularly However, these two factors alone cannot account for the .1 Clinical Perspectives 5 broad differences in treatment outcome seen in early staged, few instances where newer parameters, such as p53 muta- T1 and T2 ON tumors. tion or functional status, have been evaluated more exten- The emergence of chemotherapy as the primary treat- sively, conflicting results have been published 36-38. ment for patients with SCCHN, first in recurrent tumors 12 , These conflicting results raise another concern about valida- then in advanced, unresectable disease 22, and now in tion of another sort; i.e., tumor preparative and experimental organ preservation strategies 23,24, has also produced out- technique methodology validation, which is required before come subgroups that are not evident before treatment. Even routine research with new parameters and technologies is with the best regimens, 10-20% of previously untreated performed 39-41 . This is rarely if ever done and accounts SCCHN patients will not respond or actually progress on for the considerable "noise" in the literature concerning the treatment, 50% will not achieve a complete clinical remis- clinical value of such correlative research. sion, and no more than 25-30% have histologically negative cytotoxic responses. Each of these subgroups, defined by treatment outcome, has dramatically different survival char- I!. HUMAN CANCER SURROGATES acteristics 25,26. It is also clear from organ preservation AND MODELS strategies that substantial differences in clinical complete response rates are specific for the primary tumor site 24,25. Experimental models are employed in scientific research As the current treatment for patients with advanced as substitutes for the subject or object of the research when SCCHN is often multimodality, it is becoming more difficult such subjects are not available or cannot be used. To the to sort out these patterns of failure, and some of these sub- extent that such models do not represent the subjects or phe- groups tend to blur or disappear. For example, organ preser- nomenon under investigation, the research conclusions suf- vation approaches have been developed on the principle that fer proportionately. This is true regardless of how carefully patients failing to achieve at least a partial clinical response the work is done or how sophisticated the technology uti- with induction chemotherapy can only be salvaged with sur- lized. Laboratory models employed to investigate human gery 27,28. However, the use of sequential concurrent cancers are of three major types. chemo/radiation following induction therapy has changed this algorithm 29. Finally, and most importantly, regardless .1 In vitro and in vivo, nonhuman (usually murine) sys- of which modality is used initially, it is not clear that the tems. These models exist as either in vivo nonhuman cell same subpopulation of patients are cured with each modality. lines or tissue models 42-45. These tumors are almost If indeed they are different populations, as some correlative always induced in syngeneic animals rather than sponta- studies have suggested 30,31, how are they different and to neously occurring and, other than microscopic appearance, what extent? This has important implications for individual- bare little clinical resemblance to their human counterparts. izing patient therapy, increasing the overall cure rates for The use of syngeneic animals, inbred for decades, further patients with SCCHN, and understanding the underlying distances these models from the genetic heterogeneity and mechanisms that regulate the behavior of these tumors. complexity with which human tumors arise. 2. More recently, cell lines derived from human cancers have become models for human cancer 46,47. They suffer D. Correlative Parameters and Outcome from the same limitations as any cell line in that most human Few, if any, correlative parameters have been tested thor- cancers, except for leukemia, are tissues with all the inher- oughly and adequately enough in SCCHN clinical trials to be ent additional complexities inherent in tissues, organs, and considered validated and prospectively useful 30,31. Most organisms. Often these lines are passaged for decades (MCF correlative studies are single institution trials, which, more 7, HeLa cells). More recently, three-dimensional human often than not, produce conflicting results. In SCCHN, the tumor models (organotypic or raft cultures) derived from most commonly studied correlative laboratory parameter has human tumors have been developed 48,49. Although they been DNA content (DNA ploidy and %S phase fraction), are derived from human cancers and often have similar most often determined by flow cytometry. These parameters appearances, they may not represent human tumors any bet- have undergone large numbers of single institutional investi- ter than other models, particularly because the important gations over a period of decades and, most recently, validation tumor-host interaction is still missing. at the cooperative and intergroup phase III level 30,31. Other 3. Often human tumor cell lines are transplanted into experimental parameters, including p53, epidermal growth immune-suppressed murine systems in an attempt to simu- factor (EGF), chromosomal polysomy, loss of heterozygosity late an in vivo system 50,51, but again, these models are at 3p or 9p, C-erbB2 expression, Ki67 expression, tumor orders of magnitude removed from the spontaneously occur- angiogenesis, cell cycle (cyclin pathway) regulatory aberra- ring cancers arising in the genetically heterogeneous and tions, and integrity of apoptotic pathways, have only been immunocompetent human population. However, because studied anecdotally in small, preliminary trials 32-35. In the they are derived from human cancers, grow as tissues, have 6 .i Introduction three dimensions, and interact with an intact organism, it is method 56-58. Its components include (1) an observa- at least possible to compare some features with human tion, (2) the generation of a hypothesis to be tested based tumors in vivo for model validation such as histopathology, on the observation, (3) the development and validation of local regional invasion, and metastatic potential. an experimental design and methodology to test the hypothesis, (4) the conduct of the experiment, (5) data A potential, but unused, resource for experimental and gathering and analysis, and (6) conclusions derived from clinical cancer research exists in spontaneously occurring data regarding the hypothesis, which is relevant to the cancers in household or domesticated animals 52. Indeed, observation. in this population, which numbers in the millions, sponta- This is basically a unidirectional system and one that neous cancers occur at approximately the same rate as in the works best when not begun in the middle or run back- humans. Unfortunately, the more common cancers, with the ward! The observational step of the scientific method is, exception of canine breast cancer, occur with much less fre- and has usually been, the critical starting point for most quency than in humans (lung, prostate, and gastrointestinal). clinically relevant medical research. It is always the anvil This is an untapped potential resource for studying sponta- on which any and all conclusions must ultimately be tested neously arising cancers in more genetically diverse and less 56. Without this component, data derived from labo- inbred animals. ratory experiments "dangle" without meaningful context. This leads to the most important aspect of model use in Unfortunately, much, if not most, experimental cancer experimental research. As stated previously, model use research currently falls into this category. It seems intu- should be restricted to those instances in which the actual itive that when the goal of an investigation is the study of subject of the experiment is not available or cannot be used. human cancer, human cancer must be included somewhere Given the current state of human correlative research, it is in the process 2. While it is becoming fairly common for becoming increasingly difficult to argue that such subjects clinical cancer scientists to spend substantial portions of are not available. When and if it is proposed that models must their training time in gaining experimental laboratory substitute for the subject under investigation, it is imperative experience, it is still quite rare for basic cancer scientists that the models be validated before their use. In laboratory to spend comparable periods during their training learning cancer research, cancer models are rarely validated and, about human cancer in the clinic. Clinical observations more importantly, attempts to validate them are never under- provide the scaffolding on which laboratory data can be taken; i.e., attempts must be made to determine with what organized in a meaningful manner. As the eminent cancer fidelity these models represent the spectrum of natural history researcher Van Rensselaer Potter opined over a decade and biology seen in a particular human cancer. Humbling ago as he anticipated the emerging human molecular- reminders of these differences have come from experiences genetic revolution, "...the assumption that the total such as during the "stem cell assay" era 53 where investi- sequencing of the normal human genome will tell us how gators often found it impossible to grow a human cancer line life is organized can only lead to a technologic blitzkrieg in vitro while, simultaneously, finding it impossible to stop that will produce more descriptive data than the comput- its growth in the human host from which it was derived! erized human mind can organize into a blueprint for life-- unless some cybernetics system...is used as a scaffolding" .111 TRANSLATIONAL OR CORRELATIVE 59,60. Therefore, the "closing of the loop" of the scien- CANCER RESEARCH tific method, if you will, can and should be practiced as religiously as possible in experimental cancer research. The terms translational or correlative research are meant to represent that area of cancer research that brings together clinical observations, laboratory research, and the applica- IV. CONCLUSION tion of the product of this interaction for the treatment of patients with cancer 54. This process also implies the It is highly unlikely that models that faithfully represent potential to individualize treatment strategies that are the broad spectrum of biology seen in human cancers, in its tailored to the patient's tumor biology 55. However, entirety, will ever be created. This will certainly be unlikely for where is the optimum point, if any, to initiate this process? as long as the observational background required for their While important and valid molecular-genetic observations development, which can be provided only by the clinical are often made at cellular and subcellular levels in the knowledge of the spectrum and diversity of these diseases, is laboratory, how such observations become properly inte- lacking in the formulation and validation of such models. It is grated into the extraordinary complex panorama of human therefore imperative that basic researchers and clinicians cancer is often problematic. Guidelines for research that involved in human cancer research work closely in multi- have evolved over the centuries have culminated in an disciplinary teams. Cross training and continual learning for agreed upon format generally referred to as the scientific both clinical and basic scientific specialties in a multimodality .1 Clinical Perspectives 7 environment will be critical for translational strategies to .61 Spiro, R. H., Huvos, A. G., Berk, R, Strong, E. .W (1978). Muco- reach their full potential. It is also critical that natural exper- epidermoid carcinoma of salivary gland origin. A clinicopathologic study of 367 cases. Am. .J Surg. 136, 461-468. iments in human cancer, detected and catalogued by clinical .71 Spiro, R. H., Huvos, A. G., and Strong, E. .W (1979). Adenoid cystic observation, become the focused subject of experimental carcinoma: Factors influencing survival. Am. .J Surg. 138, 579-583. research whenever and to whatever extent possible. .81 Koch, .W M., Brennan, J. A., Zahurak, M., Goodman, .S N., Westra, .W H., Schwab, D., Yoo, G. H., Lee, D. J., Forastiere, A. A., and Sidransky, D. (1996). p53 mutations and locoregional treatment failure in head and neck squamous cancer. J. Natl. Cancer Inst. 88, References 1580-1586. .91 Vanselow, B., Eble, M. J., Ruda, ,.V Wollensack, ,.P Conradt, C., and .1 A1-Sarraf, M., Kish, J. A., and Ensley, J. .F (1991). The Wayne State Dietz, A. (2000). Oxygenation of advanced head and neck cancer: University experience with adjuvant chemotherapy of head and neck prognostic marker for the response to primary radiochemotherapy. cancer. Hem/Oncol. Clin. North Am. 5(4), 687-700. Otolaryngol. Head Neck Surg. 122, 856-862. .2 Ensley, J. E (1993). Molecular Medicine, the forests, trees, and leaves. 20. Shintani, S., Mihara, M., Nakahara, ,.Y Terakado, N., Yoshihama,Y., Arch. Otolaryngol. Head Neck Surg. 119, 1173-1177. Kiyota, A., Ueyama. ,.Y and Matsumura, .T (2000). Apoptosis and p53 .3 de Braud, E, Heilbrun, L. K., Ahmed, K., Sakr, ,.W Ensley, J., Kish, J., are associated with effect of preoperative radiation in oral squamous Tapazoglou, E., and A1-Sarraf, M. (1989). Squamous cell carcinoma of cell carcinomas. Cancer Lett. 154, 71-77. unknown primary metastatic to the neck: Advantages of an aggressive 21. Amer, M.H, A1-Sarraf, M., and Vaitkevicius, .V K. (1979). Factors that treatment. Cancer 64, 510-515. affect response to chemotherapy and survival of patients with advanced 4. Ensley, J. E, Kim, H., and Yoo, G. (2001). Locally advanced nasopha- head and neck cancer. Cancer 43, 2202-2206. ryngeal carcinoma. Curr. Treat. Opin. Oncol. 2, 15-23. 22. Amer, M. H., Izbick, R. M., Vaitkevicius, .V K., and A1-Sarraf, M. .5 LoRusso, ,.P Tapazoglou, E., Kish, J. A., Ensley, J. E, Cummings, G., (1980) Combination chemotherapy with cis-diamminedichloroplat- Kelly, J., and A1-Sarraf, M. (1988). Chemotherapy for paranasal sinus inum, oncovin, and bleomycin (COB) in advanced head and neck carcinoma: A ten-year experience at Wayne State University. Cancer cancer: Phase II. Cancer 45, 217-223. 62, 1-5. 23. (1991). Induction chemotherapy plus radiation compared with surgery .6 Kim, E. S., Khuri, E R., Lee, J. J., Winn, R, Cooper, J. M., Fu, K, plus radiation in patients with advanced laryngeal cancers. N. Engl. .J Lippman, S. M., Vokes E. E., Pajak, .T E, Goepfert, H., and Hong .W K. Med. 324, 1685-1690. (2000). Second primary tumor incidence related primary index tumor 24. Lefebvre, J. L., Chevalier, D., Luboinski, B., Kirkpatrick, A., Collette, and smoking status in a randomized chemoprevention study of head L., and Sahmoud, .T (1996). Larynx preservation in pyriform sinus and neck squamous cell cacner. Proc. ASCO 19, 1642 Abstract. cancer: Preliminary results of a European Organization for Research 7. Looser, K. G., Shah, J. ,.P Strong, E. ,.W Salesiotis, A. N., and Cullen, and Treatment of Cancer phase III trial. EORTC Head and Neck K. J. (1978). The significance of "positive" margins in surgically resected epidermoid carcinomas. Head Neck Surg. ,1 107-111. Cancer Cooperative Group. J. Natl. Cancer Inst. 88, 890-899. .8 Spiro, R. H., DeRose, G., and Strong, E. .W (1983). Cervical node 25. Rooney, M., Kish, J., Jacobs, J., Kinzie, J., Weaver, A., Crissman, J., metastasis of occult origin. Am. .J Surg. 146, 441--446. and A1-Sarraf, M. (1985). Improved complete response rate and sur- 9. Ensley, J., Crissman, J., Kish, J., Jacobs, J., Weaver, A., Kinzie, J., vival in advanced head and neck cancer after three-course induction Cummings, G., and A1-Sarraf, M. (1986). The impact of morphologi- therapy with 120-hour 5-FU infusion and cisplatin. Cancer 55, cal analysis on response rates and survival in patients with squamous 1123-1128. cell cancer of the head and neck. Cancer 57, 711-717. 26. A1-Kourainy, K., Kish, J. A., Ensley, J. E, Tapazoglou, E., Jacobs, J., .01 Ensley, J., Crissman, J., Kish, J., Weaver, A., Jacobs, J., Cummings, G., Weaver, A., Crissman, J., Cummings, G., and A1-Sarraf, M. (1987). and A1-Sarraf, M. (1989). The correlation of individual parameters of Achievement of superior survival for histologically negative vs histo- tumor differentiation with response rate and survival in patients with logically positive clinically complete responders to cisplatinum combi- advanced head and neck cancer treated with induction therapy. Cancer nation in patients with locally advanced head and neck cancer. Cancer 63, 1487-1492. 59, 233-238. .11 Sakr, ,.W Hassan, M., Zarbo, R., Ensley, J., and Crissman, J. D. (1989). 27. Ensley, J., Jacobs, J., Weaver, A., Kinzie, J., and A1-Sarraf, M. (1984). DNA quantitation and histologic characteristics of squamous cell car- The correlation between response to cisplatinum combination cinomas of the upper aerodigestive tract. Arch. Pathol. Lab. Med. 113, chemotherapy and subsequent radiotherapy in previously untreated 1009-1014. patients with advanced squamous cell cancers of the head and neck. .21 Laramore, G. E., Scott, C. B., A1-Sarraf, M., Haselow, R. E., Ervin, Cancer 54, 811-814. .T J., Wheeler, R., Jacobs, J.R, Schuller, D. E., Gahbauer, R. A., and 28. Ensley, J. E, Kish, J. A., Jacobs, J., Weaver, A., Crissman, J., and AI- Schwade, J. G. (1992). Adjuvant chemotherapy for resectable squa- Sarraf, M. (1984). Incremental improvements in median survival asso- mous cell carcinomas of the head and neck: Report on intergroup study ciated with degree of response to adjuvant chemotherapy in patients 0034. Int. .J Radiat. Oncol. Biol. Phys. 23, 705-713. with advanced squamous cell cancer of the head and neck. In .31 Looser, K. G., Shah, J. ,.P and Strong, E. .W (1978). The significance "Adjuvant Therapy of Cancer" (S. E. Jones and S. E. Salmon, eds.), of positive margins in surgically resected epidermoid carcinomas. Vol. ,VI pp. 117-126. Grune & Stratton, Orlando, FL. Head Neck Surg. ,1 107-111. 29. Ensley, J., Ahmad, K., Kish, J., Tapazoglou, E., and A1-Sarraf. M. .41 Hoffman, H. ,.T Karnel, L. H., Robinson, R. A., Pinkston J. A., (1990). Salvage of patients with advanced squamous cell cancers of the and Menck, H. R. (1999). National Cancer Data Base report on head and neck (SCCHN) following induction chemotherapy failure cancer of the head and neck: Acinic cell carcinoma. Head Neck 21, using radiation and concurrent cisplatinum (CACP). In "Adjuvant 297-309. Therapy of Cancer" (S. E. Salmon, ed.), Vol. VI, pp. 92-100. Saunders, .51 Hicks, M. J., el-Naggar, A. K., Flaitz, C. M., Luna, M. A., and Batsakis, New York. J. G. (1995) Histocytologic grading of mucoepidermoid carcinoma of 30. Ensley, J., and Maciorowski M. (1994). Clinical application of DNA major salivary glands in prognosis and survival: A clinicopathologic content parameters in patients with squamous cell carcinomas of the and flow cytometric investigation. Head Neck 17, 89-95. head and neck. Semin. Oncol. 21, 330-339. 8 I. Introduction 31. Ensley, J. E (1996). The clinical application of DNA content and 44. Hier, M.E, Black, M. J., Shenouda, G., Sadeghi, N., and Karp, S. E. kinetic parameters in the treatment of patients with squamous cell car- (1995). A murine model for the immunotherapy of head and neck squa- cinomas of the head and neck. Cancer Metast. Res. 15, 133-141. mous cell carcinoma. Laryngoscope 10, 1077-1080. 32. Salesiotis, A. N., and Cullen, K. J. (2000). Molecular markers predic- 45. Sung, M. W., Lee, S. G., Yoon, S. J. Lee, H. J., Heo, D. S., Kim. K. H., tive of response and prognosis in the patient with advanced squamous Koh, T. Y., Choi, S. H., Park, S. W., Koo, J. W., and Kwon, .T .Y (2000). cell carcinoma of the head and neck: Evolution of a model beyond Cationic liposome-enhanced adenoviral gene transfer in a murine head TNM staging. Curr. Opin. Oncol. 12, 229-239. and neck cancer model. Anticancer Res. 20(3A), 1653. 33. Chiesa, E, Mauri, S., Tradati, N., Calabrese, L., Giugliano, G., 46. Cardinalli, M., Pietraszkiewicz, H., Ensley, J. E, and Robbins, K. C. Ansarin, M., Andrle, J. Zurrida, S., Orecchia, R., and Scully, C. (1999). (1995). Tyrosine phosphorylation as a marker for aberrantly regulated Surfing prognostic factors in head and neck cancer at the millennium. growth promoting pathways in cells derived from head and neck Oral Oncol. 35, 590-6. malignancies. Int. .J Cancer 61, 98-103. 34. Liu, M., Weynand, B., Delos, M., and Marbaix, E. (2000). Prognostic 47. Shridhar, R., Shridhar, V., Rivard, S., Siegfried, J. M., Pietraszkiewicz, factors in squamous cell carcinomas of the head and neck. Cancer .J H., Ensley, J. E, Pauley, R., Grignon, D., Sakr, W., Miller, O. J., and Sci. Am. 6, 2-10. Smith, D. I. (1997). Mutations in the arginine-rich protein (ARP) gene 35. Tralongo, V., Rodolico, V., Luciani, A., Marra, G., and Daniele, E. in lung, breast prostate cancers and in squamous cell carcinomas of the (1999). Prognostic factors in oral squamous cell carcinoma. A review head and neck. Cancer Res. 56, 5576-5578. of the literature. Anticancer Res. 19, 3503-3510. 48. Park, N. H., Gujuluva, C. N., Baek, J. H., Cherrick, H. M., Shin, K. H., 36. Chomchai, J. S., Du, W., Sarkar E H., Li, .Y W., Jacobs, J. R., Ensley, and Min, B. M. (1995). Combined oral carcinogenicity of HPV-16 and J.F, Sakr, W., and Yoo, G. H. (1999). Prognostic significance benzo(a)pyrene: An in vitro multistep carcinogenesis model. Oncogene of p53 gene mutations in laryngeal cancer. Laryngoscope 109, 10, 2145-2153. 455-459. 49. Eicher, S. A., Clayman, G. L., Liu, .T J., Shillitoe, E. J., Storthz, K. A., 37. Narayana, A., Vaughan, A. T., Kathuria, S., Fisher, S. G., Walter, S. A., Roth, J. A., and Lotan, R. (1996). Evaluation of topical gene therapy and Reddy, S. E (2000). P53 overexpression is associated with bulky for head and neck squamous cell carcinoma in an organotypic model. tumor and poor local control in T 1 glottic cancer. Int. .J Radiat. Oncol. Clin. Cancer. Res. 10, 1659-1666. Biol. Phys. 46, 21-26. 50. Yeudall, W. A., Jakus, J., Ensley, J., and Robbins, K. C. (1997). 38. Bradford, C. R., Wolf, G. T., Carey, .T E., Zhu, S., Beals, .T E, Functional characterization of p53 molecules expressed in human Truelson, J. M., McClatchey, K. D., and Fisher, S. G. (1999). Pre- squamous cell carcinomas. Mol. Carcinogen. 18, 89-96. dictive markers for response to chemotherapy, organ preservation, and 51. Cardinali, M., Kratochvil, J., Ensley, J. F., Robbins, K. C., and Yeudall, survival in patients with advanced laryngeal carcinoma. Otolaryngol. W. A. (1997). Functional characterization in vivo of mutant p53 mole- Head Neck Surg. 121, 534-538. cules derived from squamous cell carcinomas of the head and neck. 39. Hitchcock, C., Zalupski, M., and Ensley, J. (1995). Solid tumor Mol. Carcinogen. 18, 78-88. preparative technology, In "Cytometry 2000. Flow Cytometric 52. Gardner, D. G. (1996). Spontaneous squamous cell carcinomas of the Analysis of Solid Tumors" (A. Nakeff, .F Valeriote, J. Crissman, S. oral region in domestic animals: A review and consideration of their Lerman, and J. Ensley, eds.), pp. 95-124. Kluwer Academic, relevance to human research. Oral Dis. 2,148-154. Boston, MA. 53. Hamburger, A. W., and Salmon, S. E. (1977). Primary bioassay of 40. Ensley, J. E, Maciorowski, Z., Pietraszkiewicz, H., Klemic, G., human tumor stem cells. Science 197, 461-463. KuKuruga, M., Sapareto, S., Corbett, T., and Crissman, J. D. (1989). 54. Chabner, B. A., Boral, A. L., and Multani, E (1998). Translational Solid tumor preparation for flow cytometry using a standard murine research: walking the bridge between idea and cure--seventeenth tumor model. Cytometry 8, 479-487. Bruce E Cain Memorial Award lecture. Cancer Res. 58, 4211-4216. 41. Ensley, J., Maciorowski, Z., Hassan, M., Pietraszkiewicz, H., Sakr, W., 55. Bartelink, H., Begg, A. C., Martin, J. C. van Dijk, M. Moonen, L., van't and Hielbrun, L. (1993).Variations in DNA aneuploid cell content Veer, L. J., Van de Vaart, ,.P and Verheij, M. (2000). Translational during tumor dissociation in human colon and head and neck cancers research offers individually tailored treatments for cancer patients. analyzed by flow cytometry. Cytometry 14, 550-558. Cancer .J Sci. Am. 6, 2-10. 42. Kage, T., Mogi, M., Katsumata, ,.Y and Chino, .T (1987). Regional 56. Krause, R. M. (1983). The beginning of health is to know the disease. lymph node metastasis created by partial excision of carcinomas Public Health Rep. 98, 531-535. induced in hamster cheek pouch with 9,10-dimethyl-l,2-benzan- 57. Rhodes, .P (1983). Research. .rB Med. .J (Clin. Res. Ed.) 286, 1271-1272. thracene. .J Dent. Res. 66, 1673-1679. 58. Medawar, S. E (1975). Scientific method in science and medicine. 43. Hawkins, B. L., Heniford, B. W., Ackermann, D. M., Leonberger, M., Perspect. Biol. Med. 18, 345-52. Martinez, S. A., and Hendler, E J. (1994). 4NQO carcinogenesis: A 59. Potter, .V R. (1988). On the road to the blocked ontogeny theory. Adv. mouse model of oral cavity squamous cell carcinoma. Head Neck 16, Oncol. 4, 43-46. 424-432. 60. Potter, .V R. (1987). Blocked ontogeny. Science 237(4818), 964.

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