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7 results on '"Teknos, Theodoros N."'

1. Chemotherapy alone for organ preservation in advanced laryngeal cancer

Author

Department of Otolaryngology-Head and Neck Surgery, Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI ; Vasu Divi and Francis P. Worden contributed equally to this work., Department of Otolaryngology-Head and Neck Surgery, Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI ; Department of Internal Medicine, Division of Hematology-Oncology, University of Michigan Medical School, Ann Arbor, MI ; Department of Otolaryngology-Head and Neck Surgery, Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI, Department of Otolaryngology-Head and Neck Surgery, Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI, Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, MI, Department of Biostatistics, University of Michigan Medical School, Ann Arbor, MI, Department of Internal Medicine, Division of Hematology-Oncology, University of Michigan Medical School, Ann Arbor, MI, Department of Otolaryngology-Head and Neck Surgery, Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI ; Department of Internal Medicine, Division of Hematology-Oncology, University of Michigan Medical School, Ann Arbor, MI, Divi, Vasu, Worden, Francis P., Prince, Mark E., Eisbruch, Avraham, Lee, Julia S., Bradford, Carol R., Chepeha, Douglas B., Teknos, Theodoros N., Hogikyan, Norman D., Moyer, Jeffrey S., Tsien, Christina I., Urba, Susan G., Wolf, Gregory T., Department of Otolaryngology-Head and Neck Surgery, Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI ; Vasu Divi and Francis P. Worden contributed equally to this work., Department of Otolaryngology-Head and Neck Surgery, Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI ; Department of Internal Medicine, Division of Hematology-Oncology, University of Michigan Medical School, Ann Arbor, MI ; Department of Otolaryngology-Head and Neck Surgery, Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI, Department of Otolaryngology-Head and Neck Surgery, Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI, Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, MI, Department of Biostatistics, University of Michigan Medical School, Ann Arbor, MI, Department of Internal Medicine, Division of Hematology-Oncology, University of Michigan Medical School, Ann Arbor, MI, Department of Otolaryngology-Head and Neck Surgery, Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI ; Department of Internal Medicine, Division of Hematology-Oncology, University of Michigan Medical School, Ann Arbor, MI, Divi, Vasu, Worden, Francis P., Prince, Mark E., Eisbruch, Avraham, Lee, Julia S., Bradford, Carol R., Chepeha, Douglas B., Teknos, Theodoros N., Hogikyan, Norman D., Moyer, Jeffrey S., Tsien, Christina I., Urba, Susan G., and Wolf, Gregory T.

Abstract

Background. For patients with advanced laryngeal cancer, a trial was designed to determine if chemotherapy alone, in patients achieving a complete histologic complete response after a single neoadjuvant cycle, was an effective treatment with less morbidity than concurrent chemoradiotherapy. Methods. Thirty-two patients with advanced laryngeal or hypopharyngeal cancer received 1 cycle of induction chemotherapy, and subsequent treatment was decided based on response. Results. A histologic complete response was achieved in 4 patients and were treated with chemotherapy alone. All 4 patients' cancer relapsed in the neck and required surgery and postoperative radiotherapy (RT). Twenty-five patients were treated with concomitant chemoradiation. Three patients were treated with surgery. Overall survival and disease-specific survival at 3 years were 68% and 78%, respectively. Conclusion. Chemotherapy alone is not feasible for long-term control of regional disease in patients with advanced laryngeal cancer even when they achieve a histologic complete response at the primary site. ?? 2009 Wiley Periodicals, Inc. Head Neck, 2010

Published
2010

2. HPV-positive/p16-positive/EBV-negative nasopharyngeal carcinoma in white North Americans

Author

University of Michigan Medical School, The University of Michigan Health System and Comprehensive Cancer Center, Ann Arbor, MI ; Department of Otolaryngology/Head and Neck Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, Departments of Otolaryngology???Head and Neck Surgery, The University of Michigan Health System and Comprehensive Cancer Center, Ann Arbor, MI ; Department of Otolaryngology/Head and Neck Surgery, Ohio State University, Columbus, OH, Radiation Oncology, The University of Michigan Health System and Comprehensive Cancer Center, Ann Arbor, MI, Pathology, The University of Michigan Health System and Comprehensive Cancer Center, Ann Arbor, MI, Pathology, The University of Michigan Health System and Comprehensive Cancer Center, Ann Arbor, MI ; Periodontics and Oral Medicine, The University of Michigan Health System and Comprehensive Cancer Center, Ann Arbor, MI, Internal Medicine, The University of Michigan Health System and Comprehensive Cancer Center, Ann Arbor, MI, Departments of Otolaryngology???Head and Neck Surgery, The University of Michigan Health System and Comprehensive Cancer Center, Ann Arbor, MI, Departments of Otolaryngology???Head and Neck Surgery, The University of Michigan Health System and Comprehensive Cancer Center, Ann Arbor, MI ; Pharmacology, The University of Michigan Health System and Comprehensive Cancer Center, Ann Arbor, MI ; Departments of Otolaryngology-Head and Neck Surgery, The University of Michigan Health System and Comprehensive Cancer Center, Ann Arbor, MI, Department of Otolaryngology/Head and Neck Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, SensiGen, LLC, Ann Arbor, MI; Sequenom, Inc, San Diego, CA, Maxwell, Jessica H., Kumar, Bhavna, Feng, Felix Y., McHugh, Jonathan B., Cordell, Kitrina G., Eisbruch, Avraham, Worden, Francis P., Wolf, Gregory T., Prince, Mark E., Moyer, Jeffrey S., Teknos, Theodoros N., Chepeha, Douglas B., Stoerker, Jay, Walline, Heather, Carey, Thomas E., Bradford, Carol R., University of Michigan Medical School, The University of Michigan Health System and Comprehensive Cancer Center, Ann Arbor, MI ; Department of Otolaryngology/Head and Neck Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, Departments of Otolaryngology???Head and Neck Surgery, The University of Michigan Health System and Comprehensive Cancer Center, Ann Arbor, MI ; Department of Otolaryngology/Head and Neck Surgery, Ohio State University, Columbus, OH, Radiation Oncology, The University of Michigan Health System and Comprehensive Cancer Center, Ann Arbor, MI, Pathology, The University of Michigan Health System and Comprehensive Cancer Center, Ann Arbor, MI, Pathology, The University of Michigan Health System and Comprehensive Cancer Center, Ann Arbor, MI ; Periodontics and Oral Medicine, The University of Michigan Health System and Comprehensive Cancer Center, Ann Arbor, MI, Internal Medicine, The University of Michigan Health System and Comprehensive Cancer Center, Ann Arbor, MI, Departments of Otolaryngology???Head and Neck Surgery, The University of Michigan Health System and Comprehensive Cancer Center, Ann Arbor, MI, Departments of Otolaryngology???Head and Neck Surgery, The University of Michigan Health System and Comprehensive Cancer Center, Ann Arbor, MI ; Pharmacology, The University of Michigan Health System and Comprehensive Cancer Center, Ann Arbor, MI ; Departments of Otolaryngology-Head and Neck Surgery, The University of Michigan Health System and Comprehensive Cancer Center, Ann Arbor, MI, Department of Otolaryngology/Head and Neck Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, SensiGen, LLC, Ann Arbor, MI; Sequenom, Inc, San Diego, CA, Maxwell, Jessica H., Kumar, Bhavna, Feng, Felix Y., McHugh, Jonathan B., Cordell, Kitrina G., Eisbruch, Avraham, Worden, Francis P., Wolf, Gregory T., Prince, Mark E., Moyer, Jeffrey S., Teknos, Theodoros N., Chepeha, Douglas B., Stoerker, Jay, Walline, Heather, Carey, Thomas E., and Bradford, Carol R.

Abstract

Background Human papillomavirus (HPV) has been detected in keratinizing nasopharyngeal carcinomas (NPCs); however, the relationship between HPV and Epstein???Barr virus (EBV) among whites with nonkeratinizing NPCs remains unclear. The HPV, p16, and EBV status was examined in current University of Michigan patients with NPC. Methods From 2003 to 2007, 89 patients, 84 with oropharyngeal cancer (OPC) and 5 with NPC, were enrolled in an organ-sparing trial. Biopsy tissues from all 89 patients were evaluated for HPV and p16 expression. A separate HPV analysis of the 84 OPC patients is in progress. Among the patients with NPC, tumor tissue was also analyzed for EBV-encoded RNA (EBER). Results Five of 89 patients (5.6%) had NPC, all with nonkeratinizing histology. The 4 white patients with NPC were HPV(+) (subtype-16, subtype-18 [2 patients], and subtype-59)/p16(+)/EBER(-). One Asian patient with NPC had an HPV(-)/p16(-)/EBER(+) NPC tumor that developed distant metastases. Conclusion We postulate that HPV may be the etiologic factor in some EBV-negative, nonkeratinizing NPCs among whites. ?? 2009 Wiley Periodicals, Inc. Head Neck, 2010

Published
2010

3. Lateral oromandibular defect: When is it appropriate to use a bridging reconstruction plate combined with a soft tissue revascularized flap?

Author

Department Otolaryngology–Head and Neck Surgery, University of Michigan, Ann Arbor, Michigan 48109-0312 ; Dr. Chepeha has reported a financial interest/relationship with KLS Martin. ; Department Otolaryngology–Head and Neck Surgery, University of Michigan, Ann Arbor, Michigan 48109-0312, Department Otolaryngology–Head and Neck Surgery, University of Michigan, Ann Arbor, Michigan 48109-0312, Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan, Cancer Center–Biostatistics, University of Michigan, Ann Arbor, Michigan, Department Otolaryngology–Head and Neck Oncology and Reconstructive Surgery, University of Western Ontario, London, Ontario, Canada, Department Otolaryngology–Head and Neck Surgical Oncology, Washington University, St. Louis, Missouri, Chepeha, Douglas B., Teknos, Theodoros N., Fung, Kevin, Shargorodsky, Josef, Sacco, Assuntina G., Nussenbaum, Brian, Jones, Lamont, Eisbruch, Avraham, Bradford, Carol R., Prince, Mark E., Moyer, Jeffrey S., Lee, Julia S., Wolf, Gregory T., Department Otolaryngology–Head and Neck Surgery, University of Michigan, Ann Arbor, Michigan 48109-0312 ; Dr. Chepeha has reported a financial interest/relationship with KLS Martin. ; Department Otolaryngology–Head and Neck Surgery, University of Michigan, Ann Arbor, Michigan 48109-0312, Department Otolaryngology–Head and Neck Surgery, University of Michigan, Ann Arbor, Michigan 48109-0312, Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan, Cancer Center–Biostatistics, University of Michigan, Ann Arbor, Michigan, Department Otolaryngology–Head and Neck Oncology and Reconstructive Surgery, University of Western Ontario, London, Ontario, Canada, Department Otolaryngology–Head and Neck Surgical Oncology, Washington University, St. Louis, Missouri, Chepeha, Douglas B., Teknos, Theodoros N., Fung, Kevin, Shargorodsky, Josef, Sacco, Assuntina G., Nussenbaum, Brian, Jones, Lamont, Eisbruch, Avraham, Bradford, Carol R., Prince, Mark E., Moyer, Jeffrey S., Lee, Julia S., and Wolf, Gregory T.

Abstract

Background A quasi-experimental retrospective study was undertaken to evaluate a new concept of free tissue volume restoration combined with bridging reconstruction plate (compartment approach) to reduce plate-related complication rates. Methods We evaluated 40 patients with large lateral mandible defects and associated complex soft tissue defects reconstructed with a revascularized soft tissue flap and titanium hollow screw reconstruction plates. A case-control comparison was performed based on reconstruction type: restoration of soft tissue defect (conventional approach—group 1) versus over-reconstruction of soft tissue defect (compartment approach—group 2). Results Plate exposure rate was 6 of 16 (38%) in group 1 versus 2 of 24 (8%) in group 2, and the difference was statistically significant ( p = .04). The mean time to exposure was 10 months. Plate fracture rate was 6 of 23 (26.1%) in dentulous patients versus 1 of 17 (5.9%) in edentulous patients. Gastrostomy tube dependence was 6 of 16 (38%) in group 1 versus 6 of 24 (25%) in group 2. Conclusion The “compartment approach” reduces plate exposure rate and gastrostomy tube dependence. Revascularized osseocutaneous reconstruction is still required in dentulous patients. © 2008 Wiley Periodicals, Inc. Head Neck, 2008

Published
2008

4. Prevention of wound complications following salvage laryngectomy using free vascularized tissue

Author

Department of Otolaryngology—Head and Neck Surgery, University of Michigan, Ann Arbor, Michigan, Department of Otolaryngology—Head and Neck Surgery, University of Michigan, Ann Arbor, Michigan ; Department of Otolaryngology—Head and Neck Surgery, University of Michigan, Ann Arbor, Michigan, Fung, Kevin, Teknos, Theodoros N., Vandenberg, Curtis D., Lyden, Teresa H., Bradford, Carol R., Hogikyan, Norman D., Kim, Jennifer, Prince, Mark E. P., Wolf, Gregory T., Chepeha, Douglas B., Department of Otolaryngology—Head and Neck Surgery, University of Michigan, Ann Arbor, Michigan, Department of Otolaryngology—Head and Neck Surgery, University of Michigan, Ann Arbor, Michigan ; Department of Otolaryngology—Head and Neck Surgery, University of Michigan, Ann Arbor, Michigan, Fung, Kevin, Teknos, Theodoros N., Vandenberg, Curtis D., Lyden, Teresa H., Bradford, Carol R., Hogikyan, Norman D., Kim, Jennifer, Prince, Mark E. P., Wolf, Gregory T., and Chepeha, Douglas B.

Abstract

Background. Total laryngectomy following radiation therapy or concurrent chemoradiation therapy is associated with unacceptably high complication rates because of wound healing difficulties. With an ever increasing reliance on organ preservation protocols as primary treatment for advanced laryngeal cancer, the surgeon must develop techniques to minimize postoperative complications in salvage laryngectomy surgery. We have developed an approach using free tissue transfer in an effort to improve tissue vascularity, reinforce the pharyngeal suture line, and minimize complications in this difficult patient population. The purpose of this study was to outline our technique and determine the effectiveness of this new approach. Methods. We conducted a retrospective review of a prospective cohort and compared it with a historical group (surgical patients of Radiation Therapy Oncology Group (RTOG)-91-11 trial). Eligibility criteria for this study included patients undergoing salvage total laryngectomy following failed attempts at organ preservation with either high-dose radiotherapy or concurrent chemo/radiation therapy regimen. Patients were excluded if the surgical defect required a skin paddle for pharyngeal closure. The prospective cohort consisted of 14 consecutive patients (10 males, 4 females; mean age, 58 years) who underwent free tissue reinforcement of the pharyngeal suture line following total laryngectomy. The historical comparison group consisted of 27 patients in the concomitant chemoradiotherapy arm of the RTOG-91-11 trial who met the same eligibility criteria (26 males, 1 female; mean age, 57 years) but did not undergo free tissue transfer or other form of suture line reinforcement. Minimum follow-up in both groups was 12 months. Results. The overall pharyngocutaneous fistula rate was similar between groups—4/14 (29%) in the flap group, compared with 8/27 (30%) in the RTOG-91-11 group. There were no major wound complications in the flap group, compared with 4

Published
2007

5. Acceleration of hyperfractionated chemoradiation regimen for advanced head and neck cancer

Author

Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan ; Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan, Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, Department of Otolaryngology/Head and Neck Surgery, University of Michigan, Ann Arbor, Michigan, Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, Allen, Aaron M., Elshaikh, Mohamed, Worden, Francis P., Bradford, Carol R., Teknos, Theodoros N., Chepeha, Douglas B., Tsien, Christina, Dawson, Laura A., Urba, Susan, Wolf, Gregory T., Normolle, Daniel, Eisbruch, Avraham, Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan ; Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan, Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, Department of Otolaryngology/Head and Neck Surgery, University of Michigan, Ann Arbor, Michigan, Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, Allen, Aaron M., Elshaikh, Mohamed, Worden, Francis P., Bradford, Carol R., Teknos, Theodoros N., Chepeha, Douglas B., Tsien, Christina, Dawson, Laura A., Urba, Susan, Wolf, Gregory T., Normolle, Daniel, and Eisbruch, Avraham

Abstract

Background. Our aim was to evaluate the acceleration of a hyperfractionated, concurrent chemoradiation regimen (HxCRT) for advanced head and neck squamous cell carcinoma (HNSCC). Methods. Patients with unresectable HNSCC were treated based on a previously published HxCRT regimen: 1.25 Gy twice daily to 70 Gy concurrent with cisplatin 12 mg/m 2 /day and5-fluorouracil 600 mg/m 2 /day for 5 days, weeks 1, 5. This regimen was accelerated in this series by shortening the treatment from 7 to 6 weeks by omitting the planned mid-treatment 1-week break. Results. Forty-six patients with T3-4/N3 disease were treated. The main acute toxicity was pharyngeal. Median weight change during therapy in patients with and without enteral feeding tubes was −3.8% and −7.9%, respectively ( p = .08). Fifteen percent had late grade III pharyngeal toxicity. Local/regional and distant failure rates were 28% and 17%, respectively; 52% are alive without evidence of disease. Conclusions. In nonresectable HNSCC, acceleration of the HxCRT regimen is feasible, requiring enteral feeding tubes during therapy in most patients. © 2006 Wiley Periodicals, Inc. Head Neck, 2007

Published
2007

6. Salivary Gland Sparing and Improved Target Irradiation by Conformal and Intensity Modulated Irradiation of Head and Neck Cancer

Author

Department of Otorhinolaryngology???Head and Neck Surgery, University of Michigan, 1500 Medical Center Drive, Ann Arbor, Michigan 48109, USA, Department of Radiation Oncology, University of Michigan, 1500 Medical Center Drive, Ann Arbor, Michigan 48109, USA, Department of Biostatistics, University of Michigan, 1500 E. Medical Center Drive, Ann Arbor, Michigan 48109, USA, Department of Radiology, University of Michigan, 1500 Medical Center Drive, Ann Arbor, Michigan 48109, USA, New York University College of Dentistry, 345 East 24th Street, New York, New York 10010, USA, Ann Arbor, Haken, Randall K., Teknos, Theodoros N., Wolf, Gregory T., Kim, Hyungjin M., Ship, Jonathan A., Eisbruch, Avraham, Dawson, Laura A., Anzai, Yoshimi, Bradford, Carol R., Chepeha, Douglas B., Terrell, Jeffrey E., Hogikyan, Norman D., Marsh, Lon H., Department of Otorhinolaryngology???Head and Neck Surgery, University of Michigan, 1500 Medical Center Drive, Ann Arbor, Michigan 48109, USA, Department of Radiation Oncology, University of Michigan, 1500 Medical Center Drive, Ann Arbor, Michigan 48109, USA, Department of Biostatistics, University of Michigan, 1500 E. Medical Center Drive, Ann Arbor, Michigan 48109, USA, Department of Radiology, University of Michigan, 1500 Medical Center Drive, Ann Arbor, Michigan 48109, USA, New York University College of Dentistry, 345 East 24th Street, New York, New York 10010, USA, Ann Arbor, Haken, Randall K., Teknos, Theodoros N., Wolf, Gregory T., Kim, Hyungjin M., Ship, Jonathan A., Eisbruch, Avraham, Dawson, Laura A., Anzai, Yoshimi, Bradford, Carol R., Chepeha, Douglas B., Terrell, Jeffrey E., Hogikyan, Norman D., and Marsh, Lon H.

Abstract

The goals of this study were to facilitate sparing of the major salivary glands while adequately treating tumor targets in patients requiring comprehensive bilateral neck irradiation (RT), and to assess the potential for improved xerostomia. Since 1994 techniques of target irradiation and locoregional tumor control with conformal and intensity modulated radiation therapy (IMRT) have been developed. In patients treated with these modalities, the salivary flow rates before and periodically after RT have been measured selectively from each major salivary gland and the residual flows correlated with glands??? dose volume histograms (DVHs). In addition, subjective xerostomia questionnaires have been developed and validated. The pattern of locoregional recurrence has been examined from computed tomography (CT) scans at the time of recurrence, transferring the recurrence volumes to the planning CT scans, and regenerating the dose distributions at the recurrence sites. Treatment plans for target coverage and dose homogeneity using static, multisegmental IMRT were found to be significantly better than standard RT plans. In addition, significant parotid gland sparing was achieved in the conformal plans. The relationships among dose, irradiated volume, and the residual saliva flow rates from the parotid glands were characterized by dose and volume thresholds. A mean radiation dose of 26 Gy was found to be the threshold for preserved stimulated saliva flow. Xerostomia questionnaire scores suggested that xerostomia was significantly reduced in patients irradiated with bilateral neck, parotid-sparing RT, compared to patients with similar tumors treated with standard RT. Examination of locoregional tumor recurrence patterns revealed that the large majority of recurrences occurred inside targets, in areas that had been judged to be at high risk and that had received RT doses according to the perceived risk. Tangible gains in salivary gland sparing and target coverage are being achi

Published
2006

7. Prognostic factors in oral cavity and oropharyngeal squamous cell carcinoma

Author

Department of Otolaryngology-Head and Neck Surgery, University of Michigan Medical Center, Ann Arbor, Michigan, Department of Internal Medicine, Division of Pulmonary Medicine, University of Michigan Medical Center, Ann Arbor, Michigan, Department of Biostatistics, University of Michigan Medical Center, Ann Arbor, Michigan, Department of Pathology, University of Michigan Medical Center, Ann Arbor, Michigan, Department of Internal Medicine, Division of Hematology/Oncology, University of Michigan Medical Center, Ann Arbor, Michigan, Department of Pediatrics, University of Michigan Medical Center, Ann Arbor, Michigan, Department of Otolaryngology-Head and Neck Surgery, University of Michigan Medical Center, Ann Arbor, Michigan ; Fax: (734) 936-9625 ; University of Michigan Medical Center, 1500 E. Medical Center Drive, 1904 Taubman Center, Ann Arbor, MI 48103, Marcus, Benjamin, Arenberg, Douglas A., Lee, Julia, Kleer, Celina G., Chepeha, Douglas B., Schmalbach, Cecelia E., Islam, Mozaffarul, Paul, Supriti, Pan, Quintin, Hanash, Samir, Kuick, Rork, Merajver, Sofia D., Teknos, Theodoros N., Department of Otolaryngology-Head and Neck Surgery, University of Michigan Medical Center, Ann Arbor, Michigan, Department of Internal Medicine, Division of Pulmonary Medicine, University of Michigan Medical Center, Ann Arbor, Michigan, Department of Biostatistics, University of Michigan Medical Center, Ann Arbor, Michigan, Department of Pathology, University of Michigan Medical Center, Ann Arbor, Michigan, Department of Internal Medicine, Division of Hematology/Oncology, University of Michigan Medical Center, Ann Arbor, Michigan, Department of Pediatrics, University of Michigan Medical Center, Ann Arbor, Michigan, Department of Otolaryngology-Head and Neck Surgery, University of Michigan Medical Center, Ann Arbor, Michigan ; Fax: (734) 936-9625 ; University of Michigan Medical Center, 1500 E. Medical Center Drive, 1904 Taubman Center, Ann Arbor, MI 48103, Marcus, Benjamin, Arenberg, Douglas A., Lee, Julia, Kleer, Celina G., Chepeha, Douglas B., Schmalbach, Cecelia E., Islam, Mozaffarul, Paul, Supriti, Pan, Quintin, Hanash, Samir, Kuick, Rork, Merajver, Sofia D., and Teknos, Theodoros N.

Abstract

BACKGROUND The survival of patients with head and neck squamous cell carcinoma (HNSCC) remains unaffected despite recent therapeutic advances. To reverse this trend, reliable and clinically applicable markers of tumor aggressiveness must be identified. One such marker may be the tumor-associated macrophage content. The authors hypothesized that tumor-associated macrophages contribute to HNSCC aggressiveness, and the objective of the current study was to prove this hypothesis using mRNA expression analysis and a large cohort of clinical specimens. METHODS Oligonucleotide microarray analysis was performed on a prospective cohort of 20 patients with previously untreated oral cavity or oropharynx squamous cell carcinoma (OC/OP SCCA) and on normal oropharyngeal mucosa from 4 patients. After determining whether macrophage chemoattractants were produced by tumors, conditioned media from three HNSCC cell lines were used to quantify macrophage migration in an in vitro assay. A high-density tissue microarray of 102 patients with previously untreated OC/OP SCCA was stained immunohistochemically for CD68 to identify tissue macrophages, and the results were correlated with clinicopathologic data and survival. RESULTS Monocyte chemoattractant protein 1 was up-regulated significantly in tumors compared with normal mucosa (P = 0.0025; fold change = 1.89). All University of Michigan SCC tumor cell line conditioned media caused a significant increase in macrophage migration (P <0.05). Tissue microarray data revealed that macrophage content of the primary tumor was associated strongly with lymph node metastasis (P <0.0001), extracapsular lymph node spread (P = 0.0001), and advanced clinical disease stage (P = 0.0002). When it was evaluated along with other clinicopathologic data, the macrophage content was found to be an independent predictor of lymph node metastasis (P <0.0001). CONCLUSIONS Primary tumor macrophage content is a strong predictor of tumor aggressiveness in HNS

Published
2006

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