Bio

Clinical Focus


  • Tongue Neoplasms
  • carcinoma of the neck; unknown primary
  • Paranasal Sinus Neoplasms
  • Paraganglioma, Carotid Body
  • Salivary Gland Tumors
  • Head and Neck Cancers
  • Maxillary Sinus Neoplasms
  • Infratemporal fossa tumors
  • Melanoma
  • squamous cell carcinoma of the head and neck
  • Head and Neck Cancers - Head and Neck Surgery
  • Otolaryngology
  • Salivary Gland Tumors - Head and Neck Surgery
  • Thyroid Neoplasms
  • Oral cavity tumors
  • Esthesioneuroblastoma, Paranasal Sinus-Nasal Cavity
  • Esophageal Cancer
  • Melanoma - Head and Neck Surgery
  • Parapharyngeal space tumors
  • Skull Base Tumors
  • Parotid Neoplasms
  • Tonsillar Neoplasms
  • Esophageal Cancer - Head and Neck Surgery
  • Otolaryngology - Head & Neck Surgery (Ear, Nose and Throat)
  • Skull Base Tumors - Head and Neck Surgery
  • Cancer > Head and Neck Cancer

Academic Appointments


Administrative Appointments


  • Head & Neck Oncology Program, Disease Management Leader, Stanford Cancer Center (2010 - Present)
  • Chief, Head & Neck Surgery, Otolaryngology-Head&Neck Surgery (2003 - Present)
  • Head & Neck Fellowship Director, Otolaryngology-Head&Neck Surgery (2003 - Present)

Honors & Awards


  • Best Doctors in America, . (1998-2012)
  • Chief Residents' Special Certificate of Merit, UCSF (1993)
  • Roger Boles Teaching award, UCSF (1987)
  • Phi Beta Kappa, Harvard College (1973)

Professional Education


  • Internship:Beth Israel Deaconess Medical Center (1978) MA
  • Fellowship:University of Virginia (1984) VA
  • Board Certification: Otolaryngology, American Board of Otolaryngology (1982)
  • Residency:Massachusetts Eye and Ear Infirmary (1982) MA
  • Residency:Beth Israel and Children's Hospital (1979) MA
  • Medical Education:Harvard Medical School (1977) MA
  • Fellowship, University of Virginia, Head & Neck; Skull Base Surgery (1984)
  • Residency, Massachusetts Eye & Ear, Otolaryngology-Head & Neck Surgery (1982)
  • MD, Harvard Medical School (1977)
  • BA, Harvard College, Molecular Biology (1973)

Community and International Work


  • Scientific Review Committee, Stanford Cancer Center

    Location

    International

    Ongoing Project

    Yes

    Opportunities for Student Involvement

    No

  • Institutional Review Board, Stanford, Stanford

    Location

    Bay Area

    Ongoing Project

    Yes

    Opportunities for Student Involvement

    No

  • Ethic Committee

    Partnering Organization(s)

    AAO-HNS

    Location

    US

    Ongoing Project

    Yes

    Opportunities for Student Involvement

    No

  • American Youth Soccer Organization referree

    Location

    Bay Area

    Ongoing Project

    Yes

    Opportunities for Student Involvement

    No

  • Mill Valley Schools Configuration Task Forc, Mill Valley

    Topic

    Advisory to School Board re: demographics and facilities

    Populations Served

    K-8

    Location

    Bay Area

    Ongoing Project

    No

    Opportunities for Student Involvement

    No

Research & Scholarship

Current Research and Scholarly Interests


1) New therapeutic approaches for head and neck cancer, including immune stimulation possibilities (IRX-2 protocol), integration of biological modifiers, and, eventually, genetic approaches.
2) Head and neck cancer stem cells: identification, characterization, control--in conjunction with the Irv Weissman and Michael Clarke labs in the Stem Cell Institute
3) Development of innovative surgical methods at the anterior cranial base

Clinical Trials


  • Identification and Characterization of Novel Proteins and Genes in Head and Neck Cancer Recruiting

    Through this study, we hope to learn more about the mechanisms, which may contribute to development and progression of head and neck cancer. The long-term goal of this study will be to develop new strategies and drugs for the diagnosis and treatment of head and neck cancer.

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  • Cisplatin and ZD1839 + Re-Irradiation in Recurrent Squamous Cell Cancer of the Head and Neck Not Recruiting

    To determine safety profile of the epidermal growth factor receptor (EGFR) antagonist, ZD1839 in combination with cisplatin and radiation therapy in patients with local-regional recurrent squamous cell cancer of the head and neck. To study the effects of ZD1839 combined with either cisplatin or radiotherapy on signal transduction pathway gene expression in tumor cells in patients with local-regional recurrent squamous cell cancer of the head and neck using micro array analysis from tumor samples taken at the time of relapse and during treatment.

    Stanford is currently not accepting patients for this trial. For more information, please contact Priscilla Wong, (650) 725 - 4777.

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  • Radiation Therapy With or Without Cetuximab in Treating Patients Who Have Undergone Surgery for Locally Advanced Head and Neck Cancer Not Recruiting

    RATIONALE: Giving radiation therapy that uses a 3-dimensional (3-D) image of the tumor to help focus thin beams of radiation directly on the tumor, and giving radiation therapy in higher doses over a shorter period of time, may kill more tumor cells and have fewer side effects. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. It is not yet known whether radiation therapy is more effective when given alone or together with cetuximab in treating patients with head and neck cancer that has been removed by surgery. PURPOSE: This randomized phase III trial is studying radiation therapy to see how well it works compared with radiation therapy given together with cetuximab in treating patients who have undergone surgery for locally advanced head and neck cancer.

    Stanford is currently not accepting patients for this trial. For more information, please contact Alice Banh, 650-723-1423.

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  • Radiation Therapy and Cisplatin With or Without Cetuximab in Treating Patients With Stage III or Stage IV Head and Neck Cancer Not Recruiting

    RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Cisplatin may also make tumor cells more sensitive to radiation therapy. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving radiation therapy and cisplatin together with cetuximab may kill more tumor cells. It is not yet known whether radiation therapy and cisplatin are more effective with or without cetuximab in treating head and neck cancer. PURPOSE: This randomized phase III trial is studying radiation therapy, cisplatin, and cetuximab to see how well they work compared to radiation therapy and cisplatin in treating patients with stage III or stage IV head and neck cancer.

    Stanford is currently not accepting patients for this trial. For more information, please contact Trevor Elizabeth Krakow, (650) 725 - 4777.

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  • Radiation Therapy With Cisplatin, Docetaxel, or Cetuximab After Surgery in Treating Patients With Stage III-IV Squamous Cell Head and Neck Cancer Recruiting

    This randomized phase II/III trial studies how well radiation therapy works when given together with cisplatin compared to docetaxel or cetuximab and docetaxel after surgery in treating patients with stage III-IV squamous cell head and neck cancer. Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Drugs used in chemotherapy, such as cisplatin and docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or transmit tumor killing molecules to them. It is not yet known whether radiation therapy is more effective when given with cisplatin, docetaxel, or cetuximab and docetaxel.

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  • A Phase 2 Clinical Trial of the Safety and Effects of IRX-2 in Treating Patients With Operable Head and Neck Cancer Not Recruiting

    IRX-2 is designed to activate your own body's immune system so that it can better fight the invasion of head and neck cancer. In pre-clinical studies, IRX-2 has been shown to activate a number of different cells of the immune system. IRX-2 was previously tested in a study of 13 patients with advanced head and neck cancer who had been previously treated and failed chemotherapy and/or radiation therapy. The trials were specifically designed to test the safety of IRX-2. Researchers found that IRX-2 did not appear to have major side effects. Also, the researchers believed that further study in less advanced head and neck cancer patients could be useful in obtaining more data on the safety of IRX-2 as well as data on possible effects on tumors and on patient survival.

    Stanford is currently not accepting patients for this trial. For more information, please contact Ruth Lira, (650) 723 - 1367.

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  • Biopsy of Human Tumors for Cancer Stem Cell Characterization: a Feasibility Study Not Recruiting

    To see if a limited sampling of tumor tissue from human subjects is a feasible way to gather adequate tissue for cancer stem cell quantification.

    Stanford is currently not accepting patients for this trial. For more information, please contact Ruth Lira, 650-723-1367.

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  • Phase II Lapatinib and Radiation for Stage III-IV Head and Neck Cancer Patients Who Cannot Tolerate Concurrent Chemotherapy Not Recruiting

    We propose to combine lapatinib with RT alone in patients with locally advanced head and neck cancer who cannot tolerate chemotherapy. The main objective of the study is to determine the efficacy of combining concurrent radiation and lapatinib in terms of time-to-progression (TTP) in this group of patients. In addition, we will determine the 2-year locoregional control rate (LRC), progression-free survival (PFS) and overall survival (OS) in these patients. We will also evaluate the profile and frequency of late toxicity, specifically mucosal and dermatologic toxicity, of the combination of lapatinib and RT in patients with locally advanced head and neck squamous cell carcinoma (HNSCC).

    Stanford is currently not accepting patients for this trial. For more information, please contact Brian Khong, (650) 725 - 4777.

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  • Cervical Nodal Mets in Squamous Cell Carcinoma of H&N - MRI, FDG-PET, & Histopathologic Correlation Not Recruiting

    The purpose of this study is to determine the value of novel non-invasive medical imaging methods for detecting the spread of head and neck squamous cell carcinoma to the lymph nodes in the neck by comparing their results to findings at the time of surgery.

    Stanford is currently not accepting patients for this trial. For more information, please contact Quynh-Thu Le, (650) 498 - 6184.

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  • Imaging and Biomarkers of Hypoxia in Solid Tumors Recruiting

    To establish PET imaging with the tracer FMISO as an accurate and reliable method for measuring the oxygen content of a tumor and to establish the measurement of secreted markers in blood as an accurate and reliable method for measuring the oxygen content of a tumor.

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Teaching

2013-14 Courses


Publications

Journal Articles


  • Long-Term Outcomes of Surgery Followed by Radiation Therapy for Minor Salivary Gland Carcinomas LARYNGOSCOPE Zeidan, Y. H., Shultz, D. B., Murphy, J. D., Chan, C., Kaplan, M. J., Colevas, A. D., Kong, C., Chang, D. T., Le, Q. 2013; 123 (11): 2675-2680

    Abstract

    OBJECTIVES/HYPOTHESIS: Postoperative radiation therapy is often used in patients with high-risk salivary gland carcinomas. In this study we evaluated the outcomes and prognostic factors in patients with minor salivary gland cancers treated with adjuvant radiation therapy. STUDY DESIGN: Retrospective cohort study. METHODS: We performed a retrospective analysis of 90 patients treated with curative intent. Median follow-up was 71 months. Fifty-eight patients (64%) had adenoid cystic carcinomas, 22 (24%) had adenocarcinomas, and 10 (11%) had mucoepidermoid cancers. Primary disease site included 39 (43%) sinonasal, 35 (39%) oral cavity, 10 (11%) oropharynx, and six (7%) others. Twenty-seven patients (30%) were treated with intensity-modulated radiation therapy. RESULTS: Eight local, four neck, and 24 distant relapses were detected. Local control rates at 5 and 10 years were 90% and 88%, respectively. Advanced T stage was associated with worse local control. Distant metastasis rates were 24% and 28% at 5 and 10 years, respectively. Tumor stage, histology, perineural invasion, and lymphovascular space invasion were significant predictors of distant metastasis on univariate analysis. However, on multivariate analysis only the American Joint Committee on Cancer stage was significant. Overall survival rates were 76% and 63% at 5 and 10 years, respectively. More advanced T stage and N stage correlated with worse overall survival. CONCLUSIONS: Tumor stage remains the best predictor for locoregional and distant disease control of minor salivary gland cancers. Postoperative radiation therapy for high-risk patients results in excellent long-term locoregional disease control. Further work is needed to improve systemic control. LEVEL OF EVIDENCE: 4. Laryngoscope, 2013.

    View details for DOI 10.1002/lary.24081

    View details for Web of Science ID 000326231200029

    View details for PubMedID 23553253

  • Radiotherapy for nonadenoid cystic carcinomas of major salivary glands. American journal of otolaryngology Chung, M. P., Tang, C., Chan, C., Hara, W. Y., Loo, B. W., Kaplan, M. J., Fischbein, N., Le, Q., Chang, D. T. 2013; 34 (5): 425-430

    Abstract

    PURPOSE: To report outcomes in patients treated with postoperative radiotherapy for nonadenoid cystic carcinomas of the major salivary glands. MATERIALS AND METHODS: From 1998-2011, 37 patients with nonadenoid cystic carcinomas of the major salivary gland underwent postoperative radiotherapy. The median radiation dose was 60Gy (range, 45-70Gy). TNM distribution included T1-2 (n=16, 44%), T3-T4 (n=21, 56%), N0 (n=19, 51%), and N+ (n=18, 49%). Histologies included adenocarcinoma (n=13, 35%), squamous cell carcinoma (n=8, 22%), mucoepidermoid carcinoma (n=8, 22%), and other (n=8, 21%). Median follow-up was 4.7years for all patients (range, 0.3-14.1years) and 5.0years for living patients (range, 1.2-12.2years). RESULTS: Five-year local-regional control, overall survival (OS), and cancer-specific survival (CSS) were 97%, 76%, and 84%. On univariate analysis, OS was significantly worse for patients ≥65years old (p=0.04). CSS was significantly worse for positive perineural invasion (p=0.02), extraparenchymal extension (p=0.04), and in patients who received no chemotherapy (p=0.02). Doses >60Gy was significantly worse for OS (p=0.003) and CSS (p=0.003), although these patients had higher TNM (>T2, p=0.01) and trended towards a higher rate of extraparenchymal extension (p=0.08). Four patients (11%) developed ≥grade 2 toxicities; 3 patients developed early toxicities and one patient developed late toxicities. CONCLUSIONS: Radiotherapy for salivary gland tumors provides excellent local-regional control when combined with surgery. Distant metastasis is the predominant pattern of failure, although chemotherapy seemed to improve cancer-specific survival.

    View details for DOI 10.1016/j.amjoto.2013.03.007

    View details for PubMedID 23583094

  • Stereotactic radiosurgery for retreatment of gross perineural invasion in recurrent cutaneous squamous cell carcinoma of the head and neck. American journal of clinical oncology Tang, C., Fischbein, N. J., Murphy, J. D., Chu, K. P., Bavan, B., Dieterich, S., Hara, W., Kaplan, M. J., Colevas, A. D., Le, Q. 2013; 36 (3): 293-298

    Abstract

    : To report outcomes, failure patterns, and toxicity after stereotactic radiosurgery (SRS) for recurrent head and neck cutaneous squamous cell carcinoma with gross perineural invasion (GPNI).: Ten patients who received SRS as part of retreatment for recurrent head and neck cutaneous squamous cell carcinoma with GPNI were included. All patients exhibited clinical and radiologic evidence of GPNI before SRS. Previous treatments included surgery alone in 3 patients and surgery with adjuvant external beam radiotherapy (EBRT) in 7 patients. Retreatment included SRS alone in 2 and EBRT boosted with SRS in 8 patients. Magnetic resonance images were obtained every 3 to 6 months after SRS to track failure patterns.: At a median 22-month follow-up, the 2-year progression-free and overall survival rates were 20% and 50%, respectively. Seven patients exhibited local failures, all of which occurred outside both SRS and EBRT fields. Five local failures occurred in previously clinically uninvolved cranial nerves (CNs). CN disease spreads through 3 distinct patterns: among different branches of CN V; between CNs V and VII; and between V1 and CNs III, IV, and/or VI. Five patients experienced side effects potentially attributable to radiation.: Although there is excellent in-field control with this approach, the rate of out-of-field failures remains unacceptably high. We found that the majority of failures occurred in previously clinically uninvolved CNs often just outside treatment fields. Novel treatment strategies targeting this mode of perineural spread are needed.

    View details for DOI 10.1097/COC.0b013e3182468019

    View details for PubMedID 22547009

  • Impact of positron emission tomography/computed tomography surveillance at 12 and 24 months for detecting head and neck cancer recurrence CANCER Ho, A. S., Tsao, G. J., Chen, F. W., Shen, T., Kaplan, M. J., Colevas, A. D., Fischbein, N. J., Quon, A., Quynh-Thu Le, Q. T., Pinto, H. A., Fee, W. E., Sunwoo, J. B., Sirjani, D., Hara, W., Yao, M. 2013; 119 (7): 1349-1356

    Abstract

    In head and neck cancer (HNC), 3-month post-treatment positron emission tomography (PET)/computed tomography (CT) reliably identifies persistent/recurrent disease. However, further PET/CT surveillance has unclear benefit. The impact of post-treatment PET/CT surveillance on outcomes is assessed at 12 and 24 months.A 10-year retrospective analysis of HNC patients was carried out with long-term serial imaging. Imaging at 3 months included either PET/CT or magnetic resonance imaging, with all subsequent imaging comprised of PET/CT. PET/CT scans at 12 and 24 months were evaluated only if preceding interval scans were negative. Of 1114 identified patients, 284 had 3-month scans, 175 had 3- and 12-month scans, and 77 had 3-, 12-, and 24-month scans.PET/CT detection rates in clinically occult patients were 9% (15 of 175) at 12 months, and 4% (3 of 77) at 24 months. No difference in outcomes was identified between PET/CT-detected and clinically detected recurrences, with similar 3-year disease-free survival (41% vs 46%, P = .91) and 3-year overall survival (60% vs 54%, P = .70) rates. Compared with 3-month PET/CT, 12-month PET/CT demonstrated fewer equivocal reads (26% vs 10%, P < .001). Of scans deemed equivocal, 6% (5 of 89) were ultimately found to be positive.HNC patients with negative 3-month imaging appear to derive limited benefit from subsequent PET/CT surveillance. No survival differences were observed between PET/CT-detected and clinically detected recurrences, although larger prospective studies are needed for further investigation.

    View details for DOI 10.1002/cncr.27892

    View details for Web of Science ID 000316811900010

  • CD44+cells have cancer stem cell-like properties in nasopharyngeal carcinoma INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY Janisiewicz, A. M., Shin, J. H., Murillo-Sauca, O., Kwok, S., Quynh-Thu Le, Q. T., Kong, C., Kaplan, M. J., Sunwoo, J. B. 2012; 2 (6): 465-470

    Abstract

    A subpopulation of cells within a tumor appears to have the exclusive ability to initiate tumors, self-renew, and differentiate. These "cancer stem cells" (CSCs) are CD44(+) in several epithelial malignancies. We examined the potential of CD44 to identify the CSC population in nasopharyngeal carcinoma (NPC).C666, an Epstein-Barr virus-positive (EBV(+) ) human NPC cell line, was stained for CD44 and sorted by fluorescence-activated cell sorting (FACS). CD44(+) and CD44(-) subpopulations were evaluated for (1) proliferative potential, (2) ability to differentiate, (3) expression of markers of epithelial-to-mesenchymal transition (EMT) and EBV genes, and (4) the ability to initiate tumors in vivo. Immunocompromised mice were injected with CD44(+) and CD44(-) populations to assess the tumor-initiating capacity. Immunohistochemistry for CD44 was performed on an 87-patient tissue microarray (TMA), and clinical correlations were examined.Heterogeneous expression of CD44 was seen among C666 cells. CD44(+) cells differentiated into CD44(-) cells, indicating a hierarchical relationship. Further, CD44(+) cells exhibited a more robust tumor-initiating capacity in the xenograft model. However, no differences were seen in proliferation rates in vitro, EBV gene expression, or expression of EMT markers between CD44(+) and CD44(-) subsets. Patient tumors were heterogeneous for CD44 staining, and a trend toward an association between CD44 expression and clinical outcome was observed.NPC contains a CD44(+) subpopulation with features consistent with CSCs. There was a trend toward an association between CD44 expression within NPC tumors and decreased time to local failure/relapse in patients.

    View details for DOI 10.1002/alr.21068

    View details for Web of Science ID 000312142200006

    View details for PubMedID 22887934

  • Targeted endoscopic salvage nasopharyngectomy for recurrent nasopharyngeal carcinoma INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY Ho, A. S., Kaplan, M. J., Fee, W. E., Yao, M., Sunwoo, J. B., Hwang, P. H. 2012; 2 (2): 166-173

    Abstract

    Despite modern radiotherapy and open surgical techniques, treatment of recurrent nasopharyngeal carcinoma (NPC) remains challenging, with substantial morbidity involved. Targeted endoscopic nasopharyngectomy was evaluated as a viable oncologic alternative to open nasopharyngectomy or radiation for recurrent NPC.Thirteen patients who underwent endoscopic nasopharyngectomy for recurrent NPC between August 2005 and August 2010 were retrospectively reviewed. Average age at surgery was 55.7 years, with mean follow-up period 24.2 months. Two-year disease-free survival, 2-year overall survival, margin status, and complication rate were measured.Including resections for subsequent recurrences, 19 endoscopic procedures were performed with curative intent. Mean operating room (OR) time was 278 minutes, mean estimated blood loss was 197 mL, and mean length of hospitalization was 1.0 days. Negative margins were obtained in 78.9% of procedures: positive margins involved the parapharyngeal space, oropharynx, fossa of Rosenmuller, and infratemporal fossa. Stereotactic radiation was given postoperatively for localized positive margins. Four patients required repeat endoscopic nasopharyngectomy for re-recurrence, despite having their margins cleared or controlled with adjuvant treatment. Two-year local disease-free and overall survival rates were 69.2% and 100.0%, respectively. The overall minor complication rate was 52.6%, with no major complications.Targeted endoscopic nasopharyngectomy is beneficial in locally recurrent NPC, with favorable morbidity and complication rates. Endoscopic surveillance and serial imaging together facilitate the early identification of re-recurrences, which often may be treated with additional directed resection. Postoperative stereotactic radiation may serve as an appropriate adjunct modality for disease control at positive margins.

    View details for DOI 10.1002/alr.20111

    View details for Web of Science ID 000308926000015

    View details for PubMedID 22170783

  • FREQUENCY OF CELLS EXPRESSING CD44, A HEAD AND NECK CANCER STEM CELL MARKER: CORRELATION WITH TUMOR AGGRESSIVENESS HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK Joshua, B., Kaplan, M. J., Doweck, I., Pai, R., Weissman, I. L., Prince, M. E., Ailles, L. E. 2012; 34 (1): 42-49

    Abstract

    We previously identified by flow cytometry a Lineage-CD44+ (Lin-CD44+) subpopulation of cells with cancer stem cell properties in head and neck squamous cell carcinoma (HNSCC). We now correlate clinical and histologic factors with Lin-CD44+ cell frequency.The study included 31 patients with HNSCC, of whom 87% had stage IV disease. The frequency of Lin-CD44+ cells and the success of xenografting patient tumors in mice were correlated with clinical and pathologic data.The mean frequency of Lin-CD44+ cells was 25% (0.4%-81%). It was 36% in patients who had recurrence versus 15% for those without recurrence (p = .04). Successful xenograft implantation occurred in 53%. Seventy-five percent of patients with successful xenografts had recurrence versus 21% of patients with unsuccessful xenografts (p = .003).Successful xenograft implantation and a high frequency of Lin-CD44+ cells correlate with known poor prognostic factors such as advanced T classification and recurrence. These findings may support the stem cell concept in HNSCC.

    View details for DOI 10.1002/hed.21699

    View details for Web of Science ID 000301972600006

    View details for PubMedID 21322081

  • A Novel Aldehyde Dehydrogenase-3 Activator Leads to Adult Salivary Stem Cell Enrichment In Vivo CLINICAL CANCER RESEARCH Banh, A., Xiao, N., Cao, H., Chen, C., Kuo, P., Krakow, T., Bavan, B., Khong, B., Yao, M., Ha, C., Kaplan, M. J., Sirjani, D., Jensen, K., Kong, C. S., Mochly-Rosen, D., Koong, A. C., Quynh-Thu Le, Q. T. 2011; 17 (23): 7265-7272

    Abstract

    To assess aldehyde dehydrogenase (ALDH) expression in adult human and murine submandibular gland (SMG) stem cells and to determine the effect of ALDH3 activation in SMG stem cell enrichment.Adult human and murine SMG stem cells were selected by cell surface markers (CD34 for human and c-Kit for mouse) and characterized for various other stem cell surface markers by flow cytometry and ALDH isozymes expression by quantitative reverse transcriptase PCR. Sphere formation and bromodeoxyuridine (BrdUrd) incorporation assays were used on selected cells to confirm their renewal capacity and three-dimensional (3D) collagen matrix culture was applied to observe differentiation. To determine whether ALDH3 activation would increase stem cell yield, adult mice were infused with a novel ALDH3 activator (Alda-89) or with vehicle followed by quantification of c-Kit(+)/CD90(+) SMG stem cells and BrdUrd(+) salispheres.More than 99% of CD34(+) huSMG stem cells stained positive for c-Kit, CD90 and 70% colocalized with CD44, Nestin. Similarly, 73.8% c-Kit(+) mSMG stem cells colocalized with Sca-1, whereas 80.7% with CD90. Functionally, these cells formed BrdUrd(+) salispheres, which differentiated into acinar- and ductal-like structures when cultured in 3D collagen. Both adult human and murine SMG stem cells showed higher expression of ALDH3 than in their non-stem cells and 84% of these cells have measurable ALDH1 activity. Alda-89 infusion in adult mice significantly increased c-Kit(+)/CD90(+) SMG population and BrdUrd(+) sphere formation compared with control.This is the first study to characterize expression of different ALDH isozymes in SMG stem cells. In vivo activation of ALDH3 can increase SMG stem cell yield, thus providing a novel means for SMG stem cell enrichment for future stem cell therapy.

    View details for DOI 10.1158/1078-0432.CCR-11-0179

    View details for Web of Science ID 000298133600009

    View details for PubMedID 21998334

  • Correlation between metabolic tumor volume and pathologic tumor volume in squamous cell carcinoma of the oral cavity RADIOTHERAPY AND ONCOLOGY Murphy, J. D., Chisholm, K. M., Daly, M. E., Wiegner, E. A., Truong, D., Iagaru, A., Maxim, P. G., Loo, B. W., Graves, E. E., Kaplan, M. J., Kong, C., Le, Q. 2011; 101 (3): 356-361

    Abstract

    To explore the relationship between pathologic tumor volume and volume estimated from different tumor segmentation techniques on (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in oral cavity cancer.Twenty-three patients with squamous cell carcinoma of the oral tongue had PET-CT scans before definitive surgery. Pathologic tumor volume was estimated from surgical specimens. Metabolic tumor volume (MTV) was defined from PET-CT scans as the volume of tumor above a given SUV threshold. Multiple SUV thresholds were explored including absolute SUV thresholds, relative SUV thresholds, and gradient-based techniques.Multiple MTV's were associated with pathologic tumor volume; however the correlation was poor (R(2) range 0.29-0.58). The ideal SUV threshold, defined as the SUV that generates an MTV equal to pathologic tumor volume, was independently associated with maximum SUV (p=0.0005) and tumor grade (p=0.024). MTV defined as a function of maximum SUV and tumor grade improved the prediction of pathologic tumor volume (R(2)=0.63).Common SUV thresholds fail to predict pathologic tumor volume in head and neck cancer. The optimal technique that allows for integration of PET-CT with radiation treatment planning remains to be defined. Future investigation should incorporate biomarkers such as tumor grade into definitions of MTV.

    View details for DOI 10.1016/j.radonc.2011.05.040

    View details for Web of Science ID 000298894700003

    View details for PubMedID 21665308

  • INTENSITY-MODULATED RADIOTHERAPY FOR ORAL CAVITY SQUAMOUS CELL CARCINOMA: PATTERNS OF FAILURE AND PREDICTORS OF LOCAL CONTROL INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Daly, M. E., Quynh-Thu Le, Q. T., Kozak, M. M., Maxim, P. G., Murphy, J. D., Hsu, A., Loo, B. W., Kaplan, M. J., Fischbein, N. J., Chang, D. T. 2011; 80 (5): 1412-1422

    Abstract

    Few studies have evaluated the use of intensity-modulated radiotherapy (IMRT) for squamous cell carcinoma (SCC) of the oral cavity (OC). We report clinical outcomes and failure patterns for these patients.Between October 2002 and June 2009, 37 patients with newly diagnosed SCC of the OC underwent postoperative (30) or definitive (7) IMRT. Twenty-five patients (66%) received systemic therapy. The median follow-up was 38 months (range, 10-87 months). The median interval from surgery to RT was 5.9 weeks (range, 2.1-10.7 weeks).Thirteen patients experienced local-regional failure at a median of 8.1 months (range, 2.4-31.9 months), and 2 additional patients experienced local recurrence between surgery and RT. Seven local failures occurred in-field (one with simultaneous nodal and distant disease) and two at the margin. Four regional failures occurred, two in-field and two out-of-field, one with synchronous metastases. Six patients experienced distant failure. The 3-year actuarial estimates of local control, local-regional control, freedom from distant metastasis, and overall survival were 67%, 53%, 81%, and 60% among postoperative patients, respectively, and 60%, 60%, 71%, and 57% among definitive patients. Four patients developed Grade ? 2 chronic toxicity. Increased surgery to RT interval predicted for decreased LRC (p = 0.04).Local-regional control for SCC of the OC treated with IMRT with or without surgery remains unsatisfactory. Definitive and postoperative IMRT have favorable toxicity profiles. A surgery-to-RT interval of < 6 weeks improves local-regional control. The predominant failure pattern was local, suggesting that both improvements in target delineation and radiosensitization and/or dose escalation are needed.

    View details for DOI 10.1016/j.ijrobp.2010.04.031

    View details for Web of Science ID 000293207600020

    View details for PubMedID 20675073

  • INTENSITY-MODULATED RADIOTHERAPY FOR LOCALLY ADVANCED CANCERS OF THE LARYNX AND HYPOPHARYNX HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK Daly, M. E., Le, Q., Jain, A. K., Maxim, P. G., Hsu, A., Loo, B. W., Kaplan, M. J., Fischbein, N. J., Colevas, A. D., Pinto, H., Chang, D. T. 2011; 33 (1): 103-111

    Abstract

    Limited data evaluate intensity-modulated radiotherapy (IMRT) for cancers of the hypopharynx and larynx. We report clinical outcomes and failure patterns for these patients.Between September 2001 and December 2007, 42 patients with squamous cell carcinoma (SCC) of the hypopharynx (n = 23) and larynx (n = 19) underwent IMRT, 11 postoperatively and 31 definitively. Thirty-six received systemic therapy. Median follow-up was 30 months among surviving patients.Three local failures occurred within the high-dose region and 3 occurred in regional nodes. Seven patients developed distant metastasis as the initial failure. Three-year actuarial estimates of locoregional control, freedom from distant metastasis, and overall survival rates were, respectively, 80%, 72%, and 46%.IMRT provides good locoregional control for SCC of the hypopharynx and larynx compared with historical controls. Locoregional relapses occurred in the high-dose volumes, suggesting adequate target volume delineation. Hypopharyngeal tumors, which fare worse than laryngeal tumors, warrant investigation of more aggressive treatment.

    View details for DOI 10.1002/hed.21406

    View details for Web of Science ID 000286290400017

    View details for PubMedID 20848427

  • Transoral Robotic Surgery (TORS): The Natural Evolution of Endoscopic Head and Neck Surgery KAPLAN ARTICLE REVIEWED ONCOLOGY-NEW YORK Kaplan, M. J., Damrose, E. J. 2010; 24 (11): 1022-1030

    View details for Web of Science ID 000293341200008

    View details for PubMedID 21155452

  • HIGHER INCIDENCE OF HEAD AND NECK CANCERS AMONG VIETNAMESE AMERICAN MEN IN CALIFORNIA HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK Filion, E. J., McClure, L. A., Huang, D., Seng, K., Kaplan, M. J., Colevas, A. D., Gomez, S. L., Chang, E. T., Le, Q. 2010; 32 (10): 1336-1344

    Abstract

    Our aim was to determine the incidence rates of head and neck cancer in Vietnamese Californians compared with other Asian and non-Asian Californians.Age-adjusted incidence rates of head and neck cancer between 1988 and 2004 were computed for Vietnamese Californians compared with other racial/ethnic groups by time period, ethnicity, neighborhood-level socioeconomic status (SES), and sex using data from the population-based California Cancer Registry (CCR). Data by smoking and alcohol status were tabulated from the California Health Interview Survey.Vietnamese men had a higher incidence rate of head and neck cancer than other Asian men. Specifically, the laryngeal cancer rate was significantly higher for Vietnamese men (6.5/100,000; 95% confidence interval [CI], 5.0-8.2) than all other Asian men (range, 2.6-3.8/100,000), except Korean men (5.1/100,000; 95% CI, 3.9-6.4). Both Vietnamese and Korean men had the highest percentage of current smokers. Neighborhood SES was inversely related to head and neck cancer rates among Vietnamese men and women.The higher incidence rate of head and neck cancer in Vietnamese men may correspond to the higher smoking prevalence in this group. Individual-level data are needed to establish the link of tobacco, alcohol, and other risk factors with head and neck cancer in these patients.

    View details for DOI 10.1002/hed.21330

    View details for Web of Science ID 000282707500008

    View details for PubMedID 20091688

  • Human melanoma-initiating cells express neural crest nerve growth factor receptor CD271 NATURE Boiko, A. D., Razorenova, O. V., van de Rijn, M., Swetter, S. M., Johnson, D. L., Ly, D. P., Butler, P. D., Yang, G. P., Joshua, B., Kaplan, M. J., Longaker, M. T., Weissman, I. L. 2010; 466 (7302): 133-U155

    Abstract

    The question of whether tumorigenic cancer stem cells exist in human melanomas has arisen in the last few years. Here we show that in melanomas, tumour stem cells (MTSCs, for melanoma tumour stem cells) can be isolated prospectively as a highly enriched CD271(+) MTSC population using a process that maximizes viable cell transplantation. The tumours sampled in this study were taken from a broad spectrum of sites and stages. High-viability cells isolated by fluorescence-activated cell sorting and re-suspended in a matrigel vehicle were implanted into T-, B- and natural-killer-deficient Rag2(-/-)gammac(-/-) mice. The CD271(+) subset of cells was the tumour-initiating population in 90% (nine out of ten) of melanomas tested. Transplantation of isolated CD271(+) melanoma cells into engrafted human skin or bone in Rag2(-/-)gammac(-/-) mice resulted in melanoma; however, melanoma did not develop after transplantation of isolated CD271(-) cells. We also show that in mice, tumours derived from transplanted human CD271(+) melanoma cells were capable of metastatsis in vivo. CD271(+) melanoma cells lacked expression of TYR, MART1 and MAGE in 86%, 69% and 68% of melanoma patients, respectively, which helps to explain why T-cell therapies directed at these antigens usually result in only temporary tumour shrinkage.

    View details for DOI 10.1038/nature09161

    View details for Web of Science ID 000279343800049

    View details for PubMedID 20596026

  • INTENSITY-MODULATED RADIOTHERAPY IN THE TREATMENT OF OROPHARYNGEAL CANCER: CLINICAL OUTCOMES AND PATTERNS OF FAILURE INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Daly, M. E., Le, Q., Maxim, P. G., Loo, B. W., Kaplan, M. J., Fischbein, N. J., Pinto, H., Chang, D. T. 2010; 76 (5): 1339-1346

    Abstract

    To report outcomes, failures, and toxicities in patients treated with intensity-modulated radiotherapy (IMRT) for squamous cell carcinoma of the oropharynx.Between Aug 2001 and Oct 2007, 107 patients were treated with IMRT with curative intent at Stanford University. Twenty-two patients were treated postoperatively, and 85 were treated definitively. Concurrent platinum-based chemotherapy was administered to 86 patients (80%) and cetuximab to 8 patients (7%). The prescribed dose was 66 Gy at 2.2 Gy/fraction for definitively treated cases and 60 Gy at 2 Gy/fraction for postoperative cases. Median follow-up was 29 months among surviving patients (range, 4-105 months).Eight patients had persistent disease or local-regional failure at a median of 6.5 months (range, 0-9.9 months). Six local failures occurred entirely within the high-risk clinical target volume (CTV) (one with simultaneous distant metastasis). One patient relapsed within the high- and intermediate-risk CTV. One patient had a recurrence at the junction between the IMRT and low-neck fields. Seven patients developed distant metastasis as the first site of failure. The 3-year local-regional control (LRC), freedom from distant metastasis, overall survival, and disease-free survival rates were 92%, 92%, 83%, and 81%, respectively. T stage (T4 vs. T1-T3) was predictive of poorer LRC (p = 0.001), overall survival (p = 0.001), and disease-free survival (p < 0.001) rates. Acute toxicity consisted of 58% grade 3 mucosal and 5% grade 3 skin reactions. Six patients (6%) developed grade >or=3 late complications.IMRT provides excellent LRC for oropharyngeal squamous cell carcinoma. Distant metastases are a major failure pattern. No marginal failures were observed.

    View details for DOI 10.1016/j.ijrobp.2009.04.006

    View details for Web of Science ID 000276675300012

    View details for PubMedID 19540068

  • Metastatic Squamous Cell Carcinoma Presenting as Diffuse and Punctate Cervical Lymph Node Calcifications Sonographic Features and Utility of Sonographically Guided Fine-Needle Aspiration Biopsy JOURNAL OF ULTRASOUND IN MEDICINE Shin, L. K., Fischbein, N. J., Kaplan, M. J., Jeffrey, R. B. 2009; 28 (12): 1703-1707

    Abstract

    The purpose of this series was to show the sonographic appearance of calcified cervical lymph nodes and the utility of sonographically guided fine-needle aspiration biopsy (FNAB) in the setting of metastatic squamous cell carcinoma (SCC).Two cases of confirmed metastatic SCC to cervical lymph nodes were identified. Sonography and sonographically guided FNAB were performed in both cases with positron emission tomography (PET)/computed tomography (CT) correlation.In case 1, sonography identified a diffusely calcified, avascular cervical lymph node. Positron emission tomography/CT suggested granulomatous disease as a cause for hypermetabolism; however, sonographically guided FNAB identified metastatic SCC. In the second case, FNAB initially performed without sonographic guidance did not show malignancy. Subsequent FNAB with sonographic guidance identified an abnormal cervical lymph node with focal calcifications and internal color Doppler flow. Metastatic SCC was diagnosed on histopathologic examination. Subsequent PET/CT confirmed multiple punctate calcifications in a hypermetabolic lymph node.Calcifications in cervical lymph nodes from metastatic SCC are very rare. These 2 cases show the variable sonographic appearances and the utility of sonographically guided FNAB in establishing the correct diagnosis.

    View details for Web of Science ID 000272375100015

    View details for PubMedID 19933485

  • Association of reactive oxygen species levels and radioresistance in cancer stem cells NATURE Diehn, M., Cho, R. W., Lobo, N. A., Kalisky, T., Dorie, M. J., Kulp, A. N., Qian, D., Lam, J. S., Ailles, L. E., Wong, M., Joshua, B., Kaplan, M. J., Wapnir, I., Dirbas, F. M., Somlo, G., Garberoglio, C., Paz, B., Shen, J., Lau, S. K., Quake, S. R., Brown, J. M., Weissman, I. L., Clarke, M. F. 2009; 458 (7239): 780-U123

    Abstract

    The metabolism of oxygen, although central to life, produces reactive oxygen species (ROS) that have been implicated in processes as diverse as cancer, cardiovascular disease and ageing. It has recently been shown that central nervous system stem cells and haematopoietic stem cells and early progenitors contain lower levels of ROS than their more mature progeny, and that these differences are critical for maintaining stem cell function. We proposed that epithelial tissue stem cells and their cancer stem cell (CSC) counterparts may also share this property. Here we show that normal mammary epithelial stem cells contain lower concentrations of ROS than their more mature progeny cells. Notably, subsets of CSCs in some human and murine breast tumours contain lower ROS levels than corresponding non-tumorigenic cells (NTCs). Consistent with ROS being critical mediators of ionizing-radiation-induced cell killing, CSCs in these tumours develop less DNA damage and are preferentially spared after irradiation compared to NTCs. Lower ROS levels in CSCs are associated with increased expression of free radical scavenging systems. Pharmacological depletion of ROS scavengers in CSCs markedly decreases their clonogenicity and results in radiosensitization. These results indicate that, similar to normal tissue stem cells, subsets of CSCs in some tumours contain lower ROS levels and enhanced ROS defences compared to their non-tumorigenic progeny, which may contribute to tumour radioresistance.

    View details for DOI 10.1038/nature07733

    View details for Web of Science ID 000265193600045

    View details for PubMedID 19194462

  • Excellent local control with stereotactic radiotherapy boost after external beam radiotherapy in patients with nasopharyngeal carcinoma INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Hara, W., Loo, B. W., Goffinet, D. R., Chang, S. D., Adler, J. R., Pinto, H. A., Fee, W. E., Kaplan, M. J., Fischbein, N. J., Le, Q. 2008; 71 (2): 393-400

    Abstract

    To determine long-term outcomes in patients receiving stereotactic radiotherapy (SRT) as a boost after external beam radiotherapy (EBRT) for locally advanced nasopharyngeal carcinoma (NPC).Eight-two patients received an SRT boost after EBRT between September 1992 and July 2006. Nine patients had T1, 30 had T2, 12 had T3, and 31 had T4 tumors. Sixteen patients had Stage II, 19 had Stage III, and 47 had Stage IV disease. Patients received 66 Gy of EBRT followed by a single-fraction SRT boost of 7-15 Gy, delivered 2-6 weeks after EBRT. Seventy patients also received cisplatin-based chemotherapy delivered concurrently with and adjuvant to radiotherapy.At a median follow-up of 40.7 months (range, 6.5-144.2 months) for living patients, there was only 1 local failure in a patient with a T4 tumor. At 5 years, the freedom from local relapse rate was 98%, freedom from nodal relapse 83%, freedom from distant metastasis 68%, freedom from any relapse 67%, and overall survival 69%. Late toxicity included radiation-related retinopathy in 3, carotid aneurysm in 1, and radiographic temporal lobe necrosis in 10 patients, of whom 2 patients were symptomatic with seizures. Of 10 patients with temporal lobe necrosis, 9 had T4 tumors.Stereotactic radiotherapy boost after EBRT provides excellent local control for patients with NPC. Improved target delineation and dose homogeneity of radiation delivery for both EBRT and SRT is important to avoid long-term complications. Better systemic therapies for distant control are needed.

    View details for DOI 10.1016/j.ijrobp.2007.10.027

    View details for Web of Science ID 000255971100013

    View details for PubMedID 18164839

  • Evaluation of patterns of failure and subjective salivary function in patients treated with intensity modulated radiotherapy for head and neck squamous cell carcinoma HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK Daly, M. E., Lieskovsky, Y., Pawlicki, T., Yau, J., Pinto, H., Kaplan, M., Fee, W. E., Koong, A., Goffinet, D. R., Xing, L., Le, Q. 2007; 29 (3): 211-220

    Abstract

    Our aim was to correlate patterns of failure with target volume delineations in patients with head and neck squamous cell carcinoma (HNSCC) treated with intensity-modulated radiation therapy (IMRT) and to report subjective xerostomia outcomes after IMRT as compared with conventional radiation therapy (CRT).Between January 2000 and April 2005, 69 patients with newly diagnosed nonmetastatic HNSCC underwent curative parotid-sparing IMRT at Stanford University. Sites included were oropharynx (n = 39), oral cavity (n = 8), larynx (n = 8), hypopharynx (n = 8), and unknown primary (n = 6). Forty-six patients received definitive IMRT (66 Gy, 2.2 Gy/fraction), and 23 patients received postoperative IMRT (60.2 Gy, 2.15 Gy/fraction). Fifty-one patients also received concomitant chemotherapy. Posttreatment salivary gland function was evaluated by a validated xerostomia questionnaire in 29 IMRT and 75 matched CRT patients >6 months after completing radiation treatment.At a median follow-up of 25 months for living patients (range, 10-60), 7 locoregional failures were observed, 5 in the gross target or high-risk postoperative volume, 1 in the clinical target volume, and 1 at the junction of the IMRT and supraclavicular fields. The 2-year Kaplan-Meier estimates for locoregional control and overall survival were 92% and 74% for definitive IMRT and 87% and 87% for postoperative IMRT patients, respectively. The mean total xerostomia questionnaire score was significantly better for IMRT than for CRT patients (p = .006).The predominant pattern of failure in IMRT-treated patients is in the gross tumor volume. Parotid sparing with IMRT resulted in less subjective xerostomia and may improve quality of life in irradiated HNSCC patients.

    View details for DOI 10.1002/hed.20505

    View details for Web of Science ID 000244459100002

    View details for PubMedID 17111429

  • Identification of a subpopulation of cells with cancer stem cell properties in head and neck squamous cell carcinoma PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Prince, M. E., Sivanandan, R., Kaczorowski, A., Wolf, G. T., Kaplan, M. J., Dalerba, P., Weissman, I. L., Clarke, M. F., Ailles, L. E. 2007; 104 (3): 973-978

    Abstract

    Like many epithelial tumors, head and neck squamous cell carcinoma (HNSCC) contains a heterogeneous population of cancer cells. We developed an immunodeficient mouse model to test the tumorigenic potential of different populations of cancer cells derived from primary, unmanipulated human HNSCC samples. We show that a minority population of CD44(+) cancer cells, which typically comprise <10% of the cells in a HNSCC tumor, but not the CD44(-) cancer cells, gave rise to new tumors in vivo. Immunohistochemistry revealed that the CD44(+) cancer cells have a primitive cellular morphology and costain with the basal cell marker Cytokeratin 5/14, whereas the CD44(-) cancer cells resemble differentiated squamous epithelium and express the differentiation marker Involucrin. The tumors that arose from purified CD44(+) cells reproduced the original tumor heterogeneity and could be serially passaged, thus demonstrating the two defining properties of stem cells: ability to self-renew and to differentiate. Furthermore, the tumorigenic CD44(+) cells differentially express the BMI1 gene, at both the RNA and protein levels. By immunohistochemical analysis, the CD44(+) cells in the tumor express high levels of nuclear BMI1, and are arrayed in characteristic tumor microdomains. BMI1 has been demonstrated to play a role in self-renewal in other stem cell types and to be involved in tumorigenesis. Taken together, these data demonstrate that cells within the CD44(+) population of human HNSCC possess the unique properties of cancer stem cells in functional assays for cancer stem cell self-renewal and differentiation and form unique histological microdomains that may aid in cancer diagnosis.

    View details for DOI 10.1073/pnas.0610117104

    View details for Web of Science ID 000243761100053

    View details for PubMedID 17210912

  • Clinical role of F-18-FDG PET/CT in the management of squamous cell carcinoma of the head and neck and thyroid carcinoma JOURNAL OF NUCLEAR MEDICINE Quon, A., Fischbein, N. J., McDougall, I. R., Le, Q., Loo, B. W., Pinto, H., Kaplan, M. J. 2007; 48: 58S-67S

    Abstract

    18F-FDG PET/CT has rapidly become a widely used imaging modality for evaluating a variety of malignancies, including squamous cell carcinoma of the head and neck and thyroid cancer. Using both published data and the multidisciplinary experience at our institution, we provide a practical set of guidelines and algorithms for the use of 18F-FDG PET/CT in the evaluation and management of head and neck cancer and thyroid cancer.

    View details for Web of Science ID 000243420900008

    View details for PubMedID 17204721

  • Plasma osteopontin is an independent prognostic marker for head and neck cancers JOURNAL OF CLINICAL ONCOLOGY Petrik, D., Lavori, P. W., Cao, H., Zhu, Y., Wong, P., Christofferson, E., Kaplan, M. J., Pinto, H. A., Sutphin, P., Koong, A. C., Giaccia, A. J., Le, Q. 2006; 24 (33): 5291-5297

    Abstract

    To confirm the relationship between plasma osteopontin (OPN) levels and treatment outcomes in head and neck squamous cell carcinoma (HNSCC) patients in an expanded study.One hundred forty patients with newly diagnosed HNSCC were enrolled onto this study, 54 previously reported and 86 new patients. Pretreatment plasma OPN levels were assessed in all patients by an enzyme-linked immunosorbent assay method. OPN levels were correlated to treatment outcomes in the new group of patients. Detailed analyses were also performed on the relationship between OPN and tumor control rate, event-free survival (EFS), and postrelapse survival for the entire group.Using a previously defined cut off point of 450 ng/mL, there was a significant correlation between OPN and freedom-from-relapse (P = .047), overall survival (P = .019), and EFS (P = .023) in the new, independent patient cohort (n = 86). Sequence of event analyses using the entire group (N = 140) revealed that OPN was an independent prognostic factor for initial tumor control, EFS in those who have achieved tumor control, and postrelapse survival.In this expanded study, we were able to replicate the prognostic significance of OPN using a predefined cut off point in an independent patient group and demonstrated that plasma OPN is an independent prognostic marker for HNSCC.

    View details for DOI 10.1200/JCO.2006.06.8627

    View details for Web of Science ID 000242342800017

    View details for PubMedID 17114663

  • Advanced-staged tonsillar squamous carcinoma: Organ preservation versus surgical management of the primary site HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK Shirazi, H. A., Sivanandan, R., Goode, R., Fee, W. E., Kaplan, M. J., Pinto, H. A., Goffinet, D. R., Le, Q. 2006; 28 (7): 587-594

    Abstract

    Our aim was to review our experience in the management of advanced tonsillar squamous cell carcinoma (SCC) and to compare treatment outcomes between patients treated with and without surgery to the primary site.The records of 74 patients with advanced-stage tonsillar SCC were reviewed. The median age at diagnosis was 58 years. Thirty-eight patients received definitive surgery to the primary site, and 36 were treated with an organ-preservation approach (OP) using radiotherapy +/- chemotherapy.No significant difference in overall survival (OS) or freedom from relapse (FFR) by treatment was found. T classification and N status were significant independent predictors on multivariate analysis for OS and FFR. Major late toxicity was noted in 10 patients in the surgical group and nine in the OP group.Patients treated with OP and primary surgery had comparable OS and FFR. T classification and N status were significant independent predictors for tumor relapse and survival. On the basis of these results, we favor organ-preservation therapy for patients with advanced-stage tonsillar SCC.

    View details for DOI 10.1002/hed.20372

    View details for Web of Science ID 000238690100003

    View details for PubMedID 16475199

  • Anterior skull base surgery OTOLARYNGOLOGIC CLINICS OF NORTH AMERICA Kaplan, M. J., Fischbein, N. J., Harsh, G. R. 2005; 38 (1): 107-?

    Abstract

    This article focuses on selected key anatomic considerations in anterior skull base surgery, briefly reviews common pathologies of the paranasal sinuses, and provides an overview of surgical approaches, complications, and results.

    View details for DOI 10.1016/j.otc.2004.09.010

    View details for Web of Science ID 000226736500011

    View details for PubMedID 15649503

  • Long-term results of 100 consecutive comprehensive neck dissections - Implications for selective neck dissections ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY Sivanandan, R., Kaplan, M. J., Lee, K. J., Lebl, D., PINTO, H., Le, Q. T., Goffinet, D. R., Fee, W. E. 2004; 130 (12): 1369-1373

    Abstract

    The optimal surgical procedure for the neck in patients with squamous head and neck cancers is controversial. Selective neck dissections have replaced modified radical neck dissections as the procedure of choice for the clinically negative (N0) neck and are now being considered for patients with early-stage neck disease. We report the long-term local recurrence rates in 100 consecutive patients undergoing a radical or modified radical neck dissection for clinically positive (N+) and N0 neck disease and review comprehensively the literature reporting and comparing regional control rates for both neck dissection types.The clinical records of 100 consecutive patients who underwent a comprehensive neck dissection (levels I-V) for squamous head and neck cancers with a minimum of a 2-year follow-up were retrospectively reviewed for primary site of disease, clinical and pathologic neck status, histopathologic grade, neck dissection type, and the site and time of recurrence.Complete data were available for 97 patients on whom 99 neck dissections were performed. Three patients died from unknown causes. Seventy-six patients with N+ disease underwent a therapeutic neck dissection, while 24 patients with clinically N0 disease underwent an elective dissection. The overall neck recurrence rate in patients with controlled primary disease was 7%. The neck or regional failure rate for patients completing the recommended adjuvant radiotherapy was 4%. Six (25%) of 24 patients with clinically N0 disease had occult metastases. The recurrence rate for this group was 4%.Further study is needed to determine the optimal surgical management of the N0 and limited N+ neck.

    View details for Web of Science ID 000225606400002

    View details for PubMedID 15611394

  • Laryngeal embryonal rhabdomyosarcoma - A case of cervical metastases 13 years after treatment and a 25-year review of existing literature ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY Sivanandan, R., Kong, C. S., Kaplan, M. J., Fee, W. E., Thu-Le, Q., Goffnet, D. R. 2004; 130 (10): 1217-1222

    Abstract

    Rhabdomyosarcoma is the most common soft tissue sarcoma in childhood, the majority of which are of the embryonal rhabdomyosarcoma (ER) variety. Present day treatment protocols involve a combination of aggressive surgery, chemotherapy, and radiation therapy. Embryonal rhabdomyosarcoma of the larynx is rare and unlike ER of other regions exhibits excellent response to multimodality treatment without the need for extensive surgery. We report a case of cervical metastases in a 29-year-old man 13 years after treatment of his laryngeal ER. To our knowledge, this is the first reported case of late neck metastases in ER of the larynx and the second reported case of delayed presentation of recurrent disease. A 25-year review of all published reports of ER of the larynx was conducted that highlights the move toward organ preservation with the multimodality treatment protocols. Embryonal rhabdomyosarcoma of the larynx is highly responsive to combination chemoradiotherapy, allowing for excellent cure rates without the need for extensive surgery. Late relapses warrant long-term follow-up.

    View details for Web of Science ID 000224353600016

    View details for PubMedID 15492173

  • Lymph node metastasis in maxillary sinus carcinoma INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Le, Q. T., Fu, K. K., Kaplan, M. J., Terris, D. J., Fee, W. E., Goffinet, D. R. 2000; 46 (3): 541-549

    Abstract

    To evaluate the incidence and prognostic significance of lymph node metastasis in maxillary sinus carcinoma.We reviewed the records of 97 patients treated for maxillary sinus carcinoma with radiotherapy at Stanford University and at the University of California, San Francisco between 1959 and 1996. Fifty-eight patients had squamous cell carcinoma (SCC), 4 had adenocarcinoma (ADE), 16 had undifferentiated carcinoma (UC), and 19 had adenoid cystic carcinoma (AC). Eight patients had T2, 36 had T3, and 53 had T4 tumors according to the 1997 AJCC staging system. Eleven patients had nodal involvement at diagnosis: 9 with SCC, 1 with UC, and 1 with AC. The most common sites of nodal involvement were ipsilateral level 1 and 2 lymph nodes. Thirty-six patients were treated with definitive radiotherapy alone, and 61 received a combination of surgical and radiation treatment. Thirty-six patients had neck irradiation, 25 of whom received elective neck irradiation (ENI) for N0 necks. The median follow-up for alive patients was 78 months.The median survival for all patients was 22 months (range: 2.4-356 months). The 5- and 10-year actuarial survivals were 34% and 31%, respectively. Ten patients relapsed in the neck, with a 5-year actuarial risk of nodal relapse of 12%. The 5-year risk of neck relapse was 14% for SCC, 25% for ADE, and 7% for both UC and ACC. The overall risk of nodal involvement at either diagnosis or on follow-up was 28% for SCC, 25% for ADE, 12% for UC, and 10% for AC. All patients with nodal involvement had T3-4, and none had T2 tumors. ENI effectively prevented nodal relapse in patients with SCC and N0 neck; the 5-year actuarial risk of nodal relapse was 20% for patients without ENI and 0% for those with elective neck therapy. There was no correlation between neck relapse and primary tumor control or tumor extension into areas containing a rich lymphatic network. The most common sites of nodal relapse were in the ipsilateral level 1-2 nodal regions (11/13). Patients with nodal relapse had a significantly higher risk of distant metastasis on both univariate (p = 0.02) and multivariate analysis (hazard ratio = 4.5, p = 0.006). The 5-year actuarial risk of distant relapse was 29% for patients with neck control versus 81% for patients with neck failure. There was also a trend for decreased survival with nodal relapse. The 5-year actuarial survival was 37% for patients with neck control and 0% for patients with neck relapse.The overall incidence of lymph node involvement at diagnosis in patients with maxillary sinus carcinoma was 9%. Following treatment, the 5-year risk of nodal relapse was 12%. SCC histology was associated with a high incidence of initial nodal involvement and nodal relapse. None of the patients presenting with SCC histology and N0 necks had nodal relapse after elective neck irradiation. Patients who had nodal relapse had a higher risk of distant metastasis and poorer survival. Therefore, our present policy is to consider elective neck irradiation in patients with T3-4 SCC of the maxillary sinus.

    View details for Web of Science ID 000085412400004

    View details for PubMedID 10701732

  • Treatment of maxillary sinus carcinoma - A comparison of the 1997 and 1977 American Joint Committee on Cancer staging systems CANCER Le, Q. T., Fu, K. K., Kaplan, M., Terris, D. J., Fee, W. E., Goffinet, D. R. 1999; 86 (9): 1700-1711

    Abstract

    This study was conducted to assess the effectiveness of the 1997 American Joint Committee on Cancer (AJCC) staging system to predict survival and local control of patients with maxillary sinus carcinoma and to identify significant factors for overall survival, local control, and distant metastases in patients with these tumors.Ninety-seven patients with maxillary sinus carcinoma were treated with radiotherapy at Stanford University and the University of California, San Francisco between 1959-1996. The histologic type of carcinoma among the 97 patients were: 58 squamous cell carcinomas, 4 adenocarcinomas, 16 undifferentiated carcinomas, and 19 adenoid cystic carcinomas. All patients were restaged clinically according to the 1977 and 1997 AJCC staging systems. The T classification of the tumors of the patients was as follows: 8 with T2, 18 with T3, and 71 with T4 according to the 1977 system and 8 with T2, 36 with T3, and 53 with T4 according to the 1997 system. Eleven patients had lymph node involvement at diagnosis. Thirty-six patients were treated with radiotherapy alone and 61 received a combination of surgical and radiation treatments. The median follow-up for surviving patients was 78 months.The 5-year and 10-year actuarial survival rates for all patients were 34% and 31%, respectively. The 5-year survival estimate by the 1977 AJCC system (P = 0.06) was 75% for Stage II, 19% for Stage III, and 34% for Stage IV and by the 1997 AJCC system (P = 0.006) was 75% for Stage II, 37% for Stage III, and 28% for Stage IV. Significant prognostic factors for survival by multivariate analysis included age (favoring younger age, P<0.001), 1997 T classification (favoring T2-3, P = 0. 001), lymph node involvement at diagnosis (favoring N0, P = 0.002), treatment modality of the primary tumor site (favoring surgery and radiotherapy, P = 0.009), and gender (favoring female patients, P = 0.04). The overall radiation time was of borderline significance (favoring shorter time, P = 0.06). The actuarial 5-year local control rate was 43%. By the 1977 AJCC system (P = 0.78) it was 62% with T2, 36% with T3, and 45% with T4 and using the 1997 AJCC system (P = 0.29) it was 62% with T2, 53% with T3, and 36% with T4. The only significant prognostic factor for local control for all patients by multivariate analysis was local therapy, favoring surgery and radiotherapy over radiotherapy alone (P< 0.001). For patients treated with surgery, pathologic margin status correlated with local control (P = 0.007) and for patients treated with radiation alone, higher tumor dose (P = 0.007) and shorter overall treatment time (P = 0.04) were associated with fewer local recurrences. The 5-year estimate of freedom from distant metastases was 66%. The 1997 T classification, N classification, and lymph node recurrence were adverse prognostic factors for distant metastases on multivariate analysis. There were 22 complications in 16 patients, representing a 30% actuarial risk of developing late complications at 10 years.The 1997 AJCC staging system was found to be superior to the 1977 AJCC staging system in predicting both survival and local control in this patient population. Combined surgical and radiation treatment to the primary tumor yielded higher survival and local control than radiotherapy alone. Other significant prognostic factors for survival were patient age, gender, and lymph node (N) classification. Prolonged overall radiation time was associated with poorer survival and local control. Late severe toxicity from the treatment of these tumors was a significant problem in long term survivors. Improved radiotherapy techniques should lead to decreased injury to the surrounding normal tissues. (c) 1999 American Cancer Society.

    View details for Web of Science ID 000083430700011

    View details for PubMedID 10547542

  • Magnetic resonance imaging of the central skull base. Topics in magnetic resonance imaging Fischbein, N. J., Kaplan, M. J. 1999; 10 (5): 325-346

    Abstract

    The central skull base is an anatomically complex region whose foundation is the sphenoid bone. It includes the sphenoid sinus, clivus, and sella turcica, as well as adjacent soft tissues such as the cavernous sinuses and nasopharynx. The central skull base may be affected by pathologies intrinsic to the sphenoid bone or by processes that arise in adjacent soft tissue and extend centrally to affect the central skull base. In general, this region is optimally imaged with magnetic resonance scanning, although in some cases computed tomography can provide complementary information. In this review, we will discuss a variety of pathologies that can affect the central skull base, such as neoplasms, infections, trauma, congenital malformations, and a variety of miscellaneous pathologies. We will discuss processes that can mimic neoplasia, such as aggressive polyposis and chronic inflammatory disease. For each pathology we will review clinical and imaging findings.

    View details for PubMedID 10643825

Conference Proceedings


  • Intensity-Modulated Radiotherapy for Tumors of the Nasal Cavity and Paranasal Sinuses: Clinical Outcomes and Patterns of Failure Wiegner, E. A., Daly, M. E., Murphy, J. D., Abelson, J., Chapman, C. H., Chung, M., Yu, Y., Colevas, A. D., Kaplan, M. J., Fischbein, N., Quynh-Thu Le, Q. T., Chang, D. T. ELSEVIER SCIENCE INC. 2012: 243-251

    Abstract

    To report outcomes in patients treated with intensity-modulated radiotherapy (IMRT) for tumors of the paranasal sinuses and nasal cavity (PNS/NC).Between June 2000 and December 2009, 52 patients with tumors of the PNS/NC underwent postoperative or definitive radiation with IMRT. Twenty-eight (54%) patients had squamous cell carcinoma (SCC). Twenty-nine patients (56%) received chemotherapy. The median follow-up was 26.6 months (range, 2.9-118.4) for all patients and 30.9 months for living patients.Eighteen patients (35%) developed local-regional failure (LRF) at median time of 7.2 months. Thirteen local failures (25%) were observed, 12 in-field and 1 marginal. Six regional failures were observed, two in-field and four out-of-field. No patients treated with elective nodal radiation had nodal regional failure. Two-year local-regional control (LRC), in-field LRC, freedom from distant metastasis (FFDM), and overall survival (OS) were 64%, 74%, 71%, and 66% among all patients, respectively, and 43%, 61%, 61%, and 53% among patients with SCC, respectively. On multivariate analysis, SCC and >1 subsite involved had worse LRC (p = 0.0004 and p = 0.046, respectively) and OS (p = 0.003 and p = 0.046, respectively). Cribriform plate invasion (p = 0.005) and residual disease (p = 0.047) also had worse LRC. Acute toxicities included Grade ?3 mucositis in 19 patients (37%), and Grade 3 dermatitis in 8 patients (15%). Six patients had Grade ?3 late toxicity including one optic toxicity.IMRT for patients with PNS/NC tumors has good outcomes compared with historical series and is well tolerated. Patients with SCC have worse LRC and OS. LRF is the predominant pattern of failure.

    View details for DOI 10.1016/j.ijrobp.2011.05.044

    View details for Web of Science ID 000302993900057

    View details for PubMedID 22019239

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