Photo of Lori J. Wirth,  MD

Lori J. Wirth, MD

Massachusetts General Hospital

Massachusetts General Hospital
Phone: (617) 724-4000


lwirth@partners.org

Lori J. Wirth, MD

Massachusetts General Hospital

EDUCATIONAL TITLES

  • Assistant Professor, Medicine, Harvard Medical School
  • Assistant Professor, Medicine, Massachusetts General Hospital

Research Abstract

I work as a medical oncologist in the Dana-Farber Head and Neck Oncology Program. One of the most appealing aspects of head and neck cancer is the accessibility of target tumor for biopsy. The majority of patients, whether newly diagnosed or with recurrent disease, will have tumor present within the head and neck region that can be readily biopsied prior to, during, and after treatment. This affords an invaluable resource for correlative studies that, beyond caring for patients with head and neck cancer and running clinical trials, is a major focus of my research efforts.

We have published the trial, “Phase I Study of Gefitnib Plus Celecoxib in Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck.” This study showed that the combination of EGFR and COX-2 inhibition was well-tolerated, and may be more effective than EGFR tyrosine kinase inhibition (TKI) alone in SCCHN. Predictive markers EGFR TKIs were evaluated, and results suggested that factors other than EGFR gene alterations or KRAS mutations account for response in SCCHN. Building on this experience, we now have a 2nd generation of clinical trials underway investigating combined target therapy in SCCHN.

Another important research initiative is a collaboration between the Dana-Farber Head and Neck Oncology Program and Dr. Frederick Wang of the Division of Virology at Brigham and Women’s Hospital. We are developing a program of immunotherapy for EBV-associated nasopharyngeal carcinoma (NPC). In conjunction with the Connell O’Reilly Families Center for Cell Therapies we have established the Standard Operating Procedures for GMP production of an autologous T cell immunotherapy product. A pilot clinical trial protocol will beunderway before the end of 2006. Extensive translational studies will investigate immune factors that may be responsible for benefit. We plan for this pilot study to generate the necessary preliminary data to not only improve our strategies for therapy, but also obtain support for more definitive study of T cell immunotherapy in NPC. Ultimately, we expect this work to lead to development of vaccine approaches that will have broad implications in EBV-associated malignancy.

Publications

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  • Schlumberger M, Tahara M, Wirth LJ. Lenvatinib in radioiodine-refractory thyroid cancer. N Engl J Med 2015; 372:1868. PubMed
  • Wirth LJ. Targeted therapy for advanced or metastatic differentiated thyroid carcinoma. Clin Adv Hematol Oncol 2015; 13 Suppl 4:9-16. PubMed
  • Shah JP, Clayman GL, Wirth LJ. New and emerging therapeutic options for thyroid carcinoma. Clin Adv Hematol Oncol 2015; 13:3-17, 1; quiz 2 p following 18. PubMed
  • Galloway TJ, Wirth LJ, Colevas AD, Gilbert J, Bauman JE, Saba NF, Raben D, Mehra R, Ma AW, Atoyan R, Wang J, Burtness B, Jimeno A. A Phase I Study of CUDC-101, a Multitarget Inhibitor of HDACs, EGFR, and HER2, in Combination with Chemoradiation in Patients with Head and Neck Squamous Cell Carcinoma. Clin Cancer Res 2015; 21:1566-73. PubMed
  • Rothenberg SM, McFadden DG, Palmer EL, Daniels GH, Wirth LJ. Redifferentiation of Iodine-Refractory BRAF V600E-Mutant Metastatic Papillary Thyroid Cancer with Dabrafenib. Clin Cancer Res 2015; 21:1028-35. PubMed
  • Goldman J, Eckhardt SG, Borad MJ, Curtis KK, Hidalgo M, Calvo E, Ryan DP, Wirth LJ, Parikh A, Partyka J, Faessel H, Gangolli E, Stewart S, Rosen LS, Bowles DW. Phase I Dose-Escalation Trial of the Oral Investigational Hedgehog Signaling Pathway Inhibitor TAK-441 in Patients with Advanced Solid Tumors. Clin Cancer Res 2015; 21:1002-9. PubMed
  • Schlumberger M, Tahara M, Wirth LJ, Robinson B, Brose MS, Elisei R, Habra MA, Newbold K, Shah MH, Hoff AO, Gianoukakis AG, Kiyota N, Taylor MH, Kim SB, Krzyzanowska MK, Dutcus CE, de las Heras B, Zhu J, Sherman SI. Lenvatinib versus placebo in radioiodine-refractory thyroid cancer. N Engl J Med 2015; 372:621-30. PubMed
  • Tuttle RM, Haddad RI, Ball DW, Byrd D, Dickson P, Duh QY, Ehya H, Haymart M, Hoh C, Hunt JP, Iagaru A, Kandeel F, Kopp P, Lamonica DM, Lydiatt WM, McCaffrey J, Moley JF, Parks L, Raeburn CD, Ridge JA, Ringel MD, Scheri RP, Shah JP, Sherman SI, Sturgeon C, Waguespack SG, Wang TN, Wirth LJ, Hoffmann KG, Hughes M. Thyroid carcinoma, version 2.2014. J Natl Compr Canc Netw 2014; 12:1671-80; quiz 1680. PubMed
  • Chong CR, Wirth LJ, Nishino M, Chen AB, Sholl LM, Kulke MH, McNamee CJ, Jänne PA, Johnson BE. Chemotherapy for locally advanced and metastatic pulmonary carcinoid tumors. Lung Cancer 2014. PubMed
  • Locati LD, Licitra L, Agate L, Ou SH, Boucher A, Jarzab B, Qin S, Kane MA, Wirth LJ, Chen C, Kim S, Ingrosso A, Pithavala YK, Bycott P, Cohen EE. Treatment of advanced thyroid cancer with axitinib: Phase 2 study with pharmacokinetic/pharmacodynamic and quality-of-life assessments. Cancer 2014. PubMed
  • Gross ND, Bauman JE, Gooding WE, Denq WH, Thomas SM, Wang L, Chiosea S, Hood BL, Flint MS, Sun M, Conrads TP, Ferris RL, Johnson JT, Kim S, Argiris A, Wirth LJ, Nikiforova MN, Siegfried JM, Grandis JR. Erlotinib, erlotinib-sulindac vs. placebo: a randomized, double-blind, placebo-controlled window trial in operable head and neck cancer. Clin Cancer Res 2014. PubMed
  • McBride SM, Busse PM, Clark JR, Wirth LJ, Ancukiewicz M, Chan AW. Long-term survival after distant metastasis in patients with oropharyngeal cancer. Oral Oncol 2014; 50:208-12. PubMed
  • Wirth LJ. Chemoprevention of squamous cell carcinoma of the head and neck: no time to lose momentum. Cancer Prev Res (Phila Pa) 2014; 7:279-82. PubMed
  • Elisei R, Schlumberger MJ, Müller SP, Schöffski P, Brose MS, Shah MH, Licitra L, Jarzab B, Medvedev V, Kreissl MC, Niederle B, Cohen EE, Wirth LJ, Ali H, Hessel C, Yaron Y, Ball D, Nelkin B, Sherman SI. Cabozantinib in progressive medullary thyroid cancer. J Clin Oncol 2013; 31:3639-46. PubMed
  • McBride SM, Rothenberg SM, Faquin WC, Chan AW, Clark JR, Ellisen LW, Wirth LJ. Mutation frequency in 15 common cancer genes in high-risk head and neck squamous cell carcinoma. Head Neck 2014. PubMed
  • Anderson RT, Linnehan JE, Tongbram V, Keating K, Wirth LJ. Clinical, safety, and economic evidence in radioactive iodine-refractory differentiated thyroid cancer: a systematic literature review. Thyroid 2013; 23:392-407. PubMed
  • Wirth LJ, Ross DS, Randolph GW, Cunnane ME, Sadow PM. Case records of the Massachusetts General Hospital. Case 5-2013. A 52-year-old woman with a mass in the thyroid. N Engl J Med 2013; 368:664-73. PubMed
  • Nardi V, Sadow PM, Juric D, Zhao D, Cosper AK, Bergethon K, Scialabba VL, Batten JM, Borger DR, Iafrate AJ, Heist RS, Lawrence DP, Flaherty KT, Bendell JC, Deschler D, Li Y, Wirth LJ, Dias-Santagata D. Detection of novel actionable genetic changes in salivary duct carcinoma helps direct patient treatment. Clin Cancer Res 2013; 19:480-90. PubMed
  • Rosen LS, Lipton L, Price TJ, Belman ND, Boccia RV, Hurwitz HI, Stephenson JJ, Wirth LJ, McCoy S, Hei YJ, Hsu CP, Tebbutt NC. The effect of different dosing regimens of motesanib on the gallbladder: a randomized phase 1b study in patients with advanced solid tumors. BMC Cancer 2013; 13:242. PubMed
  • Wirth LJ, Plotkin SR, Emerick KS, Cunnane ME, Faquin WC. Case records of the Massachusetts General Hospital. Case 29-2012. A 49-year-old man with pain and cranial-nerve palsies after treatment of oral cancer. N Engl J Med 2012; 367:1136-47. PubMed
  • Sher DJ, Balboni TA, Haddad RI, Norris CM, Posner MR, Wirth LJ, Goguen LA, Annino D, Tishler RB. Efficacy and Toxicity of Chemoradiotherapy Using Intensity-Modulated Radiotherapy for Unknown Primary of Head and Neck. Int J Radiat Oncol Biol Phys 2010. PubMed
  • Tuttle RM, Ball DW, Byrd D, Dilawari RA, Doherty GM, Duh QY, Ehya H, Farrar WB, Haddad RI, Kandeel F, Kloos RT, Kopp P, Lamonica DM, Loree TR, Lydiatt WM, McCaffrey JC, Olson JA, Parks L, Ridge JA, Shah JP, Sherman SI, Sturgeon C, Waguespack SG, Wang TN, Wirth LJ, . Thyroid carcinoma. J Natl Compr Canc Netw 2010; 8:1228-74. PubMed
  • Sher DJ, Haddad RI, Norris CM, Posner MR, Wirth LJ, Goguen LA, Annino D, Balboni T, Allen A, Tishler RB. Efficacy and toxicity of reirradiation using intensity-modulated radiotherapy for recurrent or second primary head and neck cancer. Cancer 2010; 116:4761-8. PubMed
  • Cleary JM, Sadow PM, Randolph GW, Palmer EL, Lynch TP, Nikiforov YE, Wirth LJ. Neoadjuvant treatment of unresectable medullary thyroid cancer with sunitinib. J Clin Oncol 2010; 28:e390-2. PubMed
  • Tuttle RM, Ball DW, Byrd D, Daniels GH, Dilawari RA, Doherty GM, Duh QY, Ehya H, Farrar WB, Haddad RI, Kandeel F, Kloos RT, Kopp P, Lamonica DM, Loree TR, Lydiatt WM, McCaffrey J, Olson JA, Parks L, Ridge JA, Shah JP, Sherman SI, Sturgeon C, Waguespack SG, Wang TN, Wirth LJ. Medullary carcinoma. J Natl Compr Canc Netw 2010; 8:512-30. PubMed
  • Haddad R, Sonis S, Posner M, Wirth L, Costello R, Braschayko P, Allen A, Mahadevan A, Flynn J, Burke E, Li Y, Tishler RB. Randomized phase 2 study of concomitant chemoradiotherapy using weekly carboplatin/paclitaxel with or without daily subcutaneous amifostine in patients with locally advanced head and neck cancer. Cancer 2009; 115:4514-23. PubMed
  • Haddad RI, Tishler RB, Norris C, Goguen L, Balboni TA, Costello R, Wirth L, Lorch J, Andreozzi B, Annino D, Posner MR. Phase I study of C-TPF in patients with locally advanced squamous cell carcinoma of the head and neck. J Clin Oncol 2009; 27:4448-53. PubMed
  • Schlumberger MJ, Elisei R, Bastholt L, Wirth LJ, Martins RG, Locati LD, Jarzab B, Pacini F, Daumerie C, Droz JP, Eschenberg MJ, Sun YN, Juan T, Stepan DE, Sherman SI. Phase II study of safety and efficacy of motesanib in patients with progressive or symptomatic, advanced or metastatic medullary thyroid cancer. J Clin Oncol 2009; 27:3794-801. PubMed
  • Lorch JH,Posner MR,Wirth LJ,Haddad RI. Seeking alternative biological therapies: the future of targeted molecular treatment. Oral Oncol 2008; 45:447-53. PubMed
  • Fogg MH,Wirth LJ,Posner M,Wang F. Decreased EBNA-1-specific CD8+ T cells in patients with Epstein-Barr virus-associated nasopharyngeal carcinoma. Proc Natl Acad Sci U S A 2009; 106:3318-23. PubMed
  • Lorch JH,Posner MR,Wirth LJ,Haddad RI. Induction chemotherapy in locally advanced head and neck cancer: a new standard of care? Hematol Oncol Clin North Am 2008; 22:1155-63, viii. PubMed
  • Caglar HB, Tishler RB, Othus M, Burke E, Li Y, Goguen L, Wirth LJ, Haddad RI, Norris CM, Court LE, Aninno DJ, Posner MR, Allen AM. Dose to Larynx Predicts for Swallowing Complications After Intensity-Modulated Radiotherapy. Int J Radiat Oncol Biol Phys 2008; 72:1110-8. PubMed
  • Wirth LJ,Krane JF,Li Y,Othus M,Moran AE,Dorfman DM,Norris CM Jr,Goguen L,Posner MR,Haddad RI,Bertagnolli MM. A pilot surrogate endpoint biomarker study of celecoxib in oral premalignant lesions. Cancer Prev Res (Phila Pa) 2009; 1:339-48. PubMed
  • Pennell NA, Daniels GH, Haddad RI, Ross DS, Evans T, Wirth LJ, Fidias PH, Temel JS, Gurubhagavatula S, Heist RS, Clark JR, Lynch TJ. A Phase II Study of Gefitinib in Patients with Advanced Thyroid Cancer. Thyroid 2008; 18:317-23. PubMed
  • Wirth LJ, Posner MR. Recent advances in combined modality therapy for locally advanced head and neck cancer. Curr Cancer Drug Targets 2007; 7:674-80. PubMed
  • Freedman RA, Wirth LJ, Chirieac LR, Huang EC. Glioblastoma in a patient with early-stage tonsil cancer. J Clin Oncol 2007; 25:2848-50. PubMed
  • Tishler RB, Posner MR, Norris CM, Mahadevan A, Sullivan C, Goguen L, Wirth LJ, Costello R, Case M, Stowell S, Sammartino D, Busse PM, Haddad RI. Concurrent weekly docetaxel and concomitant boost radiation therapy in the treatment of locally advanced squamous cell cancer of the head and neck. Int J Radiat Oncol Biol Phys 2006; 65:1036-44. PubMed
  • Haddad R, Tishler R, Wirth L, Norris CM, Goguen L, Sullivan C, O'Donnell L, Li Y, Posner M. Rate of pathologic complete responses to docetaxel, cisplatin, and fluorouracil induction chemotherapy in patients with squamous cell carcinoma of the head and neck. Arch Otolaryngol Head Neck Surg 2006; 132:678-81. PubMed
  • Goguen LA, Posner MR, Norris CM, Tishler RB, Wirth LJ, Annino DJ, Gagne A, Sullivan CA, Sammartino DE, Haddad RI. Dysphagia after sequential chemoradiation therapy for advanced head and neck cancer. Otolaryngol Head Neck Surg 2006; 134:916-22. PubMed
  • Goguen LA, Posner MR, Tishler RB, Wirth LJ, Norris CM, Annino DJ, Sullivan CA, Li Y, Haddad RI. Examining the need for neck dissection in the era of chemoradiation therapy for advanced head and neck cancer. Arch Otolaryngol Head Neck Surg 2006; 132:526-31. PubMed
  • Haddad RI, Posner MR, Busse PM, Norris CM, Goguen LA, Wirth LJ, Blinder R, Krane JF, Tishler RB. Chemoradiotherapy for adenoid cystic carcinoma: preliminary results of an organ sparing approach. Am J Clin Oncol 2006; 29:153-7. PubMed
  • Posner MR, Wirth LJ. Cetuximab and radiotherapy for head and neck cancer. N Engl J Med 2006; 354:634-6. PubMed
  • Haddad R, Allen A, Wirth L, Tishler R, Posner M. Integrating novel agents into the curative treatment of head and neck cancer. Expert Rev Anticancer Ther 2006; 6:157-9. PubMed
  • Wirth LJ, Haddad RI, Lindeman NI, Zhao X, Lee JC, Joshi VA, Norris CM, Posner MR. Phase I study of gefitinib plus celecoxib in recurrent or metastatic squamous cell carcinoma of the head and neck. J Clin Oncol 2005; 23:6976-81. PubMed
  • Guadagnolo BA, Haddad RI, Posner MR, Weeks L, Wirth LJ, Norris CM, Sullivan CA, Goguen L, Busse PM, Tishler R. Organ preservation and treatment toxicity with induction chemotherapy followed by radiation therapy or chemoradiation for advanced laryngeal cancer. Am J Clin Oncol 2005; 28:371-8. PubMed
  • Gokhale AS, Haddad RI, Cavacini LA, Wirth L, Weeks L, Hallar M, Faucher J, Posner MR. Serum concentrations of interleukin-8, vascular endothelial growth factor, and epidermal growth factor receptor in patients with squamous cell cancer of the head and neck. Oral Oncol 2004; 41:70-6. PubMed
  • Posner MR, Haddad RI, Wirth L, Norris CM, Goguen LA, Mahadevan A, Sullivan C, Tishler RB. Induction chemotherapy in locally advanced squamous cell cancer of the head and neck: evolution of the sequential treatment approach. Semin Oncol 2004; 31:778-85. PubMed
  • Sullivan CA, Jaklitsch MT, Haddad R, Goguen LA, Gagne A, Wirth LJ, Posner MR, Tishler RB, Norris CM. Endoscopic management of hypopharyngeal stenosis after organ sparing therapy for head and neck cancer. Laryngoscope 2004; 114:1924-31. PubMed
  • Wirth LJ, Carter MR, J. Outcome of patients with pulmonary carcinoid tumors receiving chemotherapy or chemoradiotherapy. Lung Cancer 2004; 44:213-20. PubMed
  • Haddad R, Wirth L, Costello R, Weeks L, Posner M. Phase II randomized study of concomitant chemoradiation using weekly carboplatin/paclitaxel with or without daily subcutaneous amifostine in patients with newly diagnosed locally advanced squamous cell carcinoma of the head and neck. Semin Oncol 2004; 30:84-8. PubMed
  • Wirth LJ, Haddad RI, Posner MR. Progress and perspectives in chemoprevention of head and neck cancer. Expert Rev Anticancer Ther 2003; 3:339-55. PubMed
  • Haddad RI, Wirth L, Posner MR. Integration of chemotherapy in the curative treatment of locally advanced head and neck cancer. Expert Rev Anticancer Ther 2003; 3:331-8. PubMed
  • Wirth LJ, Lucca J, Ostler P, Fidias P, Lynch C, J. Induction docetaxel and carboplatin followed by weekly docetaxel and carboplatin with concurrent radiotherapy, then surgery in stage III non-small cell lung cancer: a Phase I study. Clin Cancer Res 2003; 9:1698-704. PubMed
  • Haddad R, Tishler RB, Norris CM, Mahadevan A, Busse P, Wirth L, Goguen LA, Sullivan CA, Costello R, Case MA, Posner MR. Docetaxel, cisplatin, 5-fluorouracil (TPF)-based induction chemotherapy for head and neck cancer and the case for sequential, combined-modality treatment. Oncologist 2003; 8:35-44. PubMed
  • Kolodner RD, Hall NR, Lipford J, Kane MF, Rao MR, Morrison P, Wirth L, Finan PJ, Burn J, Chapman P. Structure of the human MSH2 locus and analysis of two Muir-Torre kindreds for msh2 mutations. Genomics 1994; 24:516-26. PubMed
  • Kolodner RD, Hall NR, Lipford J, Kane MF, Rao MR, Morrison P, Wirth L, Finan PJ, Burn J, Chapman P. Human mismatch repair genes and their association with hereditary non-polyposis colon cancer. Cold Spring Harb Symp Quant Biol 1994; 59:331-8. PubMed
  • Adra CN, Ko J, Leonard D, Wirth LJ, Cerione RA, Lim B. Identification of a novel protein with GDP dissociation inhibitor activity for the ras-like proteins CDC42Hs and rac I. Genes Chromosomes Cancer 1993; 8:253-61. PubMed
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