Adjuvant chemoradiation therapy with high-dose versus weekly cisplatin for resected, locally-advanced HPV/p16-positive and negative head and neck squamous cell carcinomaOral Oncology


Jessica L. Geiger, Ahmed F. Lazim, Francis J. Walsh, Robert L. Foote, Eric J. Moore, Scott H. Okuno, Kerry D. Olsen, Jan L. Kasperbauer, Daniel L. Price, Yolanda I. Garces, Daniel J. Ma, Michelle A. Neben-Wittich, Julian R. Molina, Joaquin J. Garcia, Katharine A.R. Price
Oncology / Oral Surgery / Cancer Research


Detection of circulating tumor cells for prediction of recurrence after adjuvant chemoradiation in locally advanced squamous cell carcinoma of the head and neck

I. Tinhofer, R. Konschak, C. Stromberger, J.- D. Raguse, J. H. Dreyer, K. Johrens, U. Keilholz, V. Budach

Intra-arterial chemoradiation therapy with weekly low-dose cisplatin for squamous cell carcinoma of the maxillary sinus

T. Kaneko, Y. Tada, S. Maruya, E. Takeishi, K. Miura, T. Masubuchi, C. Fushimi, H. Hasegawa, S. Kamata

HPV-associated P16 positive head and neck squamous cell carcinomas exhibit improved prognosis and response to radiotherapy

P. Lassen, J. Eriksen, J. Alsner, S. Hamilton-Dutoit, J. Overgaard

Neo-adjuvant chemotherapy with cisplatin and 5-fluorouracil in advanced squamous cell carcinoma of head and neck; a randomiozed phase III study

F Lewin, L Damber, H Jonsson, T Anderson, A Berthelsen, A Biörklund, E Bromquist, JF Hansen, O Hasen, O Jedlund, C Merckle, H Modig, M Overgaard, B Rosengren, J Tausjö, U Ringborg

A non-randomized comparison of gemcitabine-based chemoradiation with or without induction chemotherapy for locally advanced squamous cell carcinoma of the head and neck

Pol M Specenier, Joost Weyler, Carl Van Laer, Danielle Weyngaert, Jan Brande, Manon T Huizing, Sevilay Altintas, Jan B Vermorken


cisplatin for resected, loca and negative head and ne

Jessica L. Geiger a, Ahmed F. Lazim

Kerry D. Olsen e, Jan L. Kasperbau

Michelle A. Neben-Wittich d, Julia aDepartment of Internal Medicine, Mayo Clinic, Rochest b Hospita logy, Ma ic, Roche

Surgery hester, M vival and minimize

All rights reserved.


Locally advanced head and neck squamous cell carcinoma (HNSCC) has a five-year survival of approximately 50% despite intensification of therapy with surgery, radiation, and chemotherapy [1]. In 2004, two randomized trials were published demonstrating improved locoregional control and possibly survival with postoperative chemoradiation therapy with dose cisplatin for patients with high-risk features for recurrence [2,3]. A meta-analysis of the two trials concluded that the patients who derived the most benefit from the addition of cisplatin to radiation therapy were patients with either positive surgical margins or extracapsular extension (ECE) [4]. Thus, the standard of care for patients with resected HNSCC with either positive surgical margins or ECE is adjuvant radiation therapy concurrent with three doses of high-dose cisplatin (100 mg/m2 on days 1, 22, and 43). ⇑ Corresponding author. Address: Mayo Clinic, 200 First Street SW, Rochester, MN 55905, United States. Tel.: +1 (507) 284 4849; fax: +1 (507) 284 1803.

Oral Oncology 50 (2014) 311–318

Contents lists availab nc evE-mail address: (K.A.R. Price).better treatment for patients with HPV-positive oropharynx cancer to preserve sur toxicity.  2014 Elsevier Ltd.1368-8375/$ - see front matter  2014 Elsevier Ltd. All rights reserved. high-Keywords:

Head and neck cancer

Oropharynx cancer


Adjuvant therapy

Human papillomavirus (HPV)

Cisplatin weekly cisplatin.

Materials and methods: Retrospective review of patients with Stage III/IV HNSCC who had surgery followed by adjuvant chemoradiation therapy at Mayo Clinic, Rochester. HPV and/or p16 status was available for all oropharynx patients.

Results: 104 Patients (51 high-dose, 53 weekly) were analyzed. The 3-year overall survival was 84% and 75% for patients who received high dose and weekly cisplatin, respectively (p = 0.30). The 3-year recurrence free survival was 71% and 74% in the high dose and weekly cisplatin group, respectively (p = 0.95). Patients with HPV/p16-positive oropharynx cancer who received adjuvant chemoradiation therapy with high-dose and weekly cisplatin had three-year overall survival rates of 91% and 86% (p = 0.56), and 3-year recurrence free survival of 84% and 82% (p = 0.93). Extracapsular extension did not affect prognosis in either group.

Conclusions: No significant survival difference was seen between patients with locally advanced HNSCC treated with adjuvant chemoradiation therapy with high-dose or weekly cisplatin, although there was a trend for improved survival with high-dose cisplatin. Weekly cisplatin in the adjuvant setting may be aDepartment of Pathology, Al Jumhori Teaching cDepartment of Laboratory Medicine and Patho dDepartment of Radiation Oncology, Mayo Clin eDepartment of Otolaryngology-Head and Neck fDivision of Medical Oncology, Mayo Clinic, Roc a r t i c l e i n f o

Article history:

Received 10 July 2013

Received in revised form 31 December 2013

Accepted 3 January 2014

Available online 24 January 2014lly-advanced HPV/p16-positive ck squamous cell carcinoma b, Francis J. Walsh c, Robert L. Foote d, Eric J. Moore e, Scott H. Okuno f, er e, Daniel L. Price e, Yolanda I. Garces d, Daniel J. Ma d, n R. Molina f, Joaquin J. Garcia c, Katharine A.R. Price f,⇑ er, MN, United States l, Mosul, Iraq yo Clinic, Rochester, MN, United States ster, MN, United States , Mayo Clinic, Rochester, MN, United States

N, United States s u m m a r y

Objectives: Standard treatment for patients with poor-risk, resected head and neck squamous cell carcinoma (HNSCC) is adjuvant radiation therapy combined with high-dose cisplatin. Many patients are treated with weekly cisplatin; it is not known whether weekly and high-dose cisplatin are equivalent.

This study compares the outcomes of patients with locally-advanced HPV-negative HNSCC and HPV/p16positive oropharynx HNSCC treated with adjuvant chemoradiation therapy with either high-dose orAdjuvant chemoradiation therapy with high-dose versus weeklyOral O journal homepage: www.elsle at ScienceDirect ology ier .com/locate /ora loncology has a much better prognosis than HPV-negative HNSCC that has historically been associated with smoking and alcohol use [16].

USA) according to standard protocols and using appropriate conthe cell counts [17–19]. Survival estimates were calculated with coloThe challenge facing the field of head and neck oncology is how to preserve high cure rates while minimizing toxicity and optimizing long-term functional outcomes. With this is mind, it would be preferable to treat those patients with resected HPV/p16-positive oropharynx cancer who need adjuvant chemoradiation therapy with weekly instead of high-dose cisplatin. The aim of this retrospective analysis is to compare the survival outcomes of patients with locally advanced HNSCC treated with adjuvant chemoradiation therapy with either high-dose cisplatin or weekly cisplatin at Mayo Clinic, Rochester, with specific attention given to survival among patients with HPV/p16-positive oropharynx cancer.


Patients with locally advanced (Stage III or IV) head and neck squamous cell carcinoma who were treated with curative intent surgery followed by adjuvant chemoradiation therapy were identified from a database maintained by the Department of Radiation

Oncology at Mayo Clinic, Rochester. As adjuvant chemoradiation therapy with high-dose cisplatin became standard of care in 2004 based on the publication of two phase III trials (RTOG 9501 and EORTC 22931), patients treated before 2004 were excluded.

Charts from patients treated between 2004 and 2010 were reviewed, and demographic and clinical data was abstracted from the medical record including age at time of diagnosis, gender, tobacco use in pack-years, primary tumor site, tumor TNM stage, surgical margin status (positive or negative), presence of extracapsular extension, and HPV and p16 status for patients with oropharynx cancer. The presence of extracapsular extension was defined as evidence of focal, microscopic, or gross extension of the tumor beyond the lymph node capsule. Details of the radiation therapy and chemotherapy and treatment delivery were recorded. Patients were treated with either high-dose cisplatin or weekly cisplatin at the discretion of the treating physician based on the presence or absence of high-risk features, medical comorbidities, and performance status. A minimum follow-up time of 2 years was availableHigh-dose cisplatin, however, is an intensive regimen with a number of short and long-term toxicities including nausea and vomiting, cytopenias, ototoxicity, nephrotoxicity, and neuropathy [5]. Many patients are not eligible to receive chemoradiation with high-dose cisplatin due to medical comorbidities or poor performance status. Traditionally, alternative cisplatin regimens have been substituted for high-dose cisplatin when the patient is considered ‘‘unfit’’ for the higher dose. Although alternative cisplatin regimens using weekly (30–40 mg/m2/week) [6] or daily (6 mg/m2/day) [7] dosing have been studied, they have never been compared in a randomized trial to high-dose cisplatin, and it is unlikely that these studies will ever be conducted. In practice, many patients receive weekly cisplatin or a non-platinum regimen in lieu of high-dose cisplatin at the discretion of the treating oncologist, but it is not known if these alternative regimens are equivalent or inferior to high-dose cisplatin. The most common alternative regimen, weekly cisplatin, is better tolerated with a more favorable side effect profile [8–13].