Skip to main content
Top
Published in: Radiation Oncology 1/2020

Open Access 01-12-2020 | Dysphagia | Research

Phase I trial of dose-escalated stereotactic radiosurgery (SRS) boost for unfavorable locally advanced oropharyngeal cancer

Authors: Prashant Vempati, Aditya N. Halthore, Sewit Teckie, Zaker Rana, Emile Gogineni, Jeffrey Antone, Honglai Zhang, Mihaela Marrero, Kristin Beadle, Douglas K. Frank, Mohamed Aziz, Doru Paul, Maged Ghaly

Published in: Radiation Oncology | Issue 1/2020

Login to get access

Abstract

Background and purpose

Patients with locally advanced oropharynx squamous cell carcinoma have suboptimal outcomes with standard chemoradiation. Here, we evaluated toxicity and oncologic outcomes of dose escalation using radiosurgical boost for patients with unfavorable oropharynx squamous cell carcinoma.

Materials and methods

Between 2010–2017, Thirty four patients with intermediate- or high-risk oropharynx squamous cell carcinoma were enrolled onto this prospective phase I trial. Each patient received concurrent cisplatin and fractionated radiotherapy totaling 60 Gy or 66 Gy followed by radiosurgery boost to areas of residual gross tumor: single fraction of 8 Gy or 10 Gy, or two fractions of 5 Gy each. Primary endpoint was treatment toxicity. Secondary endpoints were local, regional, and distant disease control.

Results

Eleven, sixteen and seven patients received radiosurgery boost with 8 Gy in 1 fraction, 10 Gy in 1 fraction, and 10 Gy in 2 fractions respectively. Acute toxicities include 4 patients with tumor necrosis causing grade 3 dysphagia, of which 3 developed grade 4 pharyngeal hemorrhage requiring surgical intervention. At 24 months after treatment, 7%, 9%, and 15% had grade 2 dysgeusia, xerostomia, and dysphagia, respectively, and two patients remained feeding tube dependent. No grade 5 toxicities occurred secondary to treatment. Local, regional, and distant control at a median follow up of 4.2 years were 85.3%, 85.3% and 88.2%, respectively. Five patients died resulting in overall survival of 85.3%.

Conclusions

This study is the first to report the use of radiosurgery boost dose escalation in patients with unfavorable oropharynx squamous cell carcinoma. Longer follow-up, larger cohorts, and further refinement of boost methodology are needed prior to implementation in routine clinical practice.
Trial Registration: Northwell Health Protocol #09-309A (NCT02703493) (https://​clinicaltrials.​gov/​ct2/​show/​NCT02703493)
Literature
1.
go back to reference Eisbruch A, Schwartz M, Rasch C, et al. Dysphagia and aspiration after chemoradiotherapy for head-and-neck cancer: Which anatomic structures are affected and can they be spared by IMRT? Int J Radiat Oncol Biol Phys. 2004;60(5):1425–39.CrossRef Eisbruch A, Schwartz M, Rasch C, et al. Dysphagia and aspiration after chemoradiotherapy for head-and-neck cancer: Which anatomic structures are affected and can they be spared by IMRT? Int J Radiat Oncol Biol Phys. 2004;60(5):1425–39.CrossRef
2.
go back to reference Feng FY, Kim HM, Lyden TH, et al. Intensity-modulated radiotherapy of head and neck cancer aiming to reduce dysphagia: Early dose-effect relationships for the swallowing structures. Int J Radiat Oncol Biol Phys. 2007;68(5):1289–98.CrossRef Feng FY, Kim HM, Lyden TH, et al. Intensity-modulated radiotherapy of head and neck cancer aiming to reduce dysphagia: Early dose-effect relationships for the swallowing structures. Int J Radiat Oncol Biol Phys. 2007;68(5):1289–98.CrossRef
3.
go back to reference Gardner E, Linskey ME, Penagaricano JA, Hanna EY. Stereotactic radiosurgery for patients with cancer of the head and neck. Curr Oncol Rep. 2003;5(2):164–9.CrossRef Gardner E, Linskey ME, Penagaricano JA, Hanna EY. Stereotactic radiosurgery for patients with cancer of the head and neck. Curr Oncol Rep. 2003;5(2):164–9.CrossRef
4.
go back to reference Ang KK, Harris J, Wheeler R, et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010;363(1):24–35.CrossRef Ang KK, Harris J, Wheeler R, et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010;363(1):24–35.CrossRef
5.
go back to reference Fakhry C, Westra WH, Li S, et al. Improved survival of patients with human papillomavirus-positive head and neck squamous cell carcinoma in a prospective clinical trial. J Natl Cancer Inst. 2008;100(4):261–9.CrossRef Fakhry C, Westra WH, Li S, et al. Improved survival of patients with human papillomavirus-positive head and neck squamous cell carcinoma in a prospective clinical trial. J Natl Cancer Inst. 2008;100(4):261–9.CrossRef
6.
go back to reference Lassen P, Eriksen JG, Hamilton-Dutoit S, Tramm T, Alsner J, Overgaard J. Effect of HPV-associated p16INK4A expression on response to radiotherapy and survival in squamous cell carcinoma of the head and neck. J Clin Oncol. 2009;27(12):1992–8.CrossRef Lassen P, Eriksen JG, Hamilton-Dutoit S, Tramm T, Alsner J, Overgaard J. Effect of HPV-associated p16INK4A expression on response to radiotherapy and survival in squamous cell carcinoma of the head and neck. J Clin Oncol. 2009;27(12):1992–8.CrossRef
7.
go back to reference Posner MR, Lorch JH, Goloubeva O, et al. Survival and human papillomavirus in oropharynx cancer in TAX 324: a subset analysis from an international phase III trial. Ann Oncol. 2011;22(5):1071–7.CrossRef Posner MR, Lorch JH, Goloubeva O, et al. Survival and human papillomavirus in oropharynx cancer in TAX 324: a subset analysis from an international phase III trial. Ann Oncol. 2011;22(5):1071–7.CrossRef
8.
go back to reference Chang BK, Timmerman RD. Stereotactic body radiation therapy: a comprehensive review. Am J Clin Oncol. 2007;30(6):637–44.CrossRef Chang BK, Timmerman RD. Stereotactic body radiation therapy: a comprehensive review. Am J Clin Oncol. 2007;30(6):637–44.CrossRef
9.
go back to reference Plummer C, Henderson RD, O’Sullivan JD, Read SJ. Ischemic stroke and transient ischemic attack after head and neck radiotherapy: a review. Stroke. 2011;42(9):2410–8.CrossRef Plummer C, Henderson RD, O’Sullivan JD, Read SJ. Ischemic stroke and transient ischemic attack after head and neck radiotherapy: a review. Stroke. 2011;42(9):2410–8.CrossRef
10.
go back to reference Brinkman KL, Teh BS, Xu B. A review of stereotactic body radiation therapy (SBRT) from the molecular radiobiology perspective. J Radiat Oncol. 2012;1(4):311–6.CrossRef Brinkman KL, Teh BS, Xu B. A review of stereotactic body radiation therapy (SBRT) from the molecular radiobiology perspective. J Radiat Oncol. 2012;1(4):311–6.CrossRef
12.
go back to reference Le QT, Tate D, Koong A, et al. Improved local control with stereotactic radiosurgical boost in patients with nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys. 2003;56(4):1046–54.CrossRef Le QT, Tate D, Koong A, et al. Improved local control with stereotactic radiosurgical boost in patients with nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys. 2003;56(4):1046–54.CrossRef
13.
go back to reference Lee DS, Kim YS, Cheon JS, et al. Long-term outcome and toxicity of hypofractionated stereotactic body radiotherapy as a boost treatment for head and neck cancer: The importance of boost volume assessment. Radiat Oncol. 2012;7:85-717X-7–85. Lee DS, Kim YS, Cheon JS, et al. Long-term outcome and toxicity of hypofractionated stereotactic body radiotherapy as a boost treatment for head and neck cancer: The importance of boost volume assessment. Radiat Oncol. 2012;7:85-717X-7–85.
14.
go back to reference Yamazaki H, Ogita M, Himei K, et al. Hypofractionated stereotactic radiotherapy using CyberKnife as a boost treatment for head and neck cancer, a multi-institutional survey: impact of planning target volume. Anticancer Res. 2014;34(10):5755–9.PubMed Yamazaki H, Ogita M, Himei K, et al. Hypofractionated stereotactic radiotherapy using CyberKnife as a boost treatment for head and neck cancer, a multi-institutional survey: impact of planning target volume. Anticancer Res. 2014;34(10):5755–9.PubMed
17.
go back to reference Langendijk JA, Doornaert P, Rietveld DH, Verdonck-de Leeuw IM, Leemans CR, Slotman BJ. A predictive model for swallowing dysfunction after curative radiotherapy in head and neck cancer. Radiother Oncol. 2009;90(2):189–95.CrossRef Langendijk JA, Doornaert P, Rietveld DH, Verdonck-de Leeuw IM, Leemans CR, Slotman BJ. A predictive model for swallowing dysfunction after curative radiotherapy in head and neck cancer. Radiother Oncol. 2009;90(2):189–95.CrossRef
18.
go back to reference Cox JD, Stetz J, Pajak TF. Toxicity criteria of the radiation therapy oncology group (RTOG) and the european organization for research and treatment of cancer (EORTC). Int J Radiat Oncol Biol Phys. 1995;31(5):1341–6.CrossRef Cox JD, Stetz J, Pajak TF. Toxicity criteria of the radiation therapy oncology group (RTOG) and the european organization for research and treatment of cancer (EORTC). Int J Radiat Oncol Biol Phys. 1995;31(5):1341–6.CrossRef
19.
go back to reference Cleeland CS, Mendoza TR, Wang XS, et al. Assessing symptom distress in cancer patients: the M. D. Anderson Symp Invent. 2000;89:1634–46. Cleeland CS, Mendoza TR, Wang XS, et al. Assessing symptom distress in cancer patients: the M. D. Anderson Symp Invent. 2000;89:1634–46.
20.
go back to reference Rosenthal DI, Mendoza TR, Chambers MS, et al. Measuring head and neck cancer symptom burden: the development and validation of the M. D. anderson symptom inventory, head and neck module. Head Neck. 2007;29(10):923–31.CrossRef Rosenthal DI, Mendoza TR, Chambers MS, et al. Measuring head and neck cancer symptom burden: the development and validation of the M. D. anderson symptom inventory, head and neck module. Head Neck. 2007;29(10):923–31.CrossRef
22.
go back to reference Marur S, Li S, Cmelak AJ, et al. E1308: phase II trial of induction chemotherapy followed by reduced-dose radiation and weekly cetuximab in patients with HPV-associated resectable squamous cell carcinoma of the oropharynx- ECOG-ACRIN cancer research group. J Clin Oncol. 2017;35(5):490–7.CrossRef Marur S, Li S, Cmelak AJ, et al. E1308: phase II trial of induction chemotherapy followed by reduced-dose radiation and weekly cetuximab in patients with HPV-associated resectable squamous cell carcinoma of the oropharynx- ECOG-ACRIN cancer research group. J Clin Oncol. 2017;35(5):490–7.CrossRef
23.
go back to reference Seiwert TY, Foster CC, Blair EA, et al. OPTIMA: a phase II dose and volume de-escalation trial for human papillomavirus-positive oropharyngeal cancer. Annonc. 2018;30(2):297–302. Seiwert TY, Foster CC, Blair EA, et al. OPTIMA: a phase II dose and volume de-escalation trial for human papillomavirus-positive oropharyngeal cancer. Annonc. 2018;30(2):297–302.
24.
go back to reference Villaflor VM, Melotek JM, Karrison TG, et al. Response-adapted volume de-escalation (RAVD) in locally advanced head and neck cancer. Ann Oncol. 2016;27(5):908–13.CrossRef Villaflor VM, Melotek JM, Karrison TG, et al. Response-adapted volume de-escalation (RAVD) in locally advanced head and neck cancer. Ann Oncol. 2016;27(5):908–13.CrossRef
25.
go back to reference Amin MB, Edge S, Greene F, et al. AJCC cancer staging manual, 8th edn. Springer International Publishing: American Joint Commission on Cancer; 2017. Amin MB, Edge S, Greene F, et al. AJCC cancer staging manual, 8th edn. Springer International Publishing: American Joint Commission on Cancer; 2017.
26.
go back to reference Chao KS, Wippold FJ, Ozyigit G, Tran BN, Dempsey JF. Determination and delineation of nodal target volumes for head-and-neck cancer based on patterns of failure in patients receiving definitive and postoperative IMRT. Int J Radiat Oncol Biol Phys. 2002;53(5):1174–84.CrossRef Chao KS, Wippold FJ, Ozyigit G, Tran BN, Dempsey JF. Determination and delineation of nodal target volumes for head-and-neck cancer based on patterns of failure in patients receiving definitive and postoperative IMRT. Int J Radiat Oncol Biol Phys. 2002;53(5):1174–84.CrossRef
27.
go back to reference Cantrell SC, Peck BW, Li G, Wei Q, Sturgis EM, Ginsberg LE. Differences in imaging characteristics of HPV-positive and HPV-negative oropharyngeal cancers: a blinded matched-pair analysis. AJNR Am J Neuroradiol. 2013;34(10):2005–9.CrossRef Cantrell SC, Peck BW, Li G, Wei Q, Sturgis EM, Ginsberg LE. Differences in imaging characteristics of HPV-positive and HPV-negative oropharyngeal cancers: a blinded matched-pair analysis. AJNR Am J Neuroradiol. 2013;34(10):2005–9.CrossRef
28.
go back to reference Fowler JF. 21 years of biologically effective dose. Br J Radiol. 2010;83(991):554–68.CrossRef Fowler JF. 21 years of biologically effective dose. Br J Radiol. 2010;83(991):554–68.CrossRef
29.
go back to reference Bastos de Souza TR, Pinto CA, da Cunha Mercante AM, Nishimoto IN, Brasilino de Carvalho M, Kowalski LP. Long-term results of surgical treatment for advanced oropharyngeal squamous cell carcinoma. Head Neck. 2014;36(8):1146–54.CrossRef Bastos de Souza TR, Pinto CA, da Cunha Mercante AM, Nishimoto IN, Brasilino de Carvalho M, Kowalski LP. Long-term results of surgical treatment for advanced oropharyngeal squamous cell carcinoma. Head Neck. 2014;36(8):1146–54.CrossRef
30.
go back to reference Weinstein GS, O’Malley BW Jr, Cohen MA, Quon H. Transoral robotic surgery for advanced oropharyngeal carcinoma. Arch Otolaryngol Head Neck Surg. 2010;136(11):1079–85.CrossRef Weinstein GS, O’Malley BW Jr, Cohen MA, Quon H. Transoral robotic surgery for advanced oropharyngeal carcinoma. Arch Otolaryngol Head Neck Surg. 2010;136(11):1079–85.CrossRef
31.
go back to reference Haughey BH, Hinni ML, Salassa JR, et al. Transoral laser microsurgery as primary treatment for advanced-stage oropharyngeal cancer: a united states multicenter study. Head Neck. 2011;33(12):1683–94.CrossRef Haughey BH, Hinni ML, Salassa JR, et al. Transoral laser microsurgery as primary treatment for advanced-stage oropharyngeal cancer: a united states multicenter study. Head Neck. 2011;33(12):1683–94.CrossRef
Metadata
Title
Phase I trial of dose-escalated stereotactic radiosurgery (SRS) boost for unfavorable locally advanced oropharyngeal cancer
Authors
Prashant Vempati
Aditya N. Halthore
Sewit Teckie
Zaker Rana
Emile Gogineni
Jeffrey Antone
Honglai Zhang
Mihaela Marrero
Kristin Beadle
Douglas K. Frank
Mohamed Aziz
Doru Paul
Maged Ghaly
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Radiation Oncology / Issue 1/2020
Electronic ISSN: 1748-717X
DOI
https://doi.org/10.1186/s13014-020-01718-w

Other articles of this Issue 1/2020

Radiation Oncology 1/2020 Go to the issue