Abstract
Purpose
The goal of this work was to evaluate the efficacy and toxicity of hyperfractionated stereotactic reirradiation (re-RT) as a treatment for inoperable, recurrent, or second primary head and neck squamous cell cancer (HNSCC) that is not suitable for systemic treatment.
Patients and materials
Forty patients with recurrent or second primary HNSCC were included in this study. The patients had a median gross tumor volume of 76 ml (range 14–193 ml) and a previous radiotherapy dose greater than 60 Gy. Treatment was designed to cover 95 % of the planning target volume (PTV, defined as gross tumor volume [GTV] + 3 mm to account for microscopic spreading, with no additional set-up margin) with the prescribed dose (48 Gy in 16 fractions b.i.d.). Treatment was administered twice daily with a minimum 6 h gap. Uninvolved lymph nodes were not irradiated.
Results
Treatment was completed as planned for all patients (with median duration of 11 days, range 9–14 days). Acute toxicity was evaluated using the RTOG/EORTC scale. A 37 % incidence of grade 3 mucositis was observed, with recovery time of ≤ 4 weeks for all of these patients. Acute skin toxicity was never observed to be higher than grade 2. Late toxicity was also evaluated according to the RTOG/EORTC scale. Mandible radionecrosis was seen in 4 cases (10 %); however, neither carotid blowout syndrome nor other grade 4 late toxicity occurred. One-year overall survival (OS) and local progression-free survival (L-PFS) were found to be 33 and 44 %, respectively. Performance status and GTV proved to be significant prognostic factors regarding local control and survival.
Conclusion
Hyperfractionated stereotactic re-RT is a reasonable treatment option for patients with recurrent/second primary HNSCC who were previously exposed to high-dose irradiation and who are not candidates for systemic treatment or hypofractionation.
Zusammenfassung
Ziel
Ziel der Studie war es, die Effektivität und Toxizität der hyperfraktionierten akzelerierten stereotaktischen Wiederbestrahlung (re-RT) für die Behandlung von Patienten mit Lokalrezidiv von fortgeschrittenen Kopf-Hals-Tumoren (“head and neck squamous cell cancer”, HNSCC), die für eine systemische Therapie nicht geeignet sind, zu untersuchen.
Patienten und Methodik
In die Studie wurden 40 Patienten mit rekurrierten oder sekundären HNSCC eingeschlossen. Die Patienten hatten ein medianes makroskopisches Tumorvolumen von 76 ml (Spanne 14–193 ml) und bereits Strahlentherapiedosen des primären Tumors von 60 Gy oder größer erhalten. Die Fraktionierung betrug 48 Gy in 16 Fraktionen über 8 Tage. Die Behandlung erfolgte 2-mal täglich mit einer Pause von minimal 6 h zwischen den Fraktionen. Die Behandlung musste 95 % des Planungszielvolumens (PTV, definiert als makroskopisches Tumorvolumen [GTV] + 3 mm zur Berücksichtigung der mikroskopischen Streuung, ohne zusätzlichen Saum) abdecken.Unbeteiligte Lymphknoten wurden nicht bestrahlt.
Ergebnisse
Alle Patienten absolvierten die Behandlung plangemäß (mediane Behandlungsdauer 11 Tage; Spanne 9–14 Tage). Für die Beurteilung der Akut- und Spättoxizität wurde die RTOG/EORTC-Skala verwendet. Die Inzidenz einer akuten Mukositis vom Grad 3 betrug 37 %, mit einer Heilungszeit von höchstens 4 Wochen bei allen betroffenen Patienten. Eine akute Hauttoxizität war nie größer als Grad 2. Spättoxizitäten wurden ebenfalls mit der RTOG/EORTC-Skala bewertet. Eine Kiefernekrose hatten 4 Patienten (10 %); allerdings wurde keine,Ruptur der Karotide bzw. keine andere Grad-4-oder Grad-5-Toxizitätbeobachtet. Die Ein-Jahres-Gesamtüberlebensrate (OS) lag bei 33 %, das lokale progressionsfreie Überleben (L-PFS) bei 44 %. Patientenstatus und GTV waren signifikante prognostische Faktoren für die lokale Tumorkontrolle und das Überleben.
Schlussfolgerung
Hyperfraktionierte akzelerierte stereotaktische re-RT ist eine interessante Wahl für Patienten mit rekurrierten oder sekundären HNSCC, die für eine systemische Therapie nicht geeignet sind.
Similar content being viewed by others
References
McDonald MW, Lawson J, Garg MK et al (2011) ACR appropriateness criteria retreatment of recurrent head and neck cancer after prior definitive radiation. Int J Radiat Oncol Biol Phys 80:1292–1298
Budach V, Becker ET, Boehmer D et al (2014) Concurrent hyperfractionated accelerated radiotherapy with 5-FU and once weekly cisplatin in locally advanced head and neck cancer. Strahlenther Onkol 190:250–255
Temam S, Pape E, Janot F et al (2005) Salvage surgery after failure of very accelerated radiotherapy in advanced head and neck squamous cell carcinoma. Int J Radiat Oncol Biol Phys 62:1078–1083
Wong SJ, Bourhis J, Langer CJ (2012) Retreatment of recurrent head and neck cancer in a previously irradiated field. Semin Radiat Oncol 22:214–219
Spencer SA, Harris J, Wheeler RH et al (2001) RTOG 96-10: re-irradiation with concurrent hydroxyurea and 5-fluorouracil in patients with squamous cell cancer of the head and neck. Int J Radiat Oncol Biol Phys 51:1299–1304
Unger KR, Lominska CE, Deeken JF et al (2010) Fractionated stereotactic radiosurgery for reirradiation of head and neck cancer. Int J Radiat Oncol Biol Phys 77:1411–1419
Vargo JA, Ferris RL, Ohr J et al (2015) A prospective phase 2 trial of reirradiation with stereotactic body radiation therapy plus cetuximab in patients with previously irradiated recurrent squamous cell carcinoma of the head and neck. Int J Radiat Oncol Biol Phys 91:480–488
Popovtzer A, Gluck I, Chepeha DB et al (2009) The pattern of failure after reirradiation of recurrent squamous cell head and neck cancer: implications for defining the targets. Int J Radiat Oncol Biol Phys 74:1342–1347
Simonova G, Novotny J, Novotny J Jr et al (1995) Fractionated stereotactic radiotherapy with the Leksell Gamma Knife: feasibility study. Radiother Oncol 37:108–116
Strnad V, Lotter M, Kreppner S et al (2015) Reirradiation for recurrent head and neck cancer with salvage interstitial pulsed-dose-rate brachytherapy. Strahlenther Onkol 191:495–500
Taussky D, Dulguerov P, Allal AS (2005) Salvage surgery after radical accelerated radiotherapy with concomitant boost technique for head and neck carcinomas. Head Neck 27:182–186
Gibson MK, Li Y, Murphy B et al (2005) Randomized phase III evaluation of cisplatin plus fluorouracil versus cisplatin plus paclitaxel in advanced head and neck cancer (E1395): an intergroup trial of the Eastern Cooperative Oncology Group. J Clin Oncol 23:3562–3567
Soulieres D, Senzer NN, Vokes EE et al (2004) Multicenter phase II study of erlotinib, an oral epidermal growth factor receptor tyrosine kinase inhibitor, in patients with recurrent or metastatic squamous cell cancer of the head and neck. J Clin Oncol 22:77–85
Haraf DJ, Weichselbaum RR, Vokes EE (1996) Reirradiation with concomitant chemotherapy of unresectable recurrent head and neck cancer: a potentially curable disease. Ann Oncol 7:913–918
Chen AM, Phillips TL, Lee NY (2011) Practical considerations in the re-irradiation of recurrent and second primary head and neck cancer: who, why, how and how much? Int J Radiat Oncol Biol Phys 81:1211–1219
Buatti JM, Friedman WA, Bova FJ et al (1995) Linac radiosurgery for locally recurrent nasopharyngeal carcinoma: rationale and technique. Head Neck 17:14–19
Yamazaki H, Ogita M, Kodani N et al (2013) Frequency, outcome and prognostic factors of carotid blowout syndrome after hypofractionated re-irradiation of head and neck cancer using CyberKnife: a multi-institutional study. Radiother Oncol 107:305–309
George V, Dwight EH, Steven B et al (2006) Frameless stereotactic radiosurgery for recurrent head and neck carcinoma. Technol Cancer Res Treat 5:529–535
Lartigau EF, Tresch E, Thariat J et al (2013) Multi institutional phase II study of concomitant stereotactic reirradiation and cetuximab for recurrent head and neck cancer. Radiother Oncol 109:281–285
Donald MW, Moore MG, Johnstone PAS (2012) Risk of carotid blowout after reirradiation of the head and neck: a systematic review. Int J Radiat Oncol Biol Phys 82:1083–1089
Puthawala A, Nisar SAM, Gamie S et al (2001) Interstitial lowdose-rate brachytherapy as a salvage treatment for recurrent head and neck cancers: long-term results. Int J Radiat Oncol Biol Phys 51:354–362
Friedrich RE, Krull A, Schwarz R et al (1997) Salvage therapy of advanced squamous cell carcinoma of the moth cavity and oropharynx: results of interstitial high-dose-rate brachytherapy combined with ablative tumor surgery. Strahlenther Onkol 173:507–512
Hepel JT, Nisar AMS, Puthawala A et al (2005) Salvage high-dose-rate (HDR) brachytherapy for recurrent head and neck cancer. Int J Radiat Oncol Biol Phys 62:1444–1450
Strnad V, Lotter M, Kreppner S et al (2015) Reirradiation for recurrent head and neck cancer with salvage interstitial pulsed-dose-rate brachytherapy: long-term results. Strahlenther Onkol 191:495–500
Acknowledgment
Institutional support—RVO-FNOs/2012—was received for this work.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflicts of interest
J. Cvek, L. Knybel, E. Skacelikova, J. Stransky, P. Matousek, K. Zelenik, O. Res, B. Otahal, L. Molenda, and D. Feltl state that there are no conflicts of interest.
All studies on humans described in the present manuscript were carried out with the approval of the responsible ethics committee and in accordance with national law and the Helsinki Declaration of 1975 (in its current, revised form). Informed consent was obtained from all patients included in studies.
Rights and permissions
About this article
Cite this article
Cvek, J., Knybel, L., Skacelikova, E. et al. Hyperfractionated stereotactic reirradiation for recurrent head and neck cancer. Strahlenther Onkol 192, 40–46 (2016). https://doi.org/10.1007/s00066-015-0886-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00066-015-0886-3
Keywords
- Stereotactic radiotherapy
- Squamous cell carcinoma of the head and neck
- Reirradiation
- Overall survival
- Toxicity