International Journal of Radiation Oncology*Biology*Physics
Clinical InvestigationVolume, Dose, and Fractionation Considerations for IMRT-based Reirradiation in Head and Neck Cancer: A Multi-institution Analysis
Introduction
Although the development of recurrence or second primary (RSP) squamous carcinoma in the head and neck after a previous course of radiation therapy (RT) is relatively uncommon, this clinical scenario occurs frequently enough to form the basis of ≥3 prospective clinical trials testing the efficacy of reirradiation 1, 2, 3. In general, these trials prescribed radiation in altered schedules (eg, 1.5 Gy twice daily, given every other week) to a dose of 60 Gy and targeted gross disease (or the resection bed) with a 2-cm margin and no elective (uninvolved) volume. Although these approaches are understandable given the first forays into reirradiation with 2-dimensional or 3-dimensional techniques in the prospective setting, these fractionation schemes and doses are not often used in the current era, especially for gross disease.
With the adoption of conformal RT techniques such as intensity-modulated RT (IMRT) and volumetric-modulated arc therapy, the therapeutic ratio of reirradiation might have changed, facilitating higher doses and minimizing the incidence and severity of acute or late toxicities (4). Additionally, evidence from the initial definitive RT setting has cast doubt on the utility of accelerated fractionation with concurrent systemic therapy 5, 6. Furthermore, given the high risk of failure at the treated site, the benefit of elective nodal treatment remains an open question (7). Therefore, we performed a multi-institution study of patients with RSP squamous cell carcinoma in the head and neck who had undergone reirradiation with IMRT techniques (re-IMRT) to investigate these questions of treatment volume, dose, and fractionation.
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Materials and Methods
After institutional review board and legal approval, 9 institutions agreed to participate and formed the multi-institution reirradiation (MIRI) consortium. Eight centers contributed to the present analysis: Memorial Sloan-Kettering Cancer Center (New York, New York), Moffitt Cancer Center (Tampa, Florida), the Josephine Ford Cancer Institute at Henry Ford Health System (Detroit, Michigan), the University of Louisville (Louisville, Kentucky), University Hospitals Case Medical Center (Cleveland,
Patients
In this updated analysis, a total of 505 patients from the 8 participating institutions met the inclusion criteria. The patient, disease, and treatment characteristics of the study population are listed in Table 1. For surviving patients (n = 176), the median follow-up was 21.5 months (range 0-128.1). The initial approach to the RSP tumor consisted of surgery in 49.2%. Fractionation of re-IMRT was once daily for 79.6%. The target volume included elective treatment to the unilateral neck in
Discussion
In the accompanying analyses from this multi-institution collaboration, we have devised a prognostic grouping to aid with patient counseling and treatment selection of conventionally delivered RT or stereotactic RT 9, 10. We focused on the details that could affect the volume and prescription of re-IMRT.
In the reirradiation scenario, in which disease is presumed to be inherently radioresistant and normal organs at risk might have already received tolerance doses, the benefit of elective nodal
Conclusion
The routine use of elective neck irradiation or hyperfractionation during re-IMRT does not appear beneficial. For patients undergoing definitive re-IMRT, doses of ≥66 Gy appear to be relatively safe and might improve outcomes, especially for high-performing patients or those with a prolonged natural history such as HPV-associated RSP oropharynx cancer. For patients receiving postoperative re-IMRT in the absence of gross disease, doses of 50 to 66 Gy appear adequate.
References (21)
- et al.
IMRT reirradiation of head and neck cancer—Disease control and morbidity outcomes
Int J Radiat Oncol
(2009) - et al.
A phase III trial to test accelerated versus standard fractionation in combination with concurrent cisplatin for head and neck carcinomas (RTOG 0129): Report of efficacy and toxicity
Int J Radiat Oncol
(2010) - et al.
Concomitant chemoradiotherapy versus acceleration of radiotherapy with or without concomitant chemotherapy in locally advanced head and neck carcinoma (GORTEC 99-02): An open-label phase 3 randomised trial
Lancet Oncol
(2012) - et al.
The pattern of failure after reirradiation of recurrent squamous cell head and neck cancer: Implications for defining the targets
Int J Radiat Oncol
(2009) - et al.
Patterns of failure after reirradiation with intensity-modulated radiation therapy and the competing risk of out-of-field recurrences
Oral Oncol
(2016) - et al.
Reirradiation of head and neck cancers with intensity modulated radiation therapy: Outcomes and analyses
Int J Radiat Oncol Biol Phys
(2016) - et al.
High-dose reirradiation with intensity-modulated radiotherapy for recurrent head-and-neck cancer: Disease control, survival and toxicity
Radiother Oncol
(2014) - et al.
A nomogram to predict loco-regional control after re-irradiation for head and neck cancer
Radiother Oncol J Eur Soc Ther Radiol Oncol
(2014) - et al.
Impact of tumor HPV status on outcome in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck receiving chemotherapy with or without cetuximab: Retrospective analysis of the phase III EXTREME trial
Ann Oncol
(2014) - et al.
Reirradiation of head and neck cancers with proton therapy: Outcomes and analyses
Int J Radiat Oncol Biol Phys
(2016)
Cited by (0)
Conflict of interest: J. Bonner has a consulting role with Merck Serma, Eli Lilly, Bristol-Meyers Squibb, and Cell-Sci, all outside the submitted work. J. Caudell has a consulting role with EMD Serano outside the submitted work. N. Lee is on the advisory board for Merck, Pfizer, and Vertex, all outside the submitted work. M. Machtay has received honoraria and has consulting and advisory roles with Stemnion and Abbvie, all outside the submitted work. N. Riaz has received honoraria from Medimmunue outside the submitted work. F. Siddiqui has received honoraria and has a speaker and travel relationship with Varian Medical Systems, American College of Radiology, Med Dos advisory board, and Wayne State University, all outside the submitted work.