Refining Patient Selection for Reirradiation of Head and Neck Squamous Carcinoma in the IMRT Era: A Multi-institution Cohort Study by the MIRI Collaborative

Ward, Matthew C.; Riaz, Nadeem; Caudell, Jimmy J.; Dunlap, Neal E.; Isrow, Derek; Zakem, Sara J.; Dault, J.; Awan, Musaddiq J.; Vargo, John A.; Heron, Dwight E.; Higgins, Kristin; Beitler, Jonathan J.; Marcrom, S.; Boggs, Drexell Hunter; Hassanzadeh, Comron; Reddy, Chandana A.; Bonner, James A.; Yao, Min; Machtay, Mitchell; Siddiqui, Farzan; Trotti, Andy; Lee, Nancy Y.; Koyfman, Shlomo A.

doi:10.1016/j.ijrobp.2017.06.012

Cited by 131 publications

(184 citation statements)

References 28 publications

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“…8 Recurrent ACC of the head and neck usually has a less aggressive biological behavior compared to recurrent SCC. 8 Recurrent ACC of the head and neck usually has a less aggressive biological behavior compared to recurrent SCC.…”

Section: Discussionmentioning

confidence: 99%

“…The putative prognostic factors for OS were analyzed by estimating the survival curves using the Kaplan-Meier method and by fitting univariable Cox models. 19 Optimal re-RT volume (VRec) and BED 10 cutoffs to classify patients as high vs low risk for OS were determined according to Mandrekar et al 20 With the purpose of externally validating the MIRI RPA model, 8 we estimated the Kaplan-Meier group-stratified OS curves for both the whole population and the subgroup of patients with SCC. 16 This analysis was performed in the whole patient population and then in the subgroup of patients with SCC.…”

Section: Methodsmentioning

confidence: 99%

“…2 In this scenario, and more significantly in case of intrinsically inoperable diseases, re-irradiation (re-RT) can play a relevant role, provided that the benefits of this approach on patients' outcome do not outweigh its potentially severe and life-threatening sequelae. Even in the presence of inherent shortcomings resulting from the heterogeneous sample of population included in retrospective and randomized prospective studies, several prognostic factors can be taken as relevant, such as the burden of comorbidities, 5,6 preexisting organ dysfunctions, 7 the volume of recurrence and its histology, 8 re-RT total dose and disease-free interval (DFI) between the two RT courses. Even in the presence of inherent shortcomings resulting from the heterogeneous sample of population included in retrospective and randomized prospective studies, several prognostic factors can be taken as relevant, such as the burden of comorbidities, 5,6 preexisting organ dysfunctions, 7 the volume of recurrence and its histology, 8 re-RT total dose and disease-free interval (DFI) between the two RT courses.…”

Section: Introductionmentioning

confidence: 99%

“…9,10 However, the best re-RT approach in terms of techniques and fractionation is still far from being defined. 8,12,13 In brief, a recursive partitioning analysis (RPA) identified three prognostic subgroups with distinct and homogenous OS (P < .001): class I included patients >2 years from their initial course of RT with resected tumors (2-year OS, 61.9%); class II included patients >2 years with unresected tumors or those ≤2 years and without organ dysfunctions (2-year OS, 40.0%), and the remaining patients formed class III (2-year OS, 16.8%). 8,12,13 In brief, a recursive partitioning analysis (RPA) identified three prognostic subgroups with distinct and homogenous OS (P < .001): class I included patients >2 years from their initial course of RT with resected tumors (2-year OS, 61.9%); class II included patients >2 years with unresected tumors or those ≤2 years and without organ dysfunctions (2-year OS, 40.0%), and the remaining patients formed class III (2-year OS, 16.8%).…”

Section: Introductionmentioning

confidence: 99%

“…11 Recently, the pivotal American multi-institution reirradiation (MIRI) consortium experience provided a toolkit to identify prognostic categories for overall survival (OS) for patients receiving re-RT with both stereotactic body radiotherapy (SBRT) and intensity modulated radiotherapy (IMRT). 8 Taking into account the intrinsic uncertainty regarding the decision-making for re-RT, it would be worthwhile to assess if the MIRI data can be extrapolated to non-U.S. practice. 8 Taking into account the intrinsic uncertainty regarding the decision-making for re-RT, it would be worthwhile to assess if the MIRI data can be extrapolated to non-U.S. practice.…”

Section: Introductionmentioning

confidence: 99%

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Long‐term outcome of re‐irradiation for recurrent or second primary head and neck cancer: A multi‐institutional study of AIRO—Head and Neck working group

et al. 2019

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Background To report the long‐term outcome of patients undergoing re‐irradiation (re‐RT) for a recurrent or second primary head and neck cancer (RSPHNCs) in seven Italian tertiary centers, while testing the Multi‐Institution Reirradation (MIRI) recursive partitioning analysis (RPA) recently published. Methods We retrospectively analyzed 159 patients. Prognostic factors for overall survival (OS) selected by a random forest model were included in a multivariable Cox analysis. To externally validate MIRI RPA, we estimated the Kaplan‐Meier group‐stratified OS curves for the whole population. Results Five‐year OS was 43.5% (median follow‐up: 49.9 months). Nasopharyngeal site, no organ dysfunction, and re‐RT volume <36 cm3 were independent factors for better OS. By applying the MIRI RPA to our cohort, a Harrell C‐Index of 0.526 was found indicating poor discriminative ability. Conclusion Our data reinforce the survival benefit of Re‐RT for selected patients with RSPHNC. MIRI RPA was not validated in our population.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Long‐term outcome of re‐irradiation for recurrent or second primary head and neck cancer: A multi‐institutional study of AIRO—Head and Neck working group

et al. 2019

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Evaluation of Proton Therapy Reirradiation for Patients With Recurrent Head and Neck Squamous Cell Carcinoma

et al. 2023

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ImportanceUse of proton therapy reirradiation (PT-ReRT) for head and neck cancer is increasing; however, reports are heterogenous and outcomes can be difficult to interpret.ObjectiveTo evaluate outcomes and toxic effects following PT-ReRT in a uniform and consecutive cohort of patients with head and neck squamous cell carcinoma.Design, Setting, and ParticipantsThis retrospective cohort study included patients with recurrent primary head and neck squamous cell carcinoma who were treated with PT-ReRT from January 1, 2013, to December 31, 2020, at a single institution. Patient, clinical, and treatment characteristics were obtained, and multidisciplinary review was performed to record and grade early and late toxic effects.ExposuresProton therapy reirradiation.Main Outcomes and MeasuresFollow-up was defined from the start of PT-ReRT. The Kaplan-Meier method was used for outcomes of interest, including local control (LC), locoregional control, distant metastatic control, progression-free survival, and overall survival (OS). Cox proportional hazards regression modeling was used to assess associations of covariates with OS.ResultsA total of 242 patients (median [range] age, 63 [21-96] years; 183 [75.6%] male) were included. Of these patients, 231 (95.9%) had a Karnofsky performance status score of 70 or higher, and 145 (59.9%) had at least a 10–pack-year smoking history. Median (range) follow-up was 12.0 (5.8-26.0) months for all patients and 24.5 (13.8-37.8) months for living patients. A total of 206 patients (85.1%) had recurrent disease vs second primary or residual disease. The median (range) interval between radiation courses was 22 (1-669) months. Median PT-ReRT dose was 70 cobalt gray equivalents (CGE) for the fractionated cohort and 44.4 CGE for the quad shot cohort. For the fractionated cohort, the 1-year LC was 71.8% (95% CI, 62.8%-79.0%) and the 1-year OS was 66.6% (95% CI, 58.1%-73.8%). For the quad shot cohort, the 1-year LC was 61.6% (95% CI, 46.4%-73.6%) and the 1-year OS was 28.5% (95% CI, 19.4%-38.3%). Higher Karnofsky performance status scores (hazard ratio [HR], 0.50; 95% CI, 0.25-0.99; P = .046) and receipt of salvage surgery prior to PT-ReRT (HR, 0.57; 95% CI, 0.39-0.84; P = .005) were associated with improved OS, whereas receipt of quad shot (HR, 1.97; 95% CI, 1.36-2.86; P &lt; .001) was associated with worse OS. There were a total of 73 grade 3 and 6 grade 4 early toxic effects. There were 79 potential grade 3, 4 grade 4, and 5 grade 5 late toxic effects.Conclusions and RelevanceThe findings of this cohort study suggest that, compared with previous reports with photon-based reirradiation, patients are living longer with aggressive PT-ReRT; however, surviving patients remain at risk of early and late complications.

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Intensity-Modulated Reirradiation Therapy With Nivolumab in Recurrent or Second Primary Head and Neck Squamous Cell Carcinoma

Saba,

Wong,

Nasti

et al. 2024

JAMA Oncol

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ImportanceIntensity-modulated radiation therapy (IMRT) reirradiation of nonmetastatic recurrent or second primary head and neck squamous cell carcinoma (HNSCC) results in poor progression-free survival (PFS) and overall survival (OS).ObjectiveTo investigate the tolerability, PFS, OS, and patient-reported outcomes with nivolumab (approved standard of care for patients with HNSCC) during and after IMRT reirradiation.Design, Setting, and ParticipantsIn this multicenter nonrandomized phase 2 single-arm trial, the treatment outcomes of patients with recurrent or second primary HNSCC who satisfied recursive partitioning analysis class 1 and 2 definitions were evaluated. Between July 11, 2018, and August 12, 2021, 62 patients were consented and screened. Data were evaluated between June and December 2023.InterventionSixty- to 66-Gy IMRT in 30 to 33 daily fractions over 6 to 6.5 weeks with nivolumab, 240 mg, intravenously 2 weeks prior and every 2 weeks for 5 cycles during IMRT, then nivolumab, 480 mg, intravenously every 4 weeks for a total nivolumab duration of 52 weeks.Main Outcomes and MeasuresThe primary end point was PFS. Secondary end points included OS, incidence, and types of toxic effects, including long-term treatment-related toxic effects, patient-reported outcomes, and correlatives of tissue and blood biomarkers.ResultsA total of 62 patients were screened, and 51 were evaluable (median [range] age was 62 [56-67] years; 42 [82%] were male; 6 [12%] had p16+ disease; 38 [75%] had salvage surgery; and 36 [71%.] had neck dissection). With a median follow-up of 24.5 months (95% CI, 19.0-25.0), the estimated 1-year PFS was 61.7% (95% CI, 49.2%-77.4%), rejecting the null hypothesis of 1-year PFS rate of less than 43.8% with 1-arm log-rank test P = .002 within a 1-year timeframe. The most common treatment-related grade 3 or higher adverse event (6 [12%]) was lymphopenia with 2 patients (4%) and 1 patient each (2%) exhibiting colitis, diarrhea, myositis, nausea, mucositis, and myasthenia gravis. Functional Assessment of Cancer Therapy–General and Functional Assessment of Cancer Therapy–Head and Neck Questionnaire quality of life scores remained stable and consistent across all time points. A hypothesis-generating trend favoring worsening PFS and OS in patients with an increase in blood PD1+, KI67+, and CD4+ T cells was observed.Conclusions and RelevanceThis multicenter nonrandomized phase 2 trial of IMRT reirradiation therapy and nivolumab suggested a promising improvement in PFS over historical controls. The treatment was well tolerated and deserves further evaluation.Trial RegistrationClinicalTrials.gov Identifier: NCT03521570

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Refining Patient Selection for Reirradiation of Head and Neck Squamous Carcinoma in the IMRT Era: A Multi-institution Cohort Study by the MIRI Collaborative

Cited by 131 publications

References 28 publications

Long‐term outcome of re‐irradiation for recurrent or second primary head and neck cancer: A multi‐institutional study of AIRO—Head and Neck working group

Long‐term outcome of re‐irradiation for recurrent or second primary head and neck cancer: A multi‐institutional study of AIRO—Head and Neck working group

Evaluation of Proton Therapy Reirradiation for Patients With Recurrent Head and Neck Squamous Cell Carcinoma

Intensity-Modulated Reirradiation Therapy With Nivolumab in Recurrent or Second Primary Head and Neck Squamous Cell Carcinoma

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