Reirradiation of Recurrent and Second Primary Head and Neck Cancer With Proton Therapy

McDonald, Mark W.; Zolali-Meybodi, Omid; Lehnert, Stephen J.; Estabrook, Neil C.; Liu, Yuan; Cohen-Gadol, Aaron; Moore, Michael G.

doi:10.1016/j.ijrobp.2016.07.037

Cited by 84 publications

(35 citation statements)

References 33 publications

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“…Re-irradiation using protons or heavy ions have demonstrated promising results for recurrent or second primary H&N cancer [35][36][37][38]. In a large retrospective study including 229 H&N cancer patients treated with carbon ion re-irradiation, the authors reported about a median OS of 26.1 months which was comparable to the OS rates in our study population [39].…”

Section: Discussionsupporting

confidence: 72%

The value of moderate dose escalation for re-irradiation of recurrent or second primary head-and-neck cancer

et al. 2020

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Background: Treatment for local and locoregional recurrence or second head-and-neck (H&N) cancers after previous radiotherapy is challenging, and re-irradiation carries a significantly increased risk for radiotherapy-related normal tissue toxicities and treatment failure due to a radioresistant tumor phenotype. Here, we analyzed reirradiation management and outcomes in patients with recurrent or second primary H&N carcinoma using state-ofthe-art diagnostic procedures and radiotherapy techniques. Methods: Between 2010 and 2019, 48 patients with recurrent or second primary H&N carcinoma received reradiotherapy at the University of Freiburg Medical Center and were included in this study. Overall survival (OS) and progression-free survival (PFS) were calculated with the Kaplan-Meier method, and univariate Cox-regression analyses were performed to assess the effects of clinico-pathological factors on treatment outcomes. Acute and chronic treatment-related toxicities were quantified using the Common Terminology Criteria for Adverse Events (CTCAE v4.03). Results: Thirty-one patients (64.6%) received definitive and 17 (35.4%) adjuvant radiotherapy. Simultaneous chemotherapy was administered in 28 patients (58.3%) with cetuximab as the most commonly used systemic agent (n = 17, 60.7%). After a median time of 17 months (range 4 months to 176 months) between first and second radiotherapy, patients were re-irradiated with a median of 58.4 Gy and a treatment completion rate of 87.5% (n = 42). Median OS was 25 months with a 1-year OS amounting to 62.4%, and median PFS was 9 months with a 1-year PFS of 37.6%. Univariate analyses demonstrated that both a lower rT-status and a radiotherapy boost were associated with improved OS (p < 0.05). There was a trend towards superior OS for patients who received > 50 Gy (p = 0.091) and who completed the prescribed radiotherapy (p = 0.055). Five patients (10.4%) suffered from at least one grade 3 toxicities, while 9 patients (27.3%) experienced chronic higher-grade toxicities (≥ grade 3) with one (3.0%) grade 4 carotid blowout and one (3.0%) grade 4 osteoradionecrosis.

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Section: Discussionsupporting

confidence: 72%

The value of moderate dose escalation for re-irradiation of recurrent or second primary head-and-neck cancer

et al. 2020

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“…There was one study on re-irradiation with proton therapy in 61 patients with recurrent cancer in the orbital, nasopharyngeal, and ethmoidal regions. The median follow-up was 15.2 months and the study reported acute and late Grade 3 toxicity incidences of 14.7% and 24.6%, respectively, including three treatment-related deaths (Grade 5) [14]. Meanwhile, Jensen et al reported on the use of carbon ions reirradiation for recurrent ACC of the head and neck after CIRT [8].…”

Section: Discussionmentioning

confidence: 99%

Feasibility of Re-irradiation using carbon ions for recurrent head and neck malignancies after carbon-ion radiotherapy

Hayashi

Koto

Ikawa

et al. 2019

Radiotherapy and Oncology

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Background and purpose: Locoregional recurrence after carbon-ion radiotherapy (CIRT) for primary head and neck malignancies, such as malignant mucosal melanoma, adenoid cystic carcinoma, and sarcoma, occurs occasionally. However, the treatment options are limited. We report on the toxicity and efficacy of re-irradiation using carbon ions for recurrent head and neck malignancies after CIRT. Materials and methods: Data of 48 patients with recurrent head and neck malignancies treated with reirradiation with CIRT at our institution (2007-2016) were retrospectively analyzed. Twenty-one patients (43.8%) had malignant mucosal melanoma, 17 (35.4%) had adenoid cystic carcinoma, six (12.5%) had bone and soft tissue sarcomas, and four patients (8.3%) had other disease types. Tumor recurrences at reirradiation were located in the paranasal cavity (n = 18, 37.5%), nasal cavity (n = 9, 18.8%), nasopharynx (n = 4, 8.3%), orbit (n = 3, 6.3%), cavernous sinus (n = 3, 6.3%), and at other sites (n = 11, 22.9%). The median dose of initial CIRT and that at re-irradiation were 57.6 Gy and 54.0 Gy (relative biological effectiveness [RBE]), respectively. None of the patients received concurrent chemotherapy. Results: The median follow-up period after re-irradiation was 27.1 months. Five patients (10.4%) developed Grade 3 acute toxicities and 18 (37.5%) developed Grade 3 late toxicities, including Grade 5 central nervous system necrosis in one patient. The 2-year local control, locoregional control, progression-free survival, and overall survival rates were 40.5, 33.5%, 29.4%, and 59.6%, respectively. Conclusion: Re-irradiation using carbon ions may be a reasonable treatment option with tolerable toxicity for patients with recurrent head and neck malignancies after CIRT.

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“…It is expected that the favorable depth-dose curves and linear energy transfer (LET) characteristics of charged particles will allow a precise targeting of deep-seated tumors while reducing the ionizing dose and irradiated volume of normal tissue. It is expected that these attempts to achieve a precise and more target-specific irradiation will help to lower the toxicity rates and the risk of developing secondary tumors [5][6][7][8][9][10][11]. In fact, particles pass through normal tissues on their track without losing much energy but instead releasing the main carried energy at a specific tissue depth shortly before their complete stop.…”

Section: Introductionmentioning

confidence: 99%

Proton Irradiation Increases the Necessity for Homologous Recombination Repair Along with the Indispensability of Non-Homologous End Joining

Szymonowicz

Krysztofiak

Linden

et al. 2020

Cells

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Technical improvements in clinical radiotherapy for maximizing cytotoxicity to the tumor while limiting negative impact on co-irradiated healthy tissues include the increasing use of particle therapy (e.g., proton therapy) worldwide. Yet potential differences in the biology of DNA damage induction and repair between irradiation with X-ray photons and protons remain elusive. We compared the differences in DNA double strand break (DSB) repair and survival of cells compromised in non-homologous end joining (NHEJ), homologous recombination repair (HRR) or both, after irradiation with an equal dose of X-ray photons, entrance plateau (EP) protons, and mid spread-out Bragg peak (SOBP) protons. We used super-resolution microscopy to investigate potential differences in spatial distribution of DNA damage foci upon irradiation. While DNA damage foci were equally distributed throughout the nucleus after X-ray photon irradiation, we observed more clustered DNA damage foci upon proton irradiation. Furthermore, deficiency in essential NHEJ proteins delayed DNA repair kinetics and sensitized cells to both, X-ray photon and proton irradiation, whereas deficiency in HRR proteins sensitized cells only to proton irradiation. We assume that NHEJ is indispensable for processing DNA DSB independent of the irradiation source, whereas the importance of HRR rises with increasing energy of applied irradiation.

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Reirradiation of Recurrent and Second Primary Head and Neck Cancer With Proton Therapy

Cited by 84 publications

References 33 publications

The value of moderate dose escalation for re-irradiation of recurrent or second primary head-and-neck cancer

The value of moderate dose escalation for re-irradiation of recurrent or second primary head-and-neck cancer

Feasibility of Re-irradiation using carbon ions for recurrent head and neck malignancies after carbon-ion radiotherapy

Proton Irradiation Increases the Necessity for Homologous Recombination Repair Along with the Indispensability of Non-Homologous End Joining

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