Re-irradiation of adenoid cystic carcinoma: Analysis and evaluation of outcome in 52 consecutive patients treated with raster-scanned carbon ion therapy

Jensen, Alexandra D; Poulakis, Melanie; Nikoghosyan, Anna; Chaudhri, Naved; Uhl, Matthias; Münter, Marc W.; Herfarth, Klaus; Debus, Jürgen

doi:10.1016/j.radonc.2015.01.002

Cited by 78 publications

(52 citation statements)

References 52 publications

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“…While this is a compromise clinicians often have to accept, it is nevertheless an issue, which needs to be discussed with the patient. The risk of local relapse has to be explained to the patient especially since salvage re-irradiation in our experience rarely leads to long-term LC [38]. The rate of distant disease progression underlines the importance of identifying and introducing systemically active agents in the primary situation.…”

Section: Discussionmentioning

confidence: 81%

“…Though the overall incidence in this large patient cohort may be low, we still wish to advise caution when treating patients with dose escalation following extensive resections in or near the skull base. While carotid blowout may be more common in re-irradiation of head and neck tumors [38,42], prior surgery and doses >70 Gy were identified as risk factors [42], the risk of carotid artery damage and permanent CSF leakage may limit further dose escalation at these sites.…”

Section: Discussionmentioning

confidence: 99%

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High-LET radiotherapy for adenoid cystic carcinoma of the head and neck: 15 years’ experience with raster-scanned carbon ion therapy

Jensen

Poulakis

Nikoghosyan

et al. 2016

Radiotherapy and Oncology

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Section: Discussionmentioning

confidence: 81%

Section: Discussionmentioning

confidence: 99%

High-LET radiotherapy for adenoid cystic carcinoma of the head and neck: 15 years’ experience with raster-scanned carbon ion therapy

Jensen

Poulakis

Nikoghosyan

et al. 2016

Radiotherapy and Oncology

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“…The HIT team reported results of re-irradiation using CIRT for 52 patients with adenoid cystic carcinoma of the head and neck. Treatments were well tolerated without grade > 2 toxicity and with excellent control and survival rates [178]. The NIRS group reported an interesting phase I/II CIRT dose escalation study on recurrent, previously resected but not irradiated, rectal cancers.…”

Section: Clinical Experiences With Cirtmentioning

confidence: 99%

Carbon Ion Radiotherapy: A Review of Clinical Experiences and Preclinical Research, with an Emphasis on DNA Damage/Repair

Mohamad

Sishc

Saha

et al. 2017

Cancers

148

130

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Compared to conventional photon-based external beam radiation (PhXRT), carbon ion radiotherapy (CIRT) has superior dose distribution, higher linear energy transfer (LET), and a higher relative biological effectiveness (RBE). This enhanced RBE is driven by a unique DNA damage signature characterized by clustered lesions that overwhelm the DNA repair capacity of malignant cells. These physical and radiobiological characteristics imbue heavy ions with potent tumoricidal capacity, while having the potential for simultaneously maximally sparing normal tissues. Thus, CIRT could potentially be used to treat some of the most difficult to treat tumors, including those that are hypoxic, radio-resistant, or deep-seated. Clinical data, mostly from Japan and Germany, are promising, with favorable oncologic outcomes and acceptable toxicity. In this manuscript, we review the physical and biological rationales for CIRT, with an emphasis on DNA damage and repair, as well as providing a comprehensive overview of the translational and clinical data using CIRT.

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“…Treatment options for ACC are currently limited to surgery with or without radiation, consistent with limited insight into its molecular drivers (1). ACC has a high recurrence rate and dismal survival in part because of its intrinsic resistance to radio- and chemotherapies (2). Existence of cancer stem cells (CSC) in ACC has been suggested (3), but their molecular identity remained elusive due to difficulties with ACC culture.…”

Section: Introductionmentioning

confidence: 99%

NOTCH1 and SOX10 are Essential for Proliferation and Radiation Resistance of Cancer Stem–Like Cells in Adenoid Cystic Carcinoma

Panaccione

Chang

Carbone

et al. 2016

Clinical Cancer Research

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Purpose While the existence of CSC in ACC has been proposed, lack of assays for their propagation and uncertainty about molecular markers prevented their characterization. Our objective was to isolate CSC from ACC and provide insight into signaling pathways that support their propagation. Experimental design To isolate CSC from ACC and characterize them, we used ROCK inhibitor-supplemented cell culture, immunomagnetic cell sorting, and in vitro/in vivo assays for CSC viability and tumorigenicity. Results We identified in ACC CD133-positive CSC that expressed NOTCH1 and SOX10, formed spheroids, and initiated tumors in nude mice. CD133+ ACC cells produced activated NOTCH1 (N1ICD) and generated CD133− cells that expressed JAG1 as well as neural differentiation factors NR2F1, NR2F2, and p27Kip1. Knockdowns of NOTCH1, SOX10, and their common effector FABP7 had negative effects on each other, inhibited spheroidogenesis, and induced cell death pointing at their essential roles in CSC maintenance. Downstream effects of FABP7 knockdown included suppression of a broad spectrum of genes involved in proliferation, ribosome biogenesis, and metabolism. Among proliferation-linked NOTCH1/FABP7 targets we identified SKP2 and its substrate p27Kip1. A γ-secretase inhibitor, DAPT, selectively depleted CD133+ cells, suppressed N1ICD and SKP2, induced p27Kip1, inhibited ACC growth in vivo, and sensitized CD133+ cells to radiation. Conclusions These results establish in the majority of ACC the presence of a previously uncharacterized population of CD133+ cells with neural stem properties, which are driven by SOX10, NOTCH1, and FABP7. Sensitivity of these cells to Notch inhibition and their dependence on SKP2 offer new opportunities for targeted ACC therapies.

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Re-irradiation of adenoid cystic carcinoma: Analysis and evaluation of outcome in 52 consecutive patients treated with raster-scanned carbon ion therapy

Cited by 78 publications

References 52 publications

High-LET radiotherapy for adenoid cystic carcinoma of the head and neck: 15 years’ experience with raster-scanned carbon ion therapy

High-LET radiotherapy for adenoid cystic carcinoma of the head and neck: 15 years’ experience with raster-scanned carbon ion therapy

Carbon Ion Radiotherapy: A Review of Clinical Experiences and Preclinical Research, with an Emphasis on DNA Damage/Repair

NOTCH1 and SOX10 are Essential for Proliferation and Radiation Resistance of Cancer Stem–Like Cells in Adenoid Cystic Carcinoma

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