Randomized Phase III Trial of Concurrent Accelerated Radiation Plus Cisplatin With or Without Cetuximab for Stage III to IV Head and Neck Carcinoma: RTOG 0522

Ang, K. Kian; Zhang, Qiang; Rosenthal, David I.; Nguyen-Tân, Phuc Félix; Sherman, Eric J.; Weber, Randal S.; Galvin, James M.; Bonner, James A.; Harris, Jonathan; El‐Naggar, Adel K.; Gillison, Maura L.; Jordan, Richard C.; Konski, André; Thorstad, Wade L.; Trotti, Andy; Beitler, Jonathan J.; Garden, Adam S.; Spanos, William J.; Yom, Sue S.; Axelrod, Rita

doi:10.1200/jco.2013.53.5633

Cited by 708 publications

(582 citation statements)

References 26 publications

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“…The threshold criterion for adaptation was for 95% of the volume (D95) to be below the prescribed dose. The D95 parameter was selected following recommendations for evaluating the target coverage 26. Only the primary PTV was analyzed for each patient.…”

Section: Methodsmentioning

confidence: 99%

Online daily assessment of dose change in head and neck radiotherapy without dose‐recalculation

Vickress

Battista

Barnett

et al. 2018

J Applied Clin Med Phys

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BackgroundHead and neck cancers are commonly treated with radiation therapy, but due to possible volume changes, plan adaptation may be required during the course of treatment. Currently, plan adaptations consume significant clinical resources. Existing methods to evaluate the need for plan adaptation requires deformable image registration (DIR) to a new CT simulation or daily cone beam CT (CBCT) images and the recalculation of the dose distribution. In this study, we explore a tool to assist the decision for plan adaptation using a CBCT without re‐computation of dose, allowing for rapid online assessment.MethodsThis study involved 18 head and neck cancer patients treated with CBCT image guidance who had their treatment plan modified based on a new CT simulation (ReCT). Dose changes were estimated using different methods and compared to the current gold standard of using DIR between the planning CT scan (PCT) and ReCT with recomputed dose. The first and second methods used DIR between the PCT and daily CBCT with the planned dose or recalculated dose from the ReCT respectively, with the dose transferred to the CBCT using rigid registration. The necessity of plan adaptation was assessed by the change in dose to 95% of the planning target volume (D95) and mean dose to the parotids.ResultsThe treatment plans were adapted clinically for all 18 patients but only 7 actually needed an adaptation yielding 11 unnecessary adaptations. Applying a method using the daily CBCT with the planned dose distribution would have yielded only four unnecessary adaptations and no missed adaptations: a significant improvement from that done clinically.ConclusionUsing the DIR between the planning CT and daily CBCT can flag cases for plan adaptation before every fraction while not requiring a new re‐planning CT scan and dose recalculation.

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Section: Methodsmentioning

confidence: 99%

Online daily assessment of dose change in head and neck radiotherapy without dose‐recalculation

Vickress

Battista

Barnett

et al. 2018

J Applied Clin Med Phys

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“…Cetuximab, an inhibitor of the EGFR receptor, is the only targeted chemotherapeutic agent approved for curative treatment of HNSCC in the past decade and provides only modest survival improvement compared with radiation alone. Because radiation dose escalation is restricted by adjacent normal tissue toxicity, and recent attempts at chemoradiation dose escalation with cisplatin and cetuximab have not proven beneficial (6,7), cure rates will likely be improved by the development of effective novel radiosensitizers that selectively target tumor cells while preserving normal mucosa.…”

Section: Introductionmentioning

confidence: 99%

The Neddylation Inhibitor Pevonedistat (MLN4924) Suppresses and Radiosensitizes Head and Neck Squamous Carcinoma Cells and Tumors

Vanderdys

Allak

Guessous

et al. 2018

Molecular Cancer Therapeutics

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The cullin RING E3 ubiquitin ligase 4 (CRL4) with its substrate receptor CDT2 (CRL4-CDT2) is emerging as a critical regulator of DNA replication through targeting CDT1, SET8, and p21 for ubiquitin-dependent proteolysis. The aberrant increased stability of these proteins in cells with inactivated CRL4-CDT2 results in DNA rereplication, which is deleterious to cells due to the accumulation of replication intermediates and stalled replication forks. Here, we demonstrate that CDT2 is overexpressed in head and neck squamous cell carcinoma (HNSCC), and its depletion by siRNA inhibits the proliferation of human papilloma virusnegative (HPV-ve) HNSCC cells primarily through the induction of rereplication. Treatment of HNSCC with the NEDD8-activating enzyme inhibitor pevonedistat (MLN4924), which inhibits all cullin-based ligases, induces significant rereplication and inhibits HNSCC cell proliferation in culture and HNSCC xenografts in mice. Pevonedistat additionally sensitizes HNSCC cells to ionizing radiation (IR) and enhances IR-induced suppression of xenografts in mice. Induction of rereplication via CDT2 depletion, or via the stabilization or activation of CDT1, also radiosensitizes HNSCC cells. Collectively, these results demonstrate that induction of rereplication represents a novel approach to treating radioresistant HNSCC tumors and suggest that pevonedistat may be considered as an adjuvant for IR-based treatments.

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“…Онкологическая группа по лучевой терапии (Radiation Therapy Oncology Group) недавно завершила исследование III фазы, в которой определялась эффек-тивность цетуксимаба у пациентов с ПРГШ III или IV стадии, которые получали химиолучевое лечение (увеличенная доза облучения и цисплатин) [28]. В этой группе не наблюдалось различий в исходах у пациен-тов (смертность, выживаемость без прогрессирования, общая выживаемость, частота локорегионарного ре-цидива, отдаленное метастазирование) в сравнении с группой, где к терапии был добавлен цетуксимаб.…”

Section: возможности таргетной терапии при мутациях онкогеновunclassified

Treatment of Head and Neck Squamous Cell Carcinoma According on the Specific Molecular Features of the Tumor (A Literature Review)

Stukan¹,

Murashko²,

Бодня³

et al. 2017

Opuholi golovy šei

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Randomized Phase III Trial of Concurrent Accelerated Radiation Plus Cisplatin With or Without Cetuximab for Stage III to IV Head and Neck Carcinoma: RTOG 0522

Abstract: Adding cetuximab to radiation-cisplatin did not improve outcome and hence should not be prescribed routinely. PFS and OS were higher in patients with p16-positive OPC, but outcomes did not differ by EGFR expression.

Cited by 708 publications

References 26 publications

Online daily assessment of dose change in head and neck radiotherapy without dose‐recalculation

Online daily assessment of dose change in head and neck radiotherapy without dose‐recalculation

The Neddylation Inhibitor Pevonedistat (MLN4924) Suppresses and Radiosensitizes Head and Neck Squamous Carcinoma Cells and Tumors

Treatment of Head and Neck Squamous Cell Carcinoma According on the Specific Molecular Features of the Tumor (A Literature Review)

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