Search results for: Kevin J. Harrington

Items from 1 to 20 out of 117 results

article

Nivolumab treatment beyond RECIST‐defined progression in recurrent or metastatic squamous cell carcinoma of the head and neck in CheckMate 141: A subgroup analysis of a randomized phase 3 clinical trial

Robert Haddad, Fernando Concha‐Benavente, George Blumenschein, Jerome Fayette, more

Cancer > 125 > 18 > 3208 - 3218

Background Response patterns with immune checkpoint inhibitors may be different from those with chemotherapy. Therefore, assessment of response to immunotherapy with the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1, could result in premature treatment termination. The randomized, open‐label, phase 3 CheckMate 141 trial (NCT02105636), which evaluated nivolumab in recurrent/metastatic...

article

Development of a new fusion-enhanced oncolytic immunotherapy platform based on herpes simplex virus type 1

Suzanne Thomas, Linta Kuncheria, Victoria Roulstone, Joan N. Kyula, more

Journal for ImmunoTherapy of Cancer > 2019 > 7 > 1 > 1-17

Background Oncolytic viruses preferentially replicate in tumors as compared to normal tissue and promote immunogenic cell death and induction of host systemic anti-tumor immunity. HSV-1 was chosen for further development as an oncolytic immunotherapy in this study as it is highly lytic, infects human tumor cells broadly, kills mainly by necrosis and is a potent activator of both innate and adaptive...

article

The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of squamous cell carcinoma of the head and neck (HNSCC)

Ezra E. W. Cohen, R. Bryan Bell, Carlo B. Bifulco, Barbara Burtness, more

Journal for ImmunoTherapy of Cancer > 2019 > 7 > 1 > 1-31

Head and neck cancers, including those of the lip and oral cavity, nasal cavity, paranasal sinuses, oropharynx, larynx and nasopharynx represent nearly 700,000 new cases and 380,000 deaths worldwide per annum, and account for over 10,000 annual deaths in the United States alone. Improvement in outcomes are needed for patients with recurrent and or metastatic squamous cell carcinoma of the head and...

article

Plasmacytoid dendritic cells orchestrate innate and adaptive anti-tumor immunity induced by oncolytic coxsackievirus A21

Louise M. E. Müller, Matthew Holmes, Joanne L. Michael, Gina B. Scott, more

Journal for ImmunoTherapy of Cancer > 2019 > 7 > 1 > 1-16

Background The oncolytic virus, coxsackievirus A21 (CVA21), has shown promise as a single agent in several clinical trials and is now being tested in combination with immune checkpoint blockade. Combination therapies offer the best chance of disease control; however, the design of successful combination strategies requires a deeper understanding of the mechanisms underpinning CVA21 efficacy, in particular,...

article

Final analyses of OPTiM: a randomized phase III trial of talimogene laherparepvec versus granulocyte-macrophage colony-stimulating factor in unresectable stage III–IV melanoma

Robert H. I. Andtbacka, Frances Collichio, Kevin J. Harrington, Mark R. Middleton, more

Journal for ImmunoTherapy of Cancer > 2019 > 7 > 1 > 1-11

Background Talimogene laherparepvec is an oncolytic immunotherapy approved in the US, Europe, Australia and Switzerland. We report the final planned analysis of OPTiM, a randomized open-label phase III trial in patients with unresectable stage IIIB–IVM1c melanoma. Methods Patients were randomized 2:1 to receive intratumoral talimogene laherparepvec or subcutaneous recombinant GM-CSF. In addition...

article

The immunological consequences of radiation‐induced DNA damage

Anna C Wilkins, Emmanuel C Patin, Kevin J Harrington, Alan A Melcher

The Journal of Pathology > 247 > 5 > 606 - 614

Historically, our understanding of the cytotoxicity of radiation has centred on tumour cell‐autonomous mechanisms of cell death. Here, tumour cell death occurs when a threshold number of radiation‐induced non‐reparable double‐stranded DNA breaks is exceeded. However, in recent years, the importance of immune mechanisms of cell death has been increasingly recognised, as well as the impact of radiotherapy...

article

Near‐infrared photoimmunotherapy targeting EGFR—Shedding new light on glioblastoma treatment

Thomas A. Burley, Justyna Mączyńska, Anant Shah, Wojciech Szopa, more

International Journal of Cancer > 142 > 11 > 2363 - 2374

Glioblastomas (GBMs) are high‐grade brain tumors, differentially driven by alterations (amplification, deletion or missense mutations) in the epidermal growth factor receptor (EGFR), that carry a poor prognosis of just 12–15 months following standard therapy. A combination of interventions targeting tumor‐specific cell surface regulators along with convergent downstream signaling pathways may enhance...

article

MRI-based Assessment of 3D Intrafractional Motion of Head and Neck Cancer for Radiation Therapy

Oliver J. Gurney-Champion, Dualta McQuaid, Alex Dunlop, Kee H. Wong, more

International Journal of Radiation Oncology*Biology*Physics > 2018 > 100 > 2 > 306-316

To determine the 3-dimensional (3D) intrafractional motion of head and neck squamous cell carcinoma (HNSCC).Dynamic contrast-enhanced magnetic resonance images from 56 patients with HNSCC in the treatment position were analyzed. Dynamic contrast-enhanced magnetic resonance imaging consisted of 3D images acquired every 2.9 seconds for 4 minutes 50 seconds. Intrafractional tumor motion was studied in...

article

International guideline for the delineation of the clinical target volumes (CTV) for nasopharyngeal carcinoma

Anne W. Lee, Wai Tong Ng, Jian Ji Pan, Sharon S. Poh, more

Radiotherapy and Oncology > 2018 > 126 > 1 > 25-36

Target delineation in nasopharyngeal carcinoma (NPC) often proves challenging because of the notoriously narrow therapeutic margin. High doses are needed to achieve optimal levels of tumour control, and dosimetric inadequacy remains one of the most important independent factors affecting treatment outcome.A review of the available literature addressing the natural behaviour of NPC and correlation...

article

Practical clinical guide on the use of talimogene laherparepvec monotherapy in patients with unresectable melanoma in Europe

Ralf Gutzmer, Kevin J. Harrington, Christoph Hoeller, Celeste Lebbé, more

European Journal of Dermatology > 2018 > 28 > 6 > 736-749

Talimogene laherparepvec, a herpes simplex virus type 1-based intrale-sional oncolytic immunotherapy, is approved in Europe for the treatment of adults with unresectable stage IIIB-IVM1a melanoma, with no bone, brain, lung or other visceral disease. It has direct oncolytic effects in injected lesions, leading to the release of tumour-derived antigens and systemic immune effects mediated by the induction...

article

Changes in multimodality functional imaging parameters early during chemoradiation predict treatment response in patients with locally advanced head and neck cancer

Kee H. Wong, Rafal Panek, Alex Dunlop, Dualta Mcquaid, more

European Journal of Nuclear Medicine and Molecular Imaging > 2018 > 45 > 5 > 759-767

Objective To assess the optimal timing and predictive value of early intra-treatment changes in multimodality functional and molecular imaging (FMI) parameters as biomarkers for clinical remission in patients receiving chemoradiation for head and neck squamous cell carcinoma (HNSCC). Methods Thirty-five patients with stage III-IVb (AJCC 7th edition) HNSCC prospectively underwent ¹⁸F–FDG-PET/CT,...

article

Nivolumab versus standard, single-agent therapy of investigator's choice in recurrent or metastatic squamous cell carcinoma of the head and neck (CheckMate 141): health-related quality-of-life results from a randomised, phase 3 trial

Kevin J Harrington, Robert L Ferris, George Blumenschein, A Dimitrios Colevas, more

The Lancet Oncology > 2017 > 18 > 8 > 1104-1115

Patients with platinum-refractory recurrent or metastatic squamous cell carcinoma of the head and neck have few treatment options and poor prognosis. Nivolumab significantly improved survival of this patient population when compared with standard single-agent therapy of investigator's choice in Checkmate 141; here we report the effect of nivolumab on patient-reported outcomes (PROs). CheckMate...

article

A randomised controlled trial of Caphosol mouthwash in management of radiation-induced mucositis in head and neck cancer

Kee H. Wong, Aleksandra Kuciejewska, Mansour T.A. Sharabiani, Brian Ng-Cheng-Hin, more

Radiotherapy and Oncology > 2017 > 122 > 2 > 207-211

This phase III, non-blinded, parallel-group, randomised controlled study evaluated the efficacy of Caphosol mouthwash in the management of radiation-induced oral mucositis (OM) in patients with head and neck cancer (HNC) undergoing radical (chemo)radiotherapy.Eligible patients were randomised at 1:1 to Caphosol plus standard oral care (intervention) or standard oral care alone (control), stratified...

article

HSP90 inhibition sensitizes head and neck cancer to platin-based chemoradiotherapy by modulation of the DNA damage response resulting in chromosomal fragmentation

Martin McLaughlin, Holly E. Barker, Aadil A. Khan, Malin Pedersen, more

BMC Cancer > 2017 > 17 > 1 > 1-13

Background Concurrent cisplatin radiotherapy (CCRT) is a current standard-of-care for locally advanced head and neck squamous cell carcinoma (HNSCC). However, CCRT is frequently ineffective in patients with advanced disease. It has previously been shown that HSP90 inhibitors act as radiosensitizers, but these studies have not focused on CCRT in HNSCC. Here, we evaluated the HSP90 inhibitor, AUY922,...

article

Functional Data Analysis Applied to Modeling of Severe Acute Mucositis and Dysphagia Resulting From Head and Neck Radiation Therapy

Jamie A. Dean, Kee H. Wong, Hiram Gay, Liam C. Welsh, more

International Journal of Radiation Oncology*Biology*Physics > 2016 > 96 > 4 > 820-831

Current normal tissue complication probability modeling using logistic regression suffers from bias and high uncertainty in the presence of highly correlated radiation therapy (RT) dose data. This hinders robust estimates of dose-response associations and, hence, optimal normal tissue–sparing strategies from being elucidated. Using functional data analysis (FDA) to reduce the dimensionality of the...

article

Cutaneous head and neck melanoma in OPTiM, a randomized phase 3 trial of talimogene laherparepvec versus granulocyte‐macrophage colony‐stimulating factor for the treatment of unresected stage IIIB/IIIC/IV melanoma

Robert H. I. Andtbacka, Sanjiv S. Agarwala, David W. Ollila, Sigrun Hallmeyer, more

Head & Neck > 38 > 12 > 1752 - 1758

Background Cutaneous head and neck melanoma has poor outcomes and limited treatment options. In OPTiM, a phase 3 study in patients with unresectable stage IIIB/IIIC/IV melanoma, intralesional administration of the oncolytic virus talimogene laherparepvec improved durable response rate (DRR; continuous response ≥6 months) compared with subcutaneous granulocyte‐macrophage colony‐stimulating factor...

article

DARS: a phase III randomised multicentre study of dysphagia- optimised intensity- modulated radiotherapy (Do-IMRT) versus standard intensity- modulated radiotherapy (S-IMRT) in head and neck cancer

Imran Petkar, Keith Rooney, Justin W. G. Roe, Joanne M. Patterson, more

BMC Cancer > 2016 > 16 > 1 > 1-10

Background Persistent dysphagia following primary chemoradiation (CRT) for head and neck cancers can have a devastating impact on patients’ quality of life. Single arm studies have shown that the dosimetric sparing of critical swallowing structures such as the pharyngeal constrictor muscle and supraglottic larynx can translate to better functional outcomes. However, there are no current randomised...

article

Isolated limb perfusion with biochemotherapy and oncolytic virotherapy combines with radiotherapy and surgery to overcome treatment resistance in an animal model of extremity soft tissue sarcoma

Michelle J. Wilkinson, Henry G. Smith, Timothy D. Pencavel, David C. Mansfield, more

International Journal of Cancer > 139 > 6 > 1414 - 1422

The management of locally advanced or recurrent extremity sarcoma often necessitates multimodal therapy to preserve a limb, of which isolated limb perfusion (ILP) is a key component. However, with standard chemotherapeutic agents used in ILP, the duration of response is limited. Novel agents or treatment combinations are urgently needed to improve outcomes. Previous work in an animal model has demonstrated...

article

Contrast enhancement of carotid adventitial vasa vasorum as a biomarker of radiation-induced atherosclerosis

Dorothy M. Gujral, Wing Keung Cheung, Benoy N. Shah, Navtej S. Chahal, more

Radiotherapy and Oncology > 2016 > 120 > 1 > 63-68

Abnormal proliferation of adventitial vasa vasorum (vv) occurs early at sites of atherosclerosis and is thought to be an early biomarker of vascular damage. Contrast-enhanced ultrasound (CEUS) can detect this process. Its usefulness in irradiated arteries as a measure of accelerated atherosclerosis is unknown. This study investigates contrast intensity in carotid adventitia as an early marker of radiation-induced...

article

Normal tissue complication probability (NTCP) modelling using spatial dose metrics and machine learning methods for severe acute oral mucositis resulting from head and neck radiotherapy

Jamie A. Dean, Kee H. Wong, Liam C. Welsh, Ann-Britt Jones, more

Radiotherapy and Oncology > 2016 > 120 > 1 > 21-27

Severe acute mucositis commonly results from head and neck (chemo)radiotherapy. A predictive model of mucositis could guide clinical decision-making and inform treatment planning. We aimed to generate such a model using spatial dose metrics and machine learning.Predictive models of severe acute mucositis were generated using radiotherapy dose (dose–volume and spatial dose metrics) and clinical data...

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INFONA - science communication portal

Search results for: Kevin J. Harrington

Nivolumab treatment beyond RECIST‐defined progression in recurrent or metastatic squamous cell carcinoma of the head and neck in CheckMate 141: A subgroup analysis of a randomized phase 3 clinical trial

Development of a new fusion-enhanced oncolytic immunotherapy platform based on herpes simplex virus type 1

The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of squamous cell carcinoma of the head and neck (HNSCC)

Plasmacytoid dendritic cells orchestrate innate and adaptive anti-tumor immunity induced by oncolytic coxsackievirus A21

Final analyses of OPTiM: a randomized phase III trial of talimogene laherparepvec versus granulocyte-macrophage colony-stimulating factor in unresectable stage III–IV melanoma

The immunological consequences of radiation‐induced DNA damage

Near‐infrared photoimmunotherapy targeting EGFR—Shedding new light on glioblastoma treatment

MRI-based Assessment of 3D Intrafractional Motion of Head and Neck Cancer for Radiation Therapy

International guideline for the delineation of the clinical target volumes (CTV) for nasopharyngeal carcinoma

Practical clinical guide on the use of talimogene laherparepvec monotherapy in patients with unresectable melanoma in Europe

Changes in multimodality functional imaging parameters early during chemoradiation predict treatment response in patients with locally advanced head and neck cancer

Nivolumab versus standard, single-agent therapy of investigator's choice in recurrent or metastatic squamous cell carcinoma of the head and neck (CheckMate 141): health-related quality-of-life results from a randomised, phase 3 trial

A randomised controlled trial of Caphosol mouthwash in management of radiation-induced mucositis in head and neck cancer

HSP90 inhibition sensitizes head and neck cancer to platin-based chemoradiotherapy by modulation of the DNA damage response resulting in chromosomal fragmentation

Functional Data Analysis Applied to Modeling of Severe Acute Mucositis and Dysphagia Resulting From Head and Neck Radiation Therapy

Cutaneous head and neck melanoma in OPTiM, a randomized phase 3 trial of talimogene laherparepvec versus granulocyte‐macrophage colony‐stimulating factor for the treatment of unresected stage IIIB/IIIC/IV melanoma

DARS: a phase III randomised multicentre study of dysphagia- optimised intensity- modulated radiotherapy (Do-IMRT) versus standard intensity- modulated radiotherapy (S-IMRT) in head and neck cancer

Isolated limb perfusion with biochemotherapy and oncolytic virotherapy combines with radiotherapy and surgery to overcome treatment resistance in an animal model of extremity soft tissue sarcoma

Contrast enhancement of carotid adventitial vasa vasorum as a biomarker of radiation-induced atherosclerosis

Normal tissue complication probability (NTCP) modelling using spatial dose metrics and machine learning methods for severe acute oral mucositis resulting from head and neck radiotherapy

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