Publications by authors named "Tim Illidge"

Purpose/objectives: Radiotherapy (RT) is curative for the majority of patients with primary indolent orbital adnexal lymphoma (IOAL). Some reports suggest inferior outcomes for bilateral IOAL, leading to uncertainty regarding optimal management for this presentation. This multicentre, retrospective study evaluated long-term outcomes of bilateral IOAL patients treated with radiotherapy alone.

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Tumour bulk is an established prognostic factor in Hodgkin lymphoma (HL) but most patients with limited-stage (LS) HL do not have 'bulk' by standard binary definitions. In the RAPID trial, maximum tumor diameter (MTD) was associated with risk of relapse for LS-HL patients achieving PET-negativity after ABVD chemotherapy. We aimed to externally validate these findings in the H10 trial.

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Despite breakthroughs in immune checkpoint inhibitors (ICI), the majority of tumors, including those poorly infiltrated by CD8+ T cells or heavily infiltrated by immunosuppressive immune effector cells, are unlikely to result in clinically meaningful tumor responses. Radiation therapy (RT) has been combined with ICI to potentially overcome this resistance and improve response rates but reported clinical trial results have thus far been disappointing. Novel approaches are required to overcome this resistance and reprogram the immunosuppressive tumor microenvironment (TME) and address this major unmet clinical need.

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Introduction: The ability to modulate and enhance the anti-tumor immune responses is critical in developing novel therapies in cancer. The Tumor Necrosis Factor (TNF) Receptor Super Family (TNFRSF) are potentially excellent targets for modulation which result in specific anti-tumor immune responses. CD40 is a member of the TNFRSF and several clinical therapies are under development.

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Article Synopsis
  • The study aimed to determine if the pretreatment absolute lymphocyte count (ALC) can help identify oropharyngeal squamous cell carcinoma (OPSCC) patients who might benefit from reducing chemotherapy during treatment.
  • Researchers analyzed data from nearly 800 patients undergoing treatment, assessing overall survival (OS) and locoregional control (LRC) based on ALC levels.
  • Findings suggested that ALC is a significant predictor of OS and indicates how well patients might respond to adding cisplatin chemotherapy, potentially guiding future treatment de-escalation strategies.
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Introduction: Recent data has demonstrated that hypoxia drives an immunosuppressive tumour microenvironment (TME) via various mechanisms including hypoxia inducible factor (HIF)-dependent upregulation of programmed death ligand 1 (PD-L1). Both hypoxia and an immunosuppressive TME are targetable independent negative prognostic factors for bladder cancer. Therefore we sought to investigate whether hypoxia is associated with upregulation of PD-L1 in the disease.

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The use of F-FDG PET CT has become an essential part of the management of patients with lymphoma. The last decade has seen unrivalled progress in research efforts to personalise treatment approaches using PET as a predictive imaging biomarker. Critical to this success has been the standardisation of PET methods and reporting, including the 5-point Deauville scale, which has enabled the delivery of robust clinical trial data to develop response-adapted treatment approaches.

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Purpose: The contemporary management of early-stage Hodgkin lymphoma (ES-HL) involves balancing the risk of late adverse effects of radiotherapy against the increased risk of relapse if radiotherapy is omitted. This study provides information on the risk of radiation-related cardiovascular disease to help personalize the delivery of radiotherapy in ES-HL.

Methods: We predicted 30-year absolute cardiovascular risk from chemotherapy and involved field radiotherapy in patients who were positron emission tomography (PET)-negative following three cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine chemotherapy within a UK randomized trial of PET-directed therapy for ES-HL.

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Background: The optimal radiotherapy dose for indolent non-Hodgkin lymphoma is uncertain. We aimed to compare 24 Gy in 12 fractions (representing the standard of care) with 4 Gy in two fractions (low-dose radiation).

Methods: FoRT (Follicular Radiotherapy Trial) is a randomised, multicentre, phase 3, non-inferiority trial at 43 study centres in the UK.

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Radiotherapy (RT) is a highly effective anti-cancer therapy delivered to around 50-60% of patients. It is part of therapy for around 40% of cancer patients who are cured of their disease. Until recently, the focus of this anti-tumour efficacy has been on the direct tumour cytotoxicity and RT-induced DNA damage.

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For patients with indolent non-Hodgkin lymphoma who fail initial anti-CD20-based immunochemotherapy or develop relapsed or refractory disease, there remains a significant unmet clinical need for new therapeutic approaches to improve outcomes and quality of life. 177Lu-lilotomab satetraxetan is a next-generation single-dose CD37-directed radioimmunotherapy (RIT) which was investigated in a phase 1/2a study in 74 patients with relapsed/refractory indolent non-Hodgkin B-cell lymphoma, including 57 patients with follicular lymphoma (FL). To improve targeting of 177Lu-lilotomab satetraxetan to tumor tissue and decrease hematologic toxicity, its administration was preceded by the anti-CD20 monoclonal antibody rituximab and the "cold" anti-CD37 antibody lilotomab.

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The International Lymphoma Radiation Oncology Group (ILROG) guidelines for using radiation therapy (RT) in hematological malignancies are widely used in many countries. The emergency situation created by the COVID-19 pandemic may result in limitations of treatment resources. Furthermore, in recognition of the need to also reduce the exposure of patients and staff to potential infection with COVID-19, the ILROG task force has made recommendations for alternative radiation treatment schemes.

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Involved node radiation therapy for lymphoma was introduced with the aim of using the smallest effective treatment volume, individualized to the patient's disease distribution, to avoid the potentially unnecessary normal tissue exposure and toxicity risks associated with traditional involved field radiation therapy. The successful implementation of involved node radiation therapy requires optimal imaging and precise coregistration of baseline imaging with the radiation therapy planning computed tomography scan. Limitations of baseline imaging, changes in patient position, and anatomic changes after chemotherapy may make this difficult in routine practice.

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Cells succumbing to stress via regulated cell death (RCD) can initiate an adaptive immune response associated with immunological memory, provided they display sufficient antigenicity and adjuvanticity. Moreover, multiple intracellular and microenvironmental features determine the propensity of RCD to drive adaptive immunity. Here, we provide an updated operational definition of immunogenic cell death (ICD), discuss the key factors that dictate the ability of dying cells to drive an adaptive immune response, summarize experimental assays that are currently available for the assessment of ICD in vitro and in vivo, and formulate guidelines for their interpretation.

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Baseline maximum tumor diameter is an important predictor of relapse for patients with ES-HL achieving complete metabolic remission. Patients with baseline tumor size ≥5 cm have worse outcomes with ABVD alone and are likely to benefit from consolidation radiotherapy.

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Purpose: Accurate stratification of patients is an important goal in Hodgkin lymphoma (HL), but the role of pretreatment clinical risk stratification in the context of positron emission tomography (PET) -adapted treatment is unclear. We performed a subsidiary analysis of the RAPID trial to assess the prognostic value of pretreatment risk factors and PET score in determining outcomes.

Patients And Methods: Patients with stage IA to IIA HL and no mediastinal bulk underwent PET assessment after three cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine; 143 PET-positive patients (PET score, 3 to 5) received a fourth doxorubicin, bleomycin, vinblastine, and dacarbazine cycle and involved-field radiotherapy, and 419 patients in complete metabolic remission were randomly assigned to receive involved-field radiotherapy (n = 208) or no additional treatment (n = 211).

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Radioimmunotherapy (RIT) is a novel strategy for treating non-Hodgkin lymphoma (NHL). Several studies have shown the promising results of using RIT in NHL, which have led to FDA approval for two RIT agents in treating low grade NHL. In spite of these favorable results in low-grade NHL, most of the aggressive or relapsed/refractory NHL subjects experience relapses following RIT.

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Background: Based on the encouraging activity and manageable safety profile observed in a phase 1 study, the ECHELON-2 trial was initiated to compare the efficacy and safety of brentuximab vedotin, cyclophosphamide, doxorubicin, and prednisone (A+CHP) versus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) for the treatment of CD30-positive peripheral T-cell lymphomas.

Methods: ECHELON-2 is a double-blind, double-dummy, randomised, placebo-controlled, active-comparator phase 3 study. Eligible adults from 132 sites in 17 countries with previously untreated CD30-positive peripheral T-cell lymphomas (targeting 75% with systemic anaplastic large cell lymphoma) were randomly assigned 1:1 to receive either A+CHP or CHOP for six or eight 21-day cycles.

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Radiotherapy is a fundamental component of treatment for the majority of patients with cancer. In recent decades, technological advances have enabled patients to receive more targeted doses of radiation to the tumor, with sparing of adjacent normal tissues. There had been hope that the era of precision medicine would enhance the combination of radiotherapy with targeted anticancer drugs; however, this ambition remains to be realized.

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First-line treatments for classical Hodgkin lymphoma (HL) include ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) and BEACOPP (escalated dose bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, prednisone). To further improve overall outcomes, positron emission tomography-driven strategies and ABVD or BEACOPP variants incorporating the antibody-drug conjugate brentuximab vedotin (BV) or anti-PD1 antibodies are under investigation in advanced-stage patients. The present study aimed to elicit preferences for attributes associated with ABVD, BEACOPP and BV-AVD (BV, adriamycin, vinblastine and dacarbazine) among patients and physicians.

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