scholarly journals Combined High-Dose LATTICE Radiation Therapy and Immune Checkpoint Blockade for Advanced Bulky Tumors: The Concept and a Case Report

2021 ◽  
Vol 10 ◽  
Author(s):  
Liuqing Jiang ◽  
Xiaobo Li ◽  
Jianping Zhang ◽  
Wenyao Li ◽  
Fangfen Dong ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Immune Checkpoint ◽  
Radiation Treatment ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
High Rate ◽  
Tumor Control ◽  
High Dose ◽  
Large Tumor ◽  
Fractionated Radiotherapy

Although the combination of immune checkpoint blockades with high dose of radiation has indicated the potential of co-stimulatory effects, consistent clinical outcome has been yet to be demonstrated. Bulky tumors present challenges for radiation treatment to achieve high rate of tumor control due to large tumor sizes and normal tissue toxicities. As an alternative, spatially fractionated radiotherapy (SFRT) technique has been applied, in the forms of GRID or LATTICE radiation therapy (LRT), to safely treat bulky tumors. When used alone in a single or a few fractions, GRID or LRT can be best classified as palliative or tumor de-bulking treatments. Since only a small fraction of the tumor volume receive high dose in a SFRT treatment, even with the anticipated bystander effects, total tumor eradications are rare. Backed by the evidence of immune activation of high dose radiation, it is logical to postulate that the combination of High-Dose LATTICE radiation therapy (HDLRT) with immune checkpoint blockade would be effective and could subsequently lead to improved local tumor control without added toxicities, through augmenting the effects of radiation in-situ vaccine and T-cell priming. We herein present a case of non-small cell lung cancer (NSCLC) with multiple metastases. The patient received various types of palliative radiation treatments with combined chemotherapies and immunotherapies to multiple lesions. One of the metastatic lesions measuring 63.2 cc was treated with HDLRT combined with anti-PD1 immunotherapy. The metastatic mass regressed 77.84% over one month after the treatment, and had a complete local response (CR) five months after the treatment. No treatment-related side effects were observed during the follow-up exams. None of the other lesions receiving palliative treatments achieved CR. The dramatic differential outcome of this case lends support to the aforementioned postulate and prompts for further systemic clinical studies.

scholarly journals Radiation therapy and immunotherapy—a potential combination in cancer treatment

2018 ◽  
Vol 25 (5) ◽  
Author(s):  
N. Asna ◽  
A. Livoff ◽  
R. Batash ◽  
R. Debbi ◽  
P. Schaffer ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Immune Checkpoint ◽  
Tumour Microenvironment ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Abscopal Effect ◽  
Immune Stimulation ◽  
Significant Development ◽  
Molecular Effects ◽  
Review Current

BackgroundRadiation therapy (rt) is a longstanding treatment modality for cancer. In addition, immune checkpoint blockade has been a significant development in the field of immunotherapy, modifying key immunosuppressive pathways of cancer cells.MethodsThe aim of the present work was to review current concepts of rt and immunotherapy synergism, the abscopal effect, and the molecular effects of rt in the tumour microenvironment, its influence on immune stimulation, and potential clinical outcomes that might evolve from ongoing studies. We also discuss potential predictors of clinical response.ResultsUp-to-date literature concerning the mechanisms, interactions, and latest knowledge about rt and immunotherapy was reviewed and summarized, and is presented here.ConclusionsThe possibility of using hyperfractionated rt to combine an abscopal effect with the enhanced effect of immune treatment using checkpoint blockade is a very promising method for future tumour treatments.

Treatment of hepatocellular carcinoma using hypofractionated stereotactic radiosurgery.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 461-461
Author(s):  
Ariel Joseph Lederman ◽  
Mordecha Loksen ◽  
Thomas Lowinger ◽  
Daniel Izon ◽  
Gilbert S. Lederman
Keyword(s):  
Radiation Treatment ◽  
Progression Free Survival ◽  
Local Tumor Control ◽  
High Rate ◽  
Tumor Control ◽  
High Dose ◽  
Invasive Treatment ◽  
Non Invasive ◽  
Significant Difference

461 Background: Hypofractionated stereotactic Radiosugery (HFSR) is a non-invasive focused radiation treatment that delivers high dose therapy to cancer. HFSR for treatment of HepatocellularCarcinoma is analyzed in this prospective study. Methods: Twenty-three Hepatocellular Carcinomas (HCCs) were treated in 19 patients. All patients were prospectively evaluated before and after treatment. Age at treatment ranged from 11 to 84 years (mean 57) with 12 males and 6 females. Twenty-two percent of patients had prior chemotherapy, 17% had prior surgery and one patient had embolization. Tumor volumes ranged from 3 to 1,684cc (mean 312). The HCCs were treated with 500-800 cGy per fraction (median 600), in 5 or 6 fractions (median 5). For a total of 2,500-4,000 cGy (median 3,000). Cancers were followed with contrast CT and/or MRI scans and reviewed independently by radiologists. Control of the treated cancer is defined as cessation of growth, shrinkage or disappearance of the cancer after treatment. Results: Follow up ranged from 2 to 52 months. There was a 95.6% control rate at 14 months. By dose, volume, age, sex and prior treatment, there was no statistically significant difference in outcome. Conclusions: HFSR for HCCs is a generally well tolerated, non-invasive treatment modality with a high rate of local tumor control. Patients continue to be evaluated for longer follow up, progression free survival and overall survival. HFSR remains an attractive option for those in whom standard approaches have not produced desired results and for patients seeking an alternative to surgical or chemotherapeutic treatment.

scholarly journals Combining Radiation Therapy with Immune Checkpoint Blockade for Central Nervous System Malignancies

2016 ◽  
Vol 6 ◽  
Author(s):  
Neil M. D’Souza ◽  
Penny Fang ◽  
Jennifer Logan ◽  
Jinzhong Yang ◽  
Wen Jiang ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Radiation Therapy ◽  
Immune Checkpoint ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade

scholarly journals In Situ Crosslinked Hydrogel Depot for Sustained Antibody Release Improves Immune Checkpoint Blockade Cancer Immunotherapy

Nanomaterials ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 471
Author(s):  
Jihoon Kim ◽  
David M. Francis ◽  
Susan N. Thomas
Keyword(s):  
Cancer Immunotherapy ◽  
Immune Checkpoint ◽  
Cytotoxic T Lymphocyte ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
High Rate ◽  
Immune Checkpoints ◽  
Safe Delivery ◽  
Therapeutic Class

The therapeutic inhibition of immune checkpoints, including cytotoxic T lymphocyte-associated protein (CTLA)-4 and programmed cell death 1 (PD-1), through the use of function blocking antibodies can confer improved clinical outcomes by invigorating CD8+ T cell-mediated anticancer immunity. However, low rates of patient responses and the high rate of immune-related adverse events remain significant challenges to broadening the benefit of this therapeutic class, termed immune checkpoint blockade (ICB). To overcome these significant limitations, controlled delivery and release strategies offer unique advantages relevant to this therapeutic class, which is typically administered systemically (e.g., intravenously), but more recently, has been shown to be highly efficacious using locoregional routes of administration. As such, in this paper, we describe an in situ crosslinked hydrogel for the sustained release of antibodies blocking CTLA-4 and PD-1 signaling from a locoregional injection proximal to the tumor site. This formulation results in efficient and durable anticancer effects with a reduced systemic toxicity compared to the bolus delivery of free antibody using an equivalent injection route. This formulation and strategy thus represent an approach for achieving the efficient and safe delivery of antibodies for ICB cancer immunotherapy.

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