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Biomedicine & Pharmacotherapy =... May 2024Chimeric antigen receptor T (CAR-T) cell therapy, a groundbreaking immunotherapy. However, it faces formidable challenges in treating solid tumors, grappling with issues... (Review)
Review
Chimeric antigen receptor T (CAR-T) cell therapy, a groundbreaking immunotherapy. However, it faces formidable challenges in treating solid tumors, grappling with issues like poor trafficking, limited penetration, and insufficient persistence within the tumor microenvironment (TME). CAR-T cells are engineered to express receptors that target specific cancer antigens, enhancing their ability to recognize and eliminate cancer cells. This review paper explores the intricate interplay between CAR-T therapy and radiotherapy (RT), investigating their synergistic potential. Radiotherapy, a standard cancer treatment, involves using high doses of radiation to target and damage cancer cells, disrupting their ability to grow and divide. We highlight that RT modulates the TME, augments antigen presentation, and promotes immune cell infiltration, bolstering CAR-T cell-mediated tumor eradication. Molecular insights shed light on RT-induced alterations in tumor stroma, T cell recruitment promotion, and induction of immunogenic cell death. Noteworthy, strategies, such as combining hypofractionated radiotherapy with myeloid-derived suppressor cell blockade, underscore innovative approaches to enhance CAR-T cell therapy in solid tumors. Bridging indications for RT and CAR-T cells in hematological malignancies are discussed, emphasizing scenarios where RT strategically enhances CAR-T cell efficacy. The paper critically evaluates the RT as a bridge compared to traditional chemotherapy, highlighting timing and dosage considerations crucial for optimizing CAR-T therapy outcomes. In summary, the paper provides valuable insights into the intricate molecular mechanisms activated by RT and innovative strategies to improve CAR-T cell therapy, fostering a deeper understanding of their combined potential in cancer treatment.
Topics: Humans; Neoplasms; Tumor Microenvironment; Immunotherapy, Adoptive; Animals; Receptors, Chimeric Antigen; Combined Modality Therapy; Radiotherapy
PubMed: 38574625
DOI: 10.1016/j.biopha.2024.116532 -
Cancer Treatment Reviews Sep 2021Locoregional treatments (LRT) including radioembolisation (SIRT), transarterial chemo-embolisation (TACE), hepatic arterial infusion (HAI) of chemotherapy, external beam... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Locoregional treatments (LRT) including radioembolisation (SIRT), transarterial chemo-embolisation (TACE), hepatic arterial infusion (HAI) of chemotherapy, external beam radiotherapy (EBRT) and ablation have been studied for the management of intrahepatic cholangiocarcinoma (iCC). The aim of this systematic review was to provide outcome benchmarks for clinical trial design.
METHODS
Identification of studies reporting outcomes of patients treated with LRT for iCC was performed using PubMed and Embase. Pooled weighted means were calculated for progression-free survival (PFS) and overall survival (OS); meta-analysis of proportions was used for estimation of pooled response rate.
RESULTS
6325 entries were reviewed; 93 studies were eligible, representing 101 cohorts and 3990 patients: 15 cohorts (645 patients) for ablation, 18 cohorts (541 patients) for EBRT, 27 cohorts (1232 patients) for SIRT, 22 cohorts (1145 patients) for TACE, 16 cohorts (331 patients) for HAI and 3 cohorts (96 patients) not pooled. 74% of the studies were retrospective, 99% non-randomised. The pooled mean weighted OS was 30.2 months (95% confidence interval (CI): 21.8-38.6) for ablation, 18.9 (14.2-23.5) for EBRT, 14.1 (12.1-16.0) for SIRT, 15.9 (12.9-19.0) for TACE and 21.3 (15.4-27.1) for HAI. The pooled complete response rate was 93.9% for ablation. When analysed together, SIRT, TACE and HAI had a pooled mean weighted OS of 15.7 months, and 25.2 months for patients treated in first-line with concomitant systemic chemotherapy.
CONCLUSIONS
Available literature on LRT for iCC was heterogeneous and of insufficient quality to make strong recommendations. Ablation achieved satisfactory outcomes, and may be recommended when surgery is not feasible.
Topics: Ablation Techniques; Antineoplastic Agents; Bile Duct Neoplasms; Chemoembolization, Therapeutic; Cholangiocarcinoma; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Cohort Studies; Embolization, Therapeutic; Hepatic Artery; Humans; Infusions, Intra-Arterial; Randomized Controlled Trials as Topic; Yttrium Radioisotopes
PubMed: 34252720
DOI: 10.1016/j.ctrv.2021.102258 -
Brazilian Journal of Otorhinolaryngology 2023To determine the cut-off point of the cochlear radiation dose as a risk factor for hearing loss in patients with vestibular schwannoma treated with radiosurgery. (Review)
Review
OBJECTIVES
To determine the cut-off point of the cochlear radiation dose as a risk factor for hearing loss in patients with vestibular schwannoma treated with radiosurgery.
METHODS
A systematic review of the literature was performed without language or publication year restrictions in the MEDLINE/PubMed, EMBASE, Web of Science, LILACS/VHL and Cochrane Library databases. Studies that met the following criteria were included: 1) population: adults of both sexes who underwent radiosurgery for vestibular schwannoma treatment; 2) exposure: cochlear radiation; 3) outcome: hearing loss; 4) type of study: cohort. Two independent reviewers conducted the entire review process. The registration number in PROSPERO was CRD42020206128.
RESULTS
From the 333 articles identified in the searches, seven were included after applying the eligibility criteria. There was no standardization as to how to measure exposure or outcome in the included studies, and most studies did not present sufficient data to enable meta-analysis.
CONCLUSION
It was not possible to determine a cut-off point for high cochlear dose that could be considered a risk factor for hearing loss.
Topics: Adult; Female; Humans; Male; Deafness; Hearing Loss; Neuroma, Acoustic; Radiation Dosage; Radiosurgery; Retrospective Studies; Treatment Outcome
PubMed: 37579571
DOI: 10.1016/j.bjorl.2023.101300 -
Oral Surgery, Oral Medicine, Oral... Feb 2010Reconstructing irradiated mandibles with biomaterials is still a challenge but little investigated. We collected data that could help us understand studies in the field... (Review)
Review
OBJECTIVE
Reconstructing irradiated mandibles with biomaterials is still a challenge but little investigated. We collected data that could help us understand studies in the field of regeneration with biomaterials and irradiated bone.
STUDY DESIGN
Systematic review of the literature.
RESULTS
Delay and duration of radiation delivery and total equivalent dose are the most variable parameters in the various studies, resulting in confusion when interpreting the literature. Most reproducible experiments show that radiation reduces osteogenic cell numbers, alters cytokine capacity, and delays and damages bone remodeling. Interindividual variations and how such changes become irreversible lesions are still uncertain. In the case of regeneration using biomaterials, most studies have addressed the question of reconstruction in previously irradiated bone. The results show that osseointegration is often possible, although the failure rate is higher. The sooner the implantation takes place after the end of the radiation, the higher the likelihood of failure. Few studies have focused on primary reconstruction followed by early irradiation, and most of the currently available engineering models would be altered by radiation. Good outcomes have been obtained with bone morphogenetic protein and with total bone marrow transplanation.
CONCLUSION
This review points out the difficulties in achieving reproducible experiments and interpreting literature in this underinvestigated field.
Topics: Animals; Bone Development; Bone Marrow Transplantation; Bone Morphogenetic Proteins; Bone Remodeling; Bone Substitutes; Bone Transplantation; Bone and Bones; Cranial Irradiation; Dose-Response Relationship, Radiation; Guided Tissue Regeneration, Periodontal; Humans; Jaw Neoplasms; Mandible; Mandibular Neoplasms; Osteogenesis, Distraction; Osteoradionecrosis; Plastic Surgery Procedures; Tissue Engineering
PubMed: 20123406
DOI: 10.1016/j.tripleo.2009.10.001 -
Biomedicines Feb 2023(1) Background: Epilepsy is a frequent comorbidity in patients with brain tumors, in whom seizures are often drug-resistant. Current evidence suggests that excess of... (Review)
Review
(1) Background: Epilepsy is a frequent comorbidity in patients with brain tumors, in whom seizures are often drug-resistant. Current evidence suggests that excess of glutamatergic activity in the tumor microenvironment may favor epileptogenesis, but also tumor growth and invasiveness. The selective non-competitive α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist perampanel (PER) was demonstrated to be efficacious and well-tolerated in patients with focal seizures. Moreover, preclinical in vitro studies suggested a potential anti-tumor activity of this drug. In this systematic review, the clinical evidence on the efficacy and tolerability of PER in brain tumor-related epilepsy (BTRE) is summarized. (2) Methods: Five databases and two clinical trial registries were searched from inception to December 2022. (3) Results: Seven studies and six clinical trials were included. Sample size ranged from 8 to 36 patients, who received add-on PER (mean dosage from 4 to 7 mg/day) for BTRE. After a 6-12 month follow-up, the responder rate (% of patients achieving seizure freedom or reduction ≥ 50% of seizure frequency) ranged from 75% to 95%, with a seizure freedom rate of up to 94%. Regarding tolerability, 11-52% of patients experienced non-severe adverse effects (most frequent: dizziness, vertigo, anxiety, irritability). The retention rate ranged from 56% to 83%. However, only up to 12.5% of patients discontinued the drug because of the adverse events. (4) Conclusions: PER seems to be efficacious, safe, and well-tolerated in patients with BTRE. Further randomized studies should be conducted in more homogeneous and larger populations, also evaluating the effect of PER on tumor progression, overall survival, and progression-free survival.
PubMed: 36979629
DOI: 10.3390/biomedicines11030651 -
The Journal of Clinical and Aesthetic... Jun 2023Phototherapy has gained popularity in the recent decades for the treatment of various immune-mediated dermatological conditions since it is more-cost effective and less...
Phototherapy has gained popularity in the recent decades for the treatment of various immune-mediated dermatological conditions since it is more-cost effective and less toxic compared to systemic therapies. This systematic review aims to inform dermatology providers of the risks and benefits of phototherapy, especially in patients at risk for malignancies. Ionizing energy from phototherapy results in DNA photolesions, namely of cyclobutane pyrimidine dimers (CPDs) and 6-4 photoproducts (6-4PPs). Without adequate repair, these mutations increase the risk for carcinogenesis. Additionally, phototherapy can also indirectly cause DNA damage through the formation of reactive oxygen species (ROS), which damage of several structural and functional proteins and DNA. When choosing a phototherapy modality, it also important to take into consideration the side effect profiles associated with each modality. For instance, a 10-fold higher dose of NB-UVB is required to produce a similar amount of CPDs compared with BB-UVB. Patients who undergo UVA with psoralen (PUVA) can be susceptible to developing skin malignancies up to 25 years after receiving their last treatment. It would behoove providers to consider optimal radiation dosage given each patients' level of skin pigmentation and potential for photoadaptation. Additionally, there are measures have been proposed to minimize deleterious skin changes, such as a 42-degree Celsius heat treatment using a 308nm excimer laser prior to UVB phototherapy and low frequency, low intensity electromagnetic fields along with UVB. However, as performing routine skin exams, remain paramount in the prevention of phototherapy-induced neoplasia.
PubMed: 37361361
DOI: No ID Found -
Journal of Cancer Research and... Dec 2020Mucositis is a frequent, severe consequence of radiation therapy among patients undergoing radiotherapy for the head-and-neck cancer, often requiring hospitalization and...
Mucositis is a frequent, severe consequence of radiation therapy among patients undergoing radiotherapy for the head-and-neck cancer, often requiring hospitalization and even breaks or discontinuity in treatment. Mouth rinsing with various agents has demonstrated effectiveness in the prevention and treatment of radiation-induced mucositis (OM), but evidence for the same is lacking. This systematic review is therefore conducted with the aim of assessing the evidence for the effectiveness of mouthrinses in prevention and treatment of OM. Joanna Briggs Institute guidelines were followed to conduct this review. Six databases were searched and a total of 25 randomized clinical trials published over a period of the past 31 years were included for qualitative synthesis. Analysis of 25 studies revealed that 1299 participants, aged 46-69 years were assigned to the test groups and control groups. A total of 16 different formulations were studied among patients over a duration of 6 days to 1 year in varying dosages. The overall preventive fraction ranged from 1.9% to 77.8% for a reduction in clinical grades of mucositis, 7.6%-83.3% for a reduction in pain and 20%-50% for a reduction in bacterial counts. Adverse effects such as mouth burning, altered taste, sore throat, have been reported, especially with chlorhexidine and benzydamine hydrochloride. Evidence for the included studies is IC and ID. Studies using herbal based products and tissue regenerating agents revealed comparatively better effectiveness with lesser side effects. However, the number of studies to support such a claim is very limited.
Topics: Head and Neck Neoplasms; Humans; Mouthwashes; Mucositis; Radiation Injuries; Treatment Outcome
PubMed: 33380645
DOI: 10.4103/jcrt.JCRT_176_18 -
Annals of Oncology : Official Journal... Sep 2016The aim of this systematic review is to provide an overview of the diagnosis, treatment options and treatment-related complications of cervical esophageal carcinoma... (Review)
Review
BACKGROUND
The aim of this systematic review is to provide an overview of the diagnosis, treatment options and treatment-related complications of cervical esophageal carcinoma (CEC) and to subsequently provide recommendations to improve quality of care.
DESIGN
Studies were identified in PubMed, EMBASE and Web of Science. A total of 107 publications fulfilled the inclusion criteria and were included.
RESULTS
CEC is uncommon, accounting for 2%-10% of all esophageal carcinomas. These tumors are often locally advanced at presentation and have a poor prognosis, with a 5-year overall survival of 30%. Tobacco and alcohol consumption seem to be the major risk factors for developing CEC. Surgery is usually not possible due to the very close relationship to other organs such as the larynx, trachea and thyroid gland. Therefore, the current standard of care is definitive chemoradiation (dCRT) with curative intent. Treatment regimens used to treat CEC are adapted by established regimens in lower esophageal squamous cell carcinoma and head and neck squamous cell carcinoma. However, dCRT may be accompanied by severe side-effects and complications. Several diagnostic and predictive markers have been studied, but currently, there is no other biomarker than clinical stage to determine patient management. Suggestions to improve patient outcomes are to determine the exact radiation dose needed for adequate locoregional control and to combine radiotherapy with optimal systemic therapy backbone.
CONCLUSION
CEC remains unchartered territory for many practising physicians and patients with CEC have a poor prognosis. To improve the outcome for CEC patients, future studies should focus on the identification of new diagnostic biomarkers or targets for radiosensitizers, amelioration of radiation schedules, optimal combination of chemotherapeutic agents and/or new therapeutic targets.
Topics: Carcinoma, Squamous Cell; Chemoradiotherapy; Combined Modality Therapy; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Humans; Prognosis; Radiation Tolerance; Radiotherapy Dosage
PubMed: 27117535
DOI: 10.1093/annonc/mdw183 -
International Journal of Radiation... May 2021Dose escalation improves localized prostate cancer disease control, and moderately hypofractionated external beam radiation is noninferior to conventional fractionation....
PURPOSE
Dose escalation improves localized prostate cancer disease control, and moderately hypofractionated external beam radiation is noninferior to conventional fractionation. The evolving treatment approach of ultrahypofractionation with stereotactic body radiation therapy (SBRT) allows possible further biological dose escalation (biologically equivalent dose [BED]) and shortened treatment time.
METHODS AND MATERIALS
The American Association of Physicists in Medicine Working Group on Biological Effects of Hypofractionated Radiation Therapy/SBRT included a subgroup to study the prostate tumor control probability (TCP) with SBRT. We performed a systematic review of the available literature and created a dose-response TCP model for the endpoint of freedom from biochemical relapse. Results were stratified by prostate cancer risk group.
RESULTS
Twenty-five published cohorts were identified for inclusion, with a total of 4821 patients (2235 with low-risk, 1894 with intermediate-risk, and 446 with high-risk disease, when reported) treated with a variety of dose/fractionation schemes, permitting dose-response modeling. Five studies had a median follow-up of more than 5 years. Dosing regimens ranged from 32 to 50 Gy in 4 to 5 fractions, with total BED (α/β = 1.5 Gy) between 183.1 and 383.3 Gy. At 5 years, we found that in patients with low-intermediate risk disease, an equivalent doses of 2 Gy per fraction (EQD2) of 71 Gy (31.7 Gy in 5 fractions) achieved a TCP of 90% and an EQD2 of 90 Gy (36.1 Gy in 5 fractions) achieved a TCP of 95%. In patients with high-risk disease, an EQD2 of 97 Gy (37.6 Gy in 5 fractions) can achieve a TCP of 90% and an EQD2 of 102 Gy (38.7 Gy in 5 fractions) can achieve a TCP of 95%.
CONCLUSIONS
We found significant variation in the published literature on target delineation, margins used, dose/fractionation, and treatment schedule. Despite this variation, TCP was excellent. Most prescription doses range from 35 to 40 Gy, delivered in 4 to 5 fractions. The literature did not provide detailed dose-volume data, and our dosimetric analysis was constrained to prescription doses. There are many areas in need of continued research as SBRT continues to evolve as a treatment modality for prostate cancer, including the durability of local control with longer follow-up across risk groups, the efficacy and safety of SBRT as a boost to intensity modulated radiation therapy (IMRT), and the impact of incorporating novel imaging techniques into treatment planning.
Topics: Dose-Response Relationship, Radiation; Humans; Linear Models; Male; Models, Biological; Models, Theoretical; Probability; Prostatic Neoplasms; Radiation Dose Hypofractionation; Radiosurgery; Relative Biological Effectiveness; Risk; Time Factors; Treatment Outcome; Urethra
PubMed: 32900561
DOI: 10.1016/j.ijrobp.2020.08.014 -
Current Oncology (Toronto, Ont.) May 2022Selective internal radiation therapy (SIRT) with yttrium-90 (Y)-loaded microspheres is increasingly used for the treatment of Intrahepatic Cholangiocarcinoma (ICC).... (Review)
Review
Selective internal radiation therapy (SIRT) with yttrium-90 (Y)-loaded microspheres is increasingly used for the treatment of Intrahepatic Cholangiocarcinoma (ICC). Dosimetry verifications post-treatment are required for a valid assessment of any dose-response relationship. We performed a systematic review of the literature to determine how often clinics conducted post-treatment dosimetry verification to measure the actual radiation doses delivered to the tumor and to the normal liver in patients who underwent SIRT for ICC, and also to explore the corresponding dose-response relationship. We also investigated other factors that potentially affect treatment outcomes, including the type of microspheres used and concomitant chemotherapy. Out of the final 47 studies that entered our study, only four papers included post-treatment dosimetry studies after SIRT to quantitatively assess the radiation doses delivered. No study showed that one microsphere type provided a benefit over another, one study demonstrated better imaging-based response rates associated with the use of glass-based TheraSpheres, and two studies found similar toxicity profiles for different types of microspheres. Gemcitabine and cisplatin were the most common chemotherapeutic drugs for concomitant administration with SIRT. Future studies of SIRT for ICC should include dosimetry to optimize treatment planning and post-treatment radiation dosage measurements in order to reliably predict patient responses and liver toxicity.
Topics: Humans; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Chemoradiotherapy; Cholangiocarcinoma; Yttrium Radioisotopes
PubMed: 35735415
DOI: 10.3390/curroncol29060306