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International Journal of Radiation... Jun 2024From the Pediatric Normal Tissue Effects in the Clinic (PENTEC) initiative, a systematic review and meta-analysis of publications reporting on radiation dose-volume... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
From the Pediatric Normal Tissue Effects in the Clinic (PENTEC) initiative, a systematic review and meta-analysis of publications reporting on radiation dose-volume effects for risk of primary hypothyroidism after radiation therapy for pediatric malignancies was performed.
METHODS AND MATERIALS
All studies included childhood cancer survivors, diagnosed at age <21 years, whose radiation therapy fields exposed the thyroid gland and who were followed for primary hypothyroidism. Children who received pituitary-hypothalamic or total-body irradiation were excluded. PubMed and the Cochrane Library were searched for studies published from 1970 to 2017. Data on age at treatment, patient sex, radiation dose to neck or thyroid gland, specific endpoints for hypothyroidism that were used in the studies, and reported risks of hypothyroidism were collected. Radiation dose-volume effects were modeled using logistic dose response. Relative excess risk of hypothyroidism as a function of age at treatment and sex was assessed by meta-analysis of reported relative risks (RR) and odds ratios.
RESULTS
Fifteen publications (of 1709 identified) were included for systematic review. Eight studies reported data amenable for dose-response analysis. At mean thyroid doses of 10, 20, and 30 Gy, predicted rates of uncompensated (clinical) hypothyroidism were 4%, 7%, and 13%, respectively. Predicted rates of compensated (subclinical) hypothyroidism were 12%, 25%, and 44% after thyroid doses of 10, 20, and 30 Gy, respectively. Female sex (RR = 1.7, P < .0001) and age >15 years at radiation therapy (RR = 1.3, P = .005) were associated with higher risks of hypothyroidism. After a mean thyroid dose of 20 Gy, predicted risks of hypothyroidism were 13% for males <14 years of age, increasing to 29% for females >15 years of age.
CONCLUSION
A radiation dose response for risk of hypothyroidism is evident; a threshold radiation dose associated with no risk is not observed. Thyroid dose exposure should be minimized when feasible. Data on hypothyroidism after radiation therapy should be better reported to facilitate pooled analyses.
Topics: Humans; Hypothyroidism; Cancer Survivors; Child; Adolescent; Thyroid Gland; Male; Female; Child, Preschool; Dose-Response Relationship, Radiation; Neoplasms; Young Adult; Age Factors; Radiation Injuries; Radiotherapy Dosage; Sex Factors; Organs at Risk; Infant
PubMed: 33810948
DOI: 10.1016/j.ijrobp.2021.02.001 -
The Lancet. Oncology Mar 2021For patients diagnosed with cancer who have previously received an organ transplant, radiotherapy represents a challenging clinical scenario without well established...
For patients diagnosed with cancer who have previously received an organ transplant, radiotherapy represents a challenging clinical scenario without well established care algorithms. Immunosuppressive therapy can be a cause for concern among clinicians treating this category of patients. Potential immune modulation following irradiation could affect recipient organ tolerance and the outcomes of the transplantation itself. The main aim of this systematic review was to define the safety and effectiveness of radiotherapy in patients diagnosed with cancer who have previously received an organ transplant. We searched PubMed and Embase for articles published between Jan 1, 1995, and April 30, 2020 for studies in patients who had undergone radiotherapy for post-transplantation malignancies. The Review is framed by the PICO (population, intervention, control, and outcomes) criteria, and primarily focuses on modern treatment techniques.
Topics: Humans; Immunosuppression Therapy; Neoplasms; Organ Transplantation; Radiation Oncology
PubMed: 33662300
DOI: 10.1016/S1470-2045(20)30590-8 -
International Journal of Radiation... May 2021Ultrahypofractionationed radiation therapy for prostate cancer is increasingly studied and adopted. The American Association of Physicists in Medicine Working Group on...
PURPOSE
Ultrahypofractionationed radiation therapy for prostate cancer is increasingly studied and adopted. The American Association of Physicists in Medicine Working Group on Biological Effects of Hypofractionated Radiotherapy therefore aimed to review studies examining toxicity and quality of life after stereotactic body radiation therapy (SBRT) for prostate cancer and model its effect.
METHODS AND MATERIALS
We performed a systematic PubMed search of prostate SBRT studies published between 2001 and 2018. Those that analyzed factors associated with late urinary, bowel, or sexual toxicity and/or quality of life were included and reviewed. Normal tissue complication probability modelling was performed on studies that contained detailed dose/volume and outcome data.
RESULTS
We found 13 studies that examined urinary effects, 6 that examined bowel effects, and 4 that examined sexual effects. Most studies included patients with low-intermediate risk prostate cancer treated to 35-40 Gy. Most patients were treated with 5 fractions, with several centers using 4 fractions. Endpoints were heterogeneous and included both physician-scored toxicity and patient-reported quality of life. Most toxicities were mild-moderate (eg, grade 1-2) with a very low overall incidence of severe toxicity (eg, grade 3 or higher, usually <3%). Side effects were associated with both dosimetric and non-dosimetric factors.
CONCLUSIONS
Prostate SBRT appears to be overall well tolerated, with determinants of toxicity that include dosimetric factors and patient factors. Suggested dose constraints include bladder V(Rx Dose)Gy <5-10 cc, urethra Dmax <38-42 Gy, and rectum Dmax <35-38 Gy, though current data do not offer firm guidance on tolerance doses. Several areas for future research are suggested.
Topics: Humans; Male; Models, Biological; Models, Theoretical; Organs at Risk; Patient Reported Outcome Measures; Penis; Prostatic Neoplasms; Quality of Life; Radiation Dose Hypofractionation; Radiosurgery; Rectum; Urethra; Urinary Bladder
PubMed: 33358229
DOI: 10.1016/j.ijrobp.2020.09.054 -
Journal of Cancer Research and... 2020In recent times, research on the use of ultrahigh-dose rates delivered in super-fast times in cancer treatment has been garnering interest. This has brought about the...
In recent times, research on the use of ultrahigh-dose rates delivered in super-fast times in cancer treatment has been garnering interest. This has brought about the term "FLASH" radiotherapy (RT). Thus, in the present study, we systematically review these recent studies on FLASH RT with regard to its efficacy and safety. The reporting of this systematic review was done in line with the statement of Preferred Reporting Items for Systematic reviews and Meta-Analyses. Electronic search of the databases such as PubMed, Scopus, and Embase was conducted to retrieve relevant studies investigating the FLASH effect. From an initial search of 216 potential articles, 16 articles (in vivo, in vitro , and clinical studies) were finally included in this systematic review. Results showed that FLASH RT dose rates had protective effects on normal tissues in addition to antitumor effect. Although still in its early research stages, FLASH RT has the potential to rival present RT regimens in terms of safety and antitumor effect. However, further studies are needed to address the aspects such as optimal dose rate, effect on deep tumors, tumor recurrence, longer follow-up time, and mechanism of action.
Topics: Humans; Neoplasms; Organ Sparing Treatments; Radiation Oncology; Radiation Tolerance; Radiotherapy; Radiotherapy Dosage; Radiotherapy Planning, Computer-Assisted; Treatment Outcome
PubMed: 33342774
DOI: 10.4103/jcrt.JCRT_180_20 -
Critical Reviews in Oncology/hematology Jan 2021Radioresistance remains as an obstacle in cancer treatment. This systematic review and meta-analysis aimed to evaluate the association between the expression of miRNAs... (Meta-Analysis)
Meta-Analysis
Radioresistance remains as an obstacle in cancer treatment. This systematic review and meta-analysis aimed to evaluate the association between the expression of miRNAs and responses to radiotherapy and the prognosis of different tumors. In total, 77 miRNAs in 19 cancer types were studied, in which 24 miRNAs were upregulated and 58 miRNAs were downregulated in cancer patients. Five miRNAs were differentially expressed. Moreover, 75 miRNAs were found to be related to radioresistance, while 5 were observed to be related to radiosensitivity. The pooled HR and 95 % confidence interval for the combined studies was 1.135 (0.819-1.574; P-value = 0.4). The HR values of the subgroup analysis for miR-21 (HR = 2.344; 95 % CI: 1.927-2.850; P-value = 0.000), nasopharyngeal carcinoma (HR = 0.448; 95 % CI: 0.265-0.760; P = 0.003) and breast cancer (HR = 1.131; 95 % CI: 0.311-4.109; P = .85) were obtained. Our results highlighted that across the published literature, miRNAs can modulate tumor radioresistance or sensitivity by affecting radiation-related signaling pathways. It seems that miRNAs could be considered as a theragnostic biomarker to predict and monitor clinical response to radiotherapy. Thus, the prediction of radioresistance in malignant patients will improve radiotherapy outcomes and radiotherapeutic resistance.
Topics: Biomarkers, Tumor; Humans; MicroRNAs; Nasopharyngeal Neoplasms; Prognosis; Radiation Tolerance
PubMed: 33310279
DOI: 10.1016/j.critrevonc.2020.103183 -
International Journal of Molecular... Sep 2020Intrinsic resistance to ionizing radiation is the major impediment in the treatment and clinical management of esophageal squamous cell carcinoma (ESCC), leading to... (Meta-Analysis)
Meta-Analysis
Intrinsic resistance to ionizing radiation is the major impediment in the treatment and clinical management of esophageal squamous cell carcinoma (ESCC), leading to tumor relapse and poor prognosis. Although several biological and molecular mechanisms are responsible for resistance to radiotherapy in ESCC, the molecule(s) involved in predicting radiotherapy response and prognosis are still lacking, thus requiring a detailed understanding. Recent studies have demonstrated an imperative correlation amongst several long non-coding RNAs and their involvement in complex cellular networks like DNA damage and repair, cell cycle, apoptosis, proliferation, and epithelial-mesenchymal transition. Additionally, accumulating evidence has suggested abnormal expression of lncRNAs in malignant tumor cells before and after radiotherapy effects in tumor cells' sensitivity. Thus, lncRNAs indeed represent unique molecules that can influence tumor cell susceptibility for various clinical interventions. On this note, herein, we have summarized the current status of lncRNAs in augmenting resistance/sensitivity in ESCC against radiotherapy. In addition, we have also discussed various strategies to increase the radiosensitivity in ESCC cells under clinical settings.
Topics: DNA Damage; Esophageal Squamous Cell Carcinoma; Gene Expression Regulation, Neoplastic; Genetic Therapy; Humans; MicroRNAs; Molecular Targeted Therapy; RNA, Antisense; RNA, Long Noncoding; RNA, Neoplasm; Radiation Tolerance
PubMed: 32947897
DOI: 10.3390/ijms21186787 -
Health Physics Nov 2020A systematic review of relevant studies that determined the dose response relationship (DRR) for the hematopoietic (H) acute radiation syndrome (ARS) in the canine...
A systematic review of relevant studies that determined the dose response relationship (DRR) for the hematopoietic (H) acute radiation syndrome (ARS) in the canine relative to radiation quality of mixed neutron:gamma radiations, dose rate, and exposure uniformity relative to selected reference radiation exposure has not been performed. The datasets for rhesus macaques exposure to mixed neutron:gamma radiation are used herein as a species comparative reference to the canine database. The selection of data cohorts was made from the following sources: Ovid Medline (1957-present), PubMed (1954-present), AGRICOLA (1976-present), Web of Science (1954-present), and US HHS RePORT (2002-present). The total number of hits across all search sites was 3,077. Several referenced, unpublished, non-peer reviewed government reports were unavailable for review. Primary published studies using canines, beagles, and mongrels were evaluated to provide an informative and consistent review of mixed neutron:gamma radiation effects to establish the DRRs for the H-ARS. Secondary and tertiary studies provided additional information on the hematologic response or the effects on hematopoietic progenitor cells, radiation dosimetry, absorbed dose, and organ dose. The LD50/30 values varied with neutron quality, exposure aspect, and mixed neutron:gamma ratio. The reference radiation quality varied from 250 kVp or 1-2 MeV x radiation and Co gamma radiation. A summary of a published review of a data set describing the DRR in rhesus macaques for mixed neutron:gamma radiation exposure in the H-ARS is included for a comparative reference to the canine dataset. The available evidence provided a reliable and extensive database that characterized the DRR for the H-ARS in canines and young rhesus macaques exposed to mixed neutron:gamma radiations of variable energy relative to 250 kVp, 1-2 MeV x radiation and Co gamma, and uniform and non-uniform total-body irradiation without the benefit of medical management. The mixed neutron:gamma radiation showed an energy-dependent RBE of ~ 1.0 to 2.0 relative to reference radiation exposure within both species. A marginal database described the DRR for the gastrointestinal (GI)-ARS. Medical management showed benefit in both species relative to the mixed neutron:gamma as well as exposure to reference radiation. The DRR for the H-ARS was characterized by steep slopes and relative LD50/30 values that reflected the radiation quality, exposure aspect, and dose rate over a range in time from 1956-2012.
Topics: Acute Radiation Syndrome; Animals; Dogs; Dose-Response Relationship, Radiation; Gamma Rays; Hematopoietic Stem Cells; Neutrons; Primates; Radiation Exposure; Reference Standards
PubMed: 32947486
DOI: 10.1097/HP.0000000000001319 -
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 -
Supportive Care in Cancer : Official... Apr 2021Oral mucositis is a debilitating consequence of radiotherapy in patients with head and neck cancers. Radiation-induced oral mucositis (RIOM) can cause pain and weight...
BACKGROUND
Oral mucositis is a debilitating consequence of radiotherapy in patients with head and neck cancers. Radiation-induced oral mucositis (RIOM) can cause pain and weight loss, reduce quality of life and affect treatment outcomes.
METHODS
A systematic review was undertaken to identify and examine the efficacy of low-cost interventions to mitigate RIOM and to develop clinical guidelines based on the evidence.
RESULTS
The author identified three interventions: benzydamine hydrochloride mouth rinse (BHM), honey and oral glutamine (OG). The search identified twenty-four studies in total. Four studies examined BHM; all findings were favourable, although only one had moderate methodological quality, and the rest were low. The product was poorly tolerated by some participants in one study. Twelve studies examined honey. Eleven of these had favourable results; two studies had moderate methodological quality, and the rest were low. Eight studies examined OG. Six of these had favourable results; two studies had moderate methodological quality, and the rest were low.
CONCLUSION
The author cannot recommend BHM to mitigate RIOM due to the overall low quality of the studies and poor tolerance to the product. The author cannot recommend honey to mitigate RIOM due to weak evidence supporting the intervention. The author can recommend OG to mitigate RIOM. There is a need for high-quality studies with a consensus of the methodology to reduce heterogeneity and examination of the cost-effectiveness of the interventions.
Topics: Head and Neck Neoplasms; Humans; Quality of Life; Radiation Injuries; Stomatitis; Treatment Outcome
PubMed: 32889582
DOI: 10.1007/s00520-020-05548-0 -
Strahlentherapie Und Onkologie : Organ... Jan 2021Following neoadjuvant chemotherapy for breast cancer, postoperative systemic therapy, also called post-neoadjuvant treatment, has been established in defined risk...
PURPOSE
Following neoadjuvant chemotherapy for breast cancer, postoperative systemic therapy, also called post-neoadjuvant treatment, has been established in defined risk settings. We reviewed the evidence for sequencing of postoperative radiation and chemotherapy, with a focus on a capecitabine and trastuzumab emtansine (T-DM1)-based regimen.
METHODS
A systematic literature search using the PubMed/MEDLINE/Web of Science database was performed. We included prospective and retrospective reports published since 2015 and provided clinical data on toxicity and effectiveness.
RESULTS
Six studies were included, five of which investigated capecitabine-containing regimens. Of these, four were prospective investigations and one a retrospective matched comparative analysis. One randomized prospective trial was found for T‑DM1 and radiotherapy. In the majority of these reports, radiation-associated toxicities were not specifically addressed.
CONCLUSION
Regarding oncologic outcome, the influence of sequencing radiation therapy with maintenance capecitabine chemotherapy in the post-neoadjuvant setting is unclear. Synchronous administration of capecitabine is feasible, but reports on possible excess toxicities are partially conflicting. Dose reduction of capecitabine should be considered, especially if normofractionated radiotherapy is used. In terms of tolerance, hypofractionated schedules seem to be superior in terms of toxicity in concurrent settings. T‑DM1 can safely be administered concurrently with radiotherapy.
Topics: Ado-Trastuzumab Emtansine; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Capecitabine; Cardiomyopathies; Clinical Trials as Topic; Combined Modality Therapy; Drug Administration Schedule; Female; Fluorouracil; Humans; Multicenter Studies as Topic; Neoadjuvant Therapy; Prospective Studies; Retrospective Studies; Triple Negative Breast Neoplasms
PubMed: 32737515
DOI: 10.1007/s00066-020-01667-z