Predicting toxicity from radiation therapy--it's genetic, right?
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ABSTRACT:
SUBMITTER: Kelsey CR
PROVIDER: S-EPMC4287226 | biostudies-literature | 2012 Jul
REPOSITORIES: biostudies-literature
Publications
Predicting toxicity from radiation therapy--it's genetic, right?
Kelsey Chris R CR Rosenstein Barry S BS Marks Lawrence B LB
Cancer 20111205 14
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Project description:Stereotactic body radiation therapy (SBRT) is a technically demanding prostate cancer treatment that may be less expensive than intensity-modulated radiation therapy (IMRT). Because SBRT may deliver a greater biologic dose of radiation than IMRT, toxicity could be increased. Studies comparing treatment cost to the Medicare program and toxicity are needed.We performed a retrospective study by using a national sample of Medicare beneficiaries age ? 66 years who received SBRT or IMRT as primary treatment for prostate cancer from 2008 to 2011. Each SBRT patient was matched to two IMRT patients with similar follow-up (6, 12, or 24 months). We calculated the cost of radiation therapy treatment to the Medicare program and toxicity as measured by Medicare claims; we used a random effects model to compare genitourinary (GU), GI, and other toxicity between matched patients.The study sample consisted of 1,335 SBRT patients matched to 2,670 IMRT patients. The mean treatment cost was $13,645 for SBRT versus $21,023 for IMRT. In the 6 months after treatment initiation, 15.6% of SBRT versus 12.6% of IMRT patients experienced GU toxicity (odds ratio [OR], 1.29; 95% CI, 1.05 to 1.53; P = .009). At 24 months after treatment initiation, 43.9% of SBRT versus 36.3% of IMRT patients had GU toxicity (OR, 1.38; 95% CI, 1.12 to 1.63; P = .001). The increase in GU toxicity was due to claims indicative of urethritis, urinary incontinence, and/or obstruction.Although SBRT was associated with lower treatment costs, there appears to be a greater rate of GU toxicity for patients undergoing SBRT compared with IMRT, and prospective correlation with randomized trials is needed.
| S-EPMC3986382 | biostudies-other
Project description:Vaginal necrosis is a late radiation tissue injury with serious morbidity complications. It is rare, and its incidence is not well assessed in prospective trials. Patient comorbidities and radiation dose can significantly increase the risk. As treatment of gynecologic malignancies often involve a multidisciplinary approach, timely diagnosis and appropriate management by physicians of the team are crucial. Untreated vaginal necrosis can lead to infection, hemorrhage, necrosis-related fistulation to the bladder or rectum, perforation, and death. In this review, we describe the pathophysiology of vaginal necrosis, its clinical course, and management options.
| S-EPMC8817784 | biostudies-literature
Project description:BackgroundPulsed low dose rate radiotherapy (PLDR) is a new radiation delivery method, in which the fractional dose is divided into sub-fractional doses with periodical time breaks in between. The goal of our study is to assess the toxicity on healthy tissues resulting from PLDR as compared to conventional radiotherapy (CRT) using the same physical X-ray dose.MethodsWe analyzed the weight and survival time for CRT and PLDR groups and studied the inflammatory cytokine transforming Growth Factor-β (TGF-β), usually released following irradiation. Histopathological and immunohistochemical analyses were conducted for intestinal and bone marrow tissues from rats subjected to 8 Gy whole- body irradiation using CRT and PLDR techniques. We investigated genotoxicity by performing a comet assay (CA) in splenic tissues.ResultsOur findings showed an improvement in survival time with PLDR versus CRT by 82%.The mean survival time for CRT rats' group was 6.3 days, while it was 35.9 days for PLDR group.The weight of CRT group decreased gradually by 3.7%, while weight of PLDR group increased gradually by 2.4%.CRT resulted in more cellular atrophy in bone marrow and intestinal tissues than in PLDR treatments as shown by hematoxylin and eosin staining analysis. In addition, the transforming growth factor-β (TGF-β) expression in bone marrow and intestinal tissues of CRT was higher than those expressed in tissues from PLDR as demonstrated by the Immuno reactive score (IRS). It was10(0.53) and 9.8(0.55) for BM and intestinal tissues, respectively from CRT group and 5.8(0.63) for PLDR for both tissues. The measured CA parameters were larger with CRT compared to PLDR, where the Tail Length (TL), Tail DNA % (TD%) and Tail Moment (TM) measurements were 25.4(3.4), 56.5(7.6) % and 20.5(3.5) for CRT, 7.3(1.9), 30.0(7.2) % and 5.7(1.8) for PLDR, with P value 0.000064, 0.0004 and 0.00017, respectively.ConclusionThis study indicates that PLDR can reduce the toxicity on normal tissues compared to CRT.
| S-EPMC11558818 | biostudies-literature
Project description:Immune checkpoint inhibitor (ICI) therapy has revolutionised the treatment of various cancer types. ICIs reinstate T-cell function to elicit an anti-cancer immune response. The resulting immune response can however have off-target effects which manifest as autoimmune type serious immune-related adverse events (irAE) in ~10-55% of patients treated. It is currently challenging to predict both who will experience irAEs and to what severity. Identification of patients at high risk of serious irAE would revolutionise patient care. While the pathogenesis driving irAE development is still unclear, host genetic factors are proposed to be key determinants of these events. This review presents current evidence supporting the role of the host genome in determining risk of irAE. We summarise the spectrum and timing of irAEs following treatment with ICIs and describe currently reported germline genetic variation associated with expression of immuno-modulatory factors within the cancer immunity cycle, development of autoimmune disease and irAE occurrence. We propose that germline genetic determinants of host immune function and autoimmune diseases could also explain risk of irAE development. We also endorse genome-wide association studies of patients being treated with ICIs to identify genetic variants that can be used in polygenic risk scores to predict risk of irAE.
| S-EPMC9789157 | biostudies-literature
Project description:Peripheral blood lymphocytes from a total of 57 patients were immortalized with Epstein-Barr virus. Fourteen radiation-therapy patients suffered unusual levels of radiation toxicity (RadS). Thirteen radiation-therapy patients with limited toxicity (RadC) were enrolled as controls. Fifteen patients diagnosed with skin cancer before age 40 (SkCa) were used as a second group of controls. Fifteen healthy subjects without any history of cancer (NoCa) were matched to the skin cancer patients and used as a third group of controls. Cells were exposed to mock treatment (Mock), ultra-violet radiation (UV), or ionizing radiation (IR). For UV radiation treatment, cells were exposed to 10 J/m^2 and harvested for RNA 24 hours later. For IR treatment, cells were exposed to 5 Gy of IR and harvested for RNA 4 hours later. For example, RadS1-Mock refers to cells from radiation sensitive patient 1 exposed to mock treatment. The published manuscript (PNAS 101:6634, 2004) can be found at http://www.pnas.org/cgi/doi/10.1073/pnas.0307761101 Data were analyzed with Affymetrix MAS version 4.0. Normalization – A reference data set was generated by averaging the expression of each gene over all data sets. The data for each hybridization were compared with the reference data set in a cube root scatter plot. A linear least-squares fit to the cube root scatter plot was then used to normalize each hybridization. Keywords = Gene expression in lymphoid cells of cancer patients Keywords: repeat sample
2004-09-06 | GSE1725 | GEO
Project description:PurposeThis study aimed to report on our institutional experience in the use of stereotactic body radiation therapy (SBRT) for the treatment of adrenal gland metastases. Specifically, we examined the outcomes and toxicity from this treatment modality on adjacent organs at risk.Methods and materialsData were retrieved from patients with adrenal metastases who were treated with SBRT between 2008 and 2017. Patients with primary adrenal malignancies were excluded. Toxicities were graded in accordance with the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03. Time-to-event rates were calculated from the date of SBRT delivery.ResultsIn total, 35 patients with adrenal metastases were identified. Four patients were treated for bilateral disease. The median dose was 40 Gy (range, 20-54 Gy) in 5 fractions (range, 1-6 fractions). The median follow-up time was 37 months (range, 14-451 months) from disease diagnosis and 7 months (range, 1-54 months) from the SBRT start date. With death treated as a competing risk event, the cumulative incidence of local failure was 7.6% at 1 year after SBRT and 19.2% at 3 years. The median overall survival (OS) time was 19 months (95% confidence interval, 8-54 months) and tumor size correlated with survival (P = .0006). Patients with metastases <2.9 cm had a median OS of 54 months compared with 11 months for those with adrenal metastases ≥2.9 cm (P = .01). Incidence of grade 2 toxicity was 17% with no case of grade ≥3 toxicity. SBRT did not impact renal function with a mean estimated decline in glomerular filtration rate of only 2.6 ± 8 mL/min/1.73 m2 compared with baseline. Combined kidneys V5 and combined renal cortex V17.5 did not correlate with a change in estimated glomerular filtration rate (P = .7 and P = .9, respectively).ConclusionsSBRT offers excellent local control for the treatment of adrenal gland metastases with very low toxicity rates and no significant short-term impact on renal function.
| S-EPMC6200881 | biostudies-literature
Project description:BackgroundAlthough radiation therapy is a primary treatment for craniopharyngioma, it can exacerbate existing problems related to the tumor and pre-irradiation management. Survival is often marked by neurologic deficits, panhypopituitarism, diabetes insipidus, cognitive deficiencies, and behavioral and social problems.ProcedureThe Achenbach Child Behavior Checklist (CBCL) was used to evaluate behavioral and social problems during the first 5 years of follow-up in 27 patients with craniopharyngioma treated with conformal radiation therapy.ResultsAll group averages for the CBCL scales were within the age-typical range at pre-irradiation baseline. Extent of surgical resection was implicated in baseline differences for the internalizing, externalizing, behavior problem and social scores. Significant longitudinal changes were found in internalizing, externalizing, behavior problem and school scores that correlated with tumor and treatment-related factors.ConclusionsThe most common variables implicated in post-irradiation behavioral and social problems were CSF shunting, presence of an Ommaya reservoir, diabetes insipidus, and low pre-irradiation growth hormone levels.
| S-EPMC2727936 | biostudies-literature
Project description:PurposeTo give a preliminary report of clinical and treatment factors associated with toxicity in men receiving high-dose radiation therapy (RT) on a phase 3 dose-escalation trial.Methods and materialsThe trial was initiated with 3-dimensional conformal RT (3D-CRT) and amended after 1 year to allow intensity modulated RT (IMRT). Patients treated with 3D-CRT received 55.8 Gy to a planning target volume that included the prostate and seminal vesicles, then 23.4 Gy to prostate only. The IMRT patients were treated to the prostate and proximal seminal vesicles to 79.2 Gy. Common Toxicity Criteria, version 2.0, and Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer late morbidity scores were used for acute and late effects.ResultsOf 763 patients randomized to the 79.2-Gy arm of Radiation Therapy Oncology Group 0126 protocol, 748 were eligible and evaluable: 491 and 257 were treated with 3D-CRT and IMRT, respectively. For both bladder and rectum, the volumes receiving 65, 70, and 75 Gy were significantly lower with IMRT (all P<.0001). For grade (G) 2+ acute gastrointestinal/genitourinary (GI/GU) toxicity, both univariate and multivariate analyses showed a statistically significant decrease in G2+ acute collective GI/GU toxicity for IMRT. There were no significant differences with 3D-CRT or IMRT for acute or late G2+ or 3+ GU toxicities. Univariate analysis showed a statistically significant decrease in late G2+ GI toxicity for IMRT (P=.039). On multivariate analysis, IMRT showed a 26% reduction in G2+ late GI toxicity (P=.099). Acute G2+ toxicity was associated with late G3+ toxicity (P=.005). With dose-volume histogram data in the multivariate analysis, RT modality was not significant, whereas white race (P=.001) and rectal V70 ≥15% were associated with G2+ rectal toxicity (P=.034).ConclusionsIntensity modulated RT is associated with a significant reduction in acute G2+ GI/GU toxicity. There is a trend for a clinically meaningful reduction in late G2+ GI toxicity with IMRT. The occurrence of acute GI toxicity and large (>15%) volumes of rectum >70 Gy are associated with late rectal toxicity.
| S-EPMC3840044 | biostudies-literature
Project description:To investigate radiation-induced cytopenia and establish predictive nomograms for hematological toxicity, we reviewed 3786 patients aged 18 or older who received radiation monotherapy between 2010 and 2021 for non-hematologic malignancies. We collected data on patient background, treatment content and hematologic toxicities for 12 weeks after the start of radiotherapy. The patients were randomly divided into training and test groups in 7:3 ratio. In the training group, we conducted ordered logistic regression analysis to identify predictive factors for neutropenia, lymphocytopenia, anemia and thrombocytopenia. Nomograms to predict Grade 2-4 cytopenia were generated and validated in the test group. Grade 3 or higher hematologic toxicities were observed in 9.7, 44.6, 8.3 and 3.1% of patients with neutropenia, lymphocytopenia, anemia and thrombocytopenia, respectively. We identified six factors for neutropenia grade, nine for lymphocytopenia grade and six for anemia grade with statistical significance. In the analysis of thrombocytopenia, the statistical model did not converge because of a small number of events. Nomograms were generated using factors with high predictive power. In evaluating the nomograms, we found high area under the receiver operating characteristic curve values (neutropenia; 0.75-0.85, lymphopenia; 0.89-0.91 and anemia; 0.85-0.86) in predicting Grade 2-4 cytopenia in the test group. We established predictive nomograms for neutropenia, leukocytopenia and anemia and demonstrated high reproducibility when validated in an independent cohort of patients.
| S-EPMC10665302 | biostudies-literature
Project description:Toxicity from radiation therapy is a grave problem for cancer patients. We hypothesized that some cases of toxicity are associated with abnormal transcriptional responses to radiation. We used microarrays to measure responses to ionizing and UV radiation in lymphoblastoid cells derived from 14 patients with acute radiation toxicity. The analysis used heterogeneity-associated transformation of the data to account for a clinical outcome arising from more than one underlying cause. To compute the risk of toxicity for each patient, we applied nearest shrunken centroids, a method that identifies and cross-validates predictive genes. Transcriptional responses in 24 genes predicted radiation toxicity in 9 of 14 patients with no false positives among 43 controls (P = 2.2 x 10(-7)). The responses of these nine patients displayed significant heterogeneity. Of the five patients with toxicity and normal responses, two were treated with protocols that proved to be highly toxic. These results may enable physicians to predict toxicity and tailor treatment for individual patients.
| S-EPMC404097 | biostudies-literature