Dataset Information

Individual patient data meta-analysis shows a significant association between the ATM rs1801516 SNP and toxicity after radiotherapy in 5456 breast and prostate cancer patients.

ABSTRACT: PURPOSE:Several small studies have indicated that the ATM rs1801516 SNP is associated with risk of normal tissue toxicity after radiotherapy. However, the findings have not been consistent. In order to test this SNP in a well-powered study, an individual patient data meta-analysis was carried out by the International Radiogenomics Consortium. MATERIALS AND METHODS:The analysis included 5456 patients from 17 different cohorts. 2759 patients were given radiotherapy for breast cancer and 2697 for prostate cancer. Eight toxicity scores (overall toxicity, acute toxicity, late toxicity, acute skin toxicity, acute rectal toxicity, telangiectasia, fibrosis and late rectal toxicity) were analyzed. Adjustments were made for treatment and patient related factors with potential impact on the risk of toxicity. RESULTS:For all endpoints except late rectal toxicity, a significantly increased risk of toxicity was found for carriers of the minor (Asn) allele with odds ratios of approximately 1.5 for acute toxicity and 1.2 for late toxicity. The results were consistent with a co-dominant pattern of inheritance. CONCLUSION:This study convincingly showed a significant association between the ATM rs1801516 Asn allele and increased risk of radiation-induced normal tissue toxicity.

SUBMITTER: Andreassen CN

PROVIDER: S-EPMC5559879 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Individual patient data meta-analysis shows a significant association between the ATM rs1801516 SNP and toxicity after radiotherapy in 5456 breast and prostate cancer patients.

Andreassen Christian Nicolaj CN Rosenstein Barry S BS Kerns Sarah L SL Ostrer Harry H De Ruysscher Dirk D Cesaretti Jamie A JA Barnett Gillian C GC Dunning Alison M AM Dorling Leila L West Catharine M L CML Burnet Neil G NG Elliott Rebecca R Coles Charlotte C Hall Emma E Fachal Laura L Vega Ana A Gómez-Caamaño Antonio A Talbot Christopher J CJ Symonds R Paul RP De Ruyck Kim K Thierens Hubert H Ost Piet P Chang-Claude Jenny J Seibold Petra P Popanda Odilia O Overgaard Marie M Dearnaley David D Sydes Matthew R MR Azria David D Koch Christine Anne CA Parliament Matthew M Blackshaw Michael M Sia Michael M Fuentes-Raspall Maria J MJ Ramon Y Cajal Teresa T Barnadas Agustin A Vesprini Danny D Gutiérrez-Enríquez Sara S Mollà Meritxell M Díez Orland O Yarnold John R JR Overgaard Jens J Bentzen Søren M SM Alsner Jan J

Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology 20160718 3

<h4>Purpose</h4>Several small studies have indicated that the ATM rs1801516 SNP is associated with risk of normal tissue toxicity after radiotherapy. However, the findings have not been consistent. In order to test this SNP in a well-powered study, an individual patient data meta-analysis was carried out by the International Radiogenomics Consortium.<h4>Materials and methods</h4>The analysis included 5456 patients from 17 different cohorts. 2759 patients were given radiotherapy for breast cancer ...[more]

PMID: 27443449

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Project description:Background: A rectal sub-region (SRR) has been previously identified by voxel-wise analysis in the inferior-anterior part of the rectum as highly predictive of rectal bleeding (RB) in prostate cancer radiotherapy. Translating the SRR to patient-specific radiotherapy planning is challenging as new constraints have to be defined. A recent geometry-based model proposed to optimize the planning by determining the achievable mean doses (AMDs) to the organs at risk (OARs), taking into account the overlap between the planning target volume (PTV) and OAR. The aim of this study was to quantify the SRR dose sparing by using the AMD model in the planning, while preserving the dose to the prostate. Material and Methods: Three-dimensional volumetric modulated arc therapy (VMAT) planning dose distributions for 60 patients were computed following four different strategies, delivering 78 Gy to the prostate, while meeting the genitourinary group dose constraints to the OAR: (i) a standard plan corresponding to the standard practice for rectum sparing (STDpl), (ii) a plan adding constraints to SRR (SRRpl), (iii) a plan using the AMD model applied to the rectum only (AMD_RECTpl), and (iv) a final plan using the AMD model applied to both the rectum and the SRR (AMD_RECT_SRRpl). After PTV dose normalization, plans were compared with regard to dose distributions, quality, and estimated risk of RB using a normal tissue complication probability model. Results: AMD_RECT_SRRpl showed the largest SRR dose sparing, with significant mean dose reductions of 7.7, 3, and 2.3 Gy, with respect to the STDpl, SRRpl, and AMD_RECTpl, respectively. AMD_RECT_SRRpl also decreased the mean rectal dose by 3.6 Gy relative to STDpl and by 3.3 Gy relative to SRRpl. The absolute risk of grade ≥1 RB decreased from 22.8% using STDpl planning to 17.6% using AMD_RECT_SRRpl considering SRR volume. AMD_RECT_SRRpl plans, however, showed slightly less dose homogeneity and significant increase of the number of monitor units, compared to the three other strategies. Conclusion: Compared to a standard prostate planning, applying dose constraints to a patient-specific SRR by using the achievable mean dose model decreased the mean dose by 7.7 Gy to the SRR and may decrease the relative risk of RB by 22%.

Project description:BACKGROUND:Ataxia telangiectasia mutated (ATM) gene plays a key role in response to DNA lesions and is related to the invasion and metastasis of malignancy. Epidemiological studies have indicated associations between ATM rs1801516 polymorphism and different types of cancer, but their results are inconsistent. To further evaluate the effect of ATM rs1801516 polymorphism on cancer risk, we conducted this meta-analysis. METHODS:Studies were identified according to specific inclusion criteria by searching PubMed, Web of Science, and Embase databases. Pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) under recessive, dominant, codominant, and overdominant models of inheritance were calculated to estimate the association between rs1801516 polymorphism and cancer risk. RESULTS:A total of 37 studies with 12,879 cases and 18,054 controls were included in our study. No significant association was found between rs1801516 polymorphism and cancer risk in overall comparisons (AA vs GG?+?GA: OR?=?0.91, 95% CI, 0.78-1.07; AA+GA vs GG: OR?=?1.00, 95% CI, 0.90-1.11; AA vs GG: OR?=?0.89, 95% CI, 0.75-1.06; GA vs GG: OR?=?1.01, 95% CI, 0.91-1.13; GG?+?AA vs GA: OR?=?1.00, 95% CI, 0.88-1.10). However, after subgroup analyses by region-specified population, significant associations were found in European (AA vs GG?+?GA: OR?=?0.79, 95% CI, 0.65-0.96, P?=?0.017; AA vs GG: OR?=?0.79, 95% CI, 0.65-0.96, P?=?0.017), South American (AA+GA vs GG: OR?=?2.15, 95% CI, 1.37-3.38, P?=?0.001; GA vs GG: OR?=?2.19, 95% CI, 1.38-3.47, P?=?0.001; GG?+?AA vs GA: OR?=?0.46, 95% CI, 0.29-0.72, P?=?0.001), and Asian (AA vs GG?+?GA: OR?=?7.45, 95% CI, 1.31-42.46, P?=?0.024; AA vs GG: OR?=?7.40, 95% CI, 1.30-42.19, P?=?0.024). Subgroup analyses also revealed that compared with subjects carrying a GG genotype, those carrying a homozygote AA had a decreased risk for breast cancer (AA vs GG: OR?=?0.76, 95% CI, 0.59-0.98, P?=?0.035), and the homozygote AA was associated with decreased cancer risk in subjects with family history (AA vs GG: OR?=?0.68, 95% CI, 0.47-0.98, P?=?0.039). CONCLUSIONS:ATM rs1801516 polymorphism is not associated with overall cancer risk in total population. However, for subgroup analyses, this polymorphism is especially associated with breast cancer risk; in addition, it is associated with overall cancer risk in Europeans, South Americans, Asians, and those with family history.

Project description:PurposeTo establish the toxicity profile of high-dose pelvic lymph node intensity-modulated radiation therapy (IMRT) and to assess whether it is safely deliverable at multiple centers.Methods and materialsIn this phase 2 noncomparative multicenter trial, 124 patients with locally advanced, high-risk prostate cancer were randomized between prostate-only IMRT (PO) (74 Gy/37 fractions) and prostate and pelvic lymph node IMRT (P&P; 74 Gy/37 fractions to prostate, 60 Gy/37 fractions to pelvis). The primary endpoint was acute lower gastrointestinal (GI) Radiation Therapy Oncology Group (RTOG) toxicity at week 18, aiming to exclude a grade 2 or greater (G2+) toxicity-free rate of 80% in the P&P group. Key secondary endpoints included patient-reported outcomes and late toxicity.ResultsOne hundred twenty-four participants were randomized (62 PO, 62 P&P) from May 2011 to March 2013. Median follow-up was 37.6 months (interquartile range [IQR], 35.4-38.9 months). Participants had a median age of 69 years (IQR, 64-74 years) and median diagnostic prostate-specific androgen level of 21.6 ng/mL (IQR, 11.8-35.1 ng/mL). At week 18, G2+ lower GI toxicity-free rates were 59 of 61 (96.7%; 90% confidence interval [CI], 90.0-99.4) for the PO group and 59 of 62 (95.2%; 90% CI, 88.0-98.7) for the P&P group. Patients in both groups reported similarly low Inflammatory Bowel Disease Questionnaire symptoms and Vaizey incontinence scores. The largest difference occurred at week 6 with 4 of 61 (7%) and 16 of 61 (26%) PO and P&P patients, respectively, experiencing G2+ toxicity. At 2 years, the cumulative proportion of RTOG G2+ GI toxicity was 16.9% (95% CI, 8.9%-30.9%) for the PO group and 24.0% (95% CI, 8.4%-57.9%) for the P&P group; in addition, RTOG G2+ bladder toxicity was 5.1% (95% CI, 1.7%-14.9%) for the PO group and 5.6% (95% CI, 1.8%-16.7%) for the P&P group.ConclusionsPIVOTAL demonstrated that high-dose pelvic lymph node IMRT can be delivered at multiple centers with a modest side effect profile. Although safety data from the present study are encouraging, the impact of P&P IMRT on disease control remains to be established.

Project description:OBJECTIVES:To report on initial patient characteristics, treatment practices, toxicity, and early biochemical disease-free survival (bDFS) of localized prostate cancer treated with stereotactic body radiotherapy (SBRT) and enrolled in the RSSearch(®) Patient Registry. METHODS: A retrospective analysis was conducted on patients with clinically localized prostate cancer enrolled in RSSearch(®) from June 2006 - January 2015. Patients were classified as low-risk (PSA ? 10 ng/ml, T1c-T2a, Gleason score ? 6), intermediate-risk (PSA 10.1 - 20 ng/ml, T2b-T2c, or Gleason 7), or high-risk (PSA > 20 ng/ml, T3 or Gleason ? 8). Toxicity was reported using Common Toxicity Criteria for Adverse Events, version 3. Biochemical failure was assessed using the Phoenix definition (nadir + 2 ng/ml). The Kaplan-Meier analysis was used to calculate bDFS and association of patient and tumor characteristics with the use of SBRT. RESULTS: Four hundred thirty-seven patients (189 low, 215 intermediate, and 33 high-risk) at a median of 69 years (range: 48-88) received SBRT at 17 centers. Seventy-eight percent of patients received 36.25 Gy/5 fractions, 13% received 37 Gy/5 fractions, 6% received 35 Gy/5 fractions, 3% received 38 Gy/4 fractions, and 5% received a boost dose of 19.5-29 Gy following external beam radiation therapy. Median follow-up was 20 months (range: 1-64 months). Genitourinary (GU) and gastrointestinal (GI) toxicities were minimal, with no acute or late Grade 3+ GU or GI toxicity. Late Grade 1 and 2 urinary frequency was 25% and 8%. Late Grade 1 and 2 proctitis was 3% and 2%. Median PSA decreased from 5.8 ng/ml (range: 0.3-43) to 0.88, 0.4, and 0.3 ng/ml at one, two, and three years. Two-year bDFS for all patients was 96.1%. Two-year bDFS was 99.0%, 94.5%, and 89.8% for low, intermediate, and high-risk patients (p < 0.0001). Two-year bDFS was 99.2%, 93.2%, and 90.4% for Gleason ? 6, Gleason 7, and Gleason ? 8 (p < 0.0001). Two-year bDFS was 96.4%, 97.2%, and 62.5% for PSA ? 10 ng/ml, PSA 10.1 - 20 ng/ml, and PSA > 20 ng/ml (p < 0.0001). Clinical T Stage was not significantly associated with bDFS. CONCLUSIONS: Early disease outcomes of SBRT for the treatment of clinically localized prostate cancer from a multicenter patient registry compare favorably with reports from single institutions. Acute and late GU and GI toxicities were minimal, and PSA response to SBRT was highly encouraging. Continued accrual and follow-up will be necessary to confirm long-term results.

Dataset Information

Individual patient data meta-analysis shows a significant association between the ATM rs1801516 SNP and toxicity after radiotherapy in 5456 breast and prostate cancer patients.

Publications

Individual patient data meta-analysis shows a significant association between the ATM rs1801516 SNP and toxicity after radiotherapy in 5456 breast and prostate cancer patients.

Similar Datasets

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