Towards individualized dose constraints: Adjusting the QUANTEC radiation pneumonitis model for clinical risk factors

Appelt, Ane L; Vogelius, I.R.; Farr, Katherina P.; Khalil, Azza Ahmed; Bentzen, Søren M.

doi:10.3109/0284186x.2013.820341

Cited by 70 publications

(52 citation statements)

References 24 publications

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“…This study was approved by The Central Denmark Region Ethics Committee (study number 1-10-72- [11][12] and registered at ClinicalTrials.gov (ID-NCT01745484). Written informed consent was obtained from each patient upon inclusion.…”

Section: Patientsmentioning

confidence: 99%

See 1 more Smart Citation

Inclusion of functional information from perfusion SPECT improves predictive value of dose–volume parameters in lung toxicity outcome after radiotherapy for non-small cell lung cancer: A prospective study

Farr

Kallehauge

Møller

et al. 2015

Radiotherapy and Oncology

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Section: Patientsmentioning

confidence: 99%

“…In clinical practice, various clinical and dose-volume parameters are used to estimate the risk of RP [8,9]. Several patient-related characteristics have been identified for the prediction of RP [7,10,11], including cardiac comorbidity [12]. Measures to counteract the development of lung damage are currently being investigated [13].…”

mentioning

confidence: 99%

Inclusion of functional information from perfusion SPECT improves predictive value of dose–volume parameters in lung toxicity outcome after radiotherapy for non-small cell lung cancer: A prospective study

Farr

Kallehauge

Møller

et al. 2015

Radiotherapy and Oncology

Self Cite

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“…Clinical factors may hamper the establishment of dose-response relationships for normal tissue toxicity, such as the effects of patient and treatment related factors [19]. We found a clear effect of male gender on the observed levels of toxicity, independently of the dose to the bladder.…”

Section: Discussionmentioning

confidence: 64%

Dose-response of acute urinary toxicity of long-course preoperative chemoradiotherapy for rectal cancer

et al. 2014

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Background Long-course preoperative chemoradiotherapy (chemo-RT) improves outcomes for rectal cancer patients, but acute side effects during treatment may cause considerable patient discomfort and may compromise treatment compliance. We developed a dose-response model for acute urinary toxicity based on a large, single-institution series. Materials and Methods 345 patients were treated with (chemo-)RT for primary rectal cancer from Jan ‘07 to May ‘12. Urinary toxicity during RT was scored prospectively using the CTCAE v 3.0 cystitis score (grade 0 to 5). Clinical variables and radiation dose to the bladder were related to graded toxicity using multivariate ordinal logistic regression. Three models were optimized, each containing all available clinical variables and one of three dose metrics: Mean dose (Dmean), equivalent uniform dose (EUD), or relative volume given x Gy or above (dose cutoff model, Vx). The optimal dose metric was chosen using the Akaike Information Criterion (AIC). Results Grade 1 cystitis was experienced by 138 (40%), grade 2 by 39 (11%) and grade 3 by 2 (1%) patients, respectively. Dose metrics were significantly correlated with toxicity in all models, but the dose cutoff model provided the best AIC value. The only significant clinical risk factors in the Vx model were male gender (p=0.006) and brachytherapy boost (p=0.02). Reducing the model to include gender, brachytherapy boost and Vx yielded odds ratios ORmale = 1.82 (1.17 to 2.80), ORbrachy = 1.36 (1.02 to 1.80 for each 5 Gy), x = 35.1 Gy (28.6 to 41.5 Gy). The predicted risk of grade 2 and above cystitis ranged from 2% to 26%. Conclusion Acute cystitis correlated significantly with radiation dose to the bladder; the dose-cutoff model (V35Gy) was superior to Dmean and EUD models. Male gender and brachytherapy boost increased the risk of toxicity. Wide variation in predicted risks suggests room for treatment optimization using individual dose constraints.

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“…Development of pneumonitis during the course of treatment or shortly thereafter can potentially compromise cancer cure and, in rare instances, be life-threatening (Williams et al, 2010). In contrast, pulmonary fibrosis is more common and affects ≥50% patients treated with radiation for thoracic tumors, including lung cancers, breast cancers and mediastinal lymphomas (Appelt et al, 2014). Fibrosis is progressive, and clinical manifestations occur months to years after completion of therapy, with symptoms ranging from nonproductive cough to dyspnea on exertion.…”

Section: Introductionmentioning

confidence: 99%

Gene expression profiles among murine strains segregate with distinct differences in the progression of radiation-induced lung disease

Jackson

Baye

Goswami

et al. 2017

Disease Models &Amp; Mechanisms

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Molecular mechanisms underlying development of acute pneumonitis and/or late fibrosis following thoracic irradiation remain poorly understood. Here, we hypothesize that heterogeneity in disease progression and phenotypic expression of radiation-induced lung disease (RILD) across murine strains presents an opportunity to better elucidate mechanisms driving tissue response toward pneumonitis and/or fibrosis. Distinct differences in disease progression were observed in age- and sex-matched CBA/J, C57L/J and C57BL/6J mice over 1 year after graded doses of whole-thorax lung irradiation (WTLI). Separately, comparison of gene expression profiles in lung tissue 24 h post-exposure demonstrated >5000 genes to be differentially expressed (P<0.01; >twofold change) between strains with early versus late onset of disease. An immediate divergence in early tissue response between radiation-sensitive and -resistant strains was observed. In pneumonitis-prone C57L/J mice, differentially expressed genes were enriched in proinflammatory pathways, whereas in fibrosis-prone C57BL/6J mice, genes were enriched in pathways involved in purine and pyrimidine synthesis, DNA replication and cell division. At 24 h post-WTLI, different patterns of cellular damage were observed at the ultrastructural level among strains but microscopic damage was not yet evident under light microscopy. These data point toward a fundamental difference in patterns of early pulmonary tissue response to WTLI, consistent with the macroscopic expression of injury manifesting weeks to months after exposure. Understanding the mechanisms underlying development of RILD might lead to more rational selection of therapeutic interventions to mitigate healthy tissue damage.

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Towards individualized dose constraints: Adjusting the QUANTEC radiation pneumonitis model for clinical risk factors

Abstract: This study presents a method to combine a published dose-response function with known clinical risk factors and demonstrates the increased predictive power of the combined model. The method allows for individualization of dose constraints and individual patient risk estimates.

Cited by 70 publications

References 24 publications

Inclusion of functional information from perfusion SPECT improves predictive value of dose–volume parameters in lung toxicity outcome after radiotherapy for non-small cell lung cancer: A prospective study

Inclusion of functional information from perfusion SPECT improves predictive value of dose–volume parameters in lung toxicity outcome after radiotherapy for non-small cell lung cancer: A prospective study

Dose-response of acute urinary toxicity of long-course preoperative chemoradiotherapy for rectal cancer

Gene expression profiles among murine strains segregate with distinct differences in the progression of radiation-induced lung disease

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