Dataset Information

Is individual perfusion dose-response different than ventilation dose-response for lung cancer patients treated with radiotherapy?

ABSTRACT:

Objective

Current ventilation and perfusion dose-response studies focus on single-modalities (ventilation or perfusion) and perform pulmonary-toxicity assessment related to radiotherapy on a population-based basis. This study aims at quantitative and clinical evaluation of intrapatient differences between ventilation and perfusion dose-responses among lung cancer patients treated with radiotherapy.

Methods

20 patients enrolled on a prospective functional avoidance protocol underwent single photon emission computed tomography-CT ventilation and perfusion scans pre- and post-radiotherapy. Relative changes in pre- to post-treatment ventilation and perfusion in lung regions receiving ≥20 Gy were calculated. In addition, the slopes of the linear fit to the relative ventilation and perfusion changes in regions receiving 0-60 Gy were calculated. A radiologist read and assigned a functional defect score to pre- and post-treatment ventilation/perfusion scans.

Results

25% of patients had a difference >35% between ventilation and perfusion pre- to post-treatment changes and 20-30% of patients had opposite directions for ventilation and perfusion pre- to post-treatment changes. Using a semi-quantitative scale, radiologist assessment showed that 20% of patients had different pre- to post-treatment ventilation changes when compared to pre- to post-treatment perfusion changes.

Conclusion

Our data showed that ventilation dose-response can differ from perfusion dose-response for 20-30% of patients. Therefore, when performing thoracic dose-response in cancer patients, it is insufficient to look at ventilation or perfusion alone; but rather both modes of functional imaging may be needed when predicting for clinical outcomes.

Advances in knowledge

The significance of this study can be highlighted by the differences between the intrapatient dose-response assessments of this analysis compared to existing population-based dose-response analyses. Elucidating intrapatient ventilation and perfusion dose-response differences may be valuable in predicting pulmonary toxicity in lung cancer patients post-radiotherapy.

SUBMITTER: Forghani F

PROVIDER: S-EPMC9975372 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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Publications

Is individual perfusion dose-response different than ventilation dose-response for lung cancer patients treated with radiotherapy?

Forghani Farnoush F Castillo Richard R Castillo Edward E PhD Bernard Jones BJ Rusthoven Chad C Kwak Jennifer J Moiseenko Vitali V Grills Inga I Miften Moyed M Vinogradskiy Yevgeniy Y Guerrero Thomas T

The British journal of radiology 20230112 1143

<h4>Objective</h4>Current ventilation and perfusion dose-response studies focus on single-modalities (ventilation or perfusion) and perform pulmonary-toxicity assessment related to radiotherapy on a population-based basis. This study aims at quantitative and clinical evaluation of intrapatient differences between ventilation and perfusion dose-responses among lung cancer patients treated with radiotherapy.<h4>Methods</h4>20 patients enrolled on a prospective functional avoidance protocol underwe ...[more]

PMID: 36633096

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Project description:PurposeCurrently, several active clinical trials of functional lung avoidance radiation therapy using different imaging modalities for ventilation or perfusion are underway. Patients with lung cancer often show ventilation-perfusion mismatch, whereas the significance of dose-function metric remains unclear. The aim of the present study was to compare dose-ventilation metrics with dose-perfusion metrics for radiation therapy plan evaluation.Methods and materialsPretreatment 4-dimensional computed tomography and 99mTc-macroaggregated albumin single-photon emission computed tomography perfusion images of 60 patients with lung cancer treated with radiation therapy were analyzed. Ventilation images were created using the deformable image registration of 4-dimensional computed tomography image sets and image analysis for regional volume changes as a surrogate for ventilation. Ventilation and perfusion images were converted into percentile distribution images. Analyses included Pearson's correlation coefficient and comparison of agreements between the following dose-ventilation and dose-perfusion metrics: functional mean lung dose and functional percent lung function receiving 5, 10, 20, 30, and 40 Gy (fV5, fV10, fV20, fV30, and fV40, respectively).ResultsOverall, the dose-ventilation metrics were greater than the dose-perfusion metrics (ie, fV20, 26.3% ± 9.9% vs 23.9% ± 9.8%). Correlations between the dose-ventilation and dose-perfusion metrics were strong (range, r = 0.94-0.97), whereas the agreements widely varied among patients, with differences as large as 6.6 Gy for functional mean lung dose and 11.1% for fV20. Paired t test indicated that the dose-ventilation and dose-perfusion metrics were significantly different.ConclusionsStrong correlations were present between the dose-ventilation and dose-perfusion metrics. However, the agreement between the dose-ventilation and dose-perfusion metrics widely varied among patients, suggesting that ventilation-based radiation therapy plan evaluation may not be comparable to that based on perfusion. Future studies should elucidate the correlation of dose-function metrics with clinical pulmonary toxicity metrics.

Project description:Background and purposeFor lung cancer patients treated with radiotherapy, radiation dose to the heart has been associated with overall survival, with volumetric dose statistics widely presented. However, critical cardiac structures are present on the hearts surface, where this approach may be sub-optimal. In this work we present a methodology for creating cardiac surface dose maps and identify regions where excess dose is associated with in worse overall survival.Material and methodsA modified cylindrical coordinate system was implemented to map the cardiac surface dose for lung cancer patients. Validation was performed by mapping the cardiac chambers for 55 patients, fitting a point spread function (PSF) to the blurred edge. To account for this uncertainty, dose maps were blurred by a 2D-Gaussian with width described by the PSF. Permutation testing identified regions where excess dose was associated with worse patient survival. The 99th percentile of the max t-value then defined a cardiac surface region to extract dose, from each patient, to be analysed in a multivariable cox-proportional hazards survival model.ResultsCardiac surface maps were created for 648 lung cancer patients. Cardiac surface dose maps were blurred with a 2D- Gaussian filter of size σφ = 4.3° and σy = 1.3units to account for mapping uncertainties. Permutation testing identified significant differences across the surface of the right atria, p < 0.001, at all timepoints. The median dose to the region defined by the 99th percentile of the maximum t-value was 18.5 Gy. Multivariable analysis showed the dose to this region was significantly associated with survival, hazard ratio 1.01 Gy-1, p = 0.03, controlling for confounding variables.ConclusionsCardiac surface mapping was successfully implemented and identified a region where excess dose was associated with worse patient survival. This region extended over the right atria, potentially suggesting an interaction with the hearts electrical conduction system.

Project description:ObjectiveThe purpose of this study was to assess whether thoracic radiotherapy (TRT) combined with chemotherapy (CHT) showed promising anti-tumour activity in extensive-stage small cell lung cancer (ES-SCLC), to explore practice patterns for the radiation time and dose/fractionation and to identify prognostic factors for patients who would benefit from CHT/TRT.MethodsA total of 492 ES-SCLC patients were included from January 2010 to March 2019, 244 of whom received CHT/TRT. Propensity score matching was performed to minimize bias between the CHT/TRT and CHT-alone groups. Patients in the CHT/TRT group were categorized into four subgroups based on the number of induction CHT cycles. For effective dose fractionation calculations, we introduced the time-adjusted biological effective dose (tBED). Categorical variables were analysed with chi-square tests and Fisher's exact tests. Kaplan-Meier curves were generated to estimate survival rates using the R-project. Multivariate prognostic analysis was performed with Cox proportional hazards models.ResultsPatients who received CHT/TRT experienced improved overall survival (OS) (18.1 vs 10.8 months), progression-free survival (PFS) (9.3 vs 6.0 months) and local recurrence-free survival (LRFS) (12.0 vs 6.6 months) before matching, with similar results after matching. In the CHT/TRT group, the median LRFS times for the groups based on the radiation time were 12.7, 12.0, 12.0, and 9.0 months, respectively. Early TRT had a tendency to prolong PFS (median 10.6 vs 9.8 vs 9.0 vs 7.7 months, respectively, p = 0.091) but not OS (median 17.6 vs 19.5 vs 17.2 vs 19.0 months, respectively, p = 0.622). Notably, patients who received TRT within 6 cycles of CHT experienced prolonged LRFS (p = 0.001). Regarding the radiation dose, patients in the high-dose group (tBED > 50 Gy) who achieved complete response and partial response (CR and PR) to systemic therapy had relatively short OS (median 27.1 vs 22.7, p = 0.026) and PFS (median 11.4 vs 11.2, p = 0.032), but the abovementioned results were not obtained after the exclusion of patients who received hyperfractionated radiotherapy (all p > 0.05).ConclusionCHT/TRT could improve survival for ES-SCLC patients. TRT performed within 6 cycles of CHT and hyperfractionated radiotherapy (45 Gy in 30 fractions) may be a feasible treatment scheme for ES-SCLC patients.

Project description:ObjectiveCritical organ shortages have resulted in ex vivo lung perfusion gaining clinical acceptance for lung evaluation and rehabilitation to expand the use of donation after circulatory death organs for lung transplantation. We hypothesized that an innovative use of airway pressure release ventilation during ex vivo lung perfusion improves lung function after transplantation.MethodsTwo groups (n = 4 animals/group) of porcine donation after circulatory death donor lungs were procured after hypoxic cardiac arrest and a 2-hour period of warm ischemia, followed by a 4-hour period of ex vivo lung perfusion rehabilitation with standard conventional volume-based ventilation or pressure-based airway pressure release ventilation. Left lungs were subsequently transplanted into recipient animals and reperfused for 4 hours. Blood gases for partial pressure of oxygen/inspired oxygen fraction ratios, airway pressures for calculation of compliance, and percent wet weight gain during ex vivo lung perfusion and reperfusion were measured.ResultsAirway pressure release ventilation during ex vivo lung perfusion significantly improved left lung oxygenation at 2 hours (561.5 ± 83.9 mm Hg vs 341.1 ± 136.1 mm Hg) and 4 hours (569.1 ± 18.3 mm Hg vs 463.5 ± 78.4 mm Hg). Likewise, compliance was significantly higher at 2 hours (26.0 ± 5.2 mL/cm H2O vs 15.0 ± 4.6 mL/cm H2O) and 4 hours (30.6 ± 1.3 mL/cm H2O vs 17.7 ± 5.9 mL/cm H2O) after transplantation. Finally, airway pressure release ventilation significantly reduced lung edema development on ex vivo lung perfusion on the basis of percentage of weight gain (36.9% ± 14.6% vs 73.9% ± 4.9%). There was no difference in additional edema accumulation 4 hours after reperfusion.ConclusionsPressure-directed airway pressure release ventilation strategy during ex vivo lung perfusion improves the rehabilitation of severely injured donation after circulatory death lungs. After transplant, these lungs demonstrate superior lung-specific oxygenation and dynamic compliance compared with lungs ventilated with standard conventional ventilation. This strategy, if implemented into clinical ex vivo lung perfusion protocols, could advance the field of donation after circulatory death lung rehabilitation to expand the lung donor pool.

Project description:PurposeThe respiratory disease COVID-19 reached global pandemic status in 2020. Excessive inflammation is believed to result in the most severe symptoms and death from this disease. Because treatment options for patients with severe COVID-19 related pulmonary symptoms remain limited, whole-lung low-dose radiation therapy is being evaluated as an anti-inflammatory modality. However, there is concern about the long-term risks associated with low-dose pulmonary irradiation. To help quantify the benefit-risk balance of low-dose radiation therapy for COVID-19, we estimated radiation-induced lifetime risks of both lung cancer and heart disease (major coronary events) for patients of different sexes, treated at ages 50 to 85, with and without other relevant risk factors (cigarette smoking and baseline heart disease risk).Methods and materialsThese estimates were generated by combining state-of-the-art radiation risk models for lung cancer and for heart disease together with background lung cancer and heart disease risks and age/sex-dependent survival probabilities for the U.S.PopulationResultsEstimated absolute radiation-induced risks were generally higher for lung cancer compared with major coronary events. The highest estimated lifetime radiation-induced lung cancer risks were approximately 6% for female smokers treated between ages 50 and 60. The highest estimated radiation-induced heart disease risks were approximately 3% for males or females with high heart disease risk factors and treated between ages 50 and 60.ConclusionsThe estimated summed lifetime risk of lung cancer and major coronary events reached up to 9% in patients with high baseline risk factors. Predicted lung cancer and heart disease risks were lowest in older nonsmoking patients and patients with few cardiac risk factors. These long-term risk estimates, along with consideration of possible acute reactions, should be useful in assessing the benefit-risk balance for low-dose radiation therapy to treat severe COVID-19 pulmonary symptoms, and suggest that background risk factors, particularly smoking, should be taken into account in such assessments.

Project description:ObjectiveThe effect of functional lung avoidance planning on radiation dose-dependent changes in regional lung perfusion is unknown. We characterized dose-perfusion response on longitudinal perfusion single photon emission computed tomography (SPECT)/CT in two cohorts of lung cancer patients treated with and without functional lung avoidance techniques.MethodsThe study included 28 primary lung cancer patients: 20 from interventional (NCT02773238) (FLARE-RT) and eight from observational (NCT01982123) (LUNG-RT) clinical trials. FLARE-RT treatment plans included perfused lung dose constraints while LUNG-RT plans adhered to clinical standards. Pre- and 3 month post-treatment macro-aggregated albumin (MAA) SPECT/CT scans were rigidly co-registered to planning four-dimensional CT scans. Tumour-subtracted lung dose was converted to EQD2 and sorted into 5 Gy bins. Mean dose and percent change between pre/post-RT MAA-SPECT uptake (%ΔPERF), normalized to total tumour-subtracted lung uptake, were calculated in each binned dose region. Perfusion frequency histograms of pre/post-RT MAA-SPECT were analyzed. Dose-response data were parameterized by sigmoid logistic functions to estimate maximum perfusion increase (%ΔPERFmaxincrease), maximum perfusion decrease (%ΔPERFmaxdecrease), dose midpoint (Dmid), and dose-response slope (k).ResultsDifferences in MAA perfusion frequency distribution shape between time points were observed in 11/20 (55%) FLARE-RT and 2/8 (25%) LUNG-RT patients (p < 0.05). FLARE-RT dose response was characterized by >10% perfusion increase in the 0-5 Gy dose bin for 8/20 patients (%ΔPERFmaxincrease = 10-40%), which was not observed in any LUNG-RT patients (p = 0.03). The dose midpoint Dmid at which relative perfusion declined by 50% trended higher in FLARE-RT compared to LUNG-RT cohorts (35 GyEQD2 vs 21 GyEQD2, p = 0.09), while the dose-response slope k was similar between FLARE-RT and LUNG-RT cohorts (3.1-3.2, p = 0.86).ConclusionFunctional lung avoidance planning may promote increased post-treatment perfusion in low dose regions for select patients, though inter-patient variability remains high in unbalanced cohorts. These preliminary findings form testable hypotheses that warrant subsequent validation in larger cohorts within randomized or case-matched control investigations.Advances in knowledgeThis novel preliminary study reports differences in dose-response relationships between patients receiving functional lung avoidance radiation therapy (FLARE-RT) and those receiving conventionally planned radiation therapy (LUNG-RT). Following further validation and testing of these effects in larger patient populations, individualized estimation of regional lung perfusion dose-response may help refine future risk-adaptive strategies to minimize lung function deficits and toxicity incidence.

Dataset Information

Is individual perfusion dose-response different than ventilation dose-response for lung cancer patients treated with radiotherapy?

Objective

Methods

Results

Conclusion

Advances in knowledge

Publications

Is individual perfusion dose-response different than ventilation dose-response for lung cancer patients treated with radiotherapy?

Similar Datasets

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