Pre-treatment FDG-PET predicts the site of in-field progression following concurrent chemoradiotherapy for stage III non-small cell lung cancer

Ohri, Nitin; Piperdi, Bilal; Garg, Madhur; Bodner, William; Gucalp, Rasim; Pérez-Soler, Román; Keller, Steven M.; Guha, Chandan

doi:10.1016/j.lungcan.2014.10.016

Cited by 22 publications

(30 citation statements)

References 22 publications

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“…While modern radiotherapy has made strides in early‐stage lung, liver, metastatic, and other radioresistant cancers, there is a need to further improve the treatment efficacy of radiotherapy for challenging diseases including glioblastoma multiforme (GBM), locally advanced lung, liver, and pancreatic cancers . Future improvements in the efficacy of radiotherapy may rely on innovatively combined immune and radiotherapy, x ray dose triggered drug release, spatially modulated radiotherapy targeting tumor cell heterogeneity and niches, temporally modulated radiotherapy to disrupt tumor stem cell proliferation, or ultra‐high‐dose radiotherapy .…”

Section: Introductionmentioning

confidence: 99%

A sparse orthogonal collimator for small animal intensity‐modulated radiation therapy. Part II: hardware development and commissioning

et al. 2019

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Purpose A dose‐modulation device for small animal radiotherapy is required to use clinically analogous treatment techniques, which will likely increase the translatability of preclinical research results. Because the clinically used multileaf collimator (MLC) is impractical for miniaturization, we have developed a simpler, better‐suited sparse orthogonal collimator (SOC) for delivering small animal intensity‐modulated radiation therapy (IMRT) using a rectangular aperture optimization (RAO) treatment planning system. Methods The SOC system was modeled in computer‐aided design software and fabricated with machined tungsten leaves and three‐dimensional (3D) printed leaf housing. A graphical user interface was developed for controlling and calibrating the SOC leaves, which are driven by Arduino‐controlled stepper motors. A Winston‐Lutz test was performed to assess mechanical alignment, and abutting field and grid dose patterns were created to analyze intra‐ and intercalibration leaf positioning error. Leaf transmission and penumbra were measured over the full range of gantry angles and leaf positions, respectively. Three SOC test plans were delivered, and film measurements were compared to the intended dose distributions. The differences in maximum, mean, and minimum, as well as pixelwise absolute dose differences, were compared for each structure, and a gamma analysis was performed for the target structures using criteria of 4% dose difference and 0.3 mm distance to agreement. Results The Winston‐Lutz test revealed maximum directional offsets between the SOC and primary collimator axes of 0.53 mm at 0° and 0.68 mm over the full 360°. Upper and lower abutting field patterns had maximum dose deviations of 18.8 ± 3.1% and 15.5 ± 2.9%, respectively, and grid patterns showed intra‐ and intercalibration repeatability of 93% and 91%, respectively. Extremely low midleaf (0.15 ± 0.05%) and interleaf (0.27 ± 0.22%) transmission was measured, with no significant rotational variation. The average penumbra was ~0.8 mm for all leaves at field center, with a range of 0.17 mm for all leaf positions. A highly concave test plan was delivered with a ~ 95% gamma analysis pass rate, and a realistic mouse phantom liver irradiation plan achieved a pass rate of ~98%. A highly complex dose distribution was also created with 551 SOC apertures averaging 2.4 mm in size. Conclusions A sparse orthogonal collimator was developed and commissioned, with promising preliminary dosimetry results. The SOC design, with its limited moving components and high dose‐modulation resolution, is ideal for delivering high‐quality small animal IMRT with our RAO‐based treatment planning system.

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Section: Introductionmentioning

confidence: 99%

A sparse orthogonal collimator for small animal intensity‐modulated radiation therapy. Part II: hardware development and commissioning

et al. 2019

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“…Response assessment with FDG PET/CT can predict for poor local control and survival, whereby one study looking at mid‐treatment PET/CT showed that 60% of patients were classified as nonresponders with 2‐year overall survival of 33% compared to 92% in responders . FDG PET/CT can also identify gross tumor subregions that spatially correlate to recurrent disease . PET‐guided radiation therapy (RT) dose escalation trials are delineating FDG PET avid tumor regions prior to and during (RTOG 1106) treatment for concomitant dose escalation in randomized locally advanced NSCLC cohorts.…”

Section: Introductionmentioning

confidence: 99%

“…The avoidance of MAA SPECT‐defined lung tissue regions at risk for morbidity and response‐adaptive dose escalation to FDG PET‐defined tumor tissue regions at risk for recurrence are motivated by clinical evidence . In response to this evidence, a novel investigator‐initiated clinical trial (NCT02773238) has been launched to test the efficacy of a precision radiation oncology strategy known as Functional Lung Avoidance and Response‐adaptive Escalation Radiation Therapy (FLARE RT).…”

Section: Introductionmentioning

confidence: 99%

“…13 FDG PET/CT can also identify gross tumor subregions that spatially correlate to recurrent disease. [14][15][16] PET-guided radiation therapy (RT) dose escalation trials are delineating FDG PET avid tumor regions prior to 17 and during (RTOG 1106) treatment for concomitant dose escalation in randomized locally advanced NSCLC cohorts. Effective RT for patients with locally advanced NSCLC likely requires selection of a subpopulation with significant survival benefit from dose intensification.…”

Section: Introductionmentioning

confidence: 99%

“…31 The avoidance of MAA SPECT-defined lung tissue regions at risk for morbidity and response-adaptive dose escalation to FDG PET-defined tumor tissue regions at risk for recurrence are motivated by clinical evidence. 15,16,[32][33][34] In response to this evidence, a novel investigator-initiated clinical trial (NCT02773238) has been launched to test the efficacy of a precision radiation oncology strategy known as Functional Lung Avoidance and Response-adaptive Escalation Radiation Therapy (FLARE RT). The strategy accounts for spatial heterogeneity on FDG PET/CT and data-corrected MAA SPECT/CT imaging to dose-paint-by-numbers 35 at the voxel scale within both cancer and lung tissue regions simultaneously.…”

Section: Introductionmentioning

confidence: 99%

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Functional lung avoidance and response-adaptive escalation (FLARE) RT: Multimodality plan dosimetry of a precision radiation oncology strategy

et al. 2017

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Purpose Non-small cell lung cancer (NSCLC) patient radiation therapy (RT) is planned without consideration of spatial heterogeneity in lung function or tumor response. We assessed the dosimetric and clinical feasibility of functional lung avoidance and response-adaptive escalation (FLARE) RT to reduce dose to [99mTc]MAA-SPECT/CT perfused lung while redistributing an escalated boost dose within [18F]FDG-PET/CT-defined biological target volumes (BTV). Methods Eight stage IIB-IIIB NSCLC patients underwent FDG-PET/CT and MAA-SPECT/CT treatment planning scans. Perfused lung objectives were derived from scatter/collimator/attenuation-corrected MAA-SPECT uptake relative to ITV-subtracted lung to maintain < 20 Gy mean lung dose (MLD). Prescriptions included 60 Gy to the planning target volume (PTV) and concomitant boost of 74 Gy mean to biological target volumes (BTV=GTV+PET gradient segmentation) scaled to each BTV voxel by relative FDG-PET SUV. Dose-painting-by-numbers prescriptions were integrated into commercial treatment planning systems via uptake threshold discretization. Dose constraints for lung, heart, cord, and esophagus were defined. FLARE RT plans were optimized with volumetric modulated arc therapy (VMAT), proton pencil beam scanning (PBS) with 3%-3mm robust optimization, and combination of PBS (avoidance) plus VMAT (escalation). The high boost dose region was evaluated within a standardized SUVpeak structure. FLARE RT plans were compared to reference VMAT plans. Linear regression between radiation dose to BTV and normalized FDG PET SUV at every voxel was conducted, from which Pearson linear correlation coefficients and regression slopes were extracted. Spearman rank correlation coefficients were estimated between radiation dose to lung and normalized SPECT uptake. Dosimetric differences between treatment modalities were evaluated by Friedman non-parametric paired test with multiple sampling correction. Results No unacceptable violations of PTV and normal tissue objectives were observed in 24 FLARE RT plans. Compared to reference VMAT plans, FLARE VMAT plans achieved a higher mean dose to BTV (73.7 Gy vs. 61.3 Gy), higher mean dose to SUVpeak (89.7 Gy vs. 60.8 Gy), and lower mean dose to highly perfused lung (7.3 Gy vs. 14.9 Gy). These dosimetric gains came at the expense of higher mean heart dose (9.4 Gy vs. 5.8 Gy) and higher maximum cord dose (50.1 Gy vs. 44.6 Gy) relative to the reference VMAT plans. Between FLARE plans, FLARE VMAT achieved higher dose to the SUVpeak ROI than FLARE PBS (89.7 Gy vs. 79.2 Gy, p = 0.01), while FLARE PBS delivered lower dose to lung than FLARE VMAT (11.9 Gy vs 15.6 Gy, p < 0.001). Voxelwise linear dose redistribution slope between BTV dose and FDG PET uptake was higher in magnitude for FLARE PBS+VMAT (0.36 Gy per %SUVmax) compared to FLARE VMAT (0.27 Gy per %SUVmax) or FLARE PBS alone (0.17 Gy per %SUVmax). Conclusions FLARE RT is clinically feasible with VMAT and PBS. A combination of PBS for functional lung avoidance and VMAT for FDG PET dose escalation balanced t...

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Analysis of primary tumor metabolic volume during chemoradiotherapy in locally advanced non-small cell lung cancer

et al. 2017

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Pre-treatment FDG-PET predicts the site of in-field progression following concurrent chemoradiotherapy for stage III non-small cell lung cancer

Cited by 22 publications

References 22 publications

A sparse orthogonal collimator for small animal intensity‐modulated radiation therapy. Part II: hardware development and commissioning

A sparse orthogonal collimator for small animal intensity‐modulated radiation therapy. Part II: hardware development and commissioning

Functional lung avoidance and response-adaptive escalation (FLARE) RT: Multimodality plan dosimetry of a precision radiation oncology strategy

Analysis of primary tumor metabolic volume during chemoradiotherapy in locally advanced non-small cell lung cancer

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