Neville Eclov | University of Chicago (original) (raw)
Papers by Neville Eclov
Nature Medicine, 2014
Circulating tumor DNA (ctDNA) represents a promising biomarker for noninvasive assessment of canc... more Circulating tumor DNA (ctDNA) represents a promising biomarker for noninvasive assessment of cancer burden, but existing methods have insufficient sensitivity or patient coverage for broad clinical applicability. Here we introduce CAncer Personalized Profiling by deep Sequencing (CAPP-Seq), an economical and ultrasensitive method for quantifying ctDNA. We implemented CAPP-Seq for non-small cell lung cancer (NSCLC) with a design covering multiple classes of somatic alterations that identified mutations in >95% of tumors. We detected ctDNA in 100% of stage II-IV and 50% of stage I NSCLC patients, with 96% specificity for mutant allele fractions down to ~0.02%. Levels of ctDNA significantly correlated with tumor volume, distinguished between residual disease and treatment-related imaging changes, and provided earlier response assessment than radiographic approaches. Finally, we explored biopsy-free tumor screening and Users may view, print, copy, download and text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:
Practical Radiation …, 2012
Purpose: To determine the clinical impact of calculated dose differences between effective path l... more Purpose: To determine the clinical impact of calculated dose differences between effective path length (EPL) and Monte Carlo (MC) algorithms in stereotactic ablative radiation therapy (SABR) of lung tumors. Methods and Materials: We retrospectively analyzed the treatment plans and clinical outcomes of 77 consecutive patients treated with SABR for 82 lung tumors between 2003 and 2009 at our institution. Sixty treatments were originally planned using EPL, and 22 using MC. All plans were recalculated for the same beam specifications using MC and EPL, respectively. The doses covering 95%, 50%, and 5% (D95, D50, D5, respectively) of the target volumes were compared between EPL and MC (assumed to be the actual delivered dose), both as physical dose and biologically effective dose. Time to local recurrence was correlated with dose by Cox regression analysis. The relationship between tumor control probability (TCP) and biologically effective dose was determined via logistic regression and used to estimate the TCP decrements due to prescribing by EPL calculations. Results: EPL overestimated dose compared with MC in all tumor dose-volume histogram parameters in all plans. The difference was N10% of the MC D95 to the planning target volume and gross tumor volume in 60 of 82 (73%) and 52 of 82 plans (63%), respectively. Local recurrence occurred in 13 of 82 tumors. Controlling for gross tumor volume, higher physical and biologically effective planning target volume D95 correlated significantly with local control (P = .007 and P = .045, respectively). Compared with MC, prescribing based on EPL translated to a median TCP decrement of 4.3% (range, 1.2%-37%) and a N 5% decrement in 46% of tumors.
Fuel and Energy Abstracts, 2011
Fuel and Energy Abstracts, 2011
International journal of radiation oncology, biology, physics, 2012
Tumors of the pancreatic head are challenging radiation therapy targets because they abut several... more Tumors of the pancreatic head are challenging radiation therapy targets because they abut several critical and radiosensitive structures like the duodenum and stomach. We hypothesized that dosimetry to these normal structures could be improved by understanding the anatomic changes due to respiration when using stereotactic body radiation therapy (SBRT). Treatment at end-expiration provided superior dosimetry, likely due to subtle organ compression during inspiration. These data suggest that end-expiratory gating is the Purpose: To determine how the respiratory phase impacts dose to normal organs during stereotactic body radiation therapy (SBRT) for pancreatic cancer. Methods and Materials: Eighteen consecutive patients with locally advanced, unresectable pancreatic adenocarcinoma treated with SBRT were included in this study. On the treatment planning 4-dimensional computed tomography (CT) scan, the planning target volume (PTV), defined as the gross tumor volume plus 3-mm margin, the duodenum, and the stomach were contoured on the end-expiration (CT exp ) and end-inspiration (CT insp ) phases for each patient. A separate treatment plan was constructed for both phases with the dose prescription of 33 Gy in 5 fractions with 95% coverage of the PTV by the 100% isodose line. The dose-volume histogram (DVH) endpoints, volume of duodenum that received 20 Gy (V 20 ), V 25 , and V 30 and maximum dose to 5 cc of contoured organ (D 5cc ), D 1cc , and D 0.1cc , were evaluated. Results: Dosimetric parameters for the duodenum, including V 25 , V 30 , D 1cc , and D 0.1cc improved by planning on the CT exp compared to those on the CT insp . There was a statistically significant overlap of the PTV with the duodenum but not the stomach during the CT insp compared to the CT exp (0.38 AE 0.17 cc vs 0.01 AE 0.01 cc, PZ.048). A larger expansion of the PTV, in accordance with a Danish phase 2 trial, showed even more overlapping volume of duodenum on the CT insp compared to that on the CT exp (5.5 AE 0.9 cc vs 3.0 AE 0.8 cc, PZ.0003) but no statistical difference for any stomach dosimetric DVH parameter. Conclusions: Dose to the duodenum was higher when treating on the inspiratory than on the expiratory phase. These data suggest that expiratory gating may be preferable to inspiratory breath-hold and free breathing strategies for minimizing risk of toxicity. Ó
Purpose: Previous external beam radiation therapy is a relative contraindication for Y90 radioemb... more Purpose: Previous external beam radiation therapy is a relative contraindication for Y90 radioembolization, because the liver has a lifetime tolerance to radiation before the onset of radiation-induced liver disease (RILD). We analyzed the safety of radioembolization as salvage treatment in patients who had previously undergone external-beam radiotherapy.
Materials and Methods: Of a total of 190 patients who underwent radioembolization treatment for unresectable hepatic malignancy, 30 had previously undergone external-beam radiotherapy, 15 of them in the abdominopelvic region. Three-dimensional treatment planning with dose volume histogram analysis of the liver was used to calculate the mean external-beam hepatic radiation dose. Clinical and biochemical toxicities were reviewed after radioembolization. RILD was defined as Grade 3 hepatic toxicity according to the Common Terminology Criteria for Adverse Events of the National Cancer Institute (CTCAE-NCI).
Results: The mean and median dose delivered during radioembolization was 1.94 and 1.75 GBq. Grade 1 and 2 toxicities were noted and were not distinguishable from those in patients who had never undergone external-beam radiotherapy (p = 0.13). Two patients (6.7%) with fatal RILD were identified 6 – 8 weeks after treatment, a rate insignificantly higher than the 1.9% seen in patients without prior radiotherapy (p = 0.13). Both patients had 25% liver involvement by tumor, and both had received a mean hepatic external beam dose 20 Gy concentrated in the left lobe (p 0.005). Both had grade 3 to 4 bilirubin and aspartate aminotransferase elevation with development of ascites, and one was histopathologically proven to have venoocclusive disease.
Conclusion: Radioembolization appears to be safe for treatment of hepatic malignancies in patients who have had only limited hepatic exposure to external beam radiation. Detailed dose volume histograms are important to estimate risk of development of RILD.
Clinical Lung …, Jan 1, 2011
The optimal treatment of locally advanced non-small-cell lung cancer (NSCLC) remains controversia... more The optimal treatment of locally advanced non-small-cell lung cancer (NSCLC) remains controversial. We hypothesized that using a trimodality approach in selected patients with stage IIIA/IIIB disease would be both feasible and efficacious with reasonable toxicity. Patients/Methods: We enrolled 13 patients with resectable stage III NSCLC on a prospective phase II trial of trimodality therapy. Induction treatment consisted of weekly docetaxel 20 mg/m 2 and weekly carboplatin at an area under curve (AUC) of 2 concurrent with 45 Gy thoracic radiotherapy. Resection was performed unless felt to be unsafe or if patients had progressive disease. Postoperative consolidation consisted of docetaxel 75 mg/m 2 and carboplatin at an AUC of 6 every 3 weeks for 3 cycles with growth factor support. Results: All patients responded to induction chemoradiotherapy as measured by total gross tumor volume reductions of 43% on average (range, 27%-64%). Twelve patients underwent resection of the tumor and involved nodes, yielding a resectability rate of 92%. The primary endpoint of 2-year overall survival (OS) was 72% (95% confidence interval [CI], 36%-90%), and 2-year progression-free survival (PFS) was 36% (95% CI, 9%-64%). The maximal toxicity observed per patient was grade II in 5 patients (38%); grade III in 7 patients (54%); grade IV in 1 patient (8%); and grade V in none. Conclusion: This trimodality approach resulted in promising outcomes with reasonable toxicity in carefully selected patients with stage III NSCLC at a single institution.
Nature Medicine, 2014
Circulating tumor DNA (ctDNA) represents a promising biomarker for noninvasive assessment of canc... more Circulating tumor DNA (ctDNA) represents a promising biomarker for noninvasive assessment of cancer burden, but existing methods have insufficient sensitivity or patient coverage for broad clinical applicability. Here we introduce CAncer Personalized Profiling by deep Sequencing (CAPP-Seq), an economical and ultrasensitive method for quantifying ctDNA. We implemented CAPP-Seq for non-small cell lung cancer (NSCLC) with a design covering multiple classes of somatic alterations that identified mutations in >95% of tumors. We detected ctDNA in 100% of stage II-IV and 50% of stage I NSCLC patients, with 96% specificity for mutant allele fractions down to ~0.02%. Levels of ctDNA significantly correlated with tumor volume, distinguished between residual disease and treatment-related imaging changes, and provided earlier response assessment than radiographic approaches. Finally, we explored biopsy-free tumor screening and Users may view, print, copy, download and text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:
Practical Radiation …, 2012
Purpose: To determine the clinical impact of calculated dose differences between effective path l... more Purpose: To determine the clinical impact of calculated dose differences between effective path length (EPL) and Monte Carlo (MC) algorithms in stereotactic ablative radiation therapy (SABR) of lung tumors. Methods and Materials: We retrospectively analyzed the treatment plans and clinical outcomes of 77 consecutive patients treated with SABR for 82 lung tumors between 2003 and 2009 at our institution. Sixty treatments were originally planned using EPL, and 22 using MC. All plans were recalculated for the same beam specifications using MC and EPL, respectively. The doses covering 95%, 50%, and 5% (D95, D50, D5, respectively) of the target volumes were compared between EPL and MC (assumed to be the actual delivered dose), both as physical dose and biologically effective dose. Time to local recurrence was correlated with dose by Cox regression analysis. The relationship between tumor control probability (TCP) and biologically effective dose was determined via logistic regression and used to estimate the TCP decrements due to prescribing by EPL calculations. Results: EPL overestimated dose compared with MC in all tumor dose-volume histogram parameters in all plans. The difference was N10% of the MC D95 to the planning target volume and gross tumor volume in 60 of 82 (73%) and 52 of 82 plans (63%), respectively. Local recurrence occurred in 13 of 82 tumors. Controlling for gross tumor volume, higher physical and biologically effective planning target volume D95 correlated significantly with local control (P = .007 and P = .045, respectively). Compared with MC, prescribing based on EPL translated to a median TCP decrement of 4.3% (range, 1.2%-37%) and a N 5% decrement in 46% of tumors.
Fuel and Energy Abstracts, 2011
Fuel and Energy Abstracts, 2011
International journal of radiation oncology, biology, physics, 2012
Tumors of the pancreatic head are challenging radiation therapy targets because they abut several... more Tumors of the pancreatic head are challenging radiation therapy targets because they abut several critical and radiosensitive structures like the duodenum and stomach. We hypothesized that dosimetry to these normal structures could be improved by understanding the anatomic changes due to respiration when using stereotactic body radiation therapy (SBRT). Treatment at end-expiration provided superior dosimetry, likely due to subtle organ compression during inspiration. These data suggest that end-expiratory gating is the Purpose: To determine how the respiratory phase impacts dose to normal organs during stereotactic body radiation therapy (SBRT) for pancreatic cancer. Methods and Materials: Eighteen consecutive patients with locally advanced, unresectable pancreatic adenocarcinoma treated with SBRT were included in this study. On the treatment planning 4-dimensional computed tomography (CT) scan, the planning target volume (PTV), defined as the gross tumor volume plus 3-mm margin, the duodenum, and the stomach were contoured on the end-expiration (CT exp ) and end-inspiration (CT insp ) phases for each patient. A separate treatment plan was constructed for both phases with the dose prescription of 33 Gy in 5 fractions with 95% coverage of the PTV by the 100% isodose line. The dose-volume histogram (DVH) endpoints, volume of duodenum that received 20 Gy (V 20 ), V 25 , and V 30 and maximum dose to 5 cc of contoured organ (D 5cc ), D 1cc , and D 0.1cc , were evaluated. Results: Dosimetric parameters for the duodenum, including V 25 , V 30 , D 1cc , and D 0.1cc improved by planning on the CT exp compared to those on the CT insp . There was a statistically significant overlap of the PTV with the duodenum but not the stomach during the CT insp compared to the CT exp (0.38 AE 0.17 cc vs 0.01 AE 0.01 cc, PZ.048). A larger expansion of the PTV, in accordance with a Danish phase 2 trial, showed even more overlapping volume of duodenum on the CT insp compared to that on the CT exp (5.5 AE 0.9 cc vs 3.0 AE 0.8 cc, PZ.0003) but no statistical difference for any stomach dosimetric DVH parameter. Conclusions: Dose to the duodenum was higher when treating on the inspiratory than on the expiratory phase. These data suggest that expiratory gating may be preferable to inspiratory breath-hold and free breathing strategies for minimizing risk of toxicity. Ó
Purpose: Previous external beam radiation therapy is a relative contraindication for Y90 radioemb... more Purpose: Previous external beam radiation therapy is a relative contraindication for Y90 radioembolization, because the liver has a lifetime tolerance to radiation before the onset of radiation-induced liver disease (RILD). We analyzed the safety of radioembolization as salvage treatment in patients who had previously undergone external-beam radiotherapy.
Materials and Methods: Of a total of 190 patients who underwent radioembolization treatment for unresectable hepatic malignancy, 30 had previously undergone external-beam radiotherapy, 15 of them in the abdominopelvic region. Three-dimensional treatment planning with dose volume histogram analysis of the liver was used to calculate the mean external-beam hepatic radiation dose. Clinical and biochemical toxicities were reviewed after radioembolization. RILD was defined as Grade 3 hepatic toxicity according to the Common Terminology Criteria for Adverse Events of the National Cancer Institute (CTCAE-NCI).
Results: The mean and median dose delivered during radioembolization was 1.94 and 1.75 GBq. Grade 1 and 2 toxicities were noted and were not distinguishable from those in patients who had never undergone external-beam radiotherapy (p = 0.13). Two patients (6.7%) with fatal RILD were identified 6 – 8 weeks after treatment, a rate insignificantly higher than the 1.9% seen in patients without prior radiotherapy (p = 0.13). Both patients had 25% liver involvement by tumor, and both had received a mean hepatic external beam dose 20 Gy concentrated in the left lobe (p 0.005). Both had grade 3 to 4 bilirubin and aspartate aminotransferase elevation with development of ascites, and one was histopathologically proven to have venoocclusive disease.
Conclusion: Radioembolization appears to be safe for treatment of hepatic malignancies in patients who have had only limited hepatic exposure to external beam radiation. Detailed dose volume histograms are important to estimate risk of development of RILD.
Clinical Lung …, Jan 1, 2011
The optimal treatment of locally advanced non-small-cell lung cancer (NSCLC) remains controversia... more The optimal treatment of locally advanced non-small-cell lung cancer (NSCLC) remains controversial. We hypothesized that using a trimodality approach in selected patients with stage IIIA/IIIB disease would be both feasible and efficacious with reasonable toxicity. Patients/Methods: We enrolled 13 patients with resectable stage III NSCLC on a prospective phase II trial of trimodality therapy. Induction treatment consisted of weekly docetaxel 20 mg/m 2 and weekly carboplatin at an area under curve (AUC) of 2 concurrent with 45 Gy thoracic radiotherapy. Resection was performed unless felt to be unsafe or if patients had progressive disease. Postoperative consolidation consisted of docetaxel 75 mg/m 2 and carboplatin at an AUC of 6 every 3 weeks for 3 cycles with growth factor support. Results: All patients responded to induction chemoradiotherapy as measured by total gross tumor volume reductions of 43% on average (range, 27%-64%). Twelve patients underwent resection of the tumor and involved nodes, yielding a resectability rate of 92%. The primary endpoint of 2-year overall survival (OS) was 72% (95% confidence interval [CI], 36%-90%), and 2-year progression-free survival (PFS) was 36% (95% CI, 9%-64%). The maximal toxicity observed per patient was grade II in 5 patients (38%); grade III in 7 patients (54%); grade IV in 1 patient (8%); and grade V in none. Conclusion: This trimodality approach resulted in promising outcomes with reasonable toxicity in carefully selected patients with stage III NSCLC at a single institution.