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Hitesh Mistry
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OA13 - Therapeutics and Radiation for Small Cell Lung Cancer (ID 927)
- Event: WCLC 2018
- Type: Oral Abstract Session
- Track: Small Cell Lung Cancer/NET
- Presentations: 2
- Moderators:
- Coordinates: 9/26/2018, 10:30 - 12:00, Room 203 BD
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OA13.01 - The Impact of [<sup>18</sup>F]fludeoxyglucose PET/CT in Small-Cell Lung Cancer: Analysis of the Phase 3 CONVERT Trial (ID 13319)
10:30 - 10:40 | Author(s): Hitesh Mistry
- Abstract
- Presentation
Background
The role of 18fludeoxyglucose (18F-FDG) PET/CT in the management of limited stage small-cell lung cancer (LS-SCLC) is uncertain. Previous studies have shown that 18F-FDG PET/CT upstages up to 30% of LS-SCLC patients. Data from the CONVERT trial was analysed to investigate the impact of 18F-FDG PET/CT in the management of LS-SCLC. The prognostic significance of pre-treatment 18F-FDG PET parameters was also investigated in an exploratory analysis.
a9ded1e5ce5d75814730bb4caaf49419 Method
CONVERT is an international multi-centre phase III trial that randomly assigned fit patients to receive either twice-daily (45Gy in 30 fractions) or once-daily (66Gy in 33 fractions) radiotherapy starting on day 22 of chemotherapy cycle 1 (NCT00433563). Chemotherapy consisted of 4-6 cycles of cisplatin and etoposide. Prophylactic cranial irradiation was offered, if indicated. Contrast-enhanced thorax and abdomen CT and brain imaging (with/without bone scintigraphy according to clinical indication) were mandated for all CONVERT participants (conventional imaging). Staging with 18F-FDG PET/CT was allowed but not mandated. The primary endpoint was overall survival. Pre-treatment 18F-FDG PET metabolic parameters were investigated in a subset of patients (n=96) including standardised uptake values (max, mean and peak), volumetric and heterogeneity parameters.
4c3880bb027f159e801041b1021e88e8 Result
Of 547 patients recruited to CONVERT, 540 patients with data on staging investigations and outcome were included in this analysis. The use of staging 18F-FDG PET/CT was variable in the 8 countries recruiting to CONVERT (range, 41-100%). Compared to patients who underwent conventional imaging (n=231), patients who were also staged with 18F-FDG PET/CT (n=309) had smaller gross tumour volume (p=0·003), were less likely to have elevated pre-treatment serum lactate dehydrogenase (p=0·035), and received more chemotherapy cycles (p=0·026). There were no other significant differences in baseline and treatment characteristics between the two groups. There were no significant differences in overall (hazard ratio 0·87 [95% CI 0·70-1·08]; p=0·192) and progression-free survival (hazard ratio 0·87 [95% CI 0·71-1·07]; p=0·198) between patients staged with 18F-FDG PET/CT in addition to conventional imaging or with conventional imaging alone. These results were observed irrespective of treatment group (once-daily and twice-daily radiotherapy). Pre-treatment 18F-FDG PET parameters were also not prognostic.
8eea62084ca7e541d918e823422bd82e Conclusion
In CONVERT, survival outcomes were not different in LS-SCLC patients staged with or without 18F-FDG PET/CT. This was despite those patients staged with 18F-PET/CT having more favourable baseline and treatment characteristics. Our findings suggest that conventional imaging is sufficient to select LS-SCLC patients for concurrent chemoradiotherapy.
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OA13.05 - Prophylactic Cranial Irradiation (PCI) for Limited-Stage Small-Cell Lung Cancer: Results from the Phase 3 CONVERT Trial (ID 13762)
11:15 - 11:25 | Author(s): Hitesh Mistry
- Abstract
- Presentation
Background
PCI is considered standard of care in limited-stage small-cell lung cancer (LS-SCLC) patients. However the impact of the dose and fractionation of thoracic radiotherapy (RT) on the risk of developing brain metastasis (BM) has not been evaluated prospectively.
a9ded1e5ce5d75814730bb4caaf49419 Method
CONVERT is an international, phase 3 trial that randomly assigned patients to receive twice-daily (BD 45Gy in 30 fractions) or once-daily (OD 66Gy in 33 fractions) RT starting on day 22 of chemotherapy (CT) cycle 1 (NCT00433563). PCI was offered, if indicated. Data on thoracic and brain RT delivery and timing, rate of BM and overall survival (OS) in patients treated with PCI was analysed. The association of the risk of developing BM/OS and predictor variables, using a competing risk regression model developed by Fine and Gray for BM or the standard Cox proportional hazards model for OS, was investigated.
4c3880bb027f159e801041b1021e88e8 Result
Of 547 patients recruited to the study, 449 (82%) received PCI after completion of CTRT. PCI was delivered to 220/273 participants (81%) in the BD group and 229/270 in the OD group (85%; p=0.49). Pre-CTRT brain imaging consisted of CT-scan in 356/449 patients (79%) and MRI in 83/449 (18%) patients. Total median PCI dose was 25 Gy in both BD and OD groups (p=0.74). PCI was delivered later after CT in the OD group compared to the BD group (median days post CT 37 vs. 35 days, respectively; p=0.04). In patients who received PCI, 75 (17%) developed BM (35 [8%] in OD and 40 [9%] in BD) and 173 (39%) other extracranial progression. In the univariate analysis, GTV was associated with an increased risk of BM (HR: 1.37 [95%CI 1.09-1.73]; p=0.007) or other radiological progression events (HR: 1.43 [95%CI 1.11-1.85]; p=0.006), whereas in a multivariate analysis both GTV and PS were associated with either progression type. The median OS of patients treated with PCI was 29 months (95%CI 25.8-35.7). Median OS was 28 months in BD (95%CI 22-35) and 31 months in OD (95%CI 27-52; p=0.1). In the univariate analysis of OS, PCI timing from end of CT, weight loss >10%, and thoracic GTV were prognostic factors associated with OS. In the multivariate analysis, only thoracic GTV was associated with OS. Delay between end of CT and PCI was not associated with OS (p=0.2).
8eea62084ca7e541d918e823422bd82e Conclusion
Patients receiving OD or BD thoracic RT have the same risk of developing BM. Larger tumours are associated with a higher risk of BM.
6f8b794f3246b0c1e1780bb4d4d5dc53Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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P1.13 - Targeted Therapy (Not CME Accredited Session) (ID 945)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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P1.13-35 - Hypoxia Mapping Using Oxygen-Enhanced MRI in Lung Cancer (ID 14283)
16:45 - 18:00 | Author(s): Hitesh Mistry
- Abstract
Background
Oxygen deprivation (hypoxia) is associated with worse non-small cell lung cancer (NSCLC) outcomes and predicts poor response to NSCLC treatments, including radiotherapy. There is an unmet need to develop non-invasive hypoxia biomarkers. We report the first preclinical and clinical evidence that oxygen-enhanced MRI (OE-MRI) can map and quantify therapy-induced change in NSCLC hypoxia.
a9ded1e5ce5d75814730bb4caaf49419 Method
In the preclinical study, radiation-induced changes in OE-MRI were first examined in a Calu-6 xenograft model of NSCLC. Tumours received a single 10Gy fraction of radiotherapy (n=9), chemoradiotherapy (5 x 2Gy fractions plus cisplatin; n=6) or control (n=9). Mice were imaged longitudinally using a multi-parametric MRI protocol (diffusion-weighted imaging (DWI), OE and dynamic contrast-enhanced (DCE)-MRI) at days 0, 3, 6 and 10 in all groups and then at day 13 (control), day 18 and 25 (radiotherapy) and day 18 (chemoradiotherapy). Pathology was obtained at cull in imaged mice and in a separate Calu6 cohort treated with a single 10Gy radiotherapy fraction (n=6) or control (n=9) at day 10. In the clinical study, twenty three stage I-IV NSCLC patients underwent an identical multi-parametric MRI for protocol development (n=6), twice prior to radiotherapy (n=10) and after 14±4 radiotherapy fractions (n=12). In all tumours we quantified the validated MRI hypoxia biomarker perfused oxygen-refractory (Oxy-R), which identifies absence of OE-MRI signal change in perfused tumour.
4c3880bb027f159e801041b1021e88e8 Result
By day 10, perfused Oxy-R (hypoxic) volume decreased relative to control in xenografts treated with either radiotherapy (p=0.029) or fractionated chemoradiotherapy (p=0.047). Hypoxia modification persisted in chemoradiotherapy treated tumors to day 16 and in radiotherapy treated tumors to day 22 (both p<0.001). Pimonidazole immunohistochemistry at day 10 showed lower hypoxic fraction in tumors treated with radiotherapy (p=0.026), relative to time matched controls. In addition, imaged xenografts also showed lower hypoxic fractions in radiotherapy (p=0.042) and chemoradiotherapy (p=0.041) treated tumors, relative to size matched control at cull. In the clinical study, OE-MRI was safe, feasible and well-tolerated. Perfused Oxy-R (hypoxic) volume demonstrated excellent repeatability with interclass correlation coefficient of 0.961 (95% CI 0.858-0.990). Visual inspection revealed that MRI hypoxia maps were spatially repeatable across a range of tumour and hypoxic volumes. In the absence of volumetric tumour change, perfused Oxy-R (hypoxic) volume decreased at mid-treatment (3.23 cm3 (95% CI 0-9.41 cm3)), compared to baseline (4.16 cm3 (95% CI 0-10.6 cm3)); p=0.0150.
8eea62084ca7e541d918e823422bd82e Conclusion
Our findings support using OE-MRI to detect and monitor hypoxia in clinical trials of hypoxia-modifying therapies or radiotherapy dose painting studies in patients with NSCLC.
6f8b794f3246b0c1e1780bb4d4d5dc53
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P2.12 - Small Cell Lung Cancer/NET (Not CME Accredited Session) (ID 961)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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P2.12-15 - Prognostic and Predictive Covariates in Limited-Stage Small-Cell Lung Cancer: Analysis of the Phase 3 CONVERT Trial (ID 13320)
16:45 - 18:00 | Author(s): Hitesh Mistry
- Abstract
Background
The majority of patients with limited-stage small cell lung cancer (LS-SCLC) progress after concurrent chemo-radiotherapy (cCTRT). Data from the CONVERT trial was analysed to investigate prognostic and predictive covariates in LS-SCLC patients.
a9ded1e5ce5d75814730bb4caaf49419 Method
CONVERT is an international multi-centre phase III trial that randomly assigned fit patients to receive either twice-daily (45Gy in 30 fractions) or once-daily (66Gy in 33 fractions) radiotherapy starting on day 22 of chemotherapy cycle 1 (ClinicalTrials.gov NCT00433563). Chemotherapy consisted of 4 or 6 cycles (centres choice) of cisplatin and etoposide. Prophylactic cranial irradiation was offered, if indicated. The following covariates were investigated for prognostic and predictive significance (benefit from twice-daily radiotherapy and completion of cCTRT): clinical (age, performance score, TNM staging, smoking status, weight loss >10% and lung function), laboratory (alkaline phosphatase, sodium and lactate dehydrogenase) and dosimetric (gross tumour volume (GTV), heart and lung dose). Completion of chemotherapy was defined as delivery of all planned cycles while completion of radiotherapy was defined as delivery of all fractions. Results of the multivariate regression analysis of overall survival (OS) and progression-free survival (PFS) were reported after correcting for multiple comparisons.
4c3880bb027f159e801041b1021e88e8 Result
Of 547 patients recruited to CONVERT, 449 with complete covariate and outcome data were eligible for this analysis. GTV was the strongest prognostic covariate of OS (hazard ratio (HR) 1.37 (95% confidence interval (CI) 1.21-1.56); p<0.001). The addition of weight loss and performance score modestly improved the concordance probability (0.59 to 0.61) of this model. The HR for OS between high and low risk groups using this model was 2.72 (95% CI 1.94-3.81), median OS: 21 months (95% CI 19-26) vs 44 months (95% CI 36-not reached), respectively. For PFS, the HR between high and low risk groups was 2.55 (95% CI 1.86-3.5), median PFS: 13 months (95% CI 12-15) vs 26 months (95% CI 18-48), respectively. None of the tested covariates predicted patient benefit from twice-daily radiotherapy. Increase in patient age (continuous variable) predicted non-completion of planned chemotherapy (p=0.002). Due to the high completion of radiotherapy (86% in twice-daily and 80% in once-daily group), a multivariate analysis to predict radiotherapy completion was not performed.
8eea62084ca7e541d918e823422bd82e Conclusion
We report a clinical prognostic model in LS-SCLC, providing information that clinicians can relay to their patients to aid clinical decisions. The addition of biological covariates could help refine these prognostic models in the future.
6f8b794f3246b0c1e1780bb4d4d5dc53
