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Robert Rulach
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P05 - Early Stage/Localized Disease - Radiotherapy (ID 114)
- Event: WCLC 2020
- Type: Posters
- Track: Early Stage/Localized Disease
- Presentations: 3
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P05.02 - International Delphi Consensus on Radical Thoracic Re-Irradiation for Non-Small Cell Lung Cancer (NSCLC) (ID 1647)
00:00 - 00:00 | Presenting Author(s): Robert Rulach
- Abstract
Introduction
Local recurrence or second lung primaries are common indications for radical thoracic re-irradiation (re-RT), affecting approximately 700 patients in the UK annually. Re-RT is usually the only suitable curative-intent treatment but prospective evidence on toxicity, dose constraints, and optimal treatment technique is lacking. We performed a Delphi process to identify areas of consensus in re-RT for NSCLC.
Methods
An international panel of 15 radiation oncologists specialising in lung cancer participated in an initial survey on 23/09/2019 to capture their definition of re-RT, suitable patients, re-RT technique and dose constraints used. The most common responses to questions from the first survey were used to make statements which participants voted on in subsequent rounds using a 5-point Likert scale. Consensus was achieved once 75% of participants agreed with a statement. For the statements which did not reach consensus, respondents provided additional evidence/comments to refine them. In total, four surveys were performed using a web-based survey programme.
Results
All respondents completed three rounds of the survey, with the final round currently in progress. Consensus was achieved within two rounds regarding re-RT indications, patient eligibility and work-up (Table 1). In addition, agreement was reached to use stereotactic ablative body radiotherapy (SABR) if possible for re-RT. Dose constraints, due to the lack of supportive data, required three rounds to develop agreement. Several volumetric lung constraints were suggested, but due to post-radiotherapy fibrosis, it was concluded that there was insufficient evidence to form recommendations (Table 2).
Areas of controversy were how much overlap was significant when performing re-RT, what were the minimum lung function requirements and the minimum safe interval between treatments.
Table 1 Statement Degree of Consensus Indications Re-RT can be considered for suspected new lung primaries with minimal overlap with previous radiotherapy fields. 93% Re-RT can be considered for lung tumours which develop new nodal disease after an initial course of radiotherapy only to the primary tumour (therefore minimal overlap). 100% Re-RT can be considered where a lung tumour relapses locally (or develops a suspected second primary tumour with >50% overlap with the original primary tumour), but low overlap with serial structures in the thorax. 93% Patient eligibility In general, patients should have an ECOG PS of 0 - 2 to be considered for re-RT, with exceptions being made for selected PS 3 patients (e.g. SABR re-RT, or PS 3 due to non-respiratory issues). 93% Re-irradiation should be avoided in patients with interstitial lung disease. 86% Surgery should be considered in all appropriate patients being assessed for re-irradiation. 93% Work-up Essential investigations prior to commencing re-RT are: Whole body PET-CT, CT chest + contrast, and CT/MRI brain. 93-100% Table 2 Statement Degree of consensus Dose constraints For radical re-irradiation, the desirable cumulative maximum point dose constraint to the oesophagus is an EQD2 of 75Gy, although up to 100Gy is acceptable (using an a/b=3), with the volume of the oesophagus getting 55 Gray should be less than 35% (V55Gy<35%). 86% For radical re-irradiation, the desirable cumulative maximum point dose constraint to the spinal cord is an EQD2 of 60Gy (using a/b=2), provided that the initial irradiation dose to the cord did not exceed 50Gy and the interval between treatments is greater than 6 months. 80% For radical re-irradiation, the desirable cumulative maximum dose (Dmax) constraint to the aorta is an EQD2 of 115Gy (a/b=3). The desirable cumulative Dmax to the pulmonary artery is an EQD2 of 110Gy. 80% There is insufficient evidence to suggest volumetric cumulative dose constraints for the lung due to the changes in anatomy and function of the lung after an initial course of radiotherapy. 80% Technique Radical re-irradiation should be performed using highly conformal radiotherapy techniques (e.g. VMAT, Tomotherapy, Cyberknife). 100% Acceptable doses for conventionally fractionated re-RT include 60Gy in 30 fractions or 55Gy in 20 fractions once daily for NSCLC 93% SABR is the preferred re-RT technique where the tumour is not ultra-central, no nodal disease and the tumour volume is small with minimal overlap with OARs. 87% Any dose and fractionation that can safely deliver a BED >100Gy to the tumour is acceptable for radical re-irradiation with SABR. 87%
Conclusion
This Delphi process with international experts has developed key recommendations on the criteria for suitable re-RT patients, dose constraints and preferred technique. These statements can be used to develop prospective trials to provide better evidence for re-RT.
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P05.09 - Thoracic Re-Irradiation Dose Constraints for Late Lung Fibrosis: Preliminary Modelling Results (ID 1639)
00:00 - 00:00 | Presenting Author(s): Robert Rulach
- Abstract
Introduction
Patients who have received radical radiotherapy for non-small cell lung cancer (NSCLC) are at risk of developing local recurrence, or a second primary cancer. We predict that 700 patients/year develop this in the UK. Thoracic re-irradiation is increasingly practiced with the median overall survival from re-treatment at 17 months, but lung toxicity is a common toxicity. There is limited evidence regarding cumulative dose constraints for the lung for NSCLC re-irradiation. The aim of this project is to generate putative re-irradiation dose constraints from published data.
Methods
MEDLINE was searched for studies published between 01/01/1970 to 01/10/2018 reporting re-irradiation for any malignancy, where the cumulative lung volume (either mean lung dose (MLD), volume of lung receiving 5 or 20 Gray (V5, V20)) was paired with any encountered toxicity. Logistic regression modelling was performed using R (version 3.6.1, R Core Team, 2019).
Results
We extracted grade 2-5 lung fibrosis rates (using either CTCAE or RTOG scales) from 35 papers (n=1151). 10 papers gave MLD/V5/V20 data (n= 317). There were 50 grade 2 or above (≥G2) events, and 29 grade 3 or above (≥G3) toxic events. Univariate modelling for ≥G2 toxicities yielded no significant models. Univariate modelling for ≥G3 toxicities with cumulative MLD, V5 and V20 were all significant (p<0.01, Table 1). The V20 model includes two ≥G3 toxicities which are outliers, thus the V20 model AIC is higher than the other models. Risk of toxicity plots are presented in Figure 1. However, due to collinearity of the data, multivariate modelling failed to produce a significant model, although the lower AIC suggests that it provides the best model fit.
Lung parameter Model expression P-value OR (95% CI) AIC Missing patient data (n=317) Missing toxicity events (n=29) Univariate Cum V20 Logit P(G3toxicity) = -6.68 + 0.18(CumV20) <0.001 1.19 (1.09 -1.35) 38.03 31 0 Cum V5 Logit P(G3toxicity) = -5.12 + 0.06(CumV5) 0.001 1.05 (1.03 - 1.10) 30.05 102 2 Cum MLD Logit P(G3toxicity) = -11 + 0.54(CumMLD) 0.003 1.71 (1.29 - 2.70) 27.69 71 2 Multivariate Cum V20 and MLD Logit P(G3toxicity) = -11.34 + 0.12(CumV20) + 0.39(CumMLD) Cum V20 = 0.28, Cum MLD = 0.11 Cum V20 1.12 (0.92 - 1.41), Cum MLD 1.48 (0.94 - 2.61) 17.24 102 2
Conclusion
Univariate modelling predicts a ≥G3 re-irradiation toxicity rate of <5% if the cumulative V5 <40%, V20 <21% and MLD <15Gy. These are conservative estimates requiring validation and planning studies to assess if these constraints are achievable.
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P05.12 - Hospitalisation Rate in Radical Re-Irradiation of NSCLC are no Different Between Local Recurrences or Second Primaries (ID 1637)
00:00 - 00:00 | Presenting Author(s): Robert Rulach
- Abstract
Introduction
An estimated 700 patients annually will have a local recurrence (LR) or a second primary (SP) after radical radiotherapy for NSCLC in the UK. Radical re-irradiation (re-RT) is limited to selected patients due to concerns regarding toxicity and a lack of prospective efficacy evidence. We present a retrospective review of NSCLC re-RT in a tertiary oncology centre.
Methods
Patients with two radical radiation courses for NSCLC between 01/01/2014 - 01/08/2019 were identified from the radiotherapy database. Outcomes and toxicity were obtained from patient records. LR was defined as any overlap of the planning target volumes (PTV) of the two treatments. Overall survival (OS) was derived from the last fraction of re-RT. Analysis was performed using R (v3.6.1, R Core Team, 2019).
Results
39 patients were identified (19 males, 20 females), median age at re-irradiation was 71.2 years. Median interval between treatments was 12.7 months (2.2 – 62.9). 13 LRs and 26 SPs were re-treated. Median re-RT PTV size was 82.5cc (range 8.4 – 417.45cc). Figure 1 provides the treatment techniques (TT) used and performance status (PS) at re-RT.
There were 5 hospitalisations related to radiotherapy within 90 days of re-RT including one grade 5 haemoptysis. There were 12 hospitalisations after 90 days, 10 due to chest infections. There was no difference between the rate of hospitalisations between the LR and SP groups (38.5% and 46.2% respectively, Chi-sq = 0.013, p = 0.91).
Median OS in the LR group was 12.8 months (95% CI: 6.0 – NR) compared to 39.9 months in the SP group (95% CI: 19.2 – NR, p=0.044, Figure 2). PS, PTV size, or TT were not significant factors (Figure 1).
Conclusion
LR has worse OS than SP. There is no difference in hospitalisations between LR and SP groups after re-RT, suggesting that any retreatment to the thorax has significant toxicity.
