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J. Belderbos
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MINI 17 - WT EGFR, Angiogenesis and OMD (ID 131)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:R. Feld, R. Dziadziuszko
- Coordinates: 9/08/2015, 16:45 - 18:15, Mile High Ballroom 4a-4f
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MINI17.11 - Results of Radical Local Treatment of Non-Small Cell Lung Cancer Patients with One or Two Synchronous Metastases (ID 581)
17:45 - 17:50 | Author(s): J. Belderbos
- Abstract
- Presentation
Background:
Stage IV non-small cell lung cancer (NSCLC) patients are considered incurable and mainly treated with palliative intent. The overall survival (OS) and disease free survival (DFS) of this patient group is considered as poor. The purpose of this study was to investigate the OS and DFS of NSCLC patients, diagnosed with synchronous oligometastatic disease treated with curative intent of the intrathoracic disease as well as the metastases.
Methods:
Patients treated between 2008 and 2014 were included in this retrospective cohort analysis. Main inclusion criteria were: synchronous presentation of NSCLC and oligometastatic disease at diagnosis, and multidisciplinary consent on a radical treatment of both the intrathoracic disease and the metastases. Besides systemic treatment. The intrathoracic disease was radically irradiated (> 55 Gy biological effective dose) or resected. Treatment of the metastases consisted of: radical/stereotactic radiotherapy, surgical resection or radiofrequency ablation (RFA).
Results:
A total of 56 patients, 31 men and 25 women, were included. The mean age was 61 years (range 36-79) and all were in good condition (WHO 0-1). Most patients had a solitary metastasis (brain (22), bone (17), adrenal gland (6), lymphe node (3), liver (2), soft tissue (1), pulmonary (1), thyroid gland (1) and breast (1)). Two patients had 2 metastases (liver and bone / pleural and bone). The intrathoracic tumor stage,ignoring M-status, was IA in 3 patients, IB in 2 patients, IIA in 8 patients, IIB in 4 patients, IIIA in 24 patients and IIIB in 15 patients. Fifty patients were treated with radiotherapy and 4 patients had a surgical intervention for the primary tumor; 2 patients only received systemical treatment for the intrathoracic disease. Fifty patients received chemotherapy (89%), of which 5 (10%) concurrent with the radiotherapy of the intrathoracic disease and 45 (90%) sequential. The metastases were treated with ablative/stereotactic radiotherapy (45), surgical intervention (2), only systemical treatment (5), combination of surgical intervention and radiotherapy (3) and RFA (1). The mean follow-up was 21 months (range 4-69). Forty-one (73%) patients developed recurrent disease of whom 29 (52%) died. Only 8 (20%) recurrences occurred within the irradiated area. Most recurrences where brain (13) and pulmonary metastases (11). For the whole group, the median DFS was 14 months (range 2-69, 95% CI 11-17) and the median OS was 32 months (range 4-69, 95% CI 16-48). The 1- and 2-year OS was 86% and 58%, respectively. The 1- and 2-year DFS was 66% and 30%, respectively.
Conclusion:
Radical local treatment of a highly selected group of NSCLC patients in good condition presenting with synchronous oligometastatic stage IV disease (maximum 2 metastases) resulted in excellent local control, and also in favorable long-term DFS and OS.
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MINI 18 - Radiation Topics in Localized NSCLC (ID 139)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Treatment of Localized Disease - NSCLC
- Presentations: 2
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MINI18.02 - Stereotactic Body Radiotherapy Is Safe and Effective in Octo- and Nonagenarians for the Treatment of Early Stage Lung Cancer (ID 3072)
16:50 - 16:55 | Author(s): J. Belderbos
- Abstract
Background:
To determine the safety and efficacy of lung SBRT in older patients and to compare their outcomes to those of younger patients.
Methods:
Patients with primary lung cancer treated with SBRT were identified from a multi-institutional (5) database of 1192 cases. Details of patient factors, treatment specifics, toxicity and clinical outcomes were extracted from the database. All events were calculated from the end of radiotherapy. Estimates of local (LR), regional (RR), and distant metastases (DM) were calculated using the competing risk method. Cause specific (CSS) and overall survival (OS) were calculated using the Kaplain-Meier method. Outcomes were compared for those <70, 70-79, >=80. Toxicity was graded per CTCAE V3.0. The 90 day mortality was reported for those <70, 70-79, >=80. Univariable analysis was performed to determine associations with CSS in patients aged >70.
Results:
The median follow-up was 1.7years (1-10y) and median age 75 (41-94). There were 364 patients age <70 (28%), 546 age 70-79 (42%) and 387 age ³80 (48%). 621(48%) were female, 1125(87%) were peripheral and 852(66%) were biopsied. There was no difference in baseline SUV (p=0.6), histology (p=0.4), radiation dose (p=0.1), gender (p=0.3) or biopsy rate (p=0.2) among the three age groups. Patients aged >=80 had significantly more T2 tumors 21% vs 23% vs 32 % (p<0.01). There was no difference in 5 year LR (10% vs 11.5% vs 10%, p=0.7), RR (22% vs 10% vs 9%, p=0.1), DM (17% vs 16% vs 21%, p=0.07) or CSS (80% vs 80% vs 75%, p=0.6). Those age ³80 had significantly lower 5 year OS (75% vs 44% vs 23%, p<0.01). The grade 3+ pneumonitis rate was 1.3% vs 1.6% vs 1.5% (p=0.9) in patients ages <70,70-79, >=80 respectively. The 90 day mortality rates for patients aged <70,70-79, >=80 were 1.4%, 2.7%, and 2.6% respectively. In patients aged >70 CSS was associated with tumor size (p<0.01; HR1.4) and baseline SUV max (p=0.03; HR1.04).
Conclusion:
SBRT is a safe treatment modality in elderly patients (aged >80). Despite larger tumor volumes, the tumor control outcome were identical to the younger patients treated with SBRT. All patients, regardless of age, should be considered for treatment of early stage lung cancer (T1-T2) with SBRT.
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MINI18.06 - Validation of High Risk Features on CT for Detection of Local Recurrence After SBRT for Stage I NSCLC (ID 2138)
17:15 - 17:20 | Author(s): J. Belderbos
- Abstract
- Presentation
Background:
Fibrotic changes after SBRT for stage I NSCLC are difficult to distinguish from local recurrences (LR), hampering proper selection for salvage therapy. Huang et al. (1) defined CT high risk features (HRF) for detection of LR. This study attempts to validate these HRFs in an independent patient cohort.
Methods:
From a multicenter combined database of patients treated with SBRT for stage I NSCLC between 2006 and 2012, 53 LR were detected of which 14 were biopsy proven. The biopsy proven LR (N=14) were matched 1:2 to patients without LR (n=28) based on: 1) dose 2) PTV 3) follow up time 4) central/peripheral location 5) lung lobe. Of the resulting 42 patients 18 were male and 24 female with a median age of 73 years (range 56-89years). Median tumor size, PTV and dose were 2.3 cm (range 1.0-4.9cm), 49cc (range 9-166cc), 48 Gy (range 48-60Gy) in 4 fractions (range 3-8) respectively. Most tumors were peripheral (76%) and located in the upper lobes (55%). Median follow up (FU) was 36 months (range 14-78months) and median time to LR was 18 months (range 12-45months). For all patients, planning CT scans and at least two follow up scans were available. Two blinded observers scored eight HRFs for each scan. Sensitivity and specificity in predicting LR were assessed and compared using Fisher’s exact test. Analysis for best fit was done using AUC.
Results:
Results of sensitivity and specificity are shown in Table 1. The best performing HRF was cranio-caudal growth: sensitivity 86%, specificity 82%. The odds of LR increased on average by 2.6 (95%CI1.5-4.3) for each additional HRF detected, while the AUC was 0.86. The presence of ≥ 3 HRFs resulted in the best cut-off with sensitivity 79% and specificity 86%. Loss of linear margin and bulging margin were scored identical and therefore only the latter was included in the model. The two best combinations of HRFs were: 1) bulging margin & cranio-caudal growth, with a sensitivity of 93% and specificity of 82% or 2) bulging margin & enlarging opacity after 12 months, with a sensitivity of 86% and specificity of 89%. Table 1CT high risk factor for local recurrence Sensitivity (%) Specificity (%) p-value Any HRF 93 64 .001 enlarging opacity (≥5mm and ≥20%) 86 68 .003 sequential enlarging opacity 57 89 .002 enlarging opacity after 12 months 71 89 <.001 bulging margin 64 100 <.001 loss of linear margin 64 100 <.001 loss of air bronchograms 7 100 0.33 cranio-caudal growth (≥5mm and ≥20%) 86 82 <.001 new pleural effusion 14 93 0.59
Conclusion:
In this matched group of biopsy proven LR and controls, cranio-caudal growth was the best individual predictor of LR after SBRT. Combining HRF bulging margin with either cranio-caudal growth or enlarging opacity after 12 months resulted in higher sensitivities and specificities than number of HRFs. 1)Huang et al. Radiotherapy&Oncology 2013
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MINI 33 - Radiotherapy and Complications (ID 164)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Treatment of Locoregional Disease – NSCLC
- Presentations: 1
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MINI33.03 - Heart Dose Is Associated with Shorter Overall Survival for Patients Treated with Chemo-Radiation for Locally Advanced NSCLC (ID 2755)
18:45 - 18:50 | Author(s): J. Belderbos
- Abstract
Background:
Traditionally, sparing the heart in chemo-radiotherapy of locally advanced lung cancer has a low priority compared to the lungs and esophagus. Recently, however, the randomized phase III trial RTOG 0617 showed that the volume of the heart receiving a dose of at least 5Gy (V5) was associated with a lower overall survival (OS). The aim of the current study is to validate this in an independent database.
Methods:
Patients treated with IMRT (24x2.75Gy with daily low-dose cisplatin) at our hospital between 2006 and 2014 were retrospectively selected. For the heart both mean dose and Vx denoting the volume receiving x Gy or more (x in range 5-50Gy with 5Gy increments) were calculated. Associations of these parameters with OS were evaluated using univariate and multivariate proportional hazards analysis. In multivariate analysis we separately paired the total GTV (primary tumor plus involved lymph nodes) to Vx and mean dose.
Results:
375 pts were available for analysis. Median follow up was 16 months and median OS was 26 months. Using univariate proportional hazard modeling mean dose and all Vx for x<40Gy were significantly associated (p<0.05) with OS. For V5, which was most significant in the analyzed set, the hazard ratio (HR) was 1.008. When pts are split at the median V5 = 37.0%, the median OS was 29 ± 2.5 months versus 19 ± 2.4 months for pts below and above the median respectively (p=0.03, Log Rank). Similarly, the figure illustrates significant separation in Kaplan-Meier plots of OS with the pts divided in V5 quartiles. In the multivariate analysis the correlation between GTV (median volume 109 cc) and mean dose or Vx was less than 0.15, indicating that a higher heart dose is not the effect of larger tumor volumes and hence a worse survival due to more advanced decease. Both GTV (p<0.001, HR=1.001) and V5 (p=.003, HR=1.007) were significant in multivariate analysis as was the case with GTV (p<0.001, HR=1.001) and mean dose (p=0.033, HR=1.018).
Conclusion:
For pts treated with chemoradiation the dose received by the heart is strongly associated with overall survival. Our results are in accordance with the results of RTOG 0617 [1] for the V5 with similar HR despite the different fractionation scheme and chemo regimen. This indicates that cardial toxicity might be more important in lung cancer patients treated with chemoradiation than previously anticipated. Consequently, better sparing of the heart potentially improves outcome. [1] Bradley et.al. J Clin Oncol 31, 15 pp. 7501
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MINI 37 - SCLC Therapy (ID 165)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Small Cell Lung Cancer
- Presentations: 1
- Moderators:D. Ettinger, G.R. Simon
- Coordinates: 9/09/2015, 18:30 - 20:00, 605+607
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MINI37.11 - Inter-Observer Variability in Hippocampus Delineation on MRI Scans for Hippocampal Avoidance Prophylactic Cranial Irradiation Trial (ID 2620)
19:30 - 19:35 | Author(s): J. Belderbos
- Abstract
- Presentation
Background:
Prophylactic cranial irradiation (PCI) is the standard treatment in patients with small-cell lung cancer (SCLC) without progression after chemo-radiotherapy in stage I-III disease and after having a remission after chemotherapy in stage IV. In an international phase III trial (NCT01780675), patients with SCLC are randomised to receive PCI with or without Hippocampal Avoidance (HA). Accurate delineation of the hippocampus is crucial for this trial. In this study we evaluate the hippocampus delineation variability among radiation oncologists in multi-institutions for SCLC patients.
Methods:
The left and right hippocampus from 5 randomly selected patients (10 structures) were delineated by 5 radiation oncologists and 2 neuroradiologist in 7 institutions according to the RTOG atlas (http://www.rtog.org/CoreLab/ContouringAtlases/HippocampalSparing.aspx), together with a questionnaire. For each patient, a high resolution 3D inversion recovery T1 weighted MRI-scan was first registered to the planning CT-scan (1mm slicing). The observer then delineated the hippocampus according to the atlas on axial slices of the MRI. The mapped delineations on the CT were then used in dose planning with a 5mm margin. The mean and standard deviation (SD) of 1) volume and 2) range in medio-lateral, superior-inferior and anterior-posterior directions were computed for each structure. The corresponding inter-observer reliability was estimated by the intra-class correlation coefficient (ICC absolute agreement) using a linear mixed model. A median surface was computed and the overall delineation variability per structure was calculated by the root-mean-square (rms) of the local SD per sampled points on the median surface, while the local SD corresponds to the perpendicular distance between each observer and a sampled point.
Results:
The standard deviation of the delineated volume per structure varied from 0.14 to 0.48cm3. The corresponding inter-observer reliability (ICC) was 0.19, implying a high variability among the observers. The overall delineation variability per structure varied from 0.6 to 1.0mm. Areas with good agreements were the superior and inferior part of the hippocampus. The difficult area (Fig.1) was in the anterior medial area, close to the amygdala and uncus. The ICC in medio-lateral, superior-inferior and anterior-posterior directions were 0.55, 0.64 and 0.80, respectively. A large spread of the SD of range in medio-lateral direction and the relative low ICC imply that a better instruction, or training is desirable to improve the delineations. Figure 1
Conclusion:
There was a substantial variability in hippocampus delineation among the observers. Stricter adherence to the RTOG guidelines and (web-based) training are needed. The implication of the variations on the dose distribution is currently verified.
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ORAL 19 - Radiation for Localized Lung Cancer (ID 126)
- Event: WCLC 2015
- Type: Oral Session
- Track: Treatment of Localized Disease - NSCLC
- Presentations: 2
- Moderators:D. De Ruysscher, M. Hiraoka
- Coordinates: 9/08/2015, 10:45 - 12:15, 102+104+106
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ORAL19.02 - Higher Risk of Failure and Death after Stereotactic Lung Radiotherapy for T2 Lung Cancer (ID 2945)
10:56 - 11:07 | Author(s): J. Belderbos
- Abstract
- Presentation
Background:
Limited data are available on the use of SBRT for tumors larger than 3cm. We analyzed results from a collaborative database to compare clinical outcomes for patients with tumors > 3cm to those with smaller tumors (<3cm).
Methods:
1192 patients with 1288 T1-T3N0M0 tumors underwent cone-beam CT image-guided lung SBRT between 10/2004-12/2014. The median prescription dose was 50 Gy in 3 fractions (range 24-64 Gy in 1-10) to the PTV. Patient, tumor and treatment factors and clinical outcomes were extracted from the database. Local recurrence (LR), regional recurrence (RR), distant metastasis (DM), overall (OS) and cause-specific survival (CSS) were calculated from SBRT completion using the Kaplan-Meier method. Univariate analyses were performed using the Cox proportional hazards model. Student’s unpaired t-test and Pearson chi-square/Fisher’s Exact test were used to compare continuous and categorical variables between groups, respectively.
Results:
Mean follow-up time was 2.1y (0.02-10.12y) and similar for both groups. 295 tumors were > 3cm (T2) and 993 < 3cm (T1) (mean size 3.98 v 1.91cm (0.5-9.6cm), p<0.001). There were no statistically significant differences between groups for gender, pulmonary function (median FEV1 1.7 L (56-60% predicted); DLCO 10 ml/min/mmHg (50-51% predicted), medical inoperability (89%), PET (94%) or any invasive mediastinal staging (6%). T1 patients were slightly younger (73.5y T1 v 76.0y T2, p<0.01) and had mildly better ECOG (80% 0-1 T1 v 71% 0-1 T2, p=0.001). T2 tumors were more often biopsied (74% T2 v 63% T1, p<0.001), less often non-squamous (74% v 83%, p=0.002), had higher SUVmax (10.3 T2 v 6.4 T1, p<0.001), more often central (0236) (19% T2 v 11% T1, p=0.001) and treated to a median prescription dose of 53.8Gy T2 v 52.2Gy T1, p<0.001. 3% received chemotherapy (T1 2.6% v T2 4.4%, p=0.11). Although LR was similar between groups, large tumors had a higher risk of RR, DM and death (Table 1). On univariate analysis, LR was predicted by multiple BED parameters (p<0.001), baseline SUVmax (p=0.003) and squamous histology (p=0.012); RR was higher for lower lobe tumors (p=0.008); DM (p=0.006) was higher while OS and CSS lower for central tumors (p=0.03, 0.01).Clinical Outcome Tumor < 3 cm Tumor > 3 cm p-value Local recurrence 3y 7% 11% 0.13 5y 11% 13% Regional Recurrence 3y 9% 13% 0.006 5y 11% 24% Distant Metastasis 3y 11% 16% <0.001 5y 16% 18% Cause-Specific Survival 3y 88% 73% <0.001 5y 81% 66% Overall Survival 3y 61% 45% <0.001 5y 42% 28%
Conclusion:
Large tumors had a higher risk of RR, DM and death after SBRT. These data have implications for consideration and study of pre-SBRT invasive nodal staging and/or systemic therapy in this population. OS and CSS were lower for central tumors warranting further analysis.
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ORAL19.06 - Tumor Location Is Associated with Recurrence Pattern and Survival after SBRT in Early Stage NSCLC Patients (ID 2623)
11:39 - 11:50 | Author(s): J. Belderbos
- Abstract
Background:
For NSCLC patients treated with SBRT, we investigated if tumor location is associated with recurrence pattern and overall survival.
Methods:
From 2006-2013 1129 patients with early stage NSCLC were treated with cone beam CT guided SBRT (median 54 Gy in 3 fractions, range 23-64 Gy in 1-10 fractions) in 5 different institutes. 719 patients were analyzed after exclusion of patients with (meta)synchronous tumors (n=185), incomplete scanning data or incomplete follow-up (n=225). An average anatomy was constructed based on 109 patients of the 5 institutes using deformable image registration[1]. Subsequently, all patients were registered to this average anatomy and the corresponding dose distribution was deformed accordingly. Tumor location was defined as a 3D Gaussian distribution (standard deviation 2 cm) at the center of the high dose region. These Gaussian distributions were added to a total and per voxel a mean and standard deviation was determined. Totals were obtained for 5 different groups: local recurrence, regional recurrence, distant metastasis, all recurrent disease combined, deceased as well as their complements. By comparing 2 complimentary groups using Welch’s t-test, locations that were significantly associated (p<0.01) with recurrent disease or with overall survival were identified. Recurrent disease rates and overall survival were calculated using the Kaplan-Meier method.
Results:
With a median follow-up of 19 months, local recurrence occurred in 5% of patients, regional recurrence in 5% and distant metastasis in 9%. 74% of patients were alive and 18% was lost to follow-up. Tumors located medially in the left upper lobe were significantly associated with controlled disease (local, regional, distant and all combined). Figure 1A displays as heatmap: disease control (green), recurrent disease (purple), and the region where the two groups differ significantly (yellow). Tumors located peripherally in the left lower lobe were significantly associated with regional recurrences. Tumors located medially/centrally in the right upper lobe were significantly associated with distant metastases and all recurrent disease combined (local, regional and distant together). Tumors located medially/centrally in the right upper lobe were significantly associated with a decreased overall survival (Figure 1B). Figure 1
Conclusion:
In this group of 719 NSCLC patients treated with SBRT, an average anatomy was utilized to analyze associations of tumor location with treatment outcome. Several regions were identified that were significantly associated with disease recurrence and overall survival. Further investigations in the underlying mechanisms of these associations are warrented. 1.ADMIRE Research 2015, Elekta AB, Stockholm, Sweden
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ORAL 20 - Chemoradiotherapy (ID 124)
- Event: WCLC 2015
- Type: Oral Session
- Track: Treatment of Locoregional Disease – NSCLC
- Presentations: 1
- Moderators:G. Blumenschein, J.Y. Chang
- Coordinates: 9/08/2015, 10:45 - 12:15, 201+203
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ORAL20.03 - Radiation Dose Escalation in Patients with Locally Advanced Non-Small Cell Lung Cancer; 60 Month Follow-Up of a Randomized Phase II Trial (ID 1190)
11:07 - 11:18 | Author(s): J. Belderbos
- Abstract
- Presentation
Background:
Concurrent chemoradiotherapy imposes beneficial effects on overall survival (OS) in patients with locally advanced non-small cell lung cancer (NSCLC). Nonetheless, the optimal radiation scheme still needs to be identified. The RTOG 0617 trial showed that patients receiving a high dose radiation scheme (37 x 2 Gy) had a significant shorter median OS (22.9 months) as compared to patients receiving a conventional 30 x 2 Gy radiation scheme (28.7 months). Dose escalation using hypo-fractionation however seems promising and might contribute to a better OS. We investigated long term OS in locally advanced NSCLC patients treated with concurrent chemoradiotherapy, using a hypo-fractionation scheme of 24 x 2.75 Gy +/- Cetuximab.
Methods:
A 2-armed phase II, multi-center study (NTR2230) was performed with the initial aim to assess the effect of the addition of Cetuximab to concurrent chemoradiotherapy in locally advanced NSCLC patients. Arm A received high dose radiotherapy (24 x 2.75 Gy) and concurrent daily low-dose cisplatin (6 mg/m[2]). Arm B received an identical treatment regimen with the addition of weekly Cetuximab (400 mg/m[2] loading dose one week prior to radiotherapy followed by weekly 250 mg/m[2]). Mortality follow-up information was completed until January 2015. Overall survival (OS) rates were calculated as time from randomization until death from any cause. Kaplan-Meier survival curves were plotted and 1-, 2- and 5-year OS proportions were calculated.
Results:
Between February 2009 and May 2011, 102 patients were randomly allocated in two arms; 51 patients (50%) in arm A and 51 patients (50%) in arm B. Follow-up information was available for 101 patients (99%). Median OS was 33.0 months (interquartile (IQ) range 20.0 to 46.0) and did not significantly differ between the two arms; 33.0 months (IQ-range 13.8 to 52.2) in Arm A and 30.0 months (IQ-range 15.3 to 44.7) in Arm B (Figure 1). 1-,2- and 5-year OS was 75.5%, 59.8% and 36.6%, respectively. Figure 1
Conclusion:
In this 2-armed phase II trial in NSCLC patients receiving concurrent chemoradiotherapy, the addition of Cetuximab to concurrent chemoradiotherapy did not improve 60-month OS in unselected patients with locally advanced NSCLC, in line with the RTOG 0617. However, the median OS was remarkably high when compared to the RTOG 0617: 30 and 33 months versus 23 and 29 months, respectively. Furthermore, 5-year OS was still 36.6%. Dose escalation using hypo-fractionation of 2.75 Gy per fraction might be one of the factors contributing to extended OS in patients with locally advanced NSCLC.
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P1.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 206)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.01-029 - Dutch Radiotherapy Lung Audit: Results of 2014 (ID 1340)
09:30 - 09:30 | Author(s): J. Belderbos
- Abstract
Background:
The Dutch Radiotherapy Lung Audit (DLRA) is an outcome registration that provides the local health professionals with an instrument to compare and improve their lung cancer treatments. It ensures transparency regarding clinical outcome, quality and safety of lung cancer treatments in the radiotherapy departments throughout the Netherlands. Patients receiving thoracic radiation treatment with curative intent for (primary or recurrent) stage I-IIIB Non-Small Cell Lung Cancer (NSCLC) were included in the registry. The results of the DLRA on the first fully registered year, 2014, are reported.
Methods:
Information collected included patient, tumor and treatment characteristics, the incidence and severity of acute toxicity, mortality within three months after radical radiation treatment and the time interval between diagnostic work-up and start of the radiotherapy. The adherence to the waiting time (time between referral and start of the irradiation) and throughput time (time between planning CT scan and start of the irradiation) guidelines were registered and analyzed, as well as the use of modern treatment techniques such as stereotactic irradiation and image-guided radiotherapy.
Results:
14 out of 21 radiotherapy institutes included patients in the DLRA database. A total of 1350 patients were entered from January-December 2014. Patients were treated with concurrent (32%) or sequential chemoradiation(20%), radiotherapy only (13%) or stereotactic ablative body radiotherapy (SABR [35%]). On a patient record level, there was a high level of completeness. The mean age was 69 years (range 32-91, 59% males). Charlson comorbidity index ≥ 2 was present in 42% of patients. Most patients (45%) were cN+ with 20% cT4 tumors. Fifty eight percent of all patients started irradiation within 21 days after referral (range 0-89%). For 68% of the patients SABR started within 10 days after the planning-CT scan was acquired (range 17-100%) (fig 1). There was no correlation between the number of patients treated and the throughput times. Most patients received IMRT or VMAT irradiation. All registered patients had position verification during irradiation, mostly 3D (94%). Three-month (calculated from the end of RT) acute esophagus toxicity (grade≥ III) and pneumonitis (grade≥ II) of concurrent treatment were 12.4% and 3.9%, 6.1% and 4.1% for sequential chemoradiation, 3.3% and 4.3% for radiotherapy only, and 0.4% and 2.3% for SABR, respectively. Three-month mortality rates were 8.2%, 8.5%, 9.6%, and 1.7%, respectively. Figure 1
Conclusion:
The Dutch Radiotherapy Lung Audit on outcomes after (chemo)radiotherapy is directed towards an improvement of care for lung cancer patients. There's room for improvement in the waiting and throughput times.
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P1.03 - Poster Session/ Treatment of Locoregional Disease – NSCLC (ID 212)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Locoregional Disease – NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.03-011 - Standard Pre-Hydration May Compromise Treatment Outcome of CRT with Low-Dose Cisplatin (ID 392)
09:30 - 09:30 | Author(s): J. Belderbos
- Abstract
Background:
Cisplatin-based chemoradiation is the standard treatment for many types of cancer, including NSCLC. A main drawback of cisplatin is the high nephrotoxicity rate, that can be reduced by a stringent hydration regimen before, during, and/or after cisplatin administration. Standard pre-hydration with all cisplatin administrations is mandatory for high-dose cisplatin, and can be considered for low-dose cisplatin. However, it has recently been shown that pre-hydration not only reduces nephrotoxicity, but also reduces esophageal toxicity in lung cancer patients treated with concurrent daily low-dose cisplatin. This suggested that pre-hydration might systemically lower cisplatin dose in tissues, including in the tumor, and may therefore adversely affect treatment outcome. Aim: The aim of this study was to determine (1) if pre-hydration lowers cisplatin concentrations in tumor tissue in a mouse model, and (2) if the introduction of standard pre-hydration for low-dose cisplatin has adversely affected treatment outcome in lung cancer patients.
Methods:
Tumor-bearing Balb/c nude mice with cisplatin sensitive tumors were either pre-hydrated with saline, dehydrated, or had no intervention (control) before a single administration of cisplatin 6mg/kg or 3mg/kg. Renal function was assessed with MAG3 scintigraphy at 1, 24, 72, or 168h after treatment, and mice were subsequently sacrificed to determine tumor platinum concentrations. For the patient study, all stage III NSCLC patients who received daily concurrent low-dose cisplatin and radiotherapy in the NKI-AVL between 01-2007 and 06-2014 were evaluated for PFS. Patients treated in 2007-2010 (n=224) started pre-hydration with 1L saline only after renal function loss was detected, while patients treated in 2011-2014 (n=216) received standard pre-hydration from treatment day 1.
Results:
Pre-hydration protected mice from nephrotoxicity caused by cisplatin and dehydration worsened nephrotoxicity, confirming the validity of the mouse model. Pre-hydration significantly reduced tumor platinum concentrations (down to 50% of control mice at 1h after treatment, and comparable to mice treated with only half the dose of cisplatin), and dehydration increased tumor platinum concentrations. In patients the pre-hydration cohort demonstrated a shorter PFS (median 14 vs. 11 months, log-rank p=0.06), against the trend of gradually improving treatment outcome over the past decades.
Conclusion:
Pre-hydration reduces tumor platinum levels in mice, comparable to giving only half a dose of cisplatin. Patients treated with standard pre-hydration show a tendency to a lower PFS compared to patients with pre-hydration on indication. Further research is needed to elucidate this phenomenon. Meanwhile the application of standard pre-hydration in low-dose cisplatin regimens may be reconsidered.
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P2.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 207)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.01-051 - Determinants of Sequential versus Concurrent Chemoradiotherapy in Stage III Non-Small Cell Lung Cancer Patients (ID 1205)
09:30 - 09:30 | Author(s): J. Belderbos
- Abstract
Background:
Concurrent chemoradiotherapy (CCRT) is considered the standard treatment regimen in patients with inoperable stage III non-small cell lung cancer (NSCLC). Sequential chemoradiotherapy (SCRT) is recommended in patients who are deemed unfit to receive CCRT. As this selection criterion is not very explicit, the ‘personalized’ choice for either CCRT or SCRT is mainly dependent on the multidisciplinary team and treating physician’s judgment. Consequently, this may result in a variation of treatment policies across hospitals/radiotherapy (RT) departments. In this study, we investigated the ratio CCRT/SCRT in eight RT departments in the Netherlands. Furthermore, we explored which patient and disease characteristics determined the choice for SCRT compared to CCRT.
Methods:
Data were derived from the Dutch Lung Radiotherapy Audit (DLRA). Within the DLRA, lung cancer patients undergoing a curative intent treatment are prospectively registered with respect to patient and disease characteristics, diagnostics and treatment. For this study, from eight out of 21 Dutch RT departments, patients with stage III NSCLC undergoing chemoradiotherapy in 2014 were selected. CCRT was defined as ≤ 50 days between the start of chemotherapy and the start of radiotherapy. Furthermore, RT had to start before the end of the last chemotherapy in CCRT. Patients with < 150 days between treatments were scored as undergoing SCRT. Differences in patient and disease characteristics between CCRT and SCRT were tested with independent samples t-tests (for continuous variables) and with chi-square tests (for categorical variables). A multivariate logistic regression model was constructed to determine patient and disease characteristics associated with the choice for SCRT, using a backward selection procedure. Odds ratios (OR) with 95% confidence intervals (CI) are reported.
Results:
In total, 453 stage III NSCLC patients (mean age 65.4 years, 56.5% male) were registered. Of those, 351 (77.5%) patients underwent CCRT and 102 (22.5%) patients received SCRT. The proportion of patients treated with CCRT ranged from 51% to 89% across RT departments. Gender, smoking, gross target volume (GTV), performance score (PS), lung function, Charlson comorbidity index and tumor location were not significantly associated with SCRT in the multivariate model. Conversely, older age (OR 1.05 [95%CI 1.03-1.09]), histology (large cell carcinoma vs adenocarcinoma [OR 0.42 CI 0.19 to 0.97]) and cN-stage (N3 vs N0-1 [OR 5.71 {95%CI 2.10-15.50}]) were significantly associated with SCRT.
Conclusion:
In this selected group of registered NSCLC patients, a large variation was observed in the proportion of stage III NSCLC patients treated with CCRT, ranging from 51% to 89% across RT departments. Surprisingly, PS and comorbidity index (as indicators of a patients’ physical fitness) were not significantly different in CCRT or SCRT patients while age and cN-stage were. Based on the analyzed patient and disease characteristics, it is currently unclear why patients treated with SCRT were not eligible for CCRT.
