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J. Belderbos
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MA 13 - New Insights of Diagnosis and Update of Treatment (ID 674)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Early Stage NSCLC
- Presentations: 1
- Moderators:S. Ishikura, H. Nakayama
- Coordinates: 10/17/2017, 15:45 - 17:30, Room 311 + 312
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MA 13.09 - Toxicity and Second Primary Lung Cancers in Late Survivors Following Lung SBRT (ID 8410)
15:45 - 17:30 | Author(s): J. Belderbos
- Abstract
- Presentation
Background:
There is a paucity of data on the long-term outcomes following lung SBRT. This impacts our understanding of late toxicity, relapse patterns and rates of second lung cancers. We report our multi-institutional outcomes of those who survived ≥5 years from lung SBRT treatment.
Method:
1192 patients were treated for primary non-small cell lung cancer, T1/2N0 from 5 international institutions. For those who survived ≥5 years from lung SBRT treatment details of patient factors, treatment and outcome factors were extracted from the multi-institutional database. All events were calculated from the end of radiotherapy. Local (LR), regional (RR), and distant metastases (DM) and toxicity events after 5 years are reported. New cases of metachronous lung cancers after 5 years are reported. Univariable analyses was performed to determine factors associated with survival ≥5 years.
Result:
Of 1192 patients there were 182 (14%) ≥5 year survivors. Only 52 (8%) survived ≥ 7 years and 2 (0.2%) ≥10 years. Those surviving ≥5 years were younger (74.3 vs 71.5 years; p<0.01) and had better FEV1 (55% vs 65%; p<0.01) than those that did not survive 5 years. The Charleston Comorbidity Score was 1.4 (0-12) vs 2.1 (0-7) (p<0.001) in those who survived < vs ≥5 years. Those who survived <5 years had a trend to larger tumors (2.4cm vs 2.3 cm; p=0.07). Of the 182 patients 23 (13%) were operable, 67 (37%) were <70 years old at treatment, 115 (63%) were ECOG 0-1 and 156 (86%) had peripheral tumor location at time of initial diagnosis. 84 (46.2%) were T1a, 60 (33%) T1b, 33 (18.1%) T2a and 5 (2.7%) T2b. After 5 years there were 13 new events of grade ≥ 2 toxicity. These toxicities were 4 grade 2 fatigue, 1 grade 2 rib fracture, 7 grade 2 chronic myositis and 1 patient with grade 2 chronic myositis and fatigue. In this 182 patient cohort, after 5 years, there were 3 local recurrences, 2 regional failures and 5 distant failures. After 5 years follow-up there were 22 (12%) new primary lung tumors in the 182 patients (and 20 had a subsequent lung SBRT treatment).
Conclusion:
Late survivors after SBRT require dedicated follow-up as they remain at risk for second lung cancer, tumor recurrence and toxicity. Second cancers in these late survivors can be considered for SBRT treatments.
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MA 17 - Locally Advanced NSCLC (ID 671)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Locally Advanced NSCLC
- Presentations: 1
- Moderators:S. Jheon, Georgios Stamatis
- Coordinates: 10/17/2017, 15:45 - 17:30, F203 + F204 (Annex Hall)
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MA 17.10 - Toxicity Results from the Randomized Phase III NVALT-11 Study of Prophylactic Cranial Irradiation vs. Observation in Stage III NSCLC (ID 9262)
15:45 - 17:30 | Author(s): J. Belderbos
- Abstract
- Presentation
Background:
NVALT-11 randomized trial showed that PCI reduced the proportion of stage III NSCLC patients with symptomatic BM from 28 % to 5 % (Groen ASCO 2017). Here, we report on the toxicity.
Method:
We randomized between PCI or observation in radically treated stage III NSCLC. Primary endpoint: incidence of symptomatic brain metastases; secondary endpoints: OS, toxicity and quality of life.
Result:
Between 2009 and 2015 a total of 195 pts were registered, 175 were randomized, 87 received PCI and 88 pts were in the observation arm. Median follow up: 48.5 months (95% CI, 39-54). Neurological adverse events (AE) of all grades that occurred more frequently in the PCI vs. the observation arm: cognitive disturbance (18 vs. 2 pt; p< 10[-4]) and memory impairment (25 vs. 7 pt; p<10[-3]). No significant difference in G3-4 cognitive disturbance and memory impairment. Non-neurological AE of all grades that were more frequent in the PCI arm: alopecia (36 vs. 5 pt; p<10[-6]), fatigue (55 vs. 29 patients; p<10[-4]), nausea (30 vs. 15 patients; p=0.01), anorexia (6 vs. 0 patients; p=0.01) and dysphagia (11 vs. 2 pt; p=0.01). Of the G3-4 AE, only fatigue was significantly more present in the PCI arm (13 vs. 2 pt, p < 0.01). Scored as treatment-related, neurological toxicities of all grades that occurred more frequently in the PCI vs. the observation arm: cognitive disturbance (7 vs. 0 pt; p=0.01), dizziness (7 vs. 0 pt; p=0.01) and memory impairment (14 vs. 0 pt; p<10[-4]). No significant differences in G3-4 toxicities, with only one patient reporting severe cognitive disturbance in the PCI group. Scored as treatment-related, non-neurological toxicities of all grades that were more frequent in the PCI arm: alopecia (26 vs. 1 pt; p<10[-6]), fatigue (19 vs. 2 patients; p<10[-4]), nausea (16 vs. 0 patients; p<10[-5]), headache (19 vs. 1 pt; p<10[-5]), rash (8 vs. 0 pt; p<0.01) and vomiting (9 vs. 0 pt; p<0.01). No significant differences in G3-4 toxicities, with 3 patients reporting severe fatigue, 2 nausea and 1 vomiting, all in the PCI group. Overall Qol was worse in the PCI arm 3 months post-treatment, but was similar to observation thereafter.
Conclusion:
PCI related symptoms were mainly grade 1-2 memory and cognitive disturbances and fatigue. G3-4 toxicities were very rare. QoL was only temporarily affected by PCI. The side effects of PCI should be balanced against deteriorating BM symptoms and the lack of OS benefit (Groen ASCO 2017).
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P2.14 - Radiotherapy (ID 715)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Radiotherapy
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.14-020 - Clinical Validation of NTCP-Models for Esophagus Toxicity in Non-Small Cell Lung Cancer Patients Treated with Concurrent Chemoradiation (ID 9272)
09:30 - 16:00 | Author(s): J. Belderbos
- Abstract
Background:
Concurrent chemoradiation (CCRT) is the preferred treatment approach in inoperable non-small cell lung cancer (NSCLC) patients. However, CCRT increases the risk of acute esophagus toxicity (AET) compared to radiotherapy alone or sequential chemoradiation. To minimize the risk of AET, an international RT-dose constraint of either V50Gy or V60Gy <50% is used. However, clinical applicability of those models is not evident since assessment of the model accuracy and validity should be performed before generalizing to other populations. Therefore, the aim of this study was to clinically validate the two NTCP-models to predict acute esophagus toxicity in NSCLC patients treated with CCRT.
Method:
To validate the NTCP-models, clinical data of 274 inoperable NSCLC patients receiving CCRT using IMRT was used. The planned V50Gy and V60Gy and the prospectively scored grade ≥2 AET (CTC-AE) were retrieved and independently reviewed. The grade ≥2 AET probability for the V50Gy and V60Gy was calculated as; [1/1+[exp][[-0.515 + (0.027*V][50]] and [1/1+[exp][[-0.701 + (0.029*V6][0]]]. Validity of the model was assessed with the ability to predict the number of grade ≥2 AET events (calibration) and the ability to distinguish between those who develop grade ≥2 AET from those who do not (discrimination, area under the curve (AUC)). Furthermore, sensitivity and specificity for different cut-off points were determined.
Result:
From the 274 NSCLC patients, 125 (45.6%) patients developed grade ≥2 AET (93.8% grade 2, 6.2% grade 3), median V50Gy 23% (interquartile range 10.1-35.6%), median V60Gy 4.3% (interquartile range 0-20.5%). Calibration showed that the V50 overestimated the risk of developing grade ≥2 AET in low-risk patients while the V60 underestimated the risk of developing grade ≥2 AET in high-risk patients. Discrimination of both algorithms demonstrated a similar moderate fit (AUC 0.70 95%CI 0.64 to 0.76 and AUC 0.69 95%CI 0.63 to 0.76 for the V50Gy and V60Gy, respectively). For V50Gy, a cut-off point of more than 40% probability of developing grade ≥2 AET resulted in the most favorable sensitivity of 95.8% for grade ≥2 and 100% for grade 3, with specificity scores of 54.6% and 40.7% respectively. For V60Gy, a cut-off point of more than 60% resulted in the most favorable sensitivity of 95.1% for grade ≥2 and 100% for grade 3, with remarkably low specificity scores of 9.1% and 18.8%, respectively.
Conclusion:
The NTCP-models to predict acute esophagus toxicity in NSCLC patients both showed good predictive accuracy. For clinical practice, the V50Gy seems to be the most sensitive without compromising safety and efficacy.
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P3.01 - Advanced NSCLC (ID 621)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.01-088g - Variation in Treatment Recommendations for NSCLC Patients by Multidisciplinary Tumor Board Meetings Across the Netherlands (ID 9522)
09:30 - 16:00 | Author(s): J. Belderbos
- Abstract
Background:
The treatment choice for lung cancer patients is dependent on the expertise of the treating physician and the tumor board meetings (TBM) in which a treatment plan is discussed multidisciplinary. However, despite availability of a national guideline, the treatment selection criteria for NSCLC patients are not very explicit. Consequently, this may result in a variation of treatment recommendations across TBM. In this study, we investigated the variation in treatment recommendations by TBM within the Netherlands for 3 patients. Furthermore, patient characteristics associated with the treatment choice were explored.
Method:
A qualitative study was performed across 9 TBM at general hospitals in the Netherlands of which three hospitals had a radiotherapy(RT) department. Three existing patient cases were selected. The full medical history including imaging examinations was provided. Patient 1: 92years, cT3-4N0-1M0 (stage III). Patient 2: 73years, cT3NxM1b oligometastatic disease with a single adrenal metastasis (stage IV). Patient 3: 66years, cT2b-3N2M0 (stage III). All patients had a good performance score (WHO 0-1). The discussions and treatment plans during TBM were audiotaped. Analysis of the tapes was performed using open and axial coding techniques.
Result:
For patient 1 the recommended treatment was radical RT (45%), palliative RT (33%), surgery + RT (11%) and restaging before any treatment recommendation (11%). For patient 2 the recommended treatment was concurrent chemoradiotherapy (CRT) (45%), concurrent CRT + adrenal resection (33%), palliative RT (11%) and sequential CRT (11%). For patient 3 the recommended treatment was concurrent CRT (89%) and sequential CRT (11%). The patient characteristic ‘age’ was quoted in 96% of the treatment discussions, followed by ‘performance score’(89%) and ‘medical history’(85%). Figure 1
Conclusion:
In this qualitative study, a large variation in recommended treatment across the Netherlands was observed. The most extreme variation was seen in the treatment recommendation for the elder patient (92years), with treatment plans ranging from palliative RT to radical surgery.
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P3.14 - Radiotherapy (ID 730)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Radiotherapy
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.14-005 - Treatment Response Measured on Conebeam-CT During Concurrent Chemoradiation for NSCLC Patients (ID 9814)
09:30 - 16:00 | Author(s): J. Belderbos
- Abstract
Background:
The management of NSCLC-patients has evolved towards a more personalized care approach. Currently, the outcomes of concurrent chemoradiation (CCRT) in NSCLC patients are evaluated after the end of treatment, while individual treatment response during treatment is not taken into account. To pursue adaptive radiotherapy, it is important to distinguish responses during treatment and correlate this with outcome. Therefore, the aim was to identify subgroups that show a distinct treatment response during CCRT and correlate this with treatment outcome.
Method:
NSCLC-patients treated with CCRT between 2007-2013 were included. Treatment consisted of 66Gy/24 fractions with concurrent daily Cisplatin. Deformable image registration of the planning-CT to all Conebeam-CTs acquired during treatment was performed, and the gross tumor volumes on the ConeBeam-CTs were measured. Latent Class Growth Modeling was used to identify subgroups showing a distinct treatment response of the primary tumor during CCRT. Cox survival analysis was performed to assess the association of subgroup ‘membership’ with overall survival (OS) and progression free survival (PFS).
Result:
402 patients were included. Median follow-up was 63 months and median OS was 23 months (95%CI 20-26 months) and median PFS was 18 months (95%CI 15–21 month). Six different patterns of treatment response were identified (Figure1). Group 1&2 showed a relatively stable pattern during treatment. Group 5 showed tumor progression in the first week followed by sharp decrease in tumor volume. All other groups showed a decrease in tumor volume from start of treatment. Remarkably, the groups 1&5, that didn’t show a decrease in tumor volume from the beginning of treatment, had a significantly improved OS and PFS. Figure 1
Conclusion:
Six groups showing a distinct treatment response during CCRT were identified. This is an important finding to be able to pursue adaptive radiotherapy. First analyses revealed an association between tumor response during treatment and OS and PFS. In-depth analyses are warranted.
