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F.J. Lagerwaard



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    MA 17 - Locally Advanced NSCLC (ID 671)

    • Event: WCLC 2017
    • Type: Mini Oral
    • Track: Locally Advanced NSCLC
    • Presentations: 1
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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): F.J. Lagerwaard

      • Abstract
      • Presentation
      • Slides

      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
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      P2.14-019 - Magnetic Resonance (MR)-Guided Adaptive Stereotactic Ablative Radiotherapy for Adrenal Metastases (ID 9196)

      09:30 - 16:00  |  Author(s): F.J. Lagerwaard

      • Abstract
      • Slides

      Background:
      Stereotactic ablative radiotherapy (SABR) can result in high local control rates for adrenal metastases when biological doses of at least 100 Gy~BED10~ are delivered [Chance WW, 2017]. SABR is technically challenging due to respiration-induced displacements of the adrenals and adjacent organs at risk (OAR), both of which are poorly visualised using imaging techniques currently available at linear accelerators. MR imaging enables superior anatomical imaging of both the adrenals and OAR’s. We implemented stereotactic MR-guided adaptive radiotherapy (SMART) using daily on-table re-optimization of pretreatment SABR plans using the anatomy-of-the-day. We studied the impact such daily plan re-optimization for adrenal metastases.

      Method:
      Since mid-2016, 13 patients with adrenal metastases from lung cancer have undergone video-assisted, respiratory-gated SMART delivery on the MRIdian system (ViewRay Inc.). This entails using visual feedback involving projection of both target volume and safety margins onto a monitor visible to patients. The radiotherapy system automatically shuts-off delivery when the target is outside pre-specified safety margins (3mm). The commonest fractionation scheme delivered was 5-fractions of 10 Gy (in 9 patients). Prior to each fraction, a 17-second MR scan in shallow breath-hold was performed with patient in treatment position, in which the GTV was rigidly registered to that on the baseline MR scan. Setup was performed on the gross tumor volume (GTV), and contour deformation was used to automatically generate OAR’s according to the anatomy-of-the-day. Baseline SABR plans were recalculated on the anatomy-of-the-day (defined as ‘predicted plans’), before being routinely re-optimized.

      Result:
      The median planning target volume (PTV = GTV + 3mm) was 35.1 cc (range 6.5 – 69.8 cc). Online plan adaptation improved PTV coverage in 78% of all fractions. Re-optimized plans exhibited significantly better sparing of OAR and achieved a reduction in volumes of stomach, bowel and duodenum receiving 33Gy, with respect to predicted plans. All patients completed the planned treatments using repeated breath-holds. The total on-table duration was approximately 50 minutes for each fraction.

      Conclusion:
      Breath-hold SABR delivery under MR-guidance is advantageous for adrenal tumors. Substantial variations in OAR’s positions were observed at imaging prior to delivery of each fraction, leading to improved target coverage and OAR sparing when on-table plan re-optimization was performed.

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