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Anne-Marie C. Dingemans



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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): Anne-Marie C. Dingemans

      • 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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    P2.01 - Advanced NSCLC (ID 618)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Advanced NSCLC
    • Presentations: 1
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      P2.01-048 - Early Changes in Body Composition in Metastatic Non-Small Cell Lung Cancer (NSCLC) Are Predictive for Poor Overall Survival (ID 10236)

      09:00 - 16:00  |  Presenting Author(s): Anne-Marie C. Dingemans

      • Abstract

      Background:
      Weight loss adversely affects prognosis in metastatic NSCLC. However, the pattern of changes in muscle mass and adipose tissue during first cycle of chemotherapy and their relation to survival is unclear. Therefore, we analyzed changes in muscle cross-sectional area (CSA), inter- and intramuscular adipose tissue (IMAT), subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) on CT-images after three weeks of chemotherapy in patients with metastatic NSCLC and their influence on overall survival (OS).

      Method:
      In this post-hoc analysis of a subset of the randomized controlled NVALT12 trial (NCT01171170 [1]), body composition was characterized by CSA and distribution of both muscle and adipose tissue at the third lumbar level on CT-images obtained at baseline and three weeks after start of chemotherapy. Changes in body composition parameters were related to OS with Kaplan Meier and log-rank test. Cox multivariate analysis was performed to assess the relative contribution of muscle and adipose tissue CSA and distribution to OS.

      Result:
      Data were available of 103 patients. Cox regression analysis showed that loss of muscle CSA and IMAT independently affected survival while change in SAT and VAT did not. 74 patients (72%) exhibited muscle loss (group 1) versus 29 patients (28%) who had stable or gain of muscle CSA (group 2). Groups were comparable regarding age, WHO PS, TNM status, and Charlson comorbidity index. Median OS (95% CI) was 10.0 (7.9-12.2) months in group 1 and 15.3 (11.1-19.5) months in group 2 (p=0.004). Among muscle losing patients two sub-groups were distinguished based on IMAT change. Loss of muscle mass combined with loss of IMAT (group 1a, n=33) also showed significant loss of SAT and lower survival rates compared to loss of muscle mass with preserved IMAT (group 1b, n=40). Median OS (95% CI) was 7.3 (5.0-9.5) months in group 1a compared to 12.9 (9.2-16.6) months (p<0.001) in group 1b.

      Conclusion:
      Early changes in body composition patterns during the first cycle of chemotherapy in metastatic NSCLC are predictive for OS and might be useful for more personalised supportive intervention during follow-up treatment. Reference 1. Dingemans AM, Groen HJ, Herder GJ et al. A randomized phase II study comparing paclitaxel-carboplatin-bevacizumab with or without nitroglycerin patches in patients with stage IV nonsquamous nonsmall-cell lung cancer: NVALT12 (NCT01171170)dagger. Ann Oncol 2015; 26: 2286-2293.

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    P2.08 - Locally Advanced Nsclc (ID 709)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Locally Advanced NSCLC
    • Presentations: 1
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      P2.08-007 - Five-Year Results of Concurrent Chemotherapy and Isotoxic Radiotherapy Dose-Escalation with IMRT in Stage III NSCLC (NCT01166204) (ID 9261)

      09:30 - 16:00  |  Author(s): Anne-Marie C. Dingemans

      • Abstract
      • Slides

      Background:
      Previous studies by our group showed that that increasing the radiotherapy (RT) dose in an overall treatment time (OTT) of less than 6 weeks on basis of the isotoxic principle is feasible and could potentially increase the overall survival (OS) with non-concurrent chemo-RT without increasing the toxicity. No data were yet available for IMRT treated patients.

      Method:
      From 04-05 2009 until 26-04-2012, 185 patients with stage III NSCLC, treated with concurrent chemo-RT were included in this single center phase II trial. OS update was done on June 7, 2017. The primary endpoint of this study was OS, with in-field nodal failures (INF) and toxicity as secondary endpoints. Patients received 1 cycle of cisplatin-etoposide followed by two cycles of the same chemotherapy with concurrent radiotherapy (IMRT, 45 Gy BID followed by 2 Gy QD to the maximal organ at risk constraint).

      Result:
      Patient characteristics: Gender: Male: 61.1 %, Female: 38.9 %. Age 63.9 ± 8.9 years (44-86). Smoking: Never 2.9 %, current 36.8 %, former 60.3 %. WHO performance status: 0 (36.2 %) 1 (56.8 %), 2 11 (5.9 %), 3: 1 pt , 4:1 pt. Histology: Squamous 55 (29.7 %), Adenocarcinoma 49 (26.9 %), Large cell 26 (14.1 %), NSCLC-NOS 55 (29.7 %). GTV (T+N) 120.4 ± 132 ml (16.8-708.5), Total Tumor Dose 66.0 ± 12.8 Gy (36.0-73.0).Number of fractions: 39.7 ± 3.4 (24-44). OTT 38.2 ± 26.8 days (16-93) MLD 17.3 ± 3.0 Gy (4.9-21,2). Mean Esophageal Dose 29.0 ± 9.3 Gy (6.3-54.1). OS: stage IIIA (n=42), median 16.7 Mo (8.7-24.7), 5-year 16.7 %; stage IIIB (n=143) 20.3 (16.2-24.4), 5-year 27.3 % (P=0.10). INF: 3/185 (1.6 %). Loco-regional failures: 59/185 patients (31.8 %) Toxicity: Dyspnea Grade Baseline Maximal score 0 102 (55.1 %) 71 (38.4 %) 1 68 (36.8 %) 103 (55.7 %) 2 15 (8.1 %) 5 (2.7 %) 3 0 6 (3.2 %) 88% of patients experienced any grade of dysphagia: 22% experienced grade 1 dysphagia, 44% grade 2, while 22% experienced grade 3 dysphagia.

      Conclusion:
      Isotoxic accelerated radiotherapy delivered with IMRT and concurrently with chemotherapy leads to low INF and toxicity is comparable to the best series using standard fractionation schedules. Long term OS remains low and therefore other strategies are needed.

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