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MA05 - Improving Outcomes in Locoregional NSCLC II (ID 901)
- Event: WCLC 2018
- Type: Mini Oral Abstract Session
- Track: Treatment of Locoregional Disease - NSCLC
- Presentations: 1
- Coordinates: 9/24/2018, 13:30 - 15:00, Room 105
MA05.07 - Dose Escalated Chemo-RT to 84 Gy in Stage III NSCLC Appears Excessively Toxic: Results from a Randomized Phase II Trial (ID 11966)
14:10 - 14:15 | Author(s): Signe Friesland
Concurrent chemoradiotherapy is the mainstay treatment for NSCLC stage III disease, however, with a rather high probability of locoregional and metastatic recurrence further treatment optimization is warranted. Based on previous one-armed trials with dose escalated radiotherapy, showing feasibility, the Swedish Lung Cancer Study Group aimed to investigate whether dose escalation based on individual normal tissue constraints could improve outcome in this randomized phase II trial.a9ded1e5ce5d75814730bb4caaf49419 Method
NSCLC patients with stage III disease, good performance status (0-1), adequate lung function (FEV1 > 1.0 L and CO diff. > 40%) received three cycles of cisplatin (75 mg/m2 day 1) and vinorelbine (25 mg/m2 day 1 and 8) every third week. The radiotherapy started concurrently with the second cycle, with either 2 Gy daily, 5 days a week, to a total dose of 68 Gy (standard arm A) or escalated therapy (B) based on constraints to the spinal cord, esophagus and lungs up to 84 Gy by adding an extra fraction of 2 Gy per week while keeping the total treatment time constant at seven weeks with the same dose to involved nodes and primary tumor.4c3880bb027f159e801041b1021e88e8 Result
A pre-planned safety analysis revealed excessive toxicity and decreased survival in the escalated arm, and the study was stopped. Thirty-six patients were included during 2011-2013 (56% male, 78% with adenocarcinoma, 64% with PS 0 and 53% with stage IIIB). The median progression-free survival (PFS) and overall survival (OS) were 11 and 17 months in the dose escalated group compared to 28 and 45 months in the standard group. The 1-, 3- and 5-year survival rates were 56%, 33% and 17% in the escalated arm and 72%, 61% and 34% in the standard arm. There were four toxicity-related deaths due to esophageal perforations (one in arm A and three in arm B) and three deaths due to pneumonitis (one in arm A and two in arm B).8eea62084ca7e541d918e823422bd82e Conclusion
Dose-escalated concurrent chemoradiotherapy to 84 Gy to primary tumor and nodal disease is hazardous, with a high risk of excessive toxicity, whereas modern standard dose chemoradiotherapy with proper staging given in the control arm shows a promising outcome with a median survival of 45 months and a 5-year survival of 34%. A possible step forward will be to improve systemic therapy, but future approaches with escalated radiotherapy may include boost techniques to remaining PET positive areas or different escalation schedules to the primary tumor and mediastinal nodes.6f8b794f3246b0c1e1780bb4d4d5dc53
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P2.13 - Targeted Therapy (Not CME Accredited Session) (ID 962)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Presentations: 1
- Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
P2.13-02 - ALK-Translocation and Brain Metastases: A Retrospective Study. Correlation Between Clinical Outcome, Disease Burden and Management. (ID 12949)
16:45 - 18:00 | Author(s): Signe Friesland
Brain metastases from non‐small cell lung cancer is often regarded as the ominous sign of disease progression .
In the ALK-translocated population, brain metastases are seen in a higher incidence, either at diagnosis or as a common site of progression for patients receiving tyrosine kinase inhibitors (TKI).
The management of brain metastases in this population remains a challenge since several methods of treatment are available. TKI-treatment, especially with second or third generation drugs can be effective but the role of radiation therapy, with either whole brain radiotherapy (wbrt) or stereotactic radiosurgery (srs), has not been fully elucidated.
A retrospective study was conducted at ou Institution in order to evaluate the frequency of brain metastases in this subggroup of patients and in order to explore clinical features associated with survival.
88 consecutive patients with advanced ALK+ adenocarcinoma were treated at our institution. during the perod 2011-2018. Data on CNS imaging modality, treatment strategy and outcome was collected by chart review.4c3880bb027f159e801041b1021e88e8 Result
Cns-imaging with either MRI or CT (in 38% and 62% of the cases respectively) was performed in 73 cases. 44 patients (61%) were found to have CNS metastases (Male/female ratio 48/52%; median age 60y).
23% were found at the time of primary cancer diagnosis, 36% on time of PD on chemotherapy, 34% on PD on crizotinib and 7% at PD on 2nd gen ALKinh .
27% of the patients had 1-3 metastases, 34% 4-10 met and 39 % >10.
Pharmacological treatments in the group as a whole: chemotherapy (n=38); crizotinib (n=35); alectinib (n=10); ceritinib (n=20); brigatinib (n=3), lorlatinib (n=1).
Radiotherapy was administered in 57% as either SRS or WBRT (52/48%) .
Treatment strategies upon discover of CNS-metastes: Radiotherapy solely 27%, combination of radiotherapy and pharmacological treatment in 25%, switch to crizotinib and to 2nd gen ALKi in 18 and13 % respectively.
Median OS from the diagnosis of CNS metastasis was 29months (95% CI 11-59). 1- and 2-year survival was 61% and 51%, respectively.
Neither gender, age, timing for diagnosis of CNS metastases nor the use of radiotherapy were significant prognostic factors for OS (Cox proportional hazard analysis).
Use of 2nd gen ALKin as treatment strategy seemed to be superior to crizotinib and radiotherapy alone even if median OS not yet was reached.8eea62084ca7e541d918e823422bd82e Conclusion
The high incidence of CNS metastases in this subpopulation of patients (Caucasian with advanced ALK+ NSCLC) was confirmed in this study. The wider implementation of 2nd generation ALKi in clinical practice will probably change the prognosis of these subjects.6f8b794f3246b0c1e1780bb4d4d5dc53