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Paul Van Schil
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GR01 - Whether and How to Adapt Treatment of NSCLC Oligometastatic Disease to… (ID 29)
- Event: WCLC 2019
- Type: Grand Rounds Session
- Track: Oligometastatic NSCLC
- Presentations: 1
- Now Available
- Moderators:Jin-Soo Lee, Laurie Gaspar
- Coordinates: 9/08/2019, 13:30 - 15:00, Seoul (2007)
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GR01.05 - Site of Oligometastases (Now Available) (ID 3302)
13:30 - 15:00 | Presenting Author(s): Paul Van Schil
- Abstract
- Presentation
Abstract
The concept of oligometastatic disease representing patients with only a few or “oligo”metastases, is a relatively new entity in thoracic oncology and surgery [1-2]. Most probably, an intermediate state exists between patients with locoregional disease without distant metastases and those with multiple metastatic involvement in one or more distant organs.
The International Association for the Study of Lung Cancer (IASLC) adopted this concept and in the 8th Tumor-Node-Metastasis (TNM) edition a new category was introduced representing those patients with a single metastasis in a single distant organ, currently M1b involvement [3]. These patients belong to stage IVA, as well as patients with contralateral malignant nodules. In contrast, multiple metastases in a single or multiple distant organs are currently described as M1c disease, and they are grouped together in the new stage IVB category. In the IASLC database patients with clinical stage IVA disease had a median survival time (MST) and 5-year survival rate of 11.5 months and 10%, respectively, in contrast to 6.0 months and 0% for patients with stage IVB disease [4].
No consensus exists on the precise definition of oligometastatic disease. For this reason the European Organisation of Research and Treatment of Cancer (EORTC) created a task force to propose a definition of synchronous oligometastatic disease based on consensus by thoracic oncology experts [5]. A maximum of 5 metastases and 3 organs is proposed. Diffuse serosal metastases (meningeal, pericardial, pleural, mesenteric) as well as bone marrow involvement are not accepted as specific site as these cannot be treated with radical intent.
Is the specific organ involved important in management and prognosis of these patients? Patients with contralateral lung nodules, brain, bone and adrenal metastases are mostly reported in literature as these organs are quite accessible for local ablative treatment by surgical excision or stereotactic radiotherapy. For patients with bilateral / contralateral tumor nodules introduced in the IASLC prospective database by the electronic data capture (EDC) system, MST was 12 months, quite similar to patients with ipsilateral pleural/pericardial effusion. Although the numbers were quite small, for those patients with a single adrenal metastasis introduced by EDC, MST was 6.5 months, for a single bone metastasis 12.6 months, and for a single brain metastasis 12.1 months [3]. These survival times were significantly better than those for patients with multiple lesions at a single site. In general, most survival data are from retrospective series with an inherent selection or publication bias. For this reason, the EORTC decided not to consider the specific organ involved but this may change when more prospective data become available.
Are there any predictive factors for survival in patients with oligometastatic disease? In an individual patient data meta-analysis of 757 patients with 1-5 synchronous or metachronous metastases from non-small cell lung cancer (NSCLC), predictive factors were synchronous versus metachronous metastases, N stage and adenocarcinoma histology [6]. Surgery was the most frequently used treatment, as well for the primary tumor as for the metastatic involvement. Low-risk patients had metachronous metastases, the intermediate risk group presented with synchronous metastases and N0 disease, and the high-risk group with synchronous disease and thoracic lymph node involvement. So, adequate lymph node staging should be performed in every patient [7].
May combined modality therapy including locoregional ablative treatment by stereotactic radiotherapy or surgery improve prognosis in patients with oligometastatic disease? A recent landmark trial investigated the role of local ablative therapy in patients with stage IV NSCLC with three or fewer metastases remaining after first-line systemic therapy [8]. In this multicentre, controlled phase II study 49 patients were randomized between local consolidative therapy group consisting of surgery, radiotherapy or a combination with the aim of ablating all residual disease, and maintenance treatment which was chosen from a predefined list of regimens approved by the Food and Drug Administration (FDA). Primary endpoint was progression-free survival. Secondary outcomes were overall survival, safety and tolerability, time to progression of previous metastatic lesions, time to appearance of new metastatic lesions, and quality of life. Most frequent metastatic sites were brain, bone, adrenal gland, pleura and metastatic lung lesions. Significantly longer progression-free and overall survival rates were noted in the local consolidative therapy group than in the maintenance treatment group. Time to the appearance of a new lesion was longer among patients in the local consolidative therapy group than among patients in the treatment group. Survival after progression was also longer in the local consolidative group [8].
Regarding specific management of oligometastatic disease related to the site of involvement, the European Society of Medical Oncology (ESMO) recently published clinical practice guidelines for metastatic NSCLC including oligometastatic disease [9]. In the presence of a solitary metastatic site on imaging studies, efforts should be made to obtain a cytological or histological confirmation of stage IV disease. Stage IV patients with one to three synchronous metastases at diagnosis may experience long-term disease-free survival following systemic therapy and local consolidative therapy (high-dose radiotherapy or surgery). Because of the limited evidence, these patients should be discussed within a multidisciplinary tumor (MDT) board and inclusion in clinical trials is preferred. Although operative risk is low and long-term survival may be achieved, current evidence for surgery in oligometastatic disease is limited, and the relative contribution of surgery versus radiotherapy as local treatment modality has not been established yet. Solitary lesions in the contralateral lung should, in most cases, be considered as synchronous secondary primary tumors and, if possible, treated with curative-intent therapy [9].
Finally, even salvage surgery may be considered in highly selected patients with oligometastatic disease to improve long-term outcome [10].
REFERENCES
1. Pfannschmidt J. Lung Cancer. 2010;69:251-8
2. Shields' General Thoracic Surgery, 8th edition 2019, pp. 1289-90
3. Eberhardt WE. J Thorac Oncol. 2015;10:1515-22
4. Goldstraw P. J Thorac Oncol 2016; 11:39-51
5. Dingemans AM. IASLC 19th WCLC 2018; abstract MA25.02
6. Ashworth AB. Clin Lung Cancer 2014;15:346-55
7. Fernandez R. J Thorac Dis 2019; 11(Suppl.7):S969-S975
8. Gomez DR. J Clin Oncol 2019 May 8; doi:10.1200/JCO.19.00201
9. Planchard D. Ann Oncol 2018; 29(Suppl. 4):iv192-iv237
10. Duchateau N. Ann Thorac Surg 2017;103:e409-e11.
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P1.06 - Mesothelioma (ID 169)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Mesothelioma
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.06-06 - EORTC 1205: Randomized Study of Pleurectomy/Decortication (P/D) Preceded or Followed by Chemotherapy in Malignant Pleural Mesothelioma (ID 2511)
09:45 - 18:00 | Author(s): Paul Van Schil
- Abstract
Background
P/D is considered a valid surgical approach in selected pts with resectable MPM with less morbidity than extrapleural pneumonectomy. The procedure is however, poorly standardized and never radical, and is hence preferably preceded or followed by systemic chemotherapy.
EORTC 1205 aims at comparing the optimal sequencing of chemotherapy with P/D with regard to overall treatment time and feasibility.
Method
Functionally operable treatment-naïve pts with T1-3 N0-2 epithelial or biphasic mesothelioma and PS 0-1 are randomized between adjuvant (arm A) and neo-adjuvant chemotherapy (arm B). Chemotherapy in both arms consists of 3 cycles of cisplatin and pemetrexed at standard dosage and with premedication. P/D is performed by experienced thoracic surgeons in credentialed centers. Strict timelines between both procedures apply and surgical quality is audited with intra-operative mapping and imaging and comprehensive registration of complications. Primary endpoint in the intention-to-treat population is successful completion of the multimodality treatment within 20 weeks of randomisation and being alive with no signs of PD and/or persistent grade III-IV toxicity.
Result
As of April 10, 2019, 30 pts of the required sample size of 64 have been randomized and 17 operated. Baseline patient and tumor characteristics appear well balanced sofar (table).
Characteristics and treatment results as per 1/04/2019 Table
Arm A
Arm B
All
N
16
14
30
Male gender (%)
56
71
63
Median age (y)
62
66
64
WHO PS 0/1
10/6
7/7
17/13
TNM Stage 1/2/3 at presentation
6/6/4
9/2/3
15/8/7
% administered 3 cycles of chemotherapy
88
100
94
N operated
9
8
17
Median time between randomization and 1st treatment modality (weeks)
2.9
1.6
2.0
Median time between 1st and 2nd treatment modality
5.7
11.0
10.1
N completed treatment
9
8
17
Median overall treatment time in those completing treatment
23.7
18.7
21.3
Conclusion
Trial accrual proceeds on schedule and last patient will be included in 2020. A protocol amendment will allow carboplatin/pemetrexed as induction regimen. An updated analysis on all included patients as per 1/08/2019 will be presented at the meeting.
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P2.18 - Treatment of Locoregional Disease - NSCLC (ID 191)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Treatment of Locoregional Disease - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.18-02 - Pneumonectomy and Lung Cancer: A Treacherous Combination (ID 351)
10:15 - 18:15 | Author(s): Paul Van Schil
- Abstract
Background
In spite of the progress made in recent years regarding minimally invasive and parenchymal-sparing surgery, pneumonectomy is still necessary in cases where lesser resections are not possible. However, pneumonectomy remains a high-risk surgical procedure associated with significant postoperative morbidity and mortality. We investigated early and long-term results in a recent series of patients undergoing pneumonectomy for lung cancer.
Method
Clinical and pathological characteristics of non-small cell lung cancer (NSCLC) patients treated by pneumonectomy between January 2008 and December 2013 were retrospectively reviewed. Overall 30- and 90-day mortality and 1-, 2-, and 5-year survival rates were calculated. Postoperative complications and disease progression or recurrence were analysed by descriptive statistics. Univariate and multivariate analyses of factors related to long-term survival were also performed.
Result
A total of 61 patients, 48 men and 13 women with an overall mean age of 64±8.9 years, underwent pneumonectomy. The 30- and 90-day mortality rates were 6.6% and 16.4%, respectively. Ninety-day mortality was significantly correlated to tumour pathology (p=0.0410) and occurrence of postoperative complications (p=0.0078). Overall 1-, 2-, and 5-year survival rates were 70.5%, 57.4%, and 37.7%, respectively. Progressive or recurrent disease occurred in 45.7% of all patients. Most frequent early complications were atrial fibrillation (41.0%), pneumonia (23.0%), and acute respiratory failure (18.3%).
Conclusion
Despite careful patient selection, pneumonectomy yields high mortality and morbidity rates. Therefore, it should only be performed when no other therapeutic options are available. Furthermore, rigorous preoperative work-up and risk stratification models are necessary to determine whether pneumonectomy is the most suitable treatment option and to obtain acceptable long-term results.
