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GAVIN Michael WRIGHT
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CS01 - Controversies in NSCLC OMD (ID 3)
- Event: WCLC 2019
- Type: Controversy Session
- Track: Oligometastatic NSCLC
- Presentations: 1
- Now Available
- Moderators:Tomoyuki Hishida, Yolande Lievens
- Coordinates: 9/09/2019, 11:00 - 12:30, Colorado Springs (1994)
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CS01.04 - NSCLC OMD is Defined by a Fixed Maximum Number of Metastases, Not Technical Reasons of Local Treatment (Now Available) (ID 3147)
11:00 - 12:30 | Presenting Author(s): GAVIN Michael WRIGHT
- Abstract
- Presentation
Abstract
Other than a select group of patients with solitary brain metastases and cT1-2a N0 resectable primary cancers, the idea of aggressively ablating metastatic non-small cell lung cancer (NSCLC) has always been considered unconventional. The resectable solitary cerebral metastasis has traditionally yielded better results than any other M1b disease, and this has been put down to careful selection and perhaps a different biology in these rare cases. It wasn’t until the publication of a large individual patient data meta analysis in 20141 that more general treatment of OMD could be benchmarked and taken seriously enough to consider clinical trials. This confirmed that in select populations, long-term survival was achievable by surgical or radio-ablation of a small number of metastases. Only 1.9% of the series had more than 3 metastases and only 3% of the series had multi-organ disease. A main finding of multivariate analysis was that those with any nodal disease (effectively another metastatic site) did poorly.
The definition of the oligometastatic disease state (OMD) has always been elusive. In principle, it is defined as M1a-c disease with low metastatic burden (usually up to three or five lesions) and limited organ involvement (usually up to two sites). It is considered an intermediate condition between truly localized disease and widely metastatic disease. The reporting bias of 1-3 metastases seen in so many published treatment series is tacit acknowledgement that OMD only encompasses three or fewer metastases, and probably to just a single organ. Our own IALSC TNM staging system recognizes this in our M1 sub-stages.
Unlike oligo-metastatic colorectal carcinoma, sarcoma or renal cell carcinoma, which have reproducibly achieved long term survival after pulmonary metastasectomy (and/or hepatic metastasectomy) for several decades, the pace of disease and apparent inevitability of shortened lifespan in a patient with metastatic NSCLC has led to self-regulation of this practice for our tumour specialty. The relatively poorer average cardio-pulmonary fitness of patients with lung cancer and the maxim of ‘first do no harm’ largely tempered any enthusiasm.
As surgery has become increasingly less invasive/morbid, and therapies such as stereotactic ablative body radiotherapy (SABR) and radiofrequency ablation have become more readily available, the temptation is to expand indications for intervention well beyond their evidence base and/or cost-benefit ratio. The last 5 years has seen a proliferation of publications of eyebrow-raising SABR series outside of any clinical trial protocols. This is a slippery slope that surgeons have been accused of sliding down in pulmonary metastasectomy for colorectal carcinoma2. We must not let our enhanced ability to inflict therapy dictate whether or not a condition is appropriate to treat. The definition of OMD cannot be stretched arbitrarily to match our technological capabilities or we will waste huge resources and inevitably cause some harm by way of futile overtreatment.
The ‘breakthrough’ SABR-COMET trial3 has invigorated discussion and enthusiasm for treating NSCLC oligometastatic disease on the basis that overall survival was superior with ablation of OMD (41 months) compared to the control group treated with palliative measures (28 months). This enthusiasm does need to be tempered by a few salient observations. Firstly, this was a phase 2 trial of mixed histologies with 66 recruits in the treatment arm and 33 in the control arm. In all, only 18 enrolled patients had NSCLC, with 12 in the treatment arm. It is indeterminate from the paper how well these particular NSCLC patients performed and the confidence intervals would be wide. The follow-up tail becomes decidedly ‘bushy’ after 1 year due to censorship. There were three treatment-related deaths and four other serious adverse effects not seen in the control arm. The control rate was less optimistic than in Rusthoven’s phase 1 trial4, with 75% having no progression in targeted lesions (compared to 49% in the control arm).
The most telling information supporting the ≤3 metastasis OMD hypothesis is the number of metastases and number of organs involved in the recruited SABR-COMET patients. Only 7 recruits had more than 3 metastases, with 5 of these receiving SABR. It is not clear if ANY of these had NSCLC, but these are not dissimilar numbers to the aforementioned NSCLC meta analysis1.
Historically, there is far more data on survival after metastasectomy for series excluding NSCLC. Only 1% of pulmonary metastasectomies in the International Registry of Lung Metastases5 had NSCLC and some may have been second primaries. Whilst 26% of cases had ≥4 metastases resected, this was largely confined to sarcoma and germ cell tumours, where aggressive resection and re-resection is considered standard of care. Their survival was still inferior to patients with either solitary or 2-3 metastases. This is despite the likelihood that patients with ≥4 metastases are “hyper-selected’, based on survival characteristics such as performance status, younger age, excellent fitness, anatomical location and favourable observed tumour behaviour. This creates a false impression that this group is receiving not dissimilar survival benefit as the cohort with ablation of 1-3 metastases.
OMD as a hypothesis is very reasonable and deserves to be tested. Diluting the potential benefits by expanding that definition to match our technological wizardry is not. Clinical trial resources would be better mobilized to further study surgical and/or SABR metastasectomy in lung cancer with ≤3 metastases in a single organ before expanding umbrella trials to ≥4 metastases.
References
1. Ashworth, A. B. et al. An individual patient data metaanalysis of outcomes and prognostic factors after treatment of oligometastatic non–small-cell lung cancer. Clin Lung Cancer 15, 346–355 (2014).
2. Treasure, T., Internullo, E. & Utley, M. Resection of pulmonary metastases: a growth industry. Cancer Imaging 8, 121–124 (2008).
3. Palma, D. A. et al. Stereotactic ablative radiotherapy for comprehensive treatment of oligometastatic tumors (SABR-COMET): Study protocol for a randomized phase II trial. BMC Cancer 12, 8 (2012).
4. Rusthoven, K. E. et al. Multi-institutional phase I/II trial of stereotactic body radiation therapy for lung metastases. J. Clin. Oncol. 27, 1579–1584 (2009).
5. Pastorino, U. et al. Long-term results of lung metastasectomy: prognostic analyses based on 5206 cases. The Journal of Thoracic and Cardiovascular Surgery 113, 37–49 (1997).
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P2.08 - Oligometastatic NSCLC (ID 172)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Oligometastatic NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.08-01 - Outcomes Following Gamma Knife Radiosurgery for Oligometastatic Brain Metastases in Patients with NSCLC at Leeds Cancer Centre (ID 1856)
10:15 - 18:15 | Author(s): GAVIN Michael WRIGHT
- Abstract
Background
Gamma knife (GK) radiosurgery has increasingly been used for brain metastases from NSCLC in the oligometastatic setting. This study reports outcome results for patients with synchronous brain and new brain metastases from NSCLC at Leeds Cancer Centre (LCC).
Method
251 patients, who were treated with GK at LCC from 2009 until 2018 were analysed. Retrospective analysis of notes was performed using electronic patient records.
Statistical analysis was performed using SPSS. Kaplan-Meier curves were performed to estimate time to intracranial progression, survival from diagnosis of brain metastases, and overall survival.
Result
Median age was 65 years (range 33 – 90 years). For patients with new brain metastasis (147 patients), TNM stage at diagnosis was stage I (14 patients), stage II (42 patients), stage IIIA (26 patients) or stage IIIB/IV (65 patients).
Histology was majority adenocarcinoma (59%), squamous cell carcinoma (16%) or NSCLC NOS (13%).
Radical thoracic treatment (surgery, chemoradiotherapy or stereotactic ablative radiotherapy) was undertaken for 158 patients. 92% completed radical thoracic treatment. Median survival from diagnosis of brain metastases was 382 days (446 days for those with synchronous brain metastases (48 patients), and 325 days for those with new brain metastases (110 patients)).
For all patients, median time to intracranial progression after GK was 242 days and overall survival after GK was 293 days.
For patients with synchronous brain metastases at presentation (104 patients), median time for overall survival from date of diagnosis was 435 days. For all patients without brain metastases at presentation, median time to intracranial progression from date of diagnosis was 305 days and overall survival was 693 days.
Conclusion
In conclusion, GK radiosurgery is an effective treatment for brain metastases in NSCLC, providing high rates of local control and improved survival. Beneficial effects are seen in patients with synchronous and new brain metastases, demonstrating its role in a wide subset of patients with advanced NSCLC. Use of GK, in combination with radical thoracic therapy, therefore has the potential to dramatically improve survival in patients who may not have previously been suitable for radical treatment.
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P2.16 - Treatment in the Real World - Support, Survivorship, Systems Research (ID 187)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Treatment in the Real World - Support, Survivorship, Systems Research
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.16-33 - What Influences Patient Decision-Making About Lung-Cancer Treatment? A Discrete Choice Experiment (Now Available) (ID 485)
10:15 - 18:15 | Author(s): GAVIN Michael WRIGHT
- Abstract
Background
Despite major advances in radiotherapy, surgery remains the treatment of choice for patients with stage I non-small cell lung cancer. We sought to investigate what influenced preferences for surgery or SABR among cancer patients.
Method
Using a discrete choice experiment (DCE) survey, we asked cancer patients to choose between lung cancer treatment options described by: type of treatment, chance of being cancer free for 12 months, chance of experiencing life threatening complications, chance of ongoing complications, impact on usual activities, who recommended treatment, whether treatment is usual care and out-of-pocket (OOP) costs. Each respondent completed nine choice questions. Choices were analysed using latent class analysis.
Result
A total of 204 responses were received (57% female). Of these, 20 reported a diagnosis of lung cancer; the rest had been diagnosed with other cancers, including 53 with melanoma. Overall, the chance of being without cancer was considered the most important attribute and costs the least. The latent class analysis identified three groups: Group 1 (21%) was focussed on costs and the doctor’s recommendation; Group 2 (60%) focused on the intervention (with a preference for surgery over radiotherapy), efficacy, side effects, functioning, doctor’s recommendation and the highest level of OOP costs; Group 3 members (19%) were focused on the doctor’s recommendation only. Women are more likely to be in Group 1 relative to 3, and those with higher educational attainment are more likely to be in Group 2 than 3. A more substantive analysis showed further differences between groups in terms of their tumour status, gender, educational attainment and health-care card status.
Conclusion
The results of this study show that a doctor’s recommendation is a vital factor in patients’ decision-making. The importance of this finding is emphasised by the fact that Group 2, representing 60% of respondents, preferred surgery over radiotherapy. Advocates of radiotherapy as a curative intervention for lung cancer need to educate doctors as well as patients about its potential side-effects, benefits and costs.
