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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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GR01.03 - Nodal Status of the Primary Disease? (Now Available) (ID 3300)
13:30 - 15:00 | Presenting Author(s): David Ball
- Abstract
- Presentation
Abstract
Oligometastases from non-small cell lung cancer (NSCLC) can be classified as synchronous, which are diagnosed at the same time as the locoregional disease, or metachronous, developing after (successful) treatment of the locoregional disease. The title of this presentation implies that the nodes are present at the time of treatment, so the focus will be restricted to the treatment of synchronous oligometastases. In the absence of a universally accepted definition of oligometastatic disease we will assume that the term can be used where there are up to five metastatic sites.
Nodal involvement as a prognostic factor in patients with oligometastatic disease.
The earliest reports of attempting to improve survival outcomes for patients with limited metastastic disease were in patients with brain metastases either by resection (1) or by resection or stereotactic radiosurgery (2). Five year survivors were observed, vindicating aggressive treatment in this subset of stage IV patients with NSCLC, but patients with regional node involvement appeared to have worse survival than patients with N0 disease. This was confirmed in a subsequent large multicentre individual patient data meta-analysis reported by Ashworth et al of 757 patients who were treated with ablative treatments to all sites of disease (3). Factors that were important for survival in the meta-analysis were metachronous versus synchronous and histology (favouring adenocarcinoma) as well as N stage. Using recursive partitioning analysis, Ashworth et al were able to group patients with synchronous metastases into an intermediate risk group with N0 disease and a 5 year survival of 36.2% versus a high risk group with N1 or N2 disease and a 5 year survival of 13.8%. Why should regional node status be a prognostic factor in patients who already have distant metastatic disease? Most likely it is because nodal involvement is a surrogate for the volume of metastatic disease that may have been underestimated in the pre-PET era.
Is regional nodal involvement a contraindication to an aggressive approach?
Although Hu et al (2) recommended against an aggressive approach to the locoregional disease in patients with stage II or III NSCLC, the fact that 3 year survivors were observed in their cohort and 5 year survivors in the meta-analysis suggests that it is an option that should be discussed considered. in a retrospective study by Flannery et al if the thoracic disease was not treated definitively, survival at 5 years was 0% compared with 34.6% for surgical resection or chemoradiation (P < 0.0001) (4). Patients with N0 or N1 disease (grouped together) had longer survival than patients with N2 or N3 disease, but this was not statistically significant. A prospective phase II trial treated patients with up to 5 oligometastatic sites with chemotherapy followed by chemoradiation to the primary and involved nodes plus SABR or high dose radiotherapy (60 Gy in 30 fractions) to the metastases was associated with a median survival of 28 months, but there was no difference in survival whether nodes were or were not involved (5).
Does nodal status influence whether locoregional disease should be treated by surgery, SABR or (chemo)radiotherapy?
This will depend on the patient’s fitness for surgery, and the anatomical extent and location of disease. We have no evidence to support any one strategy. We use the same principles to select treatment to the locoregional disease as if there were no oligometastatic disease present. In the Ashworth meta-analysis, surgical management of the primary was a favourable prognostic feature with a hazard ratio of 0.74 (95% CI: 0.55 – 1.00) on univariable analysis, but not on multivariable analysis (3). In the first randomized trial in patients with NSCLC oligometatases the use of ablative treatments did improve disease free survival in patients with NSCLC who had up to 3 metastases and no evidence of progression after systemic therapy.(6) In this small trial, nearly all patients had synchronous oligometastases. Treatments used for the primary disease after first-line systemic therapy included surgery, stereotactic ablative body radiotherapy (SABR) and chemoradiation. Any involved regional nodes were regarded collectively as one “oligometastatic site”. There was no significant difference in progression-free survival comparing patients with N0-1 disease versus N2-3.
Conclusion
Where a patient has synchronous oligometastatic disease that is amenable to ablative therapy, definitive treatment to the primary site and any involved regional nodes taking into account the patient’s general condition and disease stage is a reasonable option, regardless of nodal stage.
References
1. Billing PS, Miller DL, Allen MS, Deschamps C, Trastek VF, Pairolero PC. Surgical treatment of primary lung cancer with synchronous brain metastases. J Thorac Cardiovasc Surg. 2001;122(3):548-53.
2. Hu C, Chang EL, Hassenbusch SJ, 3rd, Allen PK, Woo SY, Mahajan A, et al. Nonsmall cell lung cancer presenting with synchronous solitary brain metastasis. Cancer. 2006;106(9):1998-2004.
3. Ashworth AB, Senan S, Palma DA, Riquet M, Ahn YC, Ricardi U, et al. An individual patient data metaanalysis of outcomes and prognostic factors after treatment of oligometastatic non-small-cell lung cancer. Clin Lung Cancer. 2014;15(5):346-55.
4. Flannery TW, Suntharalingam M, Regine WF, Chin LS, Krasna MJ, Shehata MK, et al. Long-term survival in patients with synchronous, solitary brain metastasis from non-small-cell lung cancer treated with radiosurgery. Int J Radiat Oncol Biol Phys. 2008;72(1):19-23.
5. Petty WJ, Urbanic JJ, Ahmed T, Hughes R, Levine B, Rusthoven K, et al. Long-Term Outcomes of a Phase 2 Trial of Chemotherapy With Consolidative Radiation Therapy for Oligometastatic Non-Small Cell Lung Cancer. Int J Radiat Oncol Biol Phys. 2018;102(3):527-35.
6. Gomez DR, Blumenschein GR, Jr., Lee JJ, Hernandez M, Ye R, Camidge DR, et al. Local consolidative therapy versus maintenance therapy or observation for patients with oligometastatic non-small-cell lung cancer without progression after first-line systemic therapy: a multicentre, randomised, controlled, phase 2 study. Lancet Oncol. 2016;17(12):1672-82.
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OA05 - Increasing the Impact of Nursing and Allied Health Professional Interventions in Lung Cancer Care (ID 130)
- Event: WCLC 2019
- Type: Oral Session
- Track: Nursing and Allied Professionals
- Presentations: 1
- Now Available
- Moderators:Dianne Zawisza, Maria Guerin
- Coordinates: 9/08/2019, 15:15 - 16:45, San Francisco (2009)
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OA05.01 - A Prospective Study of Swallowing and Voice Outcomes After Treatment for Small-Cell Lung Cancer (Now Available) (ID 2225)
15:15 - 16:45 | Author(s): David Ball
- Abstract
- Presentation
Background
Dysphagia (difficulty swallowing) and dysphonia (impaired voice) have been identified in patients with lung cancer as being a significant problem. However, research to date has been limited in its measurement and it remains unknown which patients experience dysphagia or dysphonia, and what the impact of these problems are to the patient. The purpose of this study was to identify the prevalence and nature of dysphagia and dysphonia in patients with limited stage SCLC.
Method
A prospective cohort pilot study was conducted on 12 patients receiving chemoradiotherapy for limited-stage SCLC. Data collection included: videofluoroscopy swallowing studies (VFSS) to investigate swallowing physiology, aspiration risk and oesophageal motility disorders; limitations to oral intake; patient-reported swallowing problems; and patient-reported voice problems. Data were collected before treatment and again at one, three and six months post-treatment.
Result
No patient was observed to aspirate, and the pharyngeal swallow was safe and functional in all cases. Three patients exhibited oesophageal motility disorders before treatment, while three more exhibited these disorders at the post-treatment assessments. Oral intake was most compromised one month post-treatment; at this time one patient was tube dependent, two required a single consistency diet and two had a diet requiring special preparation. At all other time-points patients were managing a normal or near-normal diet. Despite an absence of oropharyngeal dysphagia observed on VFSS, three patients reported moderate or severe swallowing difficulties one month post-treatment; these self-reported difficulties were no more than mild at follow-up assessments. Three additional patients reported the onset of moderate or severe swallowing difficulties at three and six months post-treatment. Patients who reported swallowing difficulties at one month post-treatment had all received a mean radiation dose to the oesophagus of ≥15.7Gy and a maximum dose to the oesophagus of ≥42Gy, however these relationships were no longer apparent at three and six months post-treatment. Patient-reported voice difficulties were variable, with the worst scores being reported at one month post-treatment for a subset of patients, who continued to report problems across voice-related physical, functional and emotional domains at three and six months post-treatment.
Conclusion
This is the first time that detailed swallowing and voice outcomes have been reported in patients with SCLC. Although patient numbers are small, this study identified discordance between observed swallowing function and patient-reported problems, which may have significant clinical implications for the management of patients with SCLC, as well as identify important issues for future research.
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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): David Ball
- 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.
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P2.17 - Treatment of Early Stage/Localized Disease (ID 189)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Treatment of Early Stage/Localized Disease
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.17-21 - A Post-Hoc Analysis of TROG 09.02 (CHISEL) Phase III Trial Investigating Pulmonary Function Changes After SABR and Conformal Radiation Therapy (Now Available) (ID 2203)
10:15 - 18:15 | Author(s): David Ball
- Abstract
Background
The TROG 09.02 (CHISEL) trial compared conventional radiotherapy (CRT) administered over a period of four to six weeks with stereotactic ablative body radiotherapy (SABR).(1) Patients randomised to the SABR arm had superior freedom from local failure and longer overall survival.(1) The aim of this analysis was to assess differences in lung function and spirometry tests between SABR and CRT and describe longitudinal changes in respiratory function.
Method
We conducted a post-hoc analysis of all patients recruited to the CHISEL trial. During this trial patients underwent serial Respiratory Function Tests (RFT) including Forced Expiratory Volume in one second (FEV1), Diffusing capacity of the lungs for carbon monoxide (DLCO), Distance Walked in 6 minutes (SMWT) and Forced Vital Capacity (FVC). These were performed at baseline then 3-6 monthly post-treatment. Patients were assessed per treatment received. Linear regression models were used to compare FEV1, FVC and DLCO between SABR and CRT. Separate models at 3 and 12 months post-treatment were created to assess the two different processes impacting lung function post radiation therapy (acute pneumonitis and chronic fibrosis). Linear regression models were used to assess the association of baseline PFT Measures with decline in respiratory function at 3 and 12 months.
Result
Between December 2009 and June 2015, 101 patients were treated in 11 centres in Australia and New Zealand. 34 patients were treated with CRT and 63 with SABR. On regression analysis at 3 months there was no evidence of a difference between arms in the change from baseline in absolute values of FEV1 (beta 0.037, 95% CI [-0.063, 0.14], p=0.47), DLCO (beta -0.5, 95% CI [-1.4, 0.37], p=0.26) nor forced VC (beta 0.024, 95% CI [-0.17, 0.22], p=0.81). At 12 months there were no differences observed in change from baseline of FEV1 (beta0.031, 95% CI [-0.12, 0.18], p=0.69), DLCO (beta -0.43, 95% CI [-1.7, 0.84], p=0.51) nor forced VC (beta 0.047, 95% CI [-0.28, 0.18], p=0.69) between arms.There was no evidence of a difference in the change from baseline in SMWT (m) between two arms at 3 months (beta 35.9, 95% CI [-10, 82.3], p=0.13).Patients in both arms demonstrated similar deterioration in all RFT parameters with time.
Conclusion
Despite the considerably higher biologically effective doses delivered to the tumour in SABR there was no difference in decline in respiratory function observed between the two groups. This is likely due to the higher integral dose, steep dose gradients and reduced margins possible with SABR relative to CRT.
