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Alexander Vincent Louie
Moderator of
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GR 03 - Treatment Options for Early Stage Lung Cancer Patients with Limited Pulmonary Reserve (ID 522)
- Event: WCLC 2017
- Type: Grand Rounds
- Track: Early Stage NSCLC
- Presentations: 6
- Moderators:Alexander Vincent Louie, I. Yoshino
- Coordinates: 10/18/2017, 11:00 - 12:30, F205 + F206 (Annex Hall)
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GR 03.01 - Case Study (ID 10953)
11:00 - 11:05 | Presenting Author(s): Alexander Vincent Louie
- Abstract
- Presentation
Abstract not provided
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GR 03.02 - Case Study (ID 10954)
11:05 - 11:10 | Presenting Author(s): I. Yoshino
- Abstract
- Presentation
Abstract not provided
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GR 03.03 - Minimally Invasive Surgery for Early Stage NSCLC (ID 7636)
11:10 - 11:30 | Presenting Author(s): Thomas D'Amico
- Abstract
- Presentation
Abstract:
Lobectomy with mediastinal lymph node dissection has been established as the most effective therapy for patients with resectable non-small cell lung cancer (NSCLC). Over the past 20 years, it has also been demonstrated that thoracoscopic (VATS) approaches are associated with better outcomes than open approaches. With the adoption of lung cancer screening protocols, more patients with early stage lung cancers (<2 cm) are going to be candidates for surgical resection, and some of these patients may benefit from anatomic sublobar resection (segmentectomy). The VATS approach to segmentectomy for stage I NSCLC has been shown to be feasible and safe and has found to be associated with decreased perioperative mortality and equivalent or improved overall survival when compared to segmentectomy via thoracotomy [1]. In addition, thoracoscopic segmentectomy may be particularly advantageous in patients with poor pulmonary function, with advantages in overall complication rates and other outcomes compared to open approaches. [2-6] Sublobar resection, as opposed to lobectomy, is appropriate for some patients with lung cancer: patients with ground glass opacities which are found to be adenomatous hyperplasia (AAH), adenocarcinoma in situ (AIS), or minimally invasive adenocarcinoma (MIA). In addition, sublobar resection is considered an acceptable compromise procedure for patient with tumors less than 2 cm in diameter and co-morbidities that preclude lobectomy, although lobectomy is associated with superior outcomes in most patients [7-8]. Specific indications to consider anatomic sublobar resection in patients with tumors <2cm include: age >80, compromised pulmonary function (FEV1 or DLCO <30% predicted), and favorable tumor location. [1, 2, 5, 7, 8] While it is feasible to achieve sublobar resection of any of the 10 segments, some of the segments are more technically challenging to remove. The typical (commonly performed) sublobar resections include superior segmentectomy (S6), lingulectomy (L S4+5), lingula-sparing left upper trisegmentectomy (L S1-3), posterior segmentectomy of the right upper lobe (R S2), and basilar segmentectomy (S 7-10). [9]. Outcomes Much of the data comparing outcomes of segmentectomy to lobectomy has come from patients with GGOs. When comparing patients with solid nodules <2cm, lobectomy is associated with better outcomes in several studies. In one study of 39,403 patients from the National Cancer Database (NCDB), 29,736 (74%) underwent lobectomy. [7] Of the 26% sublobar resections, 85% were wedge resections. In addition, lymph node evaluation not performed in 29%. Sublobar resection associated with smaller T and low-volume institutions. 5-year survival for lobectomy was superior to sublobar resection: 66% vs. 51% (P < 0.001). Another study analyzed the outcomes of patients with stage I lung cancer over 80 years of age, also from the NCDB. [8] In this study, sublobar resection was associated with significant reductions in survival, even among patients with T1a tumors and patients >85 years. Sublobar resection was inferior in all patients except those >85 years of age and Charlson/Deyo comorbidity index >2. It has been demonstrated that superior oncologic outcomes are associated with lobectomy; however, anatomic sublobar resection or non-anatomic (wedge) resection may be appropriate in selected patients. One study of the Society of Thoracic Surgeons database compared the morbidity and mortality of wedge resections (n=3733) with that of anatomic lung resections (lobectomy and segmentectomy) (n=3733) for stage I and stage II NSCLC using propensity-matched analysis. [10] The operative mortality rate was 1.2% for wedge resections versus 1.9% for anatomic resection (p=0.01) while major morbidity occurred in 4.5% for wedge resections and 9.0% for anatomic resection (p<0.01). The authors noted the mortality benefit was most apparent in patients with FEV1 less than 80% predicted although the morbidity benefit was observed regardless of age, lung function or type of incision. [10] Another study from the NCDB reported by Rosen and colleagues found a higher perioperative mortality rate of 4.2% for wedge resections for NSCLC. [11] In comparison, the segmentectomy and lobectomy groups had a perioperative mortality rate of 3.6% and 2.6%, respectively. The difference in perioperative rates may be explained by a difference in baseline comorbidities between the groups; the wedge resection group was sicker than the other two groups. Summary Thoracoscopic segmentectomy is a sound option for lung-sparing, anatomic pulmonary resection in selected patients for experienced thoracoscopic surgeons and can be safely applied to the treatment of a variety of pulmonary disorders, including small primary lung cancers, metastatic pulmonary disease, and benign disorders. The minimally invasive approach appears to have distinct advantages compared with thoracotomy, including reduced hospital length of stay, less postoperative pain, and fewer overall complications. The decision to perform sublobar anatomic resection for NSCLC may be complex, and the best candidates appear to be those with clinical stage I disease and tumors <2cm in diameter and other significant co-morbidities precluding lobectomy, or in patients with AAH, AIS, or MIA. References 1. Yang CF, and D'Amico TA. Open, thoracoscopic and robotic segmentectomy for lung cancer. Annals of cardiothoracic surgery. 2014;3:142-52. 2. Atkins BZ, Harpole DH, Jr., Mangum JH, Toloza EM, D'Amico TA, and Burfeind WR, Jr. Pulmonary segmentectomy by thoracotomy or thoracoscopy: reduced hospital length of stay with a minimally-invasive approach. The Annals of thoracic surgery. 2007;84:1107-12 3. Gulack BC, Yang C-F, Yerokun B, Tong BC, et al. A risk score to assist selecting lobectomy versus sublobar resection for non-small cell lung cancer. Ann Thorac Surg 2016; 102: 1814-20 4. Smith CB, Kale M, Mhango G, Neugut AI, Hershman DL, Mandeli JP, and Wisnivesky JP. Comparative outcomes of elderly stage I lung cancer patients treated with segmentectomy via video-assisted thoracoscopic surgery versus open resection. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer. 2014;9:383-9 5. Yang CF, and D'Amico TA. Thoracoscopic segmentectomy for lung cancer. The Annals of thoracic surgery. 2012;94(2):668-81 6. Zhong C, Fang W, Mao T, Yao F, Chen W, and Hu D. Comparison of thoracoscopic segmentectomy and thoracoscopic lobectomy for small-sized stage IA lung cancer. The Annals of thoracic surgery. 2012;94(2):362-7 7. Speicher PJ, Gu L, Gulack BC, Wang X, D'Amico TA, Hartwig MG, Berry MF. Sublobar resection for clinical stage IA non-small cell lung cancer in the United States. Clin Lung Cancer. 2016; 17: 47-55 8. Gulack BC, Yang CF, Speicher PJ, Kara HV, et al. Performing sublobar resection instead of lobectomy compromises the survival of stage I non-small cell lung cancer patients 80 years of age and older. (Under review) 9. Yerokun BA , Yang C-F, Gulack BC, Xuechan XL, Mulvihill MS, et al. A national analysis of wedge resection versus stereotactic body radiation therapy for clinical Stage IA non-small cell lung cancer. J Thorac Cardiovasc Surg 2017 Aug;154(2):675-686. Pham D, Balderson, S., and D’Amico, T.A. Technique of Thoracoscopic Segmentectomy. Operative Techniques in Thoracic and Cardiovascular Surgery. 2008;13: 188-203. 10. Linden PA, D'Amico TA, Perry Y, Saha-Chaudhuri P, Sheng S, Kim S, and Onaitis M. Quantifying the safety benefits of wedge resection: a society of thoracic surgery database propensity-matched analysis. Ann Thorac Surg. 2014;98(5):1705-11; discussion 11-2. 11. Rosen JE, Hancock JG, Kim AW, Detterbeck FC, and Boffa DJ. Predictors of mortality after surgical management of lung cancer in the National Cancer Database. Ann Thorac Surg. 2014;98(6):1953-60.
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GR 03.04 - Merit and Demerit of Minimally Invasive Approach (ID 7637)
11:30 - 11:50 | Presenting Author(s): Eric Lim
- Abstract
- Presentation
Abstract not provided
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GR 03.05 - Any Roles of Systemic Therapy (Chemotherapy, Targeted Therapy, Immunotherapy) for Early Stage NSCLC with Limited Pulmonary Reserve? (ID 7638)
11:50 - 12:10 | Presenting Author(s): Shun Lu
- Abstract
- Presentation
Abstract:
The standard treatment of early stage non-small cell lung cancer (NSCLC) is lobectomy with systematic mediastinal lymph node evaluation. Unfortunately, up to 25% of patients with stage I NSCLC are not lobectomy candidates because of severe medical comorbidity including limited pulmonary reserve. During the past decade, stereotactic ablative radiotherapy (SABR) has resulted in local control in excess of 90% of tumours with medically inoperable and operable clinical stage I NSCLC. The local treatment including surgery and SABR is the stand of care for these patients . No definite evidence-based medicine data about the systemic therapy had been reported in this subgroup patients. A systemic therapy approach to the treatment of patients with medically inoperable, early stage NSCLC is not warranted. The management suggestions were unanimously agreed upon based on available literature. Systemic Therapy combined with local treatment could be a good option for these patients. 1. Chemotherapy+ local treatment: It seems that it is not recommended to add chemotherapy to local treatment for those medically inoperable, early stage NSCLC. It is reported that no evidence of an improvement in event-free survival was seen with the addition of weekly gemcitabine at this dose for patients with early stage NSCLC unfit for surgery, although the power of the study was low. 2. Targeted Therapy+ local treatment: No clear data about the targeted therapy for those medically inoperable, early stage NSCLC patients. For those driven gene positive patients, targeted therapy combined with local treatment seems to be a good choice. Some people worried about the combined therapy may increase the potential for pulmonary toxicity in patients with baseline pulmonary dysfunction, however, there is no cases of interstitial lung disease in early stage NSCLC as adjuvant therapy in 2017 ASCO (CTONG 1104). Further studies should be developed for these patients. 3. Immunotherapy + local treatment: The integration of radiation with immunotherapy is a conceptually promising strategy, as radiation has potent immune-modulatory effects and may contribute not only to local control but also augment systemic antitumor immune response. The advent of novel immunotherapy agents affords patients and clinicians therapeutic modalities to improve patient longevity and avenues to study innovative combinations of therapies. Preclinical data and case reports suggest the potential for robust clinical responses in metastatic NSCLC patients using this strategy, but prospective clinical trials evaluating the integration of radiation and immunotherapy are limited. The use of immunotherapy in non-metastatic settings is also intriguing but understudied. Summary: The assessment of treatment options for limited pulmonary reserve patients that requires uniform reporting of comorbidities and outcomes in clinical studies, which often is lacking. Systemic Therapy combined with local treatment could be a good option for these patients. Trials involving systemic therapy for patients with medically inoperable NSCLC should be developed.
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GR 03.06 - Possibility of Radiotherapy (SBRT) for Early Stage NSCLC (ID 7639)
12:10 - 12:30 | Presenting Author(s): Laurie E Gaspar
- Abstract
- Presentation
Abstract not provided
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Author of
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GR 03 - Treatment Options for Early Stage Lung Cancer Patients with Limited Pulmonary Reserve (ID 522)
- Event: WCLC 2017
- Type: Grand Rounds
- Track: Early Stage NSCLC
- Presentations: 1
- Moderators:Alexander Vincent Louie, I. Yoshino
- Coordinates: 10/18/2017, 11:00 - 12:30, F205 + F206 (Annex Hall)
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GR 03.01 - Case Study (ID 10953)
11:00 - 11:05 | Presenting Author(s): Alexander Vincent Louie
- Abstract
- Presentation
Abstract not provided
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OA 16 - Treatment Strategies and Follow Up (ID 686)
- Event: WCLC 2017
- Type: Oral
- Track: Early Stage NSCLC
- Presentations: 1
- Moderators:Jun Nakajima, T. Demmy
- Coordinates: 10/18/2017, 14:30 - 16:15, Room 315
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OA 16.01 - Stereotactic Ablative Radiotherapy Versus Surgery in Early Lung Cancer: A Meta-analysis of Propensity Score-Adjusted Studies (ID 8066)
14:30 - 14:40 | Author(s): Alexander Vincent Louie
- Abstract
- Presentation
Background:
There is currently no completed randomized controlled trial data comparing stereotactic ablative radiotherapy (SABR) and surgery in operable patients with early-stage non-small cell lung cancer (ES-NSCLC). Propensity score methods are increasingly utilized in oncology to balance the baseline characteristics of non-randomized cohorts, mimicking the setting of a clinical trial. No previous meta-analysis of propensity score analyses comparing a surgical and non-surgical modality has been conducted. Our goal was therefore to perform a systematic review and meta-analysis of all propensity score analyses comparing SABR and surgery in patients with ES-NSCLC.
Method:
A systematic review was carried out according to PRISMA guidelines by querying the MEDLINE and Embase databases from inception until December 2016. Hazard ratios (HR) with confidence intervals (CI) for overall survival (OS) and disease-specific survival (DSS) were directly extracted, if available, or estimated from Kaplan-Meier curves. Meta-analysis was carried out with inverse variance-weighted random-effects models.
Result:
After reviewing 1039 records, 17 PS-adjusted studies with a total of 20151 patients were included in the final analysis. Overall survival (OS) favoured surgery over SABR (HR = 1.52 [95% CI: 1.33-1.74], p < 0.001). However, the rate at which patients died from lung cancer (DSS) was not significantly different (HR = 1.13 [95% CI: 0.86-1.49], p = 0.38). On subgroup analysis, OS was superior for both lobectomy (HR = 1.61 [95% CI: 1.27-2.03], p < 0.001) and sublobar resection (HR = 1.33 [95% CI: 1.15-1.55], p < 0.001) versus SABR while DSS again did not significantly differ (HR = 1.35 [95% CI: 0.70-2.62] and HR = 1.18 [95% CI: 0.84-1.67], respectively). On secondary analysis, meta-analysis of proportions revealed a lymph node upstaging rate of 16.0% (95% CI: 13.6%-18.6%) and adjuvant chemotherapy usage rate of 11.5% (95% CI: 8.6%-14.8%) among patients who received surgery. On meta-regression, with every increase of 0.1 in the maximum allowable difference in propensity score within a matched pair - representing increases in imbalance between cohorts, DSS outcomes increasingly favoured surgery by 1.36-fold. Critical appraisal revealed inconsistent reporting of propensity score methods.
Conclusion:
Overall survival favoured surgery over SABR in this meta-analysis of 17 propensity score analyses. However, the effectiveness of SABR was reflected in a similar DSS to surgery, supporting ongoing clinical equipoise. A direct relationship between propensity score methodology and DSS outcomes were demonstrated. Whether this observed benefit in OS for surgery is real or due to limitations in the propensity score methodology requires confirmation through randomized data.
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P1.14 - Radiotherapy (ID 700)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Radiotherapy
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.14-018a - Stereotactic Ablative Radiotherapy for Ultra-Central Lung Tumors: Optimize Tumor Control or Minimize Toxicity? (ID 9509)
09:30 - 09:30 | Presenting Author(s): Alexander Vincent Louie
- Abstract
Background:
Lung stereotactic ablative radiotherapy (SABR) is associated with low morbidity, however there is an increased risk of treatment-related toxicity in tumors directly abutting or invading the proximal bronchial tree, termed ‘ultra-central’ tumors. For such tumors, there is no consensus regarding the most appropriate dose-fractionation scheme. The purpose of this planning study was to evaluate the therapeutic ratio of SABR treatment plans for ultra-central tumours using commonly utilized dose fractionation regimens.
Method:
In this research ethics board approved study, 10 patients with ultra-central lung tumors were identified from our institutional database. New plans were generated for each of the 10 cases using 3 different hypofractionated schedules: 50 Gy in 5 fractions, 60 Gy in 8 fractions and 60 Gy in 15 fractions. For each of the three dose regimens, 2 plans were generated, one prioritizing tumor coverage and the other plan compromising PTV coverage in order to respect the dose constraints for the esophagus, lung and proximal bronchial tree. Using published normal tissue complication probability models, plans were evaluated for likelihood of toxicity to these organs at risk.
Result:
In the scenario where PTV coverage was prioritized, the probabilities of acute esophageal or pulmonary toxicity were low, ranging from 0.9-1.2% and 3.7-4.3%, respectively. In contrast, the estimated risk of grade 4 or 5 toxicity to the proximal bronchial tree varied significantly: 68% for 50 Gy in 5 fractions, 44% for 60 Gy in 8 fractions and 2% for 60 Gy in 15 fractions. When dose to the organs at risk was prioritized, risk of toxicity to the proximal bronchial tree was reduced to <1% for all 3 dose fractionation schemes. This compromise resulted in a reduction in the calculated tumor control probabilities, from 92.9% to 60.3% for 50 Gy in 5 fractions, 92.4% to 65.7% for 60 Gy in 8 fractions and 52% to 47.8% for 60 Gy in 15 fractions.
Conclusion:
With the use of SABR or hypofractionated radiotherapy for ultra-central lung tumors, the competing risks of tumor local control and treatment toxicities need to be considered. Predicted rates of local control are inversely related to the risk of severe pulmonary toxicity due to trade-offs in the radiation planning process. Further prospective research is needed to better assess the optimal dose fractionation schedule for ultra-central lung tumors.
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P2.14 - Radiotherapy (ID 715)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Radiotherapy
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.14-009 - Assessing the Value of Radiotherapy for Lung Cancer in the Intensive Care Unit – A Population-based analysis (ID 9132)
09:30 - 09:30 | Presenting Author(s): Alexander Vincent Louie
- Abstract
Background:
As the use of radiotherapy (RT) in lung cancer patients in the ICU is poorly described; we evaluated characteristics, outcomes, RT utilization and costs in a population-based cohort of ICU lung cancer patients in Ontario, Canada.
Method:
Eligible patients between April 1, 2007 and March 31, 2014 were identified through provincial administrative healthcare databases. Given that a patient could receive multiple RT deliveries, each ICU stay was analyzed separately as an episode of care. Significant differences in patient, treatment, institution and tumor characteristics between RT and non-RT groups were compared with t-tests and chi-square tests, as appropriate. Pre-ICU disposition was by ER admission, same institution admission or different institution transfer. The Kaplan-Meier method was used to estimate overall survival (OS), measured from index ICU admission to death, censoring at the end of the observation period. Differences in OS between the RT and non-RT groups were compared using the log-rank test. Univariable and multivariable Cox proportional hazard modeling were performed to assess the effect of RT on OS. Daily costs were calculated in 2015 Canadian dollars (converted using consumer price indices) for RT patients only, based on acute hospitalizations, ER visits, cancer clinic visits, same-day surgeries, and physician billings. For all analyses, a p-value threshold of <0.05 was used to define statistical significance.
Result:
In 13,739 unique lung cancer ICU patients, RT was delivered in 133 episodes to 1.0% (n=131) of patients. The RT group tended to be younger (median age 65 vs. 68, p<0.001), on some form of ventilation (79.8% vs. 38.2%, p<0.001) and with longer ventilation durations ((median [IQR]) 6 [1-11] vs. 0 [0-2] days, p<0.001). RT patients were more likely to present from the ER (28.2% vs. 21.9%, p=0.002) or via transfer (35.3% vs. 9.7%, p<0.001). While ICU discharge was common in both RT (56.4%) and non-RT (71.4%) cohorts, 1-year OS was poor with both groups, but most notably in the RT group (11.3% vs. 42.4%). RT was associated with inferior 1-year OS on unadjusted modeling (HR=1.99, 95% CI:1.65-2.38, p<0.001), with ventilation status and pre-ICU disposition adjusting this finding towards the null on multivariable modeling (HR=1.17, 95% CI:0.97-1.40, p=0.095). The median daily cost of medical care in RT patients was $2771 (IQR $1757-$3753), with acute hospitalization accounting for more than half (median $1723) of calculated costs.
Conclusion:
The use of RT needs to be considered judiciously for lung cancer patients in the ICU, given the poor prognosis and increased costs incurred.
