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I. Yoshino
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 - 12:30 | Presenting Author(s): Alexander Vincent Louie
- Abstract
- Presentation
Abstract not provided
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GR 03.02 - Case Study (ID 10954)
11:00 - 12:30 | 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)
11:00 - 12:30 | 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)
11:00 - 12:30 | 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)
11:00 - 12:30 | 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)
11:00 - 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 03.02 - Case Study (ID 10954)
11:00 - 12:30 | Presenting Author(s): I. Yoshino
- Abstract
- Presentation
Abstract not provided
Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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P1.16 - Surgery (ID 702)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Surgery
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.16-008 - Near-Infrared Fluorescence-Guided Pulmonary Segmentectomy Following Endobronchial Indocyanine Green Injection (ID 8561)
09:30 - 16:00 | Author(s): I. Yoshino
- Abstract
Background:
Near infrared (NIR) fluorescence-guided pulmonary segmentectomy following endobronchial or intravenous indocyanine green (ICG) administration has been developed and reported. The aim of this study is to prospectively validate the feasibility and safety of NIR fluorescence-guided pulmonary segmentectomy following endobrochial ICG injection using navigational bronchoscopy.
Method:
Patients who underwent pulmonary segmentectomy were prospectively enrolled in this study. Using preoperative CT datasets a 3D image of target segments was reconstructed for lung volumetry and a bronchial road map was created to determine the bronchus for ICG injection. The ICG concentration was 0.125 mg/mL. Immediately after intubation the ICG was injected into the target bronchi using an ultrathin bronchoscope followed by air flushing to expedite ICG dispersion to the periphery. A NIR thoracoscope (PINPOINT, Novadaq) was used to detect ICG fluorescence and determine intersegmental plane for pulmonary segmentectomy. Usefulness and safety of this technique were evaluated by 1) whether ICG demarcation lines correspond to intersegmental lines expected from pulmonary veins, 2) whether large bronchi and vessels in adjacent segments emerge when dividing intersegmental planes using electrical cautery. The patients were followed up to 1 month after surgery to see if any complication existed.
Result:
Eight male and 7 female patients with a mean age of 66.5 ± 9.6 years were enrolled. Segmentectomy regions included right S1, S2, S6, S8 and S10 segments, and left S1+2+3, lingular, S6, S8, S9+10, and basilar segments. The average bronchoscopic procedure time was 14.3 ± 8.0 minutes. Vital signs were kept stable before and after the bronchoscopic procedure. The mean injected volume of ICG solution was 21.2 ± 8.8 mL as per a case. In 13 out of 15 cases (86.7%), NIR fluorescence guidance was recognized as effective for pulmonary segmentectomy. Intersegmental plane could not be determined in 2 cases likely due to insufficient air flushing, leading to the failure of ICG dispersion to the periphery. There was no complications developed intraoperatively. The average operation time was 193 ± 41 minutes, with a mean bleeding of 110 ± 101 mL. The average duration of drainage was 3.1 ± 1.0 days. Recurrent air leakage happened on postoperative day 6 in 1 case. Otherwise, no procedure related adverse event was noted.
Conclusion:
NIR fluorescence-guided pulmonary segmentectomy following endobrochial ICG injection using navigational bronchoscopy appeared to be safe and feasible. Sufficient air flushing may be the key for clear ICG demarcation of referred segments.
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P2.02 - Biology/Pathology (ID 616)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.02-063 - Oncogenic microRNAs Associated with Poor Prognosis Are Up-Regulated on the Amplicon in Squamous Cell Lung Carcinoma (ID 9901)
09:30 - 16:00 | Author(s): I. Yoshino
- Abstract
Background:
Squamous cell carcinoma (Sq) is second major histological subtype of lung cancer. Unlike in the case of adenocarcinoma (Ad), Sq has only few molecular target drug. MicroRNA (miR) is a major part of post-transcriptional regulators functioning as tumor suppressor genes or oncogenes. MiR will regulate target molecules related to carcinogenesis and malignancy in Sq.
Method:
Using The Cancer Genome Atlas dataset including copy number variation, RNA sequence, miR sequence, clinicopathological feature from 484 lung cancer cases, the correlation between genomic copy number and expression of miR was analyzed. 245 samples of Sq and 239 samples of Ad were included. The raw counts of each mature miR fragments with different precursor were merged and calculated from miR-seq isoform files by R project (http://www.r-project.org/) Segmented copy number variation datasets were processed with R package CNTools of Bioconductor project. Independent two-group Mann-Whitney U test was used to compare different expression between Sq and Ad. MiR expression according to copy number variation was analyzed using Pearson correlation coefficient r-score. To identify the miR target sites of mRNAs, targetscan-Perl scripts were used (http://www.targetscan.org/).
Result:
From 1,001 mature miR fragments, 34 miRs were identified as the candidates especially for Sq distinguished from Ad. Furthermore, four miRs were up-regulated in amplified regions and independently associated with poor prognosis in Sq. Moreover, those who had the tumor with high expression in three of four miR simultaneously showed worst prognosis. To explore miR-mRNA network, we also predicted the target genes for each miR. From 734 common target genes, three showed positive correlation with the expression of three miRs. Among them, the expression of 109 mRNAs inversely correlated with that of 3 miRs. From 109 mRNA, the expression of 24 mRNAs inversely correlated with that of all the 3 miRs and only 2 mRNA expression showed low levels in Sq compared with Ad or normal tissues.
Conclusion:
Three miRs up-regulated in Sq were associated with poor prognosis through the regulation of two common target genes.
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P2.07 - Immunology and Immunotherapy (ID 708)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Immunology and Immunotherapy
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.07-008 - Does PD-L1 Expression of the Archive Surgical Specimen of Primary Tumor Predict the Sensitivity of Recurrence to Nivolumab in Patients with NSCLC? (ID 8041)
09:30 - 16:00 | Author(s): I. Yoshino
- Abstract
Background:
Nivolumab is an immune checkpoint inhibitor targeting human IgG4 programmed death 1 for advanced or recurrent non-small lung cancer (NSCLC), and programmed death ligand 1 (PD-L1) expression of tumor tissue is expected to be a biomarker of the sensitivity to Nivolumab. More recent biopsy is likely to be more suitable since PD-L1 expression of tumor cells is influenced by time or by anti-tumor therapies such as chemotherapy or radiotherapy, and most clinical studies have referred to the PD-L1 expression using the latest biopsy samples before administration of Nivolumab. Therefore, it remains controversial whether PD-L1 expression of the archive specimen obtained at the time of initial surgery for primary disease is correlated with the sensitivity of recurrent diseases to Nivolumab.
Method:
We retrospectively reviewed 10 NSCLC patients who had undergone radical surgery for primary tumor and received Nivolumab for their recurrent diseases. The median interval between the initial surgery and Nivolumab administration was 28.1 months (2-75), and median number of anti-tumor regimens prior to Nivolumab was 2.2 (1-5). Archive specimens of primary tumors and second biopsy samples of recurrent diseases from the 10 patients were stained to measure PD-L1 expression both with the PD-L1 IHC 28-8 pharmDx Daco (assay 28-8), and with the PD-L1 IHC 22C3 pharmDx Daco (assay 22C3).
Result:
Among the 10 patients, complete response (CR)/partial response (PR)/ stable disease (SD)/progressive disease (PD) for Nivolumab were 1/2/3/4 patients, respectively. All patients had PD-L1 expressions as tumor proportion score (TPS)≧1%, of which 7 showed TPS≧10% in the assay 28-8. All 3 patients (30%) with CR/PR showed TPS≧10%. The TPS obtained by assays 28-8 and 22C3 were similar in 9 of 10 patients. Two patients underwent biopsies for their recurrent sites, which showed decreased PD-L1 expression compared with primary tumor, resulted in PD for Nivolumab.
Conclusion:
The PD-L1 expressions of surgical archive specimen might be almost associated with the sensitivity to Nivolumab, however, time and antitumor therapies may modulate the PD-L1 expressions and might be able to affect the sensitivity to Nivolumab. Further pre-clinical and clinical studies are warranted to evaluate the availability of surgical archive specimen in the treatment of postoperative recurrence by the immunocheckpoint inhibition.
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P2.12 - Pulmonology/Endoscopy (ID 713)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Pulmonology/Endoscopy
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.12-006 - Evaluation of New 25G Needle in EBUS-TBNA Comparing Conventional 22G Needle in Diagnosis for Nodal Metastasis of Lung Cancer (ID 10271)
09:30 - 16:00 | Author(s): I. Yoshino
- Abstract
Background:
Dedicated 22G needle is usually used for EBUS-TBNA, which is a main diagnostic tool for nodal staging in lung cancer. Recently new 25G needle is developed and expected less invasive nodal biopsy. Although, diagnostic yield and complication of the EBUS-TBNA using 25G needle are still unclear.
Method:
From September 2016 to May 2017, 39 hilar or mediastinal lymph nodes in 25 patients were consecutively biopsied using both 22G (Olympus, Tokyo, Japan) and 25G (Boston Scientific, MA) needles for diagnosis or staging of lung cancer. Concordance rates of rapid on-site cytologic evaluation and cytological and pathological diagnosis between the EBUS-TBNAs using the two types of needles were evaluated. And also, bleeding score of cytological specimen (0-3: higher is more contaminated) and calculated area of histological core (the number of high-power field microscopically in paraffin-embedded slides) were compared for evaluating sample qualities. The results obtained from EBUS-TBNA using 22G needle were regarded as control to evaluate the diagnostic ability of that using 25G needle in this analysis.
Result:
No complication was recorded during the study period. Thirty three Mediastinal nodes (#2(n=2), #3(n=1), #4R(n=16), #4L(n=2), #7(n=12)) and 6 hilar nodes (#10(n=1), #11(n=3), #12(n=2)) were biopsied and concordance rate between 22G and 25G was 87% (34/39) in the rapid on-site cytologic evaluation, 95% (37/39) in the cytological diagnosis and 85% (35/39) in the histological diagnosis. Final decision whether metastatic or not according to the combined cytologic and histologic diagnosis in the EBUS-TBNA using 22G needle was 19 metastases and 20 benign nodes, and the concordance rate with the two types of needles was 92% (36/39). In the 3 nodes with discrepancy, 2 nodes were diagnosed as lung cancer metastasis by the 25G needle sampling. Both bleeding score and calculated area of histological core showed no significant difference (p=0.3 and 0.7) between 22G and 25G, with respective values of 1.8±0.9 vs. 2.0 ±0.7, and 20±2.2 vs. 21±2.2.
Conclusion:
EBUS-TBNA using 25G needle is feasible and as useful as that using conventional 22G.
