Tumor In Upper Lobe Research Articles

The Relationship Between Nodal Metastases and Primary Location in Stage I Non-Small Cell Lung Cancer

IntroductionThis study examines the relationship between location of the primary tumor and specific nodal metastases in clinical stage 1 non-small cell lung cancer (NSCLC) patients undergoing lobectomy. MethodsWe retrospectively analyzed all lobectomies performed at a single institution, between January 2005 and December 2019, for clinical stage I NSCLC patients. Patients selected for this study were clinically node negative (cN0) by positron emission tomography-computed tomography scan and selectively by endobronchial ultrasound or mediastinoscopy. Cases of postoperative pathologic nodal upstaging were identified among these patients. For each patient upstaged, the specific lymph node stations found to be positive were recorded. Descriptive statistics, chi-squared tests, and Fisher's exact test were utilized to identify independent risk factors for upstaging to specific N1 and N2 lymph node stations. All clinical and pathologic staging information was retrospectively normalized to the International Association for the Study of Lung Cancer 8th Edition TNM Classification. ResultsThe research cohort included 645 patients. The mean age was 68 years (standard deviation ± 9.2), 54% were female, and 88% were White, 11% Black, and 1% other. Twelve percent (n = 75) were upstaged from cN0 to pN1 or pN2 upon final pathologic examination: 41 to pN1 (54.7%) and 34 to pN2 (45.3%). The primary tumor location with the highest rate of nodal upstaging was the left upper lobe (LUL) (12.8%). Tumors in the right middle lobe had the lowest rate of unsuspected nodal metastases (8.8%). Out of all upstaged patients, there were no positive level eight lymph nodes, and only 1 patient with a positive level nine lymph node. Lymph node levels five and six were only positive in LUL primary tumors, a relationship that approached statistical significance (P = 0.0797). No patients with a LUL primary tumor had a positive level seven lymph node. Upstaging at station 12 was significantly associated with the location of the primary tumor, occurring less often in tumors originating in the right upper lobe in comparison to other lobes (P = 0.0288). ConclusionsWe identified relationships between the location of a primary tumor and specific nodal upstaging in patients with clinical stage I NSCLC who undergo lobectomy. We found the following: 1) only 1 patient had a positive level eight or nine lymph node out of 645 patients; 2) only LUL primary tumors demonstrated upstaging to level five or six lymph nodes; and 3) right upper lobe tumors were significantly less likely to be associated with a positive level 12 lymph node.

Left Upper Lobectomy vs Trisegmentectomy for Lung Cancer: A Propensity Score–Matched Comparison

BackgroundThe left upper division (segments I-III) and the lingula (segments IV and V) are analogous to the right upper and middle lobes, respectively. Whereas bilobectomy for right upper lobe tumors is rare, left upper division tumors are often resected by left upper lobectomy (LUL) rather than by left upper trisegmentectomy (LU3S). To assess safety and oncologic efficacy of LUL vs LU3S, we compared short- and long-term outcomes after both procedures. MethodsPatients undergoing LUL or LU3S for clinical stage IA-IIA non-small cell lung cancer in the left upper division from January 2006 to December 2020 were identified from an institutional database. Propensity score matching was used to control for clinical differences. ResultsWe identified 229 cases meeting inclusion criteria: 131 (57.2%) LUL, 98 LU3S. After matching, 83 cases were included in each group. Median clinical tumor size was similar for LUL vs LU3S (2.2 cm [interquartile range, 1.6-3.0 cm] vs 2.1 cm [interquartile range, 1.7-2.9 cm]; P = .80). Total lymph nodes sampled did not differ between LUL and LU3S (median, 7 vs 6; P = .36), nor did patterns of N2 sampling (P = .11). Odds of postoperative complications did not differ after LUL vs LU3S (odds ratio, 0.75; 95% CI, 0.39-1.46). No 30-day death was observed. Median follow-up was 72 months. There was no statistically significant difference in 5-year overall survival (75.9% vs 82.1%; P = .28) or locoregional recurrence-free survival (73.7% vs 80.0%; P = .23) after LUL vs LU3S. ConclusionsOur findings suggest that LU3S and LUL have equivalent short- and long-term outcomes in patients with clinical stage IA-IIA non-small cell lung cancer in the left upper division.

Investigation of uncertainty in internal target volume definition for lung stereotactic body radiotherapy

This study evaluated the validity of internal target volumes (ITVs) defined by three- (3DCT) and four-dimensional computed tomography (4DCT), and subsequently compared them with actual movements during treatment. Five patients with upper lobe lung tumors were treated with stereotactic body radiotherapy (SBRT) at 48 Gy in four fractions. Planning 3DCT images were acquired with peak-exhale and peak-inhale breath-holds, and 4DCT images were acquired in the cine mode under free breathing. Cine images were acquired using an electronic portal imaging device during irradiation. Tumor coverage was evaluated based on the manner in which the peak-to-peak breathing amplitude on the planning CT covered the range of tumor motion (± 3 SD) during irradiation in the left–right, anteroposterior, and cranio-caudal (CC) directions. The mean tumor coverage of the 4DCT-based ITV was better than that of the 3DCT-based ITV in the CC direction. The internal margin should be considered when setting the irradiation field for 4DCT. The proposed 4DCT-based ITV can be used as an efficient approach in free-breathing SBRT for upper-lobe tumors of the lung because its coverage is superior to that of 3DCT.

Prognostic value of L4 lymph node dissection during video-assisted thoracoscopic surgery in patients with left-sided non-small cell lung cancer: a single-center, retrospective cohort study.

Lymph node dissection (LND) is crucial procedure during radical resection of non-small cell lung cancer (NSCLC), but the prognostic value of L4 LND remains elusive. To investigate the prognostic value of L4 LND in patients with left-side NSCLC who underwent video-assisted thoracoscopic surgery (VATS). Three hundred twelve patients who underwent VATS between Jan. 2007 and Dec. 2016 were reviewed. Of those, 119 underwent L4 LND (L4D+), whereas the other 193 patients did not (L4D-). The inclusion criteria were as follows: patients diagnosed with primary left-sided NSCLC who underwent VATS lobectomy combined with LND; patients subjected to R0 resection and tumor pathological stage T1-4N0-2M0. The primary endpoint was overall survival (OS). OS was calculated from the operation date to the date of death. The chi-square test was used for categorical variables, and a t test was used for continuous variables. A total of 119 patients underwent L4 LND, and the procedure was more likely to be performed on upper lobe tumors (P=0.019). Patient distributions with respect to age, gender, smoking history, clinical stage, adjuvant therapy, tumor differentiation and tumor size were well balanced between two groups. More lymph nodes (LNs) were dissected in the L4D+ group than in the L4D- group (P<0.001). The rate of metastasis to L4 lymph nodes was 9.2%, which was comparable between patients with upper and lower lobe tumors (8.9% vs. 10.0%, P=1.000). The L4D+ group exhibited a significantly better OS than the L4D- group (median OS: undefined vs. 130 months, HR 0.47; 95% CI: 0.31-0.72; P=0.002). Multivariate analysis showed that L4 LND was an independent factor for OS. However, OS did not significantly differ between the two groups of cT1aN0 and cT1bN0 patients (OS: HR 0.44; 95% CI: 0.18-1.06; P=0.12). L4 LND is recommended for patients with left-sided NSCLC as an essential component of radical resection. The role of L4 LND in cT1a-bN0 disease warrants further study.

Impact of tumor location and pleural invasion on the frequency of skip hilar lymph node metastasis in lung cancer.

The appropriate extent of hilar lymph node (LN) dissection in segmentectomy for lung cancer has not yet been fully investigated. Herein, we assessed the patterns of LN metastasis using network analyses. Patients with nodal metastases of non-small-cell lung cancer measuring ≤30 mm in diameter who underwent anatomical resection were included. The assumed pathways of metastasis were visualized using Cytoscape software. Metastasis to hilar (#10) or interlobar (#11) LNs but not to more peripheral ones was defined as skip N1 metastasis. A total of 322 patients were included, with 123 of them having pleural invasive tumors and 32 having intrapulmonary metastases. There were 130 patients with pN1 disease and 192 with pN2 disease. The overall proportion of patients with skip N1 metastasis was 17%. Patients with lower lobe tumors had more frequent skip N1 metastasis than those with upper lobe tumors (31% vs. 10%, P<0.001) but had less frequent skip N2 metastasis (10% vs. 20%, P=0.02). The rates of skip metastasis to #11i in the right S6 tumor and right S9-10 tumor were unexpectedly high (22% and 17%, respectively). Similarly, skip metastasis to #11 in the left S6 tumor was relatively high (16%). There was a significant difference in the frequency of skip LN metastasis between tumors with and without pleural invasion (44% vs. 27%, P=0.001). The pattern of LN metastasis differed according to the localized segment of the tumor and the pleural invasion status.

Endobronchial Implanted Real-Time Radiofrequency (RF) Transponder Beacon Guided, Respiratory-Gated, Stereotactic Body Radiotherapy for Moving Lung Tumors: Interim Analysis of a Prospective Phase I/II Cohort Study

<h3>Purpose/Objective(s)</h3> Endobronchially implanted real-time tracking system (technology company) radiofrequency (RF) transponder beacons provide real-time, high precision, positional data of moving lung tumors. We report interim results of a Phase I/II prospective single arm prospective cohort study evaluating feasibility and dosimetric impact of real-time tracking system beacons for patients undergoing SBRT for moving lung tumors. <h3>Materials/Methods</h3> Eligible patients were adults, ECOG 0-2, with T1-T2N0 Non-small cell lung cancer (NSCLC) or pulmonary metastasis ≤4cm of the right middle/lower lobe, or lingula. Upper lobe tumors were eligible if they moved ≥5mm. Three real-time tracking system beacons were endobronchially implanted at prespecified peritumoral locations using SuperDimension™ navigational bronchoscopy (Medtronic, USA). Four-dimensional free-breathing CT simulation scans were obtained and end-exhalation phases were selected to define a gating window (GW). A 3mm expansion of the ITV_GW defined the PTV. Real-time tracking system-guided, respiratory phase-gated, SBRT (GW-SBRT) was delivered using 10MV VMAT photon arcs at 2400MU/min to total doses of 54Gy/3# or 48Gy/4#. For each GW-SBRT plan, a corresponding 10-phase plan was generated for comparison to standard image-guided (IG)SBRT. PTV, and OAR metrics were tabulated and differences between GW-SBRT and IG-SBRT plans analyzed using non-parametric Wilcoxon Signed-Rank pair test. Treatment related toxicity was graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. <h3>Results</h3> From November 2017 to December 2021, 41 patients were screened and 17 patients consented to participate. Two patients did not undergo beacon implant: one had tumor progression; another withdrew consent. Of the 15 patients with beacon implants, median age was 73, with 7 females. 47% were T1 NSCLC, 40% were M1 and remaining 13% were T2 NSCLC. Median tumor dimension was 1.9cm. 73% of targets were located peripherally, and 27% centrally with a median respiratory tumor motion of 1.25 cm (range 0.53 cm to 4.04 cm). No beacon migration was observed between CT simulation scan and the completion of SBRT treatments. Of the N=12 tumor targets were treated with GW-SBRT, 47% of patients received 48Gy/4# and 53% received 54Gy/3#. GW-SBRT yielded an average relative reduction of PTV of 46.9% (p<0.005) compared with IG-SBRT. Lung V5, V10, V20 and D2 had mean relative reductions of 11.3%, 20.3%, 31.1% and 15.5% respectively (p<0.005). Dose to OARs was significantly reduced (p<0.05) except for spinal cord. At 6 months follow-up, mean radiographic tumor volume reduction was 53.5% (p<0.005); No treatment related grade 3 toxicity was observed. <h3>Conclusion</h3> Endobronchial RF beacons are safe and effective at reducing SBRT treatment volumes for patients with moving lung tumors and can be considered for tumors with large motion amplitude or those located in close proximity to organs at risk. This study has the ClinicalTrials.gov identifier NCT03322072.

MA12.05 Is there a Role for Surgery in Stage I Small Cell Lung Cancer? A National VA Database Analysis

Historically, limited stage Small Cell Lung Cancer (SCLC) has been treated with concurrent chemoradiation (CRT). While current NCCN guidelines recommend consideration of lobectomy in node-negative cT1-T2 SCLC, data regarding the role of surgery in very limited SCLC is lacking. To our knowledge, only one retrospective study has evaluated the role of surgery in stage I SCLC. Data from the National VA Cancer Cube were compiled. A total of 1,028 patients with pathologically confirmed Stage I SCLC were studied. Only 661 patients that either received surgery or CRT were included. Interval-censored Weibull and Cox proportional hazard regression models were used to estimate median overall survival (OS) and hazard ratio (HR), respectively. Two survival curves were compared by a Wald test. Subset analysis was performed based on the location of the tumor in the upper vs lower lobe as delineated by ICD-10 codes C34.1 and C34.3. Four-hundred and forty-two patients received concurrent CRT; while 219 underwent treatment that contained surgery (92 surgery only, 84 surgery/chemo, 39 surgery/chemo/radiation and 4 surgery/radiation). The median OS for the surgery-inclusive treatment was 3.87 years (95% CI 3.25-4.60) while median OS for the CRT cohort was 2.43 years (95% CI 2.15-2.72). HR of death for surgery-inclusive treatment when compared to CRT is 0.65 (95% CI 0.54-0.79; p<0.001). Subset analysis based on the location of the tumor in upper lobe and lower lobe showed improved survival with surgery as compared to CRT regardless of the location. HR for upper lobe was 0.61 (95% CI 0.48-0.78; p<0.001) and lower lobe 0.60 (95% CI 0.41-0.87; p=0.007). Multivariable regression analysis accounting for age and ECOG-PS shows a HR 0.60 (95% CI 0.42-0.85; p=0.004) favoring surgery. Surgery was used in less than a third of patients with stage I SCLC who received treatment. Surgery-inclusive multimodality treatment was associated with a longer overall survival as compared to chemoradiation, independent of age, performance status or tumor location. Our study suggests a more expansive role for surgery in stage I SCLC.

Correlation between tumor location and survival in stage I lung adenocarcinoma and squamous cell carcinoma: a SEER-based study.

Background: Whether location mattered remained controversial in early-stage non-small cell lung cancer.Methods: We conducted a retrospective study with the Surveillance, Epidemiology, and End Results (SEER) database. Overall survival (OS) and lung cancer-specific survival (LCSS) with landmark analysis and restricted mean survival time (RMST) were compared between patients with a tumor in upper lobe and non-upper lobe. The multivariable Cox analysis was applied to evaluate multiple prognostic factors.Results: Tumor in non-upper lobe had worse OS (hazard ratio [HR]: 1.354, p < 0.001) and LCSS (HR: 1.476, p = 0.005) than the upper lobe in stage IB adenocarcinoma in 32-month landmark and IA3 (OS, HR: 1.300, p < 0.001; LCSS, HR: 1.413, p = 0.004) adenocarcinoma in 48-month landmark, but not in stage IA1 and IA2 adenocarcinoma. The results remained positive in subgroups of < 4, ≥ 4 and ≥ 11 LN examined in stage IB tumor and ≥ 4 LN examined in stage IA3 tumor. For SCC, non-upper lobar tumor had similar OS and LCSS with upper lobar tumor in all stages. The multivariate Cox analysis confirmed that the non-upper lobe was an independent risk factor in stage IA3-IB adenocarcinoma, but not in SCC. Adjuvant chemotherapy (ACT) could improve OS in stage IB adenocarcinoma (HR: 0.586, p < 0.001) and SCC (HR: 0.708, p = 0.030) located in non-upper lobe.Conclusions: Non-upper lobar adenocarcinoma in stage IA3-IB was associated with worse prognosis. ACT may improve prognosis in stage IB tumor located in non-upper lobe.

Adaptive Radiotherapy in Locally Advanced Lung Cancers – Real World Scenario from a Tertiary Cancer Center

Concurrent chemo-radiation (CTRT) for locally advanced lung cancer (LALC) leads to dynamic changes in tumor volume and location especially in patients with large tumor or atelectasis. Using adaptive radiotherapy (ART) prevents under dosage of the tumor and over dosage of the organs at risk (OAR). One hundred forty patients of LALC from Jan 2017 to Dec 2019 were treated with concurrent CTRT. A four-dimensional computed tomography (4D CT) scan was acquired and contouring of gross target volume (GTV) was guided by PET-scan fusion. All patients were planned to receive 60Gy/30 daily fractions with volumetric modulated arc therapy. Cone-beam CT (CBCT) for set-up verification was performed at least twice weekly. Change in anatomy and tumor response was determined on CBCT during weekly radiotherapy audit. Patients suitable for ART were re-simulated and re-planned. GTV now consisted of residual tumor and 5mm isotropic clinical target volume (CTV) was generated and manually extended to include areas suspicious for residual disease. Dose delivered prior to ART and time needed to execute ART (calculated from the day of re-simulation to the day of starting ART) were documented. The volumetric and dosimetric changes were analyzed using paired t-test between the 2 plans for full prescription dose. We also evaluated local control for this cohort. Out of 140 patients, 35 (25%) required re-planning for ART. Median age was 61 years (range 50 - 65). Twenty-six patients (75%) had upper lobe tumors. Fifteen (43%) patients had squamous carcinoma, 13 (37%) had adenocarcinoma, and 7 (20%) had small cell carcinoma. Requirement for ART was anticipated in 10/35 (28%) patients prior to CTRT. The triggers for ART were resolution of atelectasis in 7 (20%) patients, tumor response in 26 (74%) and progression in 2 (6%) patients. A median of 6 CBCTs prior to ART were acquired. A median of 26Gy (IQR 14-36Gy) was delivered prior to ART. While it required 5 days (IQR:3.5-7.5) for executing ART. There was a reduction in mean planning target volume of 23% (544cc - 418 cc; p = 0.003), mean GTV primary of 47% (153cc - 80.8cc; p = 0.024), and GTV nodes of 33.7% (8 cc - 5.3 cc; p = 0.033). The V20 of total lung minus PTV and the mean lung dose increased by 3.7% (18.8% - 19.5%; p = 0.158) and 4.5% (10.9Gy - 11.4Gy; p = 0.274) respectively whereas there was a reduction in heart V20 and Spinal cord Dmax by 18.3% (9.7 Gy to 8.2 Gy; p = 0.005) and 6.7% (36.6 Gy to 34.3 Gy; p = 0.100) respectively. At a median follow up of 14.7 months, the loco regional control rate was 70% and no patient experienced ³ grade 3 toxicity. In our practice approximately 25% patients of locally advanced lung cancer required ART, with tumor response and resolution of atelectasis being the most common triggers. Anticipation of clinically significant change, frequent use of on-board imaging and implementation of ART could prevent under dosage of the tumor and over dosage of OAR.

Impact of Anatomic Tumor Location on Clinical Outcomes: A Long-Term Analysis of Early Stage Non-Small Cell Lung Cancer Treated with Stereotactic Body Radiation Therapy and Fiducial Tracking

Treatment of early stage non-small cell lung cancer (ES-NSCLC) broadly includes surgical resection and definitive radiotherapy. Although surgical resection remains the standard of care for operable patients, approximately 20% of patients are deemed inoperable. A substantial body of literature has established stereotactic body radiation therapy (SBRT) as the ideal definitive therapy for those patients ineligible for surgery. A variety of techniques exist for SBRT delivery in the thorax, each with their own accommodations for respiratory motion. Such motion is linked with the anatomical location of the tumor, with those closer to the diaphragm demonstrating larger excursions than those localized to the upper lobes. In this study, we examined the long-term outcomes of patients treated with robotic SBRT using fiducial tracking to elucidate variations in clinical outcomes as a consequence of tumor anatomical location. This is a single institutional analysis of patients with medically inoperable, biopsy-confirmed lymph-node negative (T1-3N0M0) ES-NSCLC using the AJCC 7th edition Cancer Staging Manual. Patients were treated per institutional protocol with robotic SBRT and fiducial tracking to a total dose of 45-60 Gy in 3 to 5 fractions prescribed to the planning target volume defined as a 5-mm expansion from the gross tumor volume. Estimates of overall survival, progression-free survival, local control, and locoregional control for patients were obtained using Kaplan-Meier analysis. Association with tumor stage, tumor location, histology, age, performance status, smoking history, and biologically equivalent dose were evaluated using Cox proportional hazards regression models. One-hundred medically inoperable patients with early stage NSCLC were treated from August 2005 to August 2017. The median age of all treated patients was 74 (range, 52 – 94). The majority of patients (n = 67) had tumors in the upper lobes. Most patients had T1a (n = 27), T1b (n = 27), or T2a (n = 25) tumors. After a median follow up of 3.3 years, median overall survival for the entire cohort was 50 months. At 3 years, overall survival rates were 62% for patients with upper lobe tumors and 54% for patients with lower lobe tumors (p = 0.10). Progression-free survival (62% v 54%, p = 0.38), local control (89% v 93%, p = 0.66), and locoregional control (83% v 79%, p = 0.98) rates were also similar between the two groups. Anatomical location did not appear to lead to significantly different long-term clinical outcomes. Fiducial tracking appears to work well in this diverse population of patients despite differences in respiratory motion. Future research should explore if difference in SBRT technique can lead to variations in clinical outcomes stratified by tumor anatomical location.

The role of surgery in stage I small-cell lung cancer: A national VA database analysis.

e21109 Background: Historically, limited stage Small Cell Lung Cancer (SCLC) has been treated with concurrent chemoradiation (CRT). While current NCCN guidelines recommend consideration of lobectomy in node-negative cT1-T2 SCLC, real world data regarding the role of surgery in very limited SCLC is lacking. To our knowledge, only one retrospective study has evaluated the role of surgery in stage I SCLC. Methods: Data from the National VA Cancer Cube were compiled. A total of 1,028 patients with pathologically confirmed Stage I SCLC were studied. Only 661 patients that either received surgery or CRT were included. Interval-censored Weibull and Cox proportional hazard regression models were used to estimate median overall survival (OS) and hazard ratio (HR), respectively. Two survival curves were compared by a Wald test. Subset analysis was performed based on the location of the tumor in the upper vs lower lobe as delineated by ICD-10 codes C34.1 and C34.3. Results: Four-hundred and forty-two patients received concurrent CRT; while 219 underwent treatment that contained surgery (92 surgery only, 84 surgery/chemo, 39 surgery/chemo/radiation and 4 surgery/radiation). The median OS for the surgery-inclusive treatment was 3.87 years (95% CI 3.25-4.60) while median OS for the CRT cohort was 2.43 years (95% CI 2.15-2.72). HR of death for surgery-inclusive treatment when compared to CRT was 0.65 (95% CI 0.54-0.79; p &lt; 0.001). Subset analysis based on the location of the tumor in upper lobe and lower lobe showed improved survival with surgery as compared to CRT regardless of the location. HR for upper lobe was 0.61 (95% CI 0.48-0.78; p &lt; 0.001) and lower lobe 0.60 (95% CI 0.41-0.87; p = 0.007). Multivariable regression analysis accounting for age and ECOG-PS shows a HR 0.60 (95% CI 0.42-0.85; p = 0.004) favoring surgery. Conclusions: Surgery was used in less than a third of patients with stage I SCLC who received treatment. Surgery-inclusive multimodality treatment was associated with a longer overall survival as compared to chemoradiation, independent of age, performance status or tumor location. Our study supports a more expansive role for surgery in stage I SCLC.

Is lobe specific lymph node dissection adequate for cN0\u20131 non-small cell lung cancer?

PurposeThis study aims to explore whether lobe specific lymph node dissection (LND) is adequate for cN0–1 non-small cell lung cancer (NSCLC) or not.MethodsAmong 5613 cN0–1 NSCLC patients, 394 cases (7.0%) with pN2 were enrolled and the distribution of mediastinal lymph node metastasis was analyzed. The included patients were divided into the non-lobe specific lymph node metastasis (NLSLNM) group and the lobe specific lymph node metastasis (LSLNM) group. The clinicopathological characteristics were compared between two groups and multivariable analysis was performed to find independent factors predicting NLSLNM.ResultsThe incidence of pN2 cases deserved serious attention. The proportion of upper zone lymph node metastases was not rare in right (55.0%) and left (35.7%) lower lobe tumors. The proportion of subcarinal zone lymph node involvement was also high in right (21.8%) and left (25.8%) upper lobe tumors. Multivariable analysis showed that elevated carcinoembryonic antigen (CEA) level (P = 0.034), right lower lobe (RLL) tumors (P = 0.022) and station 11 involvement (P = 0.030) were independent risk factors for NLSLNM.ConclusionSystematic LND seems to be superior to lobe specific LND in the assessment of lymph node status and high CEA level, RLL tumors and station 11 involvement are predictors for NLSLNM.

Lobe-Specific Lymph Node Dissection for Clinical Early-Stage (cIA) Peripheral Non-small Cell Lung Cancer Patients: What and How?

We investigated the possible lobe-specific lymph node (LN) metastasis pattern of early-stage peripheral non-small cell lung cancers (NSCLC) and define the extent of lobe-specific LN dissection for them. We retrospectively collected clinical data of patients undergoing lobectomy or segmentectomy with systematic lymphadenectomy for clinical T1N0M0 peripheral NSCLC from January 2015 to December 2018. The LN metastasis pattern was analyzed by tumor lobe location. A total of 590 patients were included for analysis. The mean number of total dissected LNs was 12.3 ± 5.8 and 8.2 ± 4.1 for total dissected mediastinal LNs. The rate of mediastinal LN metastasis was 9.5%. For cases of upper lobe tumor and lower lobe tumor, 8.8% and 6.0% of them respectively metastasized to the upper LN zone (P = 0.274). However, upper lobe tumors hardly metastasized to the subcarinal (0.3%) and lower (0.3%) LN zones while for lower lobe tumors, the rate of LN metastasis was 10.2% and 5.4% respectively (both P < 0.001). However, all cases (100%) metastasizing from lower lobes to the upper LN zone had a tumor size of 2-3cm, whereas cases with a tumor size ≤ 2cm had no metastasis (0%). None of the tumors in the right middle lobe metastasized to the lower LN zone (0%). A lobe-specific LN metastasis pattern was observed in clinical stage IA peripheral NSCLC. For tumors in upper lobes (≤ 3cm), there may be no need to dissect lower mediastinal LNs and for tumors in lower lobes (≤ 2cm), dissecting upper mediastinal LNs may not be required.

Thorough survey and analysis of pulmonary lymphoepithelioma-like carcinoma in Macau and multimodality treatment for advanced disease

ObjectivePulmonary lymphoepithelioma-like carcinoma (LELC) is a rare type of non-small cell lung cancer. The clinical course and prognosis of advanced LELC are largely unknown. Few reports have discussed multimodality treatment for LELC. Materials and methodsThis retrospective study identified records from 2007 to 2018 of pulmonary LELCs and other lung cancer subtypes from hospital information systems and collected demographic, treatment, and survival data. ResultsIn this cohort of 69 LELCs (median age: 55.4), more female, non-smokers, and fewer right upper lobe tumors (4.3%) were observed in the LELC subgroup compared with others. The median overall survival (OS) of LELCs was 40 months, superior to other subtypes (p < 0.05), except adenocarcinoma (p = 0.062). Patients with early stage disease and primary tumor resection tended to have better OS in univariate analysis, but surgery was the independent predictor in multivariate analysis (0.042). The median OS of 52 advanced LELCs was 22.7 months. Platinum-based chemotherapy and radiotherapy with curative purpose were independent predictors for OS of advanced LELCs (p = 0.004 and 0.003, respectively). For patients who received multimodality treatment in advanced setting, the median line of treatments was two. The overall response and disease-control rates were 61.8% and 80.6%, respectively. There were no differences in response or survival between patients receiving taxane-combined and non-taxane-combined chemotherapy. However, patients treated with radiotherapy in upfront settings had significantly favorable response and progression-free survival compared with those without. One case with PD-L1 positivity had pembrolizumab in the 4th line and achieved tumor shrinkage and stable disease for 12 months. ConclusionPatients who underwent radical resection of primary tumors had better prognoses. Patients with advanced LELC could achieve satisfactory survival by receiving multimodality treatment, including platinum-based chemotherapy and/or radiotherapy. Immune checkpoint inhibitors may be part of future therapies. A well-organized clinical trial should be performed to determine the optimal treatment regimen.

P2.17-09 Preoperative Risk Factors of Potential Failure for Lobe-Specific Nodal Dissection in Clinical Early Stage (I-IIA) Non-Small Cell Lung Cancer

Clinical early stage (I-IIA) non-small cell lung cancer (NSCLC) is treated with pulmonary resection and systematic nodal dissection (SND) or lobe-specific nodal dissection. The aim of this study was to identify the preoperative risk factors for potential failure of lobe-specific nodal dissection in clinical early stage NSCLC. A retrospective review was carried out on patients who underwent pulmonary lobectomy and SND for clinical early stage (I-IIA) NSCLC. Patients with computed tomography and positron emission tomography were included, whereas patients with invasive mediastinal staging and right middle lobe tumor were excluded. Lobe-specific nodal dissection failure was defined as unexpected metastasis at inferior mediastinal nodes (stations 7, 8, and 9) for both upper lobe tumors and at superior mediastinal nodes (stations 2R and 4R for right upper lobe tumors and stations 4L, 5 and 6 for left upper lobe tumors) for both lower lobe tumors. The incidence of pN2 disease following the tumor location and the factors for the failure of lobe-specific nodal dissection were analyzed. From July 2005 to May 2017, 2130 patients were included in this study. Overall, 12.5% (266/2130) of the patients had pN2 disease. Among them, 33.2% (78/266) of pN2 patients showed potential failure of lobe-specific nodal dissection. Lobe-specific nodal dissection failure was shown in 49 of 764 (6.4%), 21 of 468 (4.5%), 2 of 534 (0.4%), and 6 of 364 (1.6%) cases in right upper lobe, right lower lobe, left upper lobe and left lower lobe, respectively. At multivariable analysis, female (OR: 1.86; 95% CI 1.14-3.03; p = 0.012), right upper lobe tumor (OR: 20.98; 95% CI 5.05-87.08; p <0.001), right lower lobe tumor (OR:14.81; CI 3.43-63.97; p <0.001), higher SUVmax (≥4.75) (OR: 5.51; 95% CI 3.18-9.55; p <0.001), and adenocarcinoma histology (OR: 8.89; 95% CI 2.11-37.42; p = 0.003) were significant risk factors for the failure of lobe-specific nodal dissection Lobe specific nodal dissection revealed a considerable failure rate in clinical early stage NSCLC. Lobe-specific SND should be performed cautiously in clinical early stage NSCLC, especially in patients with female sex, right sided tumor, higher SUVmax (≥4.75) and adenocarcinoma histology.

&lt;p&gt;Association of tumor location with economic outcomes and air leak complications in thoracic lobectomies: results from a national hospital billing dataset&lt;/p&gt;

Purpose: To assess whether tumor location during thoracic lobectomies affects economic outcomes or air leak complications.Patients and methods: Retrospective, observational study using Premier Healthcare Database. The study included patients aged ≥18 years who underwent elective inpatient thoracic lobectomy for lung cancer between 2012 and 2014 (first qualifying=index admission). Three mutually exclusive tumor location groups were formed: upper lobe, middle lobe, and lower lobe. Primary outcomes were index admission’s length of stay (LOS), total hospital costs, and operating room time; in-hospital air leak complications (composite of air leak/pneumothorax) served as an exploratory outcome. Multivariable models were used to examine the association between tumor location and the study outcomes, accounting for covariates and hospital-level clustering.Results: 8,750 thoracic lobectomies were identified: upper lobe (n=5,284), middle lobe (n=512), and lower lobe (n=2,954). Compared with the upper lobe, the middle and lower lobe groups had statistically significant (p<0.05): shorter adjusted LOS (7.0 days upper vs 5.8 days middle, 6.6 days lower), lower adjusted mean total hospital costs ($26,177 upper vs $23,109 middle, $24,557 lower), and lower adjusted odds of air leak complications (odds ratio middle vs upper=0.81, 95% CI=0.74–0.89; odds ratio lower vs upper=0.60, 95% CI=0.46–0.78). Findings were similar but varied in statistical significance when stratified by open and video-assisted thoracoscopic surgery approach.Conclusion: Among patients undergoing elective thoracic lobectomy for lung cancer in real-world clinical practice, upper lobe tumors were significantly associated with increased in-hospital resource use and air leak complications as compared with lower or middle lobe tumors.

Marginal Failures with Stereotactic Body Radiation Therapy(SBRT) for Early Stage Lung Cancer: Room for Improvement?

SBRT is an effective treatment for early stage non-small cell lung cancer (NSCLC). Prior series distinguish local from regional/distant recurrences, but detailed patterns of local failure are not well-described. We evaluate the location of local failures to provide further insight for treatment planning. Patients treated with SBRT for T1-2N0 NSCLC from 2007-2016 at a single institution were included. Prescribed dose was 48-54Gy in 3 to 5 fractions and planning target volume (PTV) margins were generally 5mm radially and 8mm superior/inferior. Site of first failure was classified as local, regional (hilar/mediastinal lymph nodes) or metastatic. For patients with a component of local failure, post-treatment diagnostic scans at time of recurrence were fused to the initial planning scan using rigid registration to lung features proximal to recurrence. The recurrence volume was delineated and compared to the treatment PTV. For each local failure, percent overlap of the PTV and recurrence volume was calculated. Distance from centroid (geometric center) of recurrence to PTV edge was measured in 3 planes and average distance was calculated. Local failures were categorized as: in-field failure (≥80% overlap or centroid >1cm inside PTV), marginal failure (20-80% overlap and centroid <1 cm inside/outside PTV), or involved lobe failure (overlap <20% or centroid >1cm outside PTV). Parametric statistics compared characteristics of recurrences. A total of 217 patients were treated with robotic radiosurgery (94%) or linac-based (6%) SBRT. 83% were T1 tumors, 69% upper lobe tumors, and 74% biopsy-proven malignancy. With a median follow-up of 20 months (range 0-98), 38% had progression of disease. 16% (N=34) had a component of local progression at time of first failure: 18 local only, 8 locoregional, 8 metastatic. 60% were pathologically confirmed. Of the local failures, 9 were classified as in-field, 15 marginal and 10 involved lobe. For in-field, marginal, and involved lobe failures there were differences in mean PTV/recurrence overlap (93% vs 43% vs 2%) and distance from centroid to PTV margin (1.39cm vs 0.56cm vs 1.78cm). For all local failures, PTV D95 was at least prescription dose. Marginal failures developed earlier than other local failures (mean 15 vs 25 months, p<0.05). Upper and lower lobe tumors had similar rates of local failure (16% vs 18%); however, 8 of the 11 local failures seen in lower lobe tumors were marginal failures compared to only 7 of 23 local failures in upper lobe tumors. Local progression is seen in roughly 16% of patients following SBRT. Marginal failures represent nearly half of these events, and appear to be of particular concern for lower lobe tumors. These findings highlight an opportunity to further evaluate margin size, motion management, and accuracy of dose calculations at the PTV margin to further improve local control in lung SBRT.

Clinicopathological characteristics and prognosis of pulmonary pleomorphic carcinoma: a population-based retrospective study using SEER data.

Pulmonary pleomorphic carcinoma (PPC) is a rare malignancy; unique clinicopathological characteristics and prognosis have not been described. PPC patient information collected in the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2014 were extracted, evaluated, and compared with NSCLC patient data. Overall survival (OS) was evaluated by the Kaplan-Meier method. Univariate analysis (UVA) and multivariate analysis (MVA) by the Cox proportional hazards regression identified risk factors that predicted OS and the results were used to construct a nomogram to predict 1-, 3-, and 5-year OS in PPC patients. A total of 309 patients diagnosed with PPC were identified among the records of 320,510 NSCLC patients. The median age was 66 (IQR, 57-75) years, 59.2% were men, 79.3% were White, 63.9% had upper lobe tumors, 77.0% were poorly differentiated, and 38.0% were AJCC stage IV. Median OS was 9 (95% CI: 6.69-11.31) months and 5-year OS was 25.1% (95% CI: 23.6-26.6%). PPC patients had significantly larger and less differentiated tumors, a higher rate of radical surgical resection, less N+ disease, and fewer distant metastases (P<0.001) than NSCLC patients. UVA and MVA identified age, T stage, M stage, surgery, and chemotherapy as independent risk factors. The nomogram had a calibration index of 0.798. PPC had distinct clinicopathological characteristics. Age, T stage, M stage, surgery and chemotherapy were independently associated with OS. The nomogram accurately predicted 1-, 3- and 5-year OS.

Clinical Predictors of Persistent Mediastinal Nodal Disease After Induction Therapy for Stage IIIA N2 Non-Small Cell Lung Cancer

Patients with persistent N2 disease after induction have poor survival. Many of these patients may have had mediastinoscopy before induction therapy, making reassessment of the mediastinum by repeat mediastinoscopy hazardous and inaccurate. The sensitivity and specificity of endobronchial ultrasonography and nodal fine-needle aspiration in this setting is unclear. In this study, we sought to identify the clinical predictors of persistent N2 disease after induction therapy, which may help in selecting the patients most likely to benefit from surgical resection. A retrospective review of a prospective database (1990 to 2014) was performed to identify patients who had surgical resection after induction therapy for clinical stage IIIA-N2 non-small cell lung cancer. Multivariable logistic regression analysis was performed to determine independent predictors of persistent N2 disease. 203 patients (56% female; median age 64 years) underwent potentially curative lung resection after induction therapy. Ninety-seven patients (48%) had pathologic nodal downstaging (pN0/N1), which was associated with significantly better overall survival compared with patients with persistent N2 disease (5years, 56% versus 35%, p= 0.047). Univariate and multivariate analysis showed that upper or middle lobe location and less than 60% reduction of N2 SUVmax were independent predictors of persistent N2 disease. Patients with upper lobe tumors and less than 60% reduction in N2 SUVmax are more likely to have persistent N2 disease, which is often associated with poor survival rates. These clinical prognostic criteria may help surgeons in stratifying patients and properly selecting optimal surgical candidates.

Analysis of Lung Tumor Motion in a Large Sample: Patterns and Factors Influencing Precise Delineation of Internal Target Volume

To evaluate lung tumor motion during respiration and to describe factors affecting the range and variability of motion in patients treated with stereotactic ablative radiation therapy. Log file analysis from online respiratory tumor tracking was performed in 145 patients. Geometric tumor location in the lungs, tumor volume and origin (primary or metastatic), sex, and tumor motion amplitudes in the superior-inferior (SI), latero-lateral (LL), and anterior-posterior (AP) directions were recorded. Tumor motion variability during treatment was described using intrafraction/interfraction amplitude variability and tumor motion baseline changes. Tumor movement dependent on the tumor volume, position and origin, and sex were evaluated using statistical regression and correlation analysis. After analysis of >500hours of data, the highest rates of motion amplitudes, intrafraction/interfraction variation, and tumor baseline changes were in the SI direction (6.0±2.2mm, 2.2±1.8mm, 1.1±0.9mm, and -0.1±2.6mm). The mean motion amplitudes in the lower/upper geometric halves of the lungs were significantly different (P<.001). Motion amplitudes >15mm were observed only in the lower geometric quarter of the lungs. Higher tumor motion amplitudes generated higher intrafraction variations (R=.86, P<.001). Interfraction variations and baseline changes >3mm indicated tumors contacting mediastinal structures or parietal pleura. On univariate analysis, neither sex nor tumor origin (primary vs metastatic) was an independent predictive factor of different movement patterns. Metastatic lesions in women, but not men, showed significantly higher mean amplitudes (P=.03) and variability (primary, 2.7mm; metastatic, 4.9mm; P=.002) than primary tumors. Online tracking showed significant irregularities in lung tumor movement during respiration. Motion amplitude was significantly lower in upper lobe tumors; higher interfraction amplitude variability indicated tumors in contact with mediastinal structures, although adhesion to parietal pleura did not necessarily reduce tumor motion amplitudes. The most variable lung tumors were metastatic lesions in women.