T4 Non-small Cell Lung Cancer Research Articles

P3.01-71 Results of Extended Resection in T4 Non-Small Cell Lung Cancer

P3.01-71 Results of Extended Resection in T4 Non-Small Cell Lung Cancer

P2.16-02 Predicting Pathological Noninvasiveness in T1 Non-Small Cell Lung Cancer on Chest CT Scan Using Deep Learning Algorithm

P2.16-02 Predicting Pathological Noninvasiveness in T1 Non-Small Cell Lung Cancer on Chest CT Scan Using Deep Learning Algorithm

Diagnosis and staging of locally advanced non-small cell lung cancer

T4 non-small cell lung cancer (NSCLC) might include a wide range of clinical scenarios. In very selected cases a surgical treatment might be indicated, after careful staging and thorough functional evaluation. Performance status, cardiac and pulmonary function should be evaluated in detail, in a tailored fashion according to the planned surgical operation. Besides the anatomical lung unit (lobectomy or pneumonectomy), resection may involve several vital structures, including great vessels and some portion of the atria. Given the particular nature of T4, surgery is often a part of a multimodal approach. In case of induction therapies, pulmonary function should be re-assessed, to rule out any deterioration that could eventually jeopardize survival. Computed tomography (CT) scan and positron emission tomography (PET)-CT should be always performed to stage the disease, but in case of chest wall, airways or other mediastinal organs involvement, more detailed exams, such us Magnetic Resonance, echocardiography or CT angiography (CTA) and magnetic resonance angiography (MRA) should be carried out. Additionally, a careful investigation for possible mediastinal nodal involvement should be routinely performed, given the detrimental effect of nodal diffusion on survival in this subset of patients. Nowadays endobronchial ultrasound (EBUS), endoscopic (esophageal) ultrasound are reliable and semi-invasive tools that can be used as first step prior to more invasive surgical diagnostic procedures such as video assisted mediastinoscopy or even video-assisted mediastinoscopic lymph-adenectomy (VAMLA) and transcervical extended mediastinal lymphadenectomy (TEMLA). Bronchoscopy and EBUS can be safely used for yield diagnostic tissue in case of central tumors, while in case of peripheral masses, transthoracic biopsy is more sensitive.

Use of cardiopulmonary bypass in lung cancer surgery: focus on extended pulmonary resections for T4 non-small cell lung cancer

The use of cardiopulmonary bypass (CPB) in lung cancer surgery has become more prevalent and accepted over time. The original concerns of CPB induced pulmonary failure, tumor dissemination and immunocompromise remain unresolved up to today. The initial experience with combined cardiac and lung cancer resection procedures utilizing CPB may have laid the foundation for its use in the treatment of local regionally advanced non-small cell lung cancer (NSCLC). This chapter will focus on the use of CPB in the surgical resection of stage T4 NSCLC. A literature review demonstrates a published improved late survival in this setting with reasonable operative morality and complications. The surgical approach for involvement of specific anatomic structures including the carina, aorta, pulmonary veins/left atrium, right sided major veins/right atrium and main pulmonary arteries will be discussed. The specific situation of iatrogenically created “pseudo” T4 stage when NSCLC may invade a previously placed left internal mammary artery (LIMA) graft will also be presented. Finally, we will briefly discuss two other situations. That includes first the use of CPB when combined cardiac procedures and pulmonary resection are planned. Second we will address the use of CPB in the emergent setting of NSCLC resection.

A real-world observational study to explore clinical characteristics of Chinese patients with T1 non-small cell lung cancer complicated with lymph metastases.

e20523Background: Clinical characteristics of lymph metastases are hetergeneous in the patients with T1 non-small cell lung cancer (NSCLC). Preoperative assessment of lymph metastases is essential ...

Comparison of clinical characteristics and prognoses of patients with T1 non-small cell lung cancer and small cell lung cancer in a Chinese real-world study.

e20527Background: Radical resection is preferred for treatment of patients with T1 lung cancer, and patient prognoses could be significantly affected by tumor pathological types. Since the clinical...

Prognostic factors in operated T3 non-small cell lung cancer: A retrospective, single-center study of 129 patients.

This study aims to investigate the prognostic factors that affect survival rates and durations in patients with T3 non-small cell lung cancer who underwent surgery. A total of 129 patients with T3 n on-small c ell l ung c ancer (125 males, 4 females; mean age 60±9.3 years; range 23 to 80 years) who were performed surgery in our clinic between January 1997 and December 2013 were evaluated retrospectively in terms of age, gender, type of resection, tumor histopathology, tumor, node and metastasis staging, lymph node invasion, chemotherapy and radiotherapy, and recurrence. During the evaluation, while 61 patients (47.3%) were alive, 68 (52.7%) had lost their lives. One-, two- and five-year survival rates of the study population were 79.8%, 56.9% and 23.2%, respectively. Mean duration of survival was 41.5±4.0 months (range 33.7-49.4 months). Patient's age or tumor histopathology did not affect the duration of survival. Overall duration of survival was significantly longer in patients of stage IIB, patients who had low stages of lymph node invasion, who were performed lobectomy, who received chemotherapy or radiotherapy or who were without recurrence (p<0.05 for each). Multivariate regression analysis revealed that lymph node invasion, presence of recurrence or pneumonectomy, or failure to have been administered chemotherapy increased mortality risk significantly (hazard ratios 0.217, 3.369, 2.791 and 2.254, respectively). Our findings revealed that lymph node invasion, presence of recurrence or pneumonectomy, or failure to have been administered chemotherapy are poor prognostic factors in T3 non-small cell lung cancer. Prognostic factors should be taken into consideration during treatment and follow-up periods of patients with T3 non-small cell lung cancer.

MTE 03.01 Do Extended Resections Improve T4 Lung Cancer Outcomes?

MTE 03.01 Do Extended Resections Improve T4 Lung Cancer Outcomes?

Is left upper lobectomy always worthwhile for early stage lung cancer? A comparison between left upper lobectomy, trisegmentectomy, and lingulectomy

Lobectomy is the gold standard treatment for resectable Non-Small Cell Lung Cancer (NSCLC). We compared oncological outcomes of patients undergoing a "multi-segmentectomy" (trisegmentectomy or lingulectomy) and left upper lobectomy for early stage (T1-2, N0) NSCLC of the left upper lobe. We retrospectively analyzed all patients with pathological early stage (T1-T2 N0) NSCLC located in left upper lobe who underwent a lobectomy, a trisegmentectomy, or a lingulectomy between 2006 and 2013, focusing on surgical and oncological outcomes. Among 159 patients, 105 patients underwent a lobectomy and 54 patients a multi-segmentectomy (33 lingulectomy and 21 trisegmentectomy). Actuarial mean Overall Survival was 87 months (95%CI 79-95) and 89 months (95%CI 76-101) for lobectomies and multi-segmentectomies, respectively (P-value: 0.895), while actuarial mean Disease Free Interval was 91 months (95%CI 82-100) and 96 months (95%CI 84-108) respectively (P-value: 0.565). We did not observe any difference in terms of local recurrence rate between the two groups (P = 0.337). Lingulectomy and trisegmentectomy lead to similar oncological outcomes compared to left upper lobectomy for T1 and T2 N0 NSCLC, and they could be used as an alternative to lobectomy even in patients with a good pulmonary function.

No Adverse Outcomes of Video-Assisted Thoracoscopic Surgery Resection of cT2 Non-Small Cell Lung Cancer during the Learning Curve Period.

BackgroundVideo-assisted thoracoscopic surgery (VATS) anatomic lung resections are gradually becoming the standard surgical approach in early-stage non-small cell lung cancer (NSCLC). The technique is being applied in cases of larger tumors depending on the experience of the surgical team. The objective of this study was to compare early surgical and survival outcomes in patients undergoing anatomic pulmonary resections using VATS and thoracotomy techniques for clinical T2 NSCLC during the adaptation period of the surgical team to the VATS approach.MethodsThe data of all patients who underwent anatomic pulmonary resection for NSCLC using VATS and open techniques since April 2012 were recorded to create a prospective lung cancer database. Clinical T2 NSCLC patients who underwent VATS anatomic lung resection were identified and compared with cT2 patients who underwent open resection.ResultsBetween April 2012 and August 2014, 269 anatomical resections for NSCLC were performed (80 VATS and 189 thoracotomy). Thirty-four VATS patients who had clinical T2 disease were identified and stage-matched to thoracotomy patients. The average tumor diameter was comparable (34.2±11.1×29.8±10.1 mm vs. 32.3±9.8×32.5±12.2 mm, p=0.4). Major complications were higher in the thoracotomy group (n=0 vs. n=5, p=0.053). There was no 30-day mortality, and the 2-year survival rate was 91% for VATS and 82% for thoracotomy patients (p=0.4).ConclusionVATS anatomic resections in clinical T2 NSCLC tumors are safe and have perioperative and pathologic outcomes similar to those of thoracotomy, while remaining within the learning curve.

Evaluating vertebral artery dominancy before T4 lung cancer surgery requiring subclavian artery reconstruction.

To evaluate vertebral artery (VA) dominancy and the risk of brain infarction in T4 lung cancer patients with tumor invasion into the subclavian artery. We reconstructed the subclavian artery in 10 patients with T4 non-small cell lung cancer. The histological stages were IIIA in eight patients and IIIB in two patients. We evaluated the VA dominancy by performing a four-vessel study preoperatively and investigated the relationship between the methods of VA treatment and postoperative brain complications, retrospectively. Seven patients had a superior sulcus tumor (SST) and three had direct invasion into the mediastinum. Based on the tumor location, a transmanublial approach was used in five patients and a posterolateral hook incision was used in the other five. All subclavian artery (SA) reconstructions were done using an artificial woven graft. Preoperative angiography of the VA revealed poor development of the contralateral side in two patients. One of these patients suffered a severe brain infarction on postoperative day 2, which proved fatal. In the other patient, the VA was connected to the left SA graft by a side-to-end anastomosis and there was no postoperative brain complication. Preoperative SA and VA angiography is mandatory for identifying the need for VA reconstruction in lung cancer patients with major arterial invasion.

The impact of tumor size on survival in T3 non-small cell lung-cancer with direct extension.

e20033 Background: Tumor size is an important prognostic variable that affects clinical decision-making in NSCLC including the use of adjuvant therapy. However, the association between tumor size and survival in a subset of patients who have T3 NSCLC with direct extension into nearby structures (T3dx) has not been explicitly characterized. We hypothesize that tumor size impacts survival and prognosis within this cohort. Methods: Patients with T3dxin 2006-2013 who underwent lobectomy or pneumonectomy were identified in the National Cancer Database. Patients who received neoadjuvant therapy or had positive margins were excluded. Tumor size was categorized based on cutoffs used by current staging guidelines and patients were stratified by pathologic N stage (see table). Cox proportional hazard models were used to measure the independent impact of tumor size on survival. Results: Overall, 0.1-3cm tumors exhibit superior 5-year survival compared to 3.1-5cm and &gt;5cm tumors. Tumor size is significantly associated with survival in N0 patients but not in N1 and N2 patients. Use of adjuvant chemotherapy is associated with improved survival in the overall cohort and all subgroups; however, use of adjuvant chemoradiation may be associated with inferior survival in the overall cohort. Conclusions: Larger tumor size is associated with inferior survival in T3dx in the absence of nodal disease. T3dx requires a more tailored approach to adjuvant therapy than other T3 subgroups. Adjuvant chemotherapy appears to benefit all patients with T3dx; however, the role of adjuvant chemoradiation is less clear. [Table: see text]

Association of lymph node involvement with the prognosis of pathological T1 invasive non-small cell lung cancer

BackgroundLymph node involvement could help to predict the prognosis of pathological T1 (pT1, diameters of ≤3 cm) non-small cell lung cancer (NSCLC). This study assessed the clinicopathological factors and associated lymph node involvement in invasive lung adenocarcinoma (IAC) and squamous cell lung cancer (SCC) and the overall and disease-free survival associated with these factors.MethodsThree hundred and twenty-five patients with pathological T1 NSCLC (253 IAC and 72 SCC) were retrospectively analyzed from a pool of 1094 primary lung cancer patients. The data were assessed using multiple logistic regression, Kaplan-Meier curves and multivariable analyses.ResultsAmong patients with a ≤30-mm tumor lesion (N = 325), N1 and N2 lymph node involvement was found in 28 (8.6%) and 34 (10.4%) patients, respectively. Lymph node metastasis occurred in 13.0% (33/253) of pT1 IAC patients and 40.3% (29/72) of SCC patients. Carcinoembryonic antigen (CEA) levels, SCC by histology, and tumor lesions larger than 1.0 cm were associated with lymph node involvement (P < 0.0001, <0.0001, and 0.048, respectively). In IAC patients, negative lymph nodes were associated with better overall survival compared with lymph node-positive ones (P = 0.021). No significant difference was observed in SCC patients regardless of lymph node status (P = 0.40). Multivariable Cox analysis revealed that lymph node involvement was an independent prognostic predictor of overall IAC patient survival (P = 0.041), but not of SCC patient survival (P = 0.470). Chemotherapy was administered to 72.2% (52/72) of SCC patients, a significantly higher rate when compared with that of IAC patients (42.3%, 107/253).ConclusionsLymph node metastasis was inversely associated with the overall survival of IAP patients, but not with the survival of SCC patients. Patients with pT1 SCC exhibited a significantly higher rate of lymph node involvement when compared with IAC patients. Thus, a systematic lymph node dissection should be performed in pT1 IAC patients, especially in patients with IAC larger than 1.0 cm, for additional treatment selections to improve survival.

Sinoatrial node dysfunction after stereotactic ablative radiation therapy in the chest.

132 Background: Sinoatrial node (SAN) injury following stereotactic ablative radiation therapy (SABR) in the chest has not been reported in the literature. We report SAN dysfunction as a potential toxicity of SABR in the chest. Methods: We examined the clinical courses and SABR plans of 47 patients treated for T1 or T2 non-small cell lung cancer of the right upper lobe, middle lobe, lower lobe, or hilum. After developing a contouring atlas for the SAN, based upon the junction between the superior vena cava and the right atrium, dose to the SAN was retrospectively determined for each patient. We identified 13 patients whose treatment imparted significant dose to the SAN, as defined by the SAN encompassed within the 10% prescription isodose (IDL) line. Biologically effective doses (BED), acute and chronic, were correlated with SAN toxicity. Results: Patients underwent SABR to the right lung to a dose of 40-50 Gy in 4 or 5 fractions, with mean acute BED (alpha/beta ratio = 10) of 100.2 Gy and late BED (alpha/beta ratio = 3) of 222.7 Gy. Mean volume of the GTV and PTV were 26.1 and 75.1 mL, respectively. Mean follow-up was 25.5 months. The mean volume of the SAN was 0.37 mL. Average max dose and mean dose to the SAN were 24.7 and 70.7 Gy, respectively. Of the 13 patients whose treatment imparted significant dose to the SAN, one patient without prior arrhythmia developed symptomatic SAN dysfunction requiring pacemaker placement at 6 months after completion of treatment. The sinoatrial node of the patient received a maximum dose of 44.8 Gy in 4 fractions, correlated with an acute BED (alpha/beta ratio = 10) of 90 Gy and late BED (alpha/beta ratio = 3) of 194.1 Gy, and a mean dose of 35.5 Gy in 4 fractions, correlated with an acute BED (alpha/beta ratio = 10) of 71 Gy and late BED (alpha/beta ratio = 3) of 153.8 Gy. This was the third highest max dose and second highest mean dose to SAN in the cohort. Conclusions: We report sinoatrial node dysfunction as a potential toxicity of SABR in the chest for non-small cell lung cancer. Caution is advised when treatment imparts significant dose to the sinoatrial node.

P1.08-081 Resection of T4 Non-Small Cell Lung Cancer Invading the Spine

Surgical treatment of non-small cell lung cancer (NSCLC) invading the spine is controversial. We evaluated surgical results and long-term outcome of patients with T4 NSCLC who underwent vertebral resection (VR) due to the infiltration by lung tumor. Retrospective analysis of 16 consecutive patients undergoing VR for NSCLC invading the spine between 1998 and 2015 was performed. Ten patients (62.5%) received induction therapy. Vertebral resection was divided into 5 types; type 1: only transverse process; type 2A: transverse process with a portion of the vertebral body; type 2B: a portion of vertebral body without transverse process; type 3, hemivertebrectomy; type 4: total vertebrectomy. There were 15 men and one woman with a median age of 62 years (range, 41-80). Ten patients had induction therapy. Vertebral resection included 3 type 1 resection, 6 type 2A, 4 type 2B, 2 type 3, and 1 type 4. Pneumonectomy was performed in 3 patients, lobectomy in 7, segmentectomy in 3 and wedge in 3. Complete resection was achieved in 14 patients (87.5%). Surgical nodal status was N0 in 11 patients, N1 in 2, and N2 in 3, each. There were no postoperative mortality. Morbidity was observed in 7 patients (43.7%), including 1 (6.2%) neurologic complication, 3 (18.7%) ARDS, and 2 (12.5%) cardiac . Seven patients (43.7%) are alive without disease after e mean follow up of 44.4 months. The 1- and 5-year predicted survivals were 79% and 40.4%, respectively. Patients without nodal involvement had the best prognosis (56.3% vs 0%; p=0.0009). Induction therapy did not influence survival. Resection of NSCLC with vertebrectomy is technically demanding and is associated with acceptable morbidity. However, an encouraging long-term survival observed in this series suggest that resection could be a valid option in selected patients with vertebral invasion by NSCLC.

Resection of Lung Cancer Involving the Aorta

The early and long-term results from surgery for locally advanced T4 non-small cell lung cancer (NSCLC) has significantly improved over the past 20 years. Resection of non-small cell lung cancer (NSCLC) invading the aorta can be safely performed in well-selected patients. In most situations, the aortic adventitia can be resected to obtain adequate margins. However, when the tumor extends into the media, resection and reconstruction of the aorta is required. In these situations, the approach depends on the location of the tumor along the aortic arch or the descending aorta. Extracorporeal membrane oxygenation (ECMO) and thoracic endografts have provided improved technology to facilitate aortic resection. Thoracic endografts are particularly helpful for tumors invading the aortic arch or the spine in combination with the descending aorta.

Survey of the Patterns of Using Stereotactic Ablative Radiotherapy for Early-Stage Non-small Cell Lung Cancer in Korea.

PurposeStereotactic ablative radiotherapy (SABR) is an effective emerging technique for early-stage non-small cell lung cancer (NSCLC). We investigated the current practice of SABR for early-stage NSCLC in Korea.Materials and MethodsWe conducted a nationwide survey of SABR for NSCLC by sending e-mails to all board-certified members of the Korean Society for Radiation Oncology. The survey included 23 questions focusing on the technical aspects of SABR and 18 questions seeking the participants’ opinions on specific clinical scenarios in the use of SABR for early-stage NSCLC. Overall, 79 radiation oncologists at 61/85 specialist hospitals in Korea (71.8%) responded to the survey.ResultsSABR was used at 33 institutions (54%) to treat NSCLC. Regarding technical aspects, the most common planning methods were the rotational intensity-modulated technique (59%) and the static intensity-modulated technique (49%). Respiratory motion was managed by gating (54%) or abdominal compression (51%), and 86% of the planning scans were obtained using 4-dimensional computed tomography. In the clinical scenarios, the most commonly chosen fractionation schedule for peripherally located T1 NSCLC was 60 Gy in four fractions. For centrally located tumors and T2 NSCLC, the oncologists tended to avoid SABR for radiotherapy, and extended the fractionation schedule.ConclusionThe results of our survey indicated that SABR is increasingly being used to treat NSCLC in Korea. However, there were wide variations in the technical protocols and fractionation schedules of SABR for early-stage NSCLC among institutions. Standardization of SABR is necessary before implementing nationwide, multicenter, randomized studies.

Prognostic Differences in Subgroups of Patients With Surgically Resected T3 Non-Small Cell Lung Cancer

This study determined the characteristics and prognosis of each descriptor of T3 non-small cell lung cancer (NSCLC). A total of 3,241 patients underwent an operation for NSCLC between 2001 and 2013, and this study included 461 patients who received complete anatomic resection of T3 NSCLC. The T3 descriptors were coded as follows: tumor invading main bronchus within 2 cm of the carina (T3-cent), tumor invading beyond visceral pleura (T3-inv), tumor larger than 7 cm (T3-size), separate tumor nodules (T3-sep), or tumor with combined T3 descriptors (T3-comb). The T3 distribution was as follows: T3-cent, 75 patients (16.3%); T3-inv, 157 patients (34.1%); T3-size, 132patients (28.6%); T3-sep, 34 patients (7.4%); and T3-comb, 63 patients (13.7%). Subgroup analyses revealed asignificantsurvival benefit in the T3-cent group compared with the other groups (all p < 0.05). The 5-year disease-free survival (DFS) values were 55.4%, 36.7%, 40.9%, 30.3%, and 32.0% in the T3-cent, T3-inv, T3-size, T3-sep, and T3-comb subgroups, respectively. Multivariable analyses revealed that age (p= 0.019), N status (p=0.001), adjuvant chemotherapy (p < 0.001), and T3 descriptors (T3-cent versus others, p < 0.001) were the mostimportant independent prognostic factors for DFS. Additional analyses were performed to evaluate prognostic factors for DFS in the T3-cent group. Multivariable analysis revealed that bronchoplastic procedures (p= 0.004) was an independent prognostic factor for DFS. Survival for centrally located T3 NSCLC is better than other types of T3 NSCLC. Lung-preserving operations such as bronchoplastic procedures might result in improved survival of these patients.

Outcomes After Resection of T4 Non-Small Cell Lung Cancer Using Cardiopulmonary Bypass

Complete, en bloc resection offers the greatest chance of long-term survival in T4 non-small cell lung cancer (NSCLC). The use of cardiopulmonary bypass (CPB) to achieve an en bloc resection is controversial because of potentially increased bleeding, lung dysfunction, and tumor dissemination. We reviewed our institutional experience to assess CPB's effect on survival. All patients who underwent resection for T4 NSCLC at our institution between 1980 and 2013 were retrospectively reviewed and stratified according to whether they did (CPB group, n= 20) or did not (No CPB group, n= 355) undergo CPB. Primary outcomes of interest were overall and disease-free survival and perioperative complications. Baseline characteristics and medical therapy were similar between the groups. Median overall survival for all patients was 31 months, with 1-, 3-, 5-, and 10-year survival of 73%, 47%, 40%, and 26%, respectively. Median disease-free survival for all patients was 19 months, with 1-, 3-, 5-, and 10-year disease-free survival of 61%, 40%, 33%, and 21%, respectively. No difference was found in overall or disease-free survival at 1, 3, 5, and 10 years between the No CPB and CPB groups (p= 0.89 and p= 0.88). In addition, no differences were found in the rates of major perioperative complications. The use of CPB allows for complete, en bloc resection in otherwise inoperable patients with T4 NSCLC and offers similar overall and disease-free survival to patients resected without CPB. All thoracic surgeons who manage T4 NSCLC should consider the use of CPB if it is necessary to achieve a complete, en bloc resection.

Patient outcomes of monotherapy with hypofractionated three-dimensional conformal radiation therapy for stage T2 or T3 non-small cell lung cancer: a retrospective study.

BackgroundHypofractionated three-dimensional conformal radiation therapy (3D-CRT) is a treatment option for patients with early-stage non-small cell lung cancer (NSCLC) who are medically unable to tolerate surgery and who are not amenable to treatment with stereotactic body radiotherapy. This study assessed the efficacy and safety of 3D-CRT as a monotherapy in patients with localized stage T2 or T3 NSCLC.MethodsThis retrospective study consisted of 29 patients (20 males) aged 56–89 years (median, 76 years) with histologically confirmed NSCLC who underwent 3D-CRT between 2005 and 2014.ResultsThe median duration of patient observation was 17.0 months (range, 1.0–64.0 months). Complete and partial responses occurred in 13.8 and 44.8 % of patients, respectively, and the overall response rate was 58.2 %. Meanwhile, the 1- and 3-year survival rates were 65.8 and 33.8 %, respectively. In T2 NSCLC, the median survival time (MST) was 12 months, and the 1- and 3-year survival rates were 62.4 and 21.4 %, respectively. In T3 NSCLC, the MST was 17 months, and the 1- and 3-year survival rates were 72.9 and 48.6 %, respectively. Severe toxicities (Common Terminology Criteria Grade 3) were not observed. The mean biologically effective dose required to improve local control exceeded 80 Gy (range, 67.2–96.0 Gy).ConclusionThese findings support a role for 3D-CRT as a treatment option for patients who refuse or could not tolerate surgical therapy with early-stage NSCLC. Although this was a small, retrospective study, it may form the basis for future, larger controlled studies on 3D-CRT as a monotherapy for NSCLC.