T4 Non-small Cell Lung Cancer Research Articles

1035 Heterogeneous presentation of patients diagnosed with T1 non-small cell lung cancer (NSCLC) across race and ethnicity in contemporary United States population

1035 Heterogeneous presentation of patients diagnosed with T1 non-small cell lung cancer (NSCLC) across race and ethnicity in contemporary United States population

MDT lung cancer care: input from the Surgical Oncologist.

Although there have been many advancements in the multidisciplinary management of non-small cell lung cancer (NSCLC), surgery remains the primary modality of choice for resectable lung cancer when the patient is able to tolerate lung resection physiologically. There have been recent advances in surgical diagnosis and treatment of lung cancer. Increasing use of low-dose computed tomography (CT) screening for lung cancer has resulted in increased detection of small peripheral nodules or semi-solid ground glass opacities. Here, we review different modalities of localization techniques that have been used to aid surgical excisional biopsy when needle biopsy has failed to provide tissue diagnosis. We also report on the current debates regarding the use of sublobar resections for Stage I NSCLC as well as the surgical management of locally advanced NSCLC. Finally, we discuss the complex surgical management of T4 NSCLC lung cancers.

Advances of mediastinal lymph node metastasis and the extent of lymph node dissection in patients with stage T1 non-small cell lung cancer

肺癌是我国发病率和死亡率最高的恶性肿瘤。非小细胞肺癌（non-small cell lung cancer, NSCLC）约占肺癌80%。临床上，早期NSCLC以手术治疗为主要治疗方式，淋巴结分期及手术中清扫程度直接影响着患者的预后。不同肺叶原发NSCLC的淋巴结转移区域存在一定规律。解剖性肺叶切除加系统性淋巴结清扫一直以来被认为是NSCLC的标准手术方式，但近年来T1期NSCLC手术中纵隔淋巴结清扫的程度存在较大争议，选择性淋巴结清扫已逐渐被大多数学者所重视。

Clinical significance of patterns of intrathoracic lymph node metastasis in non-small cell lung cancer:an analysis of 314 patients

Objective To investigate the patterns of intrathoracic lymph node metastasis in nonsmall cell lung cancer (NSCLC) and to provide a theoretical basis for the delineation of radiotherapy target volume.Methods A retrospective analysis was performed on the clinical data of 314 NSCLC patients after operation.Our focus was to investigate the distribution characteristics and metastatic extent of intrathoracic lymph nodes and their relationship with tumor size,pathological type,and primary site.Comparisons between groups were made by one-way analysis of variance.Results The frequencies of metastases to lymph nodes at stations 4,5,7,10,and 11 were all above 12％,while those at stations 1,2,3,6,8,and 9 were all below 12％.The lymph node metastasis rate was similar on the primary tumor site (P =0.102).The patients with T3 and T4 NSCLC had a significantly higher frequency of N2 lymph node metastasis than those with T1 and T2 NSCLC (17.0％ vs.11.6％,P =0.002) ;the patients with adenocarcinoma had a significantly higher frequency of N2 lymph node metastasis than those with squamous cell carcinoma (34.5 ％ vs.23.2％,P =0.008).Conclusions For patients with T3 and T4 NSCLC of adenocarcinoma subtype,we should highlight the lymph nodes at stations 4,5,7,10,and 11 when delineating the radiotherapy target volume after operation. Key words: Non-small cell lung cancer; Lung adenocarcinoma; Lung squamous carcinoma; Lymph node metastasis

Individualized altered fractionation as a more effective radiotherapy for non-small cell lung cancer.

Individualized altered fractionation as a more effective radiotherapy for non-small cell lung cancer.

Pretreatment [18F]-fluoro-2-deoxy-glucose Positron Emission Tomography Maximum Standardized Uptake Value as Predictor of Distant Metastasis in Early-Stage Non-Small Cell Lung Cancer Treated With Definitive Radiation Therapy: Rethinking the Role of Positron Emission Tomography in Personalizing Treatment Based on Risk Status

The aim of this study was to determine whether the preradiation maximum standardized uptake value (SUVmax) of the primary tumor for [(18)F]-fluoro-2-deoxy-glucose positron emission tomography (FDG-PET) has a prognostic significance in patients with Stage T1 or T2N0 non-small cell lung cancer (NSCLC) treated with curative radiation therapy, whether conventional or stereotactic body radiation therapy (SBRT). Between January 2007 and December 2011, a total of 163 patients (180 tumors) with medically inoperable histologically proven Stage T1 or T2N0 NSCLC and treated with radiation therapy (both conventional and SBRT) were entered in a research ethics board approved database. All patients received pretreatment FDG-PET / computed tomography (CT) at 1 institution with consistent acquisition technique. The medical records and radiologic images of these patients were analyzed. The overall survival at 2 years and 3 years for the whole group was 76% and 67%, respectively. The mean and median SUVmax were 8.1 and 7, respectively. Progression-free survival at 2 years with SUVmax <7 was better than that of the patients with tumor SUVmax ≥7 (67% vs 51%; P=.0096). Tumors with SUVmax ≥7 were associated with a worse regional recurrence-free survival and distant metastasis-free survival. In the multivariate analysis, SUVmax ≥7 was an independent prognostic factor for distant metastasis-free survival. In early-stage NSCLC managed with radiation alone, patients with SUVmax ≥7 on FDG-PET / CT scan have poorer outcomes and high risk of progression, possibly because of aggressive biology. There is a potential role for adjuvant therapies for these high-risk patients with intent to improve outcomes.

大血管浸潤を伴うT4非小細胞肺癌切除症例の検討

大血管浸潤を伴うT4非小細胞肺癌切除症例の検討

Particle Therapy: A Suitable Alternative to Stereotactic Body Radiotherapy for stage I Non-Small-Cell Lung Cancer?

353 ISSN 1758-1966 10.2217/LMT.13.40 © 2013 Future Medicine Ltd Lung Cancer Manage. (2013) 2(5), 353–356 Many new particle therapy centers are now under construction all over the world. In Japan, ten centers (one center with a proton and carbon accelerator, two centers with a carbon accelerator and seven centers with a proton accelerator) are now in service, and four are now preparing for the start of clinical service or under construction as of July 2013. Nearly 20 years have passed since the National Institute for Radiological Sciences (NIRS) in Chiba (Japan), started carbon-ion therapy in 1994. Longterm results of particle therapy, including those on stage I non-small-cell lung cancer (NSCLC), are gradually accumulating. Recently, clinical results of particle therapy with a median follow-up of 51 months for patients with T2a/bN0M0 NSCLC have been published from the Hyogo Ion Beam Medical Center (HIBMC) in Japan; of the 70 patients reported, 43 were treated with proton beams and 27 received carbon-ion therapy [1]. These patients were not randomized, but both proton and carbonion therapy plans were made, and either modality that showed superior dose distribution was chosen for treatment. The 4-year overall survival rate was 58% and the 4-year local control rate was 75% (70% for T2a and 84% for T2b). Toxicities were acceptable, with only two cases of grade 3 pulmonary toxicity. There appeared to be no difference in outcome between proton and carbon-ion therapy. For T1 NSCLC, a 3-year overall survival rate of 74% and a 3-year local control rate of 87% were previously reported from the same institution [2]. Clinical outcomes reported from other proton therapy centers are in line with these results, although follow-up data are shorter [3–5]. Published clinical results from NIRS on carbon-ion therapy appear to show slightly higher local control rates, but the patient number is relatively small and follow-up is relatively short [6,7]. On the other hand, the role of stereotactic body radiotherapy (SBRT) using photons has been established for patients with stage I NSCLC who are medically inoperable or refuse surgery. The reported results of SBRT generally indicate local control rates of 80–90% for T1 tumors and 65–80% for T2 tumors at 3–5 years [8–10]. The 5-year overall survival rates are 65–75% for operable patients and 35–50% for medically inoperable patients. The best

Vagal and recurrent laryngeal neuropathy following stereotactic ablative radiation therapy in the chest

PurposeTo identify clinical and dosimetric factors associated with vagus nerve (VN) and recurrent laryngeal nerve (RecLN) injury following stereotactic ablative radiation therapy (SABR) in the chest. Methods and MaterialsWe examined the clinical courses and SABR plans of 67 patients treated for T1 or T2 non-small cell lung cancer of the upper right or left lung, including 2 who developed vocal cord paresis (VCP) following treatment. After developing a contouring atlas for the VN and RecLN in the thorax, dose to those structures was retrospectively determined for each patient, and we identified 12 patients whose treatment imparted significant dose to either nerve and who were assessable for more than 12 months follow-up. Biologically effective doses using linear-quadratic (LQ) and linear quadratic-linear (LQ-L) modeling were correlated with VN and RecLN toxicity. ResultsOf 12 patients, 2 developed VCP. The first underwent repeat SABR and received a cumulative single fraction equivalent dose (alpha/beta = 3; SFED3) of 37.4 or 64.5 Gy to the VN and 13.7 or 15.3 Gy to the RecLN (by LQ or LQ-L modeling, respectively). This was the highest VN dose and fifth highest RecLN dose in the cohort. The second had rheumatoid arthritis and connective tissue disease and received a SFED3 of 16 Gy to the VN and 19.5 Gy to the RecLN (by both LQ and LQ-L modeling). This was in the upper tertile of VN and RecLN doses for the cohort. ConclusionsFollowing SABR for non-small cell lung cancer, VCP was associated with high cumulative dose to the VN in 1 patient and a moderately high dose to the VN and RecLN in another patient with rheumatoid arthritis and connective tissue disease. Particularly in the setting of reirradiation or connective tissue disease, potential toxicity to the VN or RecLN should be considered.

Outcome of Surgical Resection as a First Line Therapy in T3 Non‐small Cell Lung Cancer Patients

The T3 category of the 7th Edition of the TNM classification of non-small cell lung cancer (NSCLC) has added two factors that do not appear in the 6th Edition, large tumor size (>7 cm) and pulmonary metastasis of the same lobe. These factors are considered to have different biological and clinical features. In the present study we assessed the outcome of surgical resection as a first line therapy for T3 NSCLC. A total of 145 patients who were diagnosed according to the TNM 7th Edition with pathologic T3 NSCLC received surgical resection in our institution as a first line treatment. The outcomes of their treatment were analyzed. The 5-year survival rate was 46.9 %. On the basis of the 6th TNM Edition, the 5-year survival rate was 63.1 % for patients diagnosed with T2 disease (large tumor size), 44.3 % for patients diagnosed with T3 disease, and 33.1 % for patients diagnosed with T4 disease (pulmonary metastasis of the same lobe). There were no significant correlations between these categories and overall survival (OS). Nevertheless, 6th Edition T factors were found to be significantly correlated with lymph node status (p < 0.01). The univariate analyses showed that age, lymph node metastasis, and curative resection had significant effects on OS. In addition, the multivariate analysis identified age and N factor as independent prognostic factors in this cohort. Indications for surgical resection as a first line therapy in T3 NSCLC should be based on N factors and patient age. Lymph node metastasis, especially N2 disease, was increasingly frequent in patients with 6th Edition T classifications.

Extensive Invasion of the Left Atrium by Lung Cancer

A 52-year-old man complained of cough and hemoptysis for 1 month. Chest computed tomography scan revealed a 9 cm × 7 cm right lung mass invading the right inferior pulmonary vein and left atrium extensively, and the inferior pulmonary vein was completely occluded. Transsternal echocardiogram confirmed that the lesion invaded the apex of left atrium adjacent to the right pulmonary inferior vein. Positron emission tomography scan showed no other metastatic disease. Bronchoscopy with endobronchial biopsy demonstrated a low-grade squamous cell carcinoma. After 2 cycles of induction chemotherapy, he underwent resection with cardiopulmonary bypass. Postoperative pathology was sarcoma mixed with squamous carcinoma (10%), without lymph node metastasis. Both the bronchial and atrial margins were negative, pathology stage T4N0M0, IIIA. He recovered without postoperative complications, and went back to work 20 days after surgery. He received four cycles of subsequent chemotherapy, but a solitary brain metastasis was discovered 7 months later, and he died 9 months after surgery.

Video-assisted thoracoscopic surgery with posterior spinal reconstruction for the resection of upper lobe lung tumors involving the spine

Video-assisted thoracoscopic surgery (VATS) is associated with less morbidity and recovery time compared with traditional open thoracotomy (OT) for the resection of early stage non-small cell lung cancer (NSCLC). Local invasion of NSCLC into adjacent vertebrae confers a TNM T status of T4. Anatomical lobectomy by VATS with simultaneous posterior spinal reconstruction (PSR), as a single procedure, offers advantages to selected patients judged as suitable candidates for resection. To report the preliminary results of a novel, multidisciplinary surgical technique for the treatment of upper lobe lung cancers with direct extension to the spine. Consecutive case series. Eight adults who underwent PSR with either VATS or OT for the treatment of a T4 (vertebral body invasion) NSCLC. Total operative time, estimated blood loss, length of hospital stay, postoperative tumor recurrence and metastasis, survival, reoperations, and any other intraoperative or postoperative complication. Eight consecutive patients who underwent instrumented PSR with corpectomy for the treatment of an upper lobe NSCLC at a single institution were identified. Either VATS (n=4) or OT (n=4) was performed at the time of the reconstruction in each patient. All tumors were stage III NSCLC without metastasis. Patients who underwent VATS and OT were aged 54±11 and 54±2.9 years, respectively. Mean operative time and blood loss were similar between the groups: VATS: 367±117 minutes versus OT: 518±264 minutes; VATS: 813±463 mL versus OT: 1,250±1,500 mL. Mean follow-up was 16±13 months after surgery. Complications occurred in all eight patients. One OT patient had wound dehiscence requiring a tissue flap, and another suffered from a septic shock. No wound complications developed after VATS. Death secondary to tumor recurrence occurred once in each group. For the six surviving patients, 23±15 months (range, 4.5-43 months) have elapsed since surgery. Video-assisted thoracoscopic surgery with PSR is a novel and viable method for the complete resection of T4 NSCLC.

Surgery on Extracorporeal Circulation in Early and Advanced Non-Small Cell Lung Cancer

Locally advanced (T4) non-small cell lung cancer (NSCLC) is principally amenable to surgery. For radical resection of cardiovascular structures, extracorporeal circulation (ECC) may be required. Tumor dissemination is a concern in this situation. In this study, we evaluate the long-term results of T4 NSCLC surgery with ECC and compare them with combined cardiopulmonary surgery for early-stage NSCLC and heart disease. We retrospectively analyzed 16 patients undergoing surgery on ECC over a 13-year period. Eight patients suffered from T4 NSCLC (group A), and another eight patients suffered from coincidental T1-T2 NSCLC and heart disease (group B). In group A, five patients received neoadjuvant radiochemotherapy. Complete resection was achieved in all patients. Thirty-day mortality was one patient (12.5%) in each group. Six patients died from recurrent cancer with a median survival of 13.6 months in group A. Prognosis in patients with direct tumor invasion of the aortopulmonary window was a lot worse compared to those with atrial infiltration. One T4 patient who had only received surgery survived for 155 months without relapse. In group B, no NSCLC relapse occurred, and median survival was 21.6 months. All but one death in group B occurred due to cardiovascular incidents. Surgery on ECC for T4 NSCLC gives satisfactory results. The site of infiltration appears to be most important for local tumor relapse. Long-term survival is possible in some cases. Simultaneous cardiac and pulmonary surgery resulted in good early and midterm outcomes without surgery-induced tumor propagation.

Impact of Lung Function Changes After Induction Radiochemotherapy on Resected T4 Non-Small Cell Lung Cancer Outcome

Induction radiochemotherapy, followed by resection, for T4 non-small cell lung cancer, has shown promising long-term survival but may be associated with increased postoperative morbidity and death, depending on patient selection. Here, we determined the effect of induction radiochemotherapy on pulmonary function and whether postinduction pulmonary function changes predict hospital morbidity and death and long-term survival. A consecutive prospective cohort of 72 patients with T4 N0-2 M0 non-small cell lung cancer managed by radiochemotherapy, followed by resection, is reported. All patients underwent thoracoabdominal computed tomography or fusion positron emission tomography-computed tomography, brain imaging, mediastinoscopy, echocardiography, ventilation-perfusion scintigraphy, and pulmonary function testing before and after induction therapy. Resection was performed if the postoperative forced expiratory volume in 1 second and diffusion capacity of the lung for carbon monoxide exceeded 30% predicted and if the postoperative maximum oxygen consumption exceeded 10 mL/kg/min. The postoperative 90-day mortality rate was 8% (lobectomy, 2%; pneumonectomy, 21%; p=0.01). All deaths after pneumonectomy occurred after right-sided procedures. The 3-year and 5-year survival was 50% (95% confidence interval, 36% to 62%) and 45% (95% confidence interval, 31% to 57%) and was significantly associated with completeness of resection (p=0.004) and resection type (pneumonectomy vs lobectomy, p=0.01). There was no correlation between postinduction pulmonary function changes and postoperative morbidity or death or long-term survival in patients managed by lobectomy or pneumonectomy. In properly selected patients with T4 N0-2 M0 non-small cell lung cancer, resection after induction radiochemotherapy can be performed with a reasonable postoperative mortality rate and long-term survival, provided the resection is complete and a right-sided pneumonectomy is avoided. Postinduction pulmonary function changes did not correlate with postoperative morbidity or death or with long-term outcome.

What is the Impact of External Beam Radiation Therapy (EBRT) Following Limited Resection of T1 or T2 Non-small Cell Lung Cancer (NSCLC)? A SEER Analysis

Historical series and one randomized trial have guided surgeons in selecting the appropriate surgical procedure for patients presenting with localized NSCLC. Data to this point indicate that anatomical lobectomy remains the standard of care. However, many patients are still offered limited resections. The impact of post-operative EBRT in patients undergoing limited resection is unknown. The Surveillance Epidemiology and End Results (SEER) database was queried to identify patients with T1 or T2 NSCLC of squamous cell or adenocarcinoma histology who underwent primary surgical resection (wedge, segmental or lobectomy with lymph node evaluation) for the years 1998 – 2004. Demographic, clinical and pathologic data were culled and analyzed to determine the impact of radiation therapy following resection. Survival rates were estimated using the Kaplan-Meier method and significance was determined using the log-rank test (p <.05). Cox proportional hazards model was performed to determine factors significant for overall (OS) and cause-specific survival (CSS). A total of 14,149 patients meeting inclusion criteria were included. The majority of patients underwent lobectomy (n = 9,526). A total of 1,147 patients received EBRT following surgery. The median follow-up for the entire group was 1.8 years (range 1 month - 6.9 years). Lobectomy was statistically superior to wedge or segmental resection for both OS and CSS. The addition of EBRT following wedge or segmental resection did not enhance OS or CSS relative to lobectomy or compared to wedge or segmental resection without EBRT (Table). The effect of EBRT following limited resection was not influenced by the size of the tumor. Advancing age and grade, male sex, larger tumor size, limited resection, and the addition of EBRT were statistically significant negative predictors for OS.Poster Viewing Abstract 3007; TableNo EBRTLobectomySegmentalWedgep-value5-yr OS, %57.843.737<.00015-yr CSS, %70.959.252.3<.0001With EBRT5-yr OS, %33.212.5165-yr CSS,%42.915.825.6 Open table in a new tab Lobectomy remains the standard of care for management of localized NSCLC. Generally, patients receiving post-operative EBRT in this population experienced poorer OS and CSS compared to surgery alone regardless of the surgical extent. These data suggest that planned limited resection followed by EBRT is an inferior approach to lobectomy. When lobectomy is not feasible, noninvasive alternatives to surgery, including stereotactic radiation therapy, should be considered.

Prognostic Value of Pretreatment FDG-PET Parameter for Early Stage Non-small Cell Lung Cancer Treated With Stereotactic Ablative Radiation Therapy

Prognostic Value of Pretreatment FDG-PET Parameter for Early Stage Non-small Cell Lung Cancer Treated With Stereotactic Ablative Radiation Therapy

A Prediction Model for N2 Disease in T1 Non-small Cell Lung Cancer: Implications for Cost-effective Mediastinal Staging

A Prediction Model for N2 Disease in T1 Non-small Cell Lung Cancer: Implications for Cost-effective Mediastinal Staging

Clinical Characteristics of Resected T3 Non-small Cell Lung Cancer Characterized by Parietal Pleural Invasion or Chest Wall Invasion

This study investigated the clinicopathological characteristics and the surgical outcome in patients with non-small cell carcinoma (NSCLC) with parietal pleura invasion or chest wall invasion (p3/T3). This study clinicopathologically evaluated 760 patients who had undergone a resection for NSCLC between 1999 and 2008. There were 43 (5.7%) patients with p3/T3 NSCLC. The patients included 37 males and 6 females. The histological types included 23 squamous cell carcinomas, 13 adenocarcinomas, 3 large cell carcinomas, 3 pleomorphic carcinomas, and 1 spindle cell carcinoma. Pneumonectomy was performed in 2 patients, bilobectomy in 1, lobectomy in 31, segmentectomy in 3, and partial resection of the lung in 6. The combined resection regions were parietal pleural in 23, ribs in 16, pericardium in 2, and diaphragm in 2 patients. Major complications included empyema in 1, chylothorax in 1, and postoperative bleeding in 1 patient. The first recurrence sites in 16 patients with recurrent disease were the lung in 5 patients, brain in 3, bone in 2, adrenal gland in 2, skin in 2, liver in 1, mesenterium in 1, mediastinal lymph node in 1, axillary lymph node in 1, and carcinomatous pleuritis in 1. The overall 5-year survival rate after surgery was 50.6%. An en bloc resection for p3/T3 NSCLC provides a modestly favorable prognosis. Local recurrence was observed in a minority of case, and recurrence by distant metastasis was observed in most cases, suggesting a greater need for postoperative chemotherapy.

A prediction model for N2 disease in T1 non–small cell lung cancer

Controversy remains over the routine use of mediastinoscopy or positron emission tomography in T1 non-small cell lung cancer without lymph node enlargement on computed tomography because the risk of N2 involvement is comparatively low. We aimed to develop a prediction model for N2 disease in cT1N0 non-small cell lung cancer to aid in the decision-making process. We reviewed the records of 530 patients with computed tomography-defined T1N0 non-small cell lung cancer who underwent surgical resection with systematic lymph node dissection. Correlations between N2 involvement and clinicopathologic parameters were assessed using univariate analysis and binary logistic regression analysis. A prediction model was built on the basis of logistic regression analysis and was internally validated using bootstrapping. The incidence of N2 disease was 16.8%. Four independent predictors were identified in multivariate logistic regression analysis and included in the prediction model: younger age at diagnosis (odds ratio, 0.974; 95% confidence interval, 0.952-0.997), larger tumor size (odds ratio, 2.769; 95% confidence interval, 1.818-4.217), central tumor location (odds ratio, 3.204; 95% confidence interval, 1.512-6.790), and invasive adenocarcinoma histology (odds ratio, 3.537; 95% confidence interval, 1.740-7.191). This model shows good calibration (Hosmer-Lemeshow test: P=.784), reasonable discrimination (area under the receiver operating characteristic curve, 0.726; 95% confidence interval, 0.669-0.784), and minimal overfitting demonstrated by bootstrapping. We developed a 4-predictor model that can estimate the probability of N2 disease in computed tomography-defined T1N0 non-small cell lung cancer. This prediction model can help to determine the cost-effective use of mediastinal staging procedures.

Surgical results and staging of non-small cell lung cancer with interlobar pleural invasion

The aim of this study was to compare the survival rates of non-small cell lung cancer (NSCLC) with interlobar pleural invasion (IPI) with that of patients with other T2 and T3 diseases according to the seventh TNM staging system. One thousand and one patients with pathologic T2 and T3 NSCLC (according to the seventh staging criteria) treated between 1980 and 2004 were retrospectively evaluated. Among these, 682 patients were pathologically staged as T2 without IPI (T2 group), 25 as T2 with IPI (IPI group) and 294 as T3 (T3 group). The 5-year survival rate for the T2, IPI and T3 groups were 52.0, 31.1 and 36.3%, respectively. In patients without nodal involvement, the 5-year survival rates of the T2N0, IPIN0 and T3N0 groups were 60.9, 40.0 and 45.9%, respectively. The survival rate was significantly different between the T3N0 and T2N0 groups (P < 0.001) and between the IPIN0 and T2N0 (P = 0.020) groups. There was no significant difference in the survival rate between the IPIN0 and T3N0 groups (P = 0.644). In patients without nodal involvement, the survival of NSCLC with IPI is similar to that of the T3 disease.