Stage IIIB Non-small Cell Lung Cancer Research Articles

Chemotherapy in the Elderly with Non-Small Cell Lung Cancer: A Non-Interventional, Prospective, Multicentric Observational Study

Background Elderly patients (70 years or older) with non-small cell lung cancer (NSCLC) do benefit from systemic chemotherapy as shown in many studies. We prospectively collected multicentric data on therapeutic decisions from patients 70 years or older to reflect the reality in the German health care system. Material and Methods Patients 70 years or older with NSCLC Stage IIIB or IV were eligible. No more than 20 consecutive patients from each center were included. Comorbidities, weighted by the Charlson-comorbidity-index, and survival data were collected. Results 253 patients were documented. Median age was 75.5 years (range 70 to 92) and 75 % were male. 2 % had no comorbidities, 5 % one, 15 % two, 24 % three and 55 % more than three. 237 patients (94 %) received systemic chemotherapy: 172 (73 %) as a combination and 58 (24 %) as monotherapy. Data from seven patients regarding therapy are missing. Combination regimens were in 66 % carboplatin- and in 30 % cisplatin-based. The most frequently given monotherapy was vinorelbin in 50 % of cases. In the group of the patients older than 80 years (n = 38), 53 % received mono therapy, 29 % a carboplatin-based regimen and 16 % no chemotherapy. Cisplatin was not administered in this age group. Median overall survival (OS) was 16.9months. Patients with a Charlson-score ≤ 6 had 17.9 months, those > 6 12.0 months. With combination chemotherapy median OS was 23.5 months. Patients > 80 years had a median OS of 5.7 months. Conclusion A high percentage of patients older than 70 years received systemic therapy. Survival depended more on comorbidities than on age.

Results of a Single Institution Experience with Dose-Escalated Chemoradiation for Locally Advanced Unresectable Non-Small Cell Lung Cancer.

We determined factors associated with morbidity and outcomes of a series of non-small cell lung cancer (NSCLC) patients treated with dose-escalated chemoradiotherapy at the University of Pittsburgh Lung Cancer Program. The records of 170 stage III NSCLC patients treated with definitive intent were retrospectively reviewed. All patients received four-dimensional CT simulation scan and had respiratory gating if tumor movement exceeded 5 mm. Overall survival (OS), locoregional control (LRC), and freedom from distant metastasis (FFDM) were calculated using log-rank and Cox regression analysis. For the present series of patients, median follow-up was 36.6 months, median survival 27.4 months, and the 2- and 4-year OS was 56.0 and 30.7%, respectively. The 4-year LRC and FFDM were 43.9 and 40.7%, respectively. No benefit was associated with irradiation doses above 66 Gy in OS (p = 0.586), LRC (p = 0.440), or FFDM (p = 0.230). On univariate analysis, variables associated with worse survival included: clinical stage IIIB (p = 0.037), planning target volume (PTV) over 450 cc (p < 0.001), heart V30 over 40% (p = -0.048), and esophageal mean dose over 20% (p = 0.024), V5 (p = -0.015), and V60 (p = -0.011). On multivariable analysis, PTV above 450 cc (52.2 vs. 25.3 months, p < 0.001) and esophageal V60 >20% (43.8 vs. 21.3 months, p = -0.01) were associated with lower survival. Grade 2 or higher acute lung toxicity and esophagitis were detected in 9.5 and 59.7%, respectively of patients. Grade 2 or higher acute lung toxicity was reduced if lung V5 was ≤65 (7.4 vs. 23.8%, p = 0.03). Grade 2 or higher acute esophagitis was reduced if V60 ≤ 20% (62 vs. 81.3%, p = 0.018). The use of intensity-modulated radiation therapy was more frequent in stage IIIB compared to stage IIIA patients (56.5 vs. 39.5%, p = 0.048) and was associated with a higher lung V5 and V10. The outcomes of a program of dose-escalated chemoradiotherapy for unresectable stage IIIA and IIIB NSCLC patients were consistent with other studies and showed no benefit to radiation doses above 66 Gy. Furthermore, maintaining low esophageal V60 and lung V5 were associated with lower morbidity and mortality.

OA09.02 Should Surgery Be Part of the Multimodality Treatment for Stage IIIB Non-Small Cell Lung Cancer

Stage IIIB non-small cell lung cancer (NSCLC) is a heterogeneous patient group, including T4N2 and T1-4N3 NSCLC. Traditionally, treatment for stage IIIB consists in definitive chemoradiation. Surgical treatment for stage IIIB NSCLC is used anecdotally in highly selected patients. Here, we studied patient outcome who underwent surgical resection as part of multimodality treatment for stage IIIB NSCLC. All patients from a single institution who underwent surgery for stage IIIB between 2000 and 2015 were included. Surgical candidates were selected on a case-by-case basis during multidisciplinary tumor board conference. In general, N2-N3 diseases are not considered an absolute contraindication to surgery if lymph node involvement is limited to a non-bulky single site, the tumor is deemed completely resectable without major morbidity and the patient will tolerate multimodality treatment. Mediastinal staging comprised cervical mediastinoscopy, positron emission tomography coupled with CT from 2005 and endobronchial ultrasound guided fine-needle aspiration from 2011. Charts were retrospectively reviewed and data analyzed. Survival was calculated from the date of surgery until last follow-up. Univariate and multivariate analysis were performed to identify prognostic factors. From 2000 to 2015, 5416 patients underwent lung resection for NSCLC in our center. Sixty patients (1%) underwent surgery for stage IIIB NSCLC. Forty-three were males (72%). Median age was 58 years (from 22 to 79). Thirty-two patients had T4N2 NSCLC involving the carina (n=16, 50%), superior vena cava (n=4, 12%), carina and superior vena cava (n=5, 16%), left atrium (n=5, 16%), pulmonary artery (n=1, 3%) and spine (n=1, 3%). Twenty-eight patients had N3-disease, involving supraclavicular (n=14, 50%) or contralateral mediastinal lymph nodes (n=14, 50%). Pneumonectomy was performed in 27 patients (45%). Twenty-nine patients (48%) had induction therapy, consisting in chemotherapy alone for all patients. Adjuvant therapy was administered to 52 patients (87%) and consisted mostly of chemoradiation (n=35, 67%). Complete resection (R0) was performed in 55 patients (92%). Post-operative mortality was 3% (n=2). Three- and 5-year overall survivals were 51% and 39%, respectively. Median survival was 40 months. Median follow-up was 17 months. Results of the multivariate analysis identified incomplete resection (p=0.008) and absence of adjuvant treatment (p=0.032) as prognostic factors for poor survival. An excellent 5-year survival of 39% was achieved in highly selected patients with stage IIIB NSCLC and treated with multimodality including surgery. Patients with stage IIIB NSCLC should therefore be discussed in a multidisciplinary setting, including thoracic surgeons.

P2.02-025 Continuous Intravenous Pumping Endostar Combined with Radiochemotherapy in Unresectable Stage III Non-Small-Cell Lung Cancer

Preclinical models have shown that recombinant human endostatin (Endostar) can transiently normalize the tumor vasculature to make it more efficient for oxygen delivery, which provides a treatment window of enhancing tumor radiosensitivity. This study is to evaluate the safety and efficacy of continuous intravenous pumping (CIP) of Endostar combined with standard concurrent radiochemotherapy for unresectable stage III non-small-cell lung cancer (NSCLC). In this prospective study, patients with unresectable stage IIIA or IIIB NSCLC received CIP of Endostar (7.5mg/m2) over 5 days at weeks 1, 3, 5, and 7. During week 2-8, patients received two 28-day cycles of etoposide 50mg/m2 on day 1-5 and cisplatin 50mg/m2 on day 1, 8, with concurrent thoracic radiation of 60-66 Gy in 30-33 fractions over 6-7 weeks. Acute toxicities were evaluated using CTCAE 3.0. Tumor response was evaluated using RECIST 1.1 criteria. Between Nov. 2012 and May. 2016, 67 patients were eligible for toxicity and efficacy evaluation, including 56 (83.6%) male and 11 (16.4%) female, 44 (65.7%) with squamous cell carcinoma, 20(29.9%) with adenocarcinoma, 1 (1.5%) with large cell carcinoma and 2 (3.0%) with undifferentiated carcinoma, and 28 (41.8%) with stage III A disease and 39 (58.2%) with III B disease, respectively. The median age was 59 (31-69) years. All patients completed the treatment as planned, except that 3 patient missed one cycle chemotherapy. There were 8 (11.9%), 43 (64.2%), 11 (16.4%) and 4 (6.0%) patients achieved complete response, partial response, stable disease and progressive disease, respectively. The objective remission rate (ORR) is 76.1%. There were 23 patients (34.3%) with grade 3+4 neutropenia, 9 (13.4%) with grade 3+4 anemia, and 10 (14.9%) with grade 3+4 thrombocytopenic. Three patients (4.5%) developed grade 3 nausea/vomiting. Grade 3 acute esophagitis, grade 1+2 and grade 3 pneumonitis were observed in 8 (11.9%), 12 (17.9%) and 2 (3.0%) patients, respectively. One patient died of pneumonitis before efficacy evaluation. No grade 2 cardiovascular toxicity was observed. Up to the last follow-up, the med. For patients with unresectable stageIII NSCLC, CIP of Endostar enhanced patient compliance, and combined with concurrent radiochemotherapy is tolerable and the short term outcomes are promising. Long term survival data wait further follow up.

P3.02c-015 Phase II Trial of S-1/Cisplatin Combined with Bevacizumab for Advanced Non-Squamous Non-Small Cell Lung Cancer: TCOG LC-1202: Topic: Targeted Therapy

S-1 plus cisplatin is a standard chemotherapy regimen for advanced non-small cell lung cancer (NSCLC) (Ann. Oncol. 2015; 26:1401-8). The addition of bevacizumab significantly improved overall survival (OS) in patients with advanced non-squamous (non-SQ) NSCLC who received carboplatin plus paclitaxel but failed to show an OS advantage in patients who received cisplatin plus gemcitabine. Few studies of bevacizumab have evaluated quality of life (QOL) in patients with non-SQ NSCLC. Chemotherapy-naïve patients with stage IIIB, IV, or recurrent non-SQ NSCLC, Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0–1, age 20–74 years, and measurable lesions were treated with a 3-week cycle of S-1 40 mg/m2 twice a day on days 1–14, cisplatin 60 mg/m2 on day 8, and bevacizumab 15 mg/kg on day 8, for 4–6 cycles. Patients without progressive disease received maintenance bevacizumab 15 mg/kg on day 1 with a 3-week cycle and S-1 40 mg/m2 twice a day every other day. The primary endpoint was progression-free survival (PFS). Secondary endpoints were objective response rate (ORR), OS, toxicity profile, and QOL. From June 2013 to January 2015, 39 evaluable patients were enrolled from 8 institutions: 10 women and 29 men; median age 65 (range, 38–74) years; epidermal growth factor receptor positive/anaplastic lymphoma kinase positive: two patients/two patients; performance status 0/1: 22/17; stage IIIB/IV/recurrence: 1/35/3; adeno/large cell/other: 35/1/3. Thirty one patients (80%) completed 4 cycles of induction chemotherapy, and 23 patients (59%) were started on maintenance chemotherapy. Median PFS, OS, and ORR were 7.3 months (95% confidence interval (CI): 5.9–8.7), 21.4 months (95% CI: 14.7–not reached), and 64%, respectively. The worst hematologic and non-hematologic adverse events were as follows (%): grade 3/4 leukopenia: 13/0; neutropenia: 18/5; thrombocytopenia: 0/0; anemia: 0/0; neutropenic fever: 3/0; and hypertension: 28/0; diarrhea: 3/0. QOL data will be presented at the meeting. S-1 plus cisplatin in combination with bevacizumab met the primary endpoint in patients with advanced non-SQ NSCLC in the present trial. Additionally, the response rate is anticipated to be high, and the regimen was well tolerated. Clinical trial information: UMIN000009476.

PUB084 Long Term Survival of Stage IIIb Non-Small Cell Lung Cancer (NSCLC) Patients Treated with Concurrent Chemoradiation

The optimal treatment strategy for Stage IIIB NSCLC patients with a T4N0-1 tumor is a matter of debate. In prospective combined modality series including surgery, the median overall survival (OS) is approximately 24 months. We hypothesized that results comparable to regimens including surgery can be achieved with concurrent chemoradiation in this patient group. In our retrospectively collected database of NSCLC patients, all patients with T4 (mediastinal invasion) N0-1 NSCLC receiving concurrent chemoradiation were included. One patient had a recurrence after previous pneumonectomy. All patients were given 3 cycles of chemotherapy (cisplatin and etoposide). Radiotherapy (RT) was started at the 2nd course of chemotherapy. OS was calculated from date of diagnosis (Kaplan-Meier method). Toxicity was scored according to CTCAEv3.0. 42 patients (8 female, 34 male) with a median age of 62.5 ± 9 years (44-80 years) were included from January 2005 until December 2009. Stage distribution: 86% T4N0 (n=36), 14% T4N1 (n=6). The maximal tumor dose was 66 Gy using conventional fractionation. The median prescribed mean lung dose was 15 ± 4.4 Gy (5.03 -19.9 Gy). Acute toxicity: 1 patient experienced grade 3 dyspnea during RT. Grade 3 dysphagia occurred in 5 patients (12%) during RT requiring tube feeding in 3 of these patients (7%). Dysphagia persisted later than 1 month after RT in 1 patient (2%). Grade 3 dysphagia only occurred in patients treated concurrently. Grade 3 cough occurred in 1 patient during RT, no patient experienced grade 3 cough 1 month after RT. 2 patients died within 3 months after start of RT, one due to myocardial infarction, one of unknown causes. Severe late toxicity was not present: no grade 3 complications more than 3 months after the end of radiotherapy. With a median follow-up of 42 months, the median OS for the whole group is 34 months (95% CI 24-43 months). 2-year OS survival is 55%. Concurrent accelerated chemoradiation using an individualized dose prescription is a valid treatment strategy for stage IIIb, T4N0-1 NSCLC patients yielding very promising OS results with low toxicity.

Correlation of DNA Repair Gene Polymorphisms With Clinical Outcome in Patients With Locally Advanced Non–Small-Cell Lung Cancer Receiving Induction Chemotherapy Followed by Surgery

ObjectiveThe aim of this study was to evaluate whether xeroderma pigmentosum group D (XPD) and ribonucleotide reductase subunit M1 (RRM1) polymorphisms influenced clinical outcome in patients with stage IIIA-B non–small-cell lung cancer (NSCLC) treated with neoadjuvant gemcitabine/cisplatin/docetaxel followed by surgery. Materials and MethodsA total of 109 patients with stage IIIA and IIIB NSCLC were prospectively genotyped to examine a potential association between XPD 312 (aspartic acid [Asp]/asparagine [Asn]), XPD 751 (lysine [Lys]/glutamine [Gln]), and RRM1 (−37 C/A) polymorphisms with response and survival. ResultsThe median survival was 32.14 months for carriers of XPD 312 Asp/Asp and 12.04 months for those with the variant Asn allele (P = .05). In addition, event-free survival was longer for patients with the XPD 312 Asp/Asp genotype compared with patients with Asp/Asn or Asn/Asn (P = .03). A similar but nonsignificant trend was observed for the XPD 751 genotype. In a multivariate analysis, complete resection and age emerged as prognostic factors for overall survival; in patients with incomplete resection or exploratory thoracotomy, XPD 312 was the most significant prognostic factor (P = .03). ConclusionThe XPD 312 single nucleotide polymorphism is a prognostic factor for survival in patients with locally advanced NSCLC receiving induction chemotherapy followed by surgery. The Asn allele is associated with unfavorable outcome and could be used for better stratification of patients.

Prognosis and it related factors in patients of stage III non-smallcell lung cancer after three-dimensional conformal radiotherapy

Objective To evaluate the efficacy of three-dimensional conformal radiotherapy (3DCRT) and prognostic factors for stage Ⅲ non-small cell lung cancer (NSCLC). Methods From 2000 to 2010, 474 patients with stage Ⅲ NSCLC undergoing 3DCRT were enrolled as subjects. Those patients, consisting of 382 males and 92 females, had a median age of 63 years. In those patients, 211 had stage ⅢA NSCLC and 263 had stage ⅢB NSCLC; 165 were treated with radiotherapy alone and 309 with chemoradiotherapy; 55 were treated with conventional radiotherapy plus 3DCRT, 340 with 3DCRT, and 79 with intensity-modulated radiotherapy; the median equivalent dose was 60 Gy (44-77 Gy). The Kaplan-Meier method, log-rank test, and Cox model were used for survival rate calculation, univariate analysis, and multivariate analysis, respectively. Results The follow-up rate was 96.6%.In all patients, the 1-, 3-, and 5-year overall survival rates were 63.0%, 24.9%, and 17.8%, respectively; the median survival time was 18 months. The univariate analysis showed that sex, age, immediate response, radiotherapy method, fractionation scheme, chemotherapy, and radiation pneumonitis (RP) were prognostic factors (P=0.004, 0.001, 0.000, 0.007, 0.004, 0.009, 0.049). The multivariate analysis showed that sex, age, immediate response, radiotherapy method, and RP were independent prognostic factors (P=0.006, 0.000, 0.000, 0.003, 0.048). Patients with radiation doses of 60-66 Gy had the best prognosis of all. Conclusions In patients with stage Ⅲ NSCLC undergoing 3DCRT, female patients, patients at a young age, patients with satisfactory immediate response, patients treated with full-course 3DCRT, and patients with grade 0-1 RP have better prognosis than others.3DCRT combined with chemotherapy improves survival in patients. A radiation dose of 60-66 Gy is recommended. Key words: Lung neoplasms/radiotherapy; Radiotherapy, two-dimensional; Radiotherapy, three-dimensional; Prognosis

Cancer cachexia, sarcopenia and biochemical markers in patients with advanced non-small cell lung cancer-chemotherapy toxicity and prognostic value.

Cancer cachexia and sarcopenia are frequently observed in cancer patients and associated with poor survival. The majority of studies of cancer cachexia and sarcopenia have been done in patients with solid tumors of different origins, and there are currently no good predictors of the benefit of chemotherapy or factors that predict survival in advanced cancer. The purpose of our prospective study was to evaluate prevalence of cachexia and sarcopenia using international consensus definition and criteria for diagnosis in patients with diagnosed advanced non-small cell lung cancer (NSCLC) stage IIIB and IV and their relation to chemotherapy toxicity and survival prediction. A secondary aim was to compare several biochemical markers (CRP, IL-6, protein, and albumin) with time to tumor progression in order to assess prognostic value or to guide a treatment. Between December 2013 and April 2015, the prospective cohort study of 100 Caucasian patients with advanced NSCLC stage IIIB or IV, who were referred consecutively to Department for Respiratory Diseases "Jordanovac," was evaluated. Anthropometric measurements and biochemical data (CRP, albumin, protein, IL-6, haemoglobin) together with body composition measurements (total muscle cross-sectional area, lumbar skeletal muscle index) were obtained for each patient before starting with platinum-doublet therapy. Skeletal muscle cross-sectional area at the third lumbar vertebra was measured by computerized tomography, and sarcopenia was defined using a previously published cutoff point. Toxicity was assessed after cycle 1 of treatment and time-to-tumor progression was determined prospectively. One hundred patients with advanced lung cancer were recruited: 67 were male and median age was 64years. The median time to disease progression was 187days. The prevalence of cachexia and sarcopenia in study cohort was 69 and 47%, respectively. CRP, IL-6, and albumin concentration in cachectic compared to non-cachectic patients demonstrated statistically significant difference (p = 0.020, p = 0.040, p = 0.003). Cachexia and sarcopenia were not found to be predictors of chemotoxicity nor was time to tumor progression. On the contrary, albumin concentration with established cutoff point of 37.5g/L was clearly proved as the predictive factor of both chemotoxicity (OR (95% CI) = 0.85; p < 0.001) and survival (HR (95% CI) = 0.55). Albumin level has been shown to be more important predictive marker of chemotherapy toxicity and survival than cachexia and sarcopenia are. This approach in clinical settings can be used to guide the choice of oncologic treatment.

Prognostic factors for long term survival in patients with advanced non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) represents 85% of all lung cancers. It is estimated that 60% of patients with NSCLC at time of diagnosis have advanced disease. The aim of this study was to investigate clinical and demographic prognostic factors of long term survival in patients with unresectable NSCLC. We retrospectively reviewed data of 1,156 patients with NSCLC stage IIIB or IV who survived more than 60 days from the time of diagnosis and treated from August 1987 until March 2013 in the Oncology Department of Pulmonary Clinic of the General Hospital Papanikolaou. Initially univariate analysis using the log-rank test was conducted and then multivariate analysis using the proportional hazards model of Cox. Also Kaplan Meier curves were used to describe the distribution of survival times of patients. The level of significance was set at 0.05. The mean age at diagnosis was 62 years. About 11.9% of patients were women and 88.1% were male. The majority of cases were adenocarcinomas (42.2%), followed squamous (33%) and finally the large cell (6%). Unlike men, most common histological type among women was adenocarcinoma rather than squamous (63% vs. 10.9%). In univariate analysis statistically significant factors in the progression free survival (PFS) and overall survival (OS) were: weight loss ≥5%, histological type, line 1 drugs, line 1 combination, line 1 cycles and radio lung. Specifically radio lung gives clear survival benefit in the PFS and OS in stage IIIB (P=0.002) and IV (P<0.001). On the other hand, the number of distant metastases in stage IV patients did not affect OS, neither PFS. In addition patients who received platinum and taxane had better PFS (P=0.001) and OS (P<0.001) than those who received platinum without taxane. Also the third drug administration proved futile, since survival (682.06±34.9) (P=0.023) and PFS (434.93±26.93) (P=0.012) of patients who received less than three drugs was significantly larger. Finally, large cell carcinoma recorded the shortest OS and PFS compared with adenocarcinoma (P=0.043 and P=0.016 respectively) and squamous cell carcinoma (P=0.021 and P=0.004 respectively). In multivariate analysis the same predictors were statistically significant except for line 1 drugs. This study confirms the increased incidence of adenocarcinoma in women than in men and the aggressiveness of large cell carcinoma. It also underlines the vitality of factors such as weight loss, radio lung and doublet platinum-based. On the other hand, it excludes significant factors such as gender, age and smoking.

Percutaneous CT-guided microwave ablation as maintenance after first-line treatment for patients with advanced NSCLC.

BackgroundSystemic therapy is recommended for advanced non-small-cell lung cancer (NSCLC). However, conventional first-line treatment has generated a plateau in response rate of 25% to 35%. Few studies have shown patients benefit from microwave ablation (MWA) in combination with radiotherapy and chemotherapy. This study aims to evaluate safety and efficacy of percutaneous computed tomography-guided MWA as maintenance after first-line treatment for patients with advanced NSCLC.MethodsPatients with histologically verified NSCLC stage IIIB or IV between January 2010 and March 2014 were involved. After completion of first-line treatment with partial response or stable disease, 35 patients with 39 tumors underwent 39 MWA procedures. Complications, progression-free survival (PFS), overall survival (OS), and correlated predictors were analyzed.ResultsDuring a median follow-up of 17.7 months and 10.8 months after initial MWA, local efficacy was 87.2%, median MWA-related local control time was 10.6 months, and tumor size was the only predictor (P=0.002). Median MWA-related PFS, MWA-related OS, PFS, and OS were 5.4, 10.6, 11.8 and 17.7 months, respectively. Local efficacy was significantly correlated with MWA-related PFS (P=0.003), MWA-related OS (P=0.000), and OS (P=0.001). There were no procedure-specific deaths. Total incidence of major complications was 12.8%, including pneumothorax resolved by closed pleural drainage and pneumonia controlled by antibiotics in a short time.ConclusionThis study concluded two points, including: 1) patients benefited from MWA as maintenance both in local control and survival; 2) as maintenance MWA was superior to conventional maintenance therapy with improved survival and well-tolerated complications. Therefore, MWA was a safe and effective maintenance after first-line treatment in patients with advanced NSCLC.

Role for Surgical Resection in the Multidisciplinary Treatment of Stage IIIB Non–Small Cell Lung Cancer

The role of multimodality therapy in stage IIIB non-small cell lung cancer (NSCLC) remains inadequately studied. Although chemoradiation is currently the mainstay of treatment, randomized trials evaluating surgical intervention are lacking, and resection is offered selectively. Data from patients with clinical stage IIIB NSCLC (T4N2 or any N3) undergoing definitive multimodality therapy were obtained from the National Cancer Database (NCDB). Multivariable Cox regression models were fitted to evaluate variables influencing overall survival (OS). From 1998 to 2010, 7,459 patients with clinical stage IIIB NSCLC were treated with definitive chemoradiation (CR group), whereas 1,714 patients underwent chemotherapy, radiation, and surgical intervention in any sequence (CRS group). CRS patients were more likely to be younger and white and have slightly smaller tumors (all p < 0.01). There was no difference in Charlson Comorbidity Index (CCI) between the groups (p= 0.5). In the CRS group, 79% of patients received neoadjuvant therapy. Thirty-day surgical mortality was 3%. Factors associated with improved OS in multivariate analysis included younger age, female sex, decreased CCI, smaller tumor size, and surgical resection (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.52-0.63). Among patients treated with surgical intervention, incomplete resection was associated with decreased OS (HR, 1.52; 95% CI, 1.20-1.92). Median OS was longer in the CRS group (25.9 months versus 16.3 months; p < 0.001). Propensity matched analysis on 631 patient pairs treated with CRS versus CR confirmed these findings (median OS, 28.9 versus 17.2 months; p < 0.001). Surgical resection as a part of multimodality therapy may be associated with improved OS in highly selected patients with stage IIIB NSCLC. Multidisciplinary evaluation of these patients is critical.

Immunotherapeutic Agents in Non-small-cell Lung Cancer Finally Coming to the Front Lines

Non-small-cell lung cancer usually carries a dismal prognosis. Novel treatment approaches are clearly warranted. Immunotherapy has emerged as a promising area of research developing agents that manipulate the immune system to induce antitumor responses while avoiding major toxicity. New vaccines and checkpoint inhibitors are currently undergoing investigation in phase II and phase III clinical trials. In advanced non-small-cell lung cancer (NSCLC), belagenpumatucel-L, an allogeneic cell vaccine directed against transforming growth factor β in the tumor microenvironment, knocks down the immune suppression caused by the tumor and has demonstrated a dose- and time-dependent efficacy in some subgroups of patients. L-BLP25 and TG4010 are both antigenic vaccines that target mucin 1, whose encoding proto-oncogene is commonly mutated in solid tumors. The L-BLP25 vaccine achieved a significant improvement in overall survival in the subgroup of patients with stage IIIB NSCLC treated with chemoradiotherapy. TG4010 vaccination resulted in better progression-free survival when added to cisplatin-gemcitabine chemotherapy. These results are being addressed in the currently ongoing phase III TIME trial. In the adjuvant setting, MAGE-A3, an antigen-based vaccine, showed promising results in melanoma-associated antigen A3 positive lung cancer patients who underwent resection in the phase II study; however, no improvement in progression-free survival was observed in the phase III MAGRIT study. CIMAVax is a recombinant human epidermal growth factor (EGF) vaccine that induces anti-EGF antibody production and prevents EGF from binding to its receptor. It has improved overall survival in patients with advanced NSCLC who achieve seroconversion. Ipilimumab, an immune checkpoint inhibitor that targets cytotoxic T-lymphocyte antigen 4, demonstrated improved progression-free survival in advanced NSCLC patients who received the drug after chemotherapy in a phased regimen. Finally, anti-programmed death receptor 1 agents have achieved durable response rates in phase I studies. This review gives an overview of the current data and the most promissory immunotherapeutic agents for NSCLC.

Role for surgical resection in the multidisciplinary treatment of stage IIIB non-small cell lung cancer (NSCLC).

7573 Background: The role of multi-modality therapy in stage IIIB NSCLC remains inadequately studied. Although chemoradiation is currently the mainstay of treatment, randomized trials evaluating th...

Endobronchial/Endoesophageal Ultrasound (EBUS/EUS) Guided Fine Needle Aspiration (FNA) and 18F-FDG PET/CT Scanning in Restaging of Locally Advanced Non-small Cell Lung Cancer (NSCLC) Treated with Chemo-radiotherapy: A Mono-institutional Pilot Experience.

Chemo-radiotherapy is standard treatment of stage IIIA-N2 bulky or IIIB non-small cell lung cancer (NSCLC). Surgical resection of residual disease in downstaged patients may improve overall survival. In this setting, restaging disease is still a challenge. 18F-FDG PET/CT represents the gold standard although accuracy results are disappointing. Endoscopic bronchial/ esophageal ultrasound (EBUS/EUS)-guided fine needle aspiration (FNA) may confirm lymph node (LN) involvement. We analyzed 16 patients with stage IIIA-N2 bulky or IIIB NSCLC treated with chemo-radiotherapy. At restaging, all patients performed EBUS/EUS with FNA and PET/CT scan and results were compared. Patients underwent PET/CT scan 43 days (range: 24-89) and EBUS/EUS 42 days (range: 14-71) after therapy. Overall, 7 EBUS and 9 EUS procedures were performed: no complications resulting from the procedure occurred. In 6 patients EBUS/EUS did not reveal any suspicious lesions; in 2 the exam showed enlarged mediastinal LN that were biopsied, but with no evidence of tumor cells; in 2 the sample was not considered diagnostic; 6 had persistent mediastinal LN involvement. PET/CT scan showed 4 cases of complete metabolic response, 9 partial metabolic response, 2 stable metabolic disease and one progressive metabolic disease. Notably, all 7 patients with .80% decrease in SUV with respect to basal value showed a pathological complete response or negative EBUS/EUS. EBUS/EUS could be used to complement PET/CT scanning to verify mediastinal LN clearance. Further prospective trials are warranted to confirm the utility of EBUS/EUS together with PET/CT in restaging locally advanced NSCLC.

Prognostic Factors in the Radical Nonsurgical Treatment of Stage IIIB Non–Small-Cell Lung Cancer

BackgroundMany patients diagnosed with stage IIIB (AJCC sixth edition; T4, N3, or both; no pleural effusion) non–small-cell lung cancer (NSCLC) are treated with curative intent, despite a low cure rate. Guidelines are required to help select patients for radical therapy so that the patients with little chance of cure may be spared the toxicities of aggressive treatment. A retrospective analysis was performed to investigate factors influencing outcomes in these patients. Materials and MethodsFrom 2002 to 2009, all cases of stage IIIB NSCLC from the authors' institution were identified. Patients treated with radical radiotherapy (minimum dose, 50 Gy), with or without chemotherapy, were included. Charts were reviewed for patient demographic data, baseline blood work, tumor factors, treatment factors, and hospitalizations. The primary outcome was overall survival (OS), measured from time of diagnosis. ResultsOf 238 patients identified, 184 eligible cases were reviewed. The median follow-up for all patients was 17.2 months (range, 1.7-237.1). The median progression-free survival was 10.8 months (95% CI, 9.6-12.4). Median survival was 17.9 months, and OS was 68%, 42%, and 28% at 1, 2, and 3 years, respectively. In multivariate analysis, female gender (hazard ratio [HR], 0.58; 95% CI, 0.37-0.88; P = .0013), ≤ 5% weight loss (HR, 0.64; 95% CI, 0.43-0.93; P = .01), and absence of N3 disease (HR, 0.64; 95% CI, 0.42-0.96; P = .03) were associated with significantly longer survival. ConclusionOS was significantly longer in women, in patients with ≤ 5% weight loss, and in those without N3 disease. Good patient selection remains important in the radical treatment of stage IIIB NSCLC.

Value of surgery for stage IIIa non-small cell lung cancer

背景与目的对于Ⅲ期非小细胞肺癌（non-small cell lung cancer, NSCLC），目前普遍倡导手术、化疗、放疗的多学科综合治疗，但许多研究者对是否应该手术提出了质疑。该研究探讨了手术对于Ⅲ期NSCLC患者的价值。方法回顾性分析2002年3月-2012年10月北京协和医院收治的经病理学确诊的Ⅲ期NSCLC患者310例。根据最初确诊时是否手术可分为手术组和非手术组。Ⅲa期根据N分期的不同可分为T4N0/T3-4N1M0期和T1-3N2M0期。采用χ2检验比较计数资料，Kaplan-Meier方法比较总生存期（overall survival, OS）和无进展生存期（progression free survival, PFS），并绘制生存曲线。结果ECOG评分0分和Ⅲa期NSCLC患者更倾向于手术治疗。Ⅲa期手术与非手术组的中位OS分别为38.9个月和21.8个月，中位PFS分别为19.2个月和11.9个月。两组OS的差异有统计学意义（P=0.041），PFS的差异无统计学意义（P=0.209）。Ⅲa期中的T4N0/T3-4N1M0期手术与非手术组的中位OS分别为48.7个月和20.1个月，中位PFS分别为14.6个月和10.5个月，两组OS和PFS的差异均无统计学意义（P>0.05）；T1-3N2M0期手术与非手术组中位OS分别为38.9和30.8月，中位PFS分别为19.8个月和12.7个月，两组OS和PFS的差异亦无统计学意义（P>0.05）。肿瘤最大径和辅助化疗对Ⅲa-N2期患者的OS和PFS的影响有统计学意义，而肿瘤的病理类型仅影响患者的OS（P < 0.05）。结论ECOG评分0分和Ⅲa期NSCLC患者更适于手术治疗。手术可延长Ⅲa期尤其是T4N0/T3-4N1M0期NSCLC患者的OS，但对PFS无改善作用。肿瘤最大径和辅助化疗对Ⅲa-N2期患者的OS和PFS均有明显影响，而肿瘤的病理类型只影响其OS。

Effect of hypofractionated palliative thoracic radiotherapy for advanced non-small cell lung cancer

Objective: To investigate the effect and toxicity of short-course and hypofractionated palliative thoracic radiotherapy (PTR) for advanced non-small cell lung cancer (NSCLC). Methods: A total of 25 patients with stageIIIB and stageIV NSCLC, who underwent PTR from September 2010 to July 2006, were retrospectively analyzed. The PTR regime was 45 Gy in 15 fractions. Symptom relief, effect, and toxicity after completion of PTR were assessed. Survival was analyzed using the Kaplan-Meier method. Results: Except for one patient who completed only 36 Gy in 12 fractions, all other patients completed all plans. The thoracic symptoms of 18 patients were relieved. The response rates for the five main symptoms were: hemoptysis 87.5% (7/8), cough 70.6% (12/17), pain 73.3% (11/15), dyspnea 57.1% (8/14), and hoarseness 50% (1/2). The complete response and partial response after PTR was 28%, and no grade 3 or higher toxicities occurred. The median time of overall survival (OS) is 13 months (95% CI: 6.6 months to 19.5 months), and one-year OS is 51.5%. According to the univariate analysis, KPS before PTR, the number of post-PTR was significantly related to the survival. Conclusion: For advanced NSCLC patients, the PTR regime given as 45 Gy in 15 fractions evidently relieved thoracic symptoms, improved OS, and shortened treatment time. Recent relevant adverse radiotherapy reactions are low, and more prospective clinical studies must be conducted.

A phase III concurrent chemoradiotherapy trial with cisplatin and paclitaxel or docetaxel or gemcitabine in unresectable non-small cell lung cancer: KASLC 0401

Concurrent chemoradiotherapy (CCRT) is recommended for the management of patients with unresectable non-small cell lung cancer (NSCLC). This prospective study aimed to compare the efficacy of concurrently delivered cisplatin doublets with paclitaxel, or docetaxel, or gemcitabine. The main eligibility criteria consisted of previously untreated stage IIIB NSCLC. The subjects were randomized into three arms: paclitaxel 45 mg/m(2)/week (TP), docetaxel 20 mg/m(2)/week (DP), and gemcitabine 350 mg/m(2)/week (GP) in addition to cisplatin 20 mg/m(2)/week. Three-dimensional conformal radiotherapy was given once daily, weekly 5 fractions and the total prescription dose was 60-66 Gy. The primary endpoint was response rate, and the secondary endpoints were survival and toxicity. A total of 101 patients were recruited into this trial of whom 93 (TP: 33, DP: 29, GP: 31) patients were treated with CCRT from March 2005 to July 2007. Similar response rates were observed across arms: TP: 63.6 %, DP: 72.4 %, GP: 61.3 % (p = 0.679). There was no statistically significant difference of median survival (TP: 27.3, DP: 27.6, GP: 16.5 months, p = 0.771). In subgroup analysis, a survival benefit of consolidation chemotherapy was not seen, but leucopenia (63.2 %) and neutropenia (68.4 %) more than grade 3 were significantly high in DP arm. The grade ≥3 radiation esophagitis was more frequent in the GP arm (22.6 %, p = 0.163). Among the three arms, no statistically significant difference in response rate, survival, and toxicity was observed. However, clinically significant radiation toxicity was more frequent in the GP arm.

Increasing Pretreatment Tumor SUVmean Is Associated With Local Regional Failure After Chemoradiation for Locally-Advanced Non-Small Cell Lung Cancer

Local regional failure (LRF) after definitive chemoradiation for stage IIIA and IIIB non-small cell lung cancer (NSCLC) remains high. The purpose of this study was to determine if pre-treatment [F-18] fluoro-D-glucose-positron emission tomography (FDG PET) parameters are associated with LRF after chemoradiation. This IRB-approved retrospective study analyzed patients with stage IIIA and IIIB NSCLC treated with definitive chemoradiation between the years of 2006 and 2011 at Emory University Hospital. Patient and treatment characteristics were collected from electronic charts. The SUVmean, SUVmax, and SUVpeak of the primary tumor and involved lymph nodes were extracted from the pre-treatment FDG PET CT by a single user. Locoregional failure was defined as failure within the ipsilateral lung, hilum or mediastinum. Multivariate analysis for factors associated with LRF was performed using the Cox proportional hazard method. SUV parameters were analyzed as continuous variables. Sixty-one patients were identified. Median follow-up was 19 months. Eighteen percent of patients were treated with Intensity Modulated Radiation therapy (IMRT), 10% with 3D and IMRT techniques, and 72% with 3D conformal technique. Thirty-nine percent of patients received daily on board imaging (OBI). Median total RT dose for all patients was 66 Gy. Concurrent chemotherapy was delivered to 90% of patients. The median pre-treatment SUVmax, SUVmean, and SUVpeak values were 15.2 (6.6-50.1), 4.52 (2.2-9.04), and 13.7 (4.85-44), respectively. A LRF occurred in 36% of patients. Median time to LRF was 11.4 months. On multivariate analysis, increasing pre-treatment tumor SUV mean was significantly associated with LRF (HR: 1.77; 95% CI, 1.18-2.65; p < 0.01). Lower T stage (HR: 0.04; 95% CI, 0.004-0.51; p = 0.013), lower N stage (HR 0.038, 95% CI, 0.004-0.34, p < 0.01) and white race (HR: 0.266; 95% CI, 0.076-0.931; p = 0.04) were associated with a decreased risk of LRF. Other factors, including radiation technique, use of OBI, SUVmax, and SUVpeak were not significantly associated with LRF on multivariate analysis. Pretreatment FDG PET tumor SUVmean is associated with LRF after chemoradiation for stage III NSCLC, and warrants further investigation.