Definitive Bimodality Concurrent Chemoradiotherapy in Patients with Inoperable N2-positive Stage IIIA Non-small Cell Lung Cancer

Jae Myoung Noh; Yong Chan Ahn; Hyebin Lee; Hongryull Pyo; BoKyong Kim; Dongryul Oh; Hyojung Park; Eonju Lee; Keunchil Park; Jin Seok Ahn; Myung-Ju Ahn; Jong-Mu Sun

doi:10.4143/crt.2014.144

Articles

Page Path: HOME > Cancer Res Treat > Volume 47(4); 2015 > Article

Original Article Definitive Bimodality Concurrent Chemoradiotherapy in Patients with Inoperable N2-positive Stage IIIA Non-small Cell Lung Cancer: Jae Myoung Noh, MD¹, Yong Chan Ahn, MD, PhD^1,, Hyebin Lee, MD², Hongryull Pyo, MD, PhD¹, BoKyong Kim, MD, PhD¹, Dongryul Oh, MD¹, Hyojung Park, MD¹, Eonju Lee, MD¹, Keunchil Park, MD, PhD³, Jin Seok Ahn, MD, PhD³, Myung-Ju Ahn, MD, PhD³, Jong-Mu Sun, MD, PhD³; Cancer Research and Treatment : Official Journal of Korean Cancer Association 2015;47(4):645-652.
DOI: https://doi.org/10.4143/crt.2014.144
Published online: February 12, 2015

¹Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

²Department of Radiation Oncology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea

³Division of Hematology-Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

Correspondence: Yong Chan Ahn, MD, PhD Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea
Tel: 82-2-3410-2602 Fax: 82-2-3410-2619 E-mail: ahnyc@skku.edu

• Received: June 9, 2014 • Accepted: August 1, 2014

This is an Open-Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

14,012 Views
89 Download
5 Web of Science
7 Crossref
6 Scopus

prev next

Full Article

Download PDF

Abstract

Purpose
This study was conducted to evaluate the treatment outcomes following definitive bimodality concurrent chemoradiotherapy (CCRT) in patients with inoperable N2-positive stage IIIA (N2-IIIA) non-small cell lung cancer (NSCLC).
Materials and Methods
From May 1997 to December 2012, 65 out of 633 patients with N2-IIIA NSCLC received bimodality therapy. The treatment modality was selected during/after neoadjuvant CCRT in 21 patients or primarily at diagnosis in 44 through a multidisciplinary consensus meeting. The median age was 65 years (range, 36 to 76 years). Sixty patients (92.3%) had clinically evident N2 disease, while 22 (33.8%) had multi-station N2 involvement. The median radiation therapy dose was 66 Gy in 33 fractions, while the dose was elevated to 72 Gy in 13 patients who had a treatment break due to delayed decision regarding resectability. The most frequent chemotherapy regimen was weekly paclitaxel or docetaxel plus cisplatin or carboplatin (54, 83.1%).
Results
During the median follow-up of 18.8 months (range, 1.6 to 173.1 months), 34 patients (52.3%) experienced disease progression, with distant metastasis being the most common first treatment failure pattern (23, 34.8%). The median and 2-year rates of progression-free survival were 18.8 months and 45.9%, respectively. The median and 2-year rates of overall survival were 28.6 months and 50.1%, respectively.
Conclusion
Definitive bimodality therapy in patients with N2-IIIA NSCLC demonstrated favorable outcomes, while trimodality therapy could be considered for candidates for less than pneumonectomy.
Key words: Non-small cell lung carcinoma, Concurrent chemoradiotherapy, Stage IIIA-N2

Introduction

The selection of an optimal treatment modality for patients with N2-positive stage IIIA (N2-IIIA) non-small cell lung cancer (NSCLC) has been a major controversial issue in thoracic oncology. A multimodality approach rather than a single modality therapy has been preferred [1], and the current National Comprehensive Cancer Network (NCCN) guideline recommends definitive concurrent chemoradiotherapy (CCRT) as the category 1 option, while induction chemotherapy, with or without radiation therapy (RT), and surgical resection is the alternative option [2]. The recent practice guidelines from the American College of Chest Physicians (ACCP) primarily recommends either definitive CCRT or induction therapy followed by surgery in the patients with discrete N2-IIIA NSCLC over either surgery or RT alone [3]. Both guidelines have multimodality treatment in common, and the ACCP guideline recommends that the treatment plan be made with input from a multidisciplinary team [3].

A multidisciplinary lung cancer team was established at Samsung Medical Center (SMC) when it was opened in 1994. Since then, SMC’s lung cancer team has actively implemented decision-making during lung cancer therapy, which has consisted of a full spectrum of lung cancer diagnoses and treatments including pulmonology, thoracic surgery, radiation oncology, medical oncology, diagnostic radiology, pathology, and nuclear medicine. Because of frequent locoregional failures following definitive CCRT without surgery [4,5], we have incorporated surgical resection following preoperative CCRT since 1997, and this trimodality therapy strategy has been the primary policy at SMC during treatment of patients with N2-IIIA NSCLC. Following trimodality therapy, the authors reported that the 5-year progression-free survival (PFS) and overall survival (OS) rates were 26.9% and 43.3%, respectively [6]. Although this strategy has demonstrated improved and favorable locoregional control and survival outcomes, surgical resection cannot be undertaken following preoperative CCRT in some patients. Accordingly, these patients underwent definitive CCRT without surgical resection (bimodality therapy). There are two main clinical settings in which bimodality therapy is undertaken at SMC. First, treatment policy changes from trimodality to bimodality therapy during or after the preoperative CCRT course, and second, bimodality therapy is primarily recommended from the onset of treatment. Typical patient factors necessitating a change in treatment policy include poor to marginal cardio-pulmonary function status, medical comorbidity, and the patient’s refusal of surgical resection. Typical disease factors leading to such a change include extensive and infiltrative nature of the tumor and/or lymph nodes that are judged to impede curative resection or necessitate pneumonectomy rather than lobectomy. The purpose of this study was to evaluate the treatment outcomes following bimodality therapy in patients with N2-IIIA NSCLC at SMC.

Materials and Methods

From May 1997 to December 2012, a total of 633 patients were diagnosed as having N2-IIIA NSCLC at SMC based on the American Joint Committee on Cancer (AJCC) seventh edition cancer staging manual (Fig. 1). After physiologic staging, 528 patients (83.4%) were judged to be medically operable with resectable or marginally resectable disease, while 105 (16.6%) were either medically inoperable or had unresectable disease because of the extensive and infiltrative nature of the tumor and/or lymph nodes. According to the SMC lung cancer center treatment policy, trimodality therapy including preoperative CCRT and surgical resection was used in 528 eligible patients. However, the planned preoperative CCRT course could not be completed in 51 patients (9.7%) due to disease progression in 22 (4.2%), patient refusal in 17 (3.2%), treatment-related mortality in six (1.1%) morbidity in four (0.8%), and other co-morbidity in two (0.4%). After re-assessment of resectability following preoperative CCRT, 456 patients (86.4%) underwent curative resection as initially planned, while the remaining 21 (4.0%), who had a presumed high risk of surgical resection or refused surgical resection, received boost CCRT (bimodality group I, hereafter). Among 105 patients who had unresectable disease at diagnosis, 61 who were not fit for aggressive treatment received either RT alone (n=50) or chemotherapy alone (n=11). Definitive CCRT was recommended to 44 patients as a primary therapy (bimodality group II, hereafter). After approval by the Institutional Review Board (2013-08-085), the medical and RT records of the 65 patients in bimodality groups I and II were retrospectively reviewed.

The median RT dose was 66 Gy in 33 fractions using 4-10 MV photon beams generated by a linear accelerator (Varian Medical Systems Inc., Palo Alto, CA). A median treatment break of 36 days was imposed during the RT course for 13 patients in bimodality group I, mainly because judgment on resectability was made 4 to 6 weeks after preoperative CCRT. To compensate for this unintended treatment break, the total RT dose was intentionally escalated to a median of 72 Gy in these patients. Therefore, the mean RT dose was higher in bimodality group I (p=0.002). The most common chemotherapeutic regimen during RT was weekly paclitaxel or docetaxel plus cisplatin or carboplatin in 54 patients (83.1%), followed by cisplatin plus oral etoposide at 4-week intervals in 11 patients (16.9%). Thirteen patients received 1 to 4 cycles of additional consolidation chemotherapy following bimodality therapy.

The primary endpoints of the current study were PFS and OS, and the secondary endpoints were in-field locoregional control (LRC) and patterns of disease progression. The durations of observation were calculated from the first date of CCRT until the date of event, death or censoring. Disease progression included any type of treatment failure, while in-field locoregional progression was defined as persistent or newly developing lesion within the actual RT target volume. Neither out-field remote intrathoracic failure nor hematogenous lung metastasis were considered as locoregional progression. t tests were used to compare continuous variables such as age, forced expiratory volume in 1 second, tumor size, and radiation dose. Chi-square or Fisher exact tests were used to compare categorical variables between treatment groups. The rates of PFS, OS, and in-field LRC were calculated using the Kaplan-Meier method and compared using the log-rank test. A p-value of ≤ 0.05 was considered statistically significant, and SAS software (ver. 9.1.3, SAS Institute Inc., Cary, NC) was used for all statistical analyses.

Results

The patients’ characteristics are summarized in Table 1. The median age of the 65 patients in both groups was 65 years (range, 36 to 76 years), and the vast majority of the patients were male (59, 90.8%) and ex-smokers (60, 92.3%). Squamous cell carcinoma was the most common histology in 39 patients (60.0%), followed by adenocarcinoma in 22 (33.8%). Based on initial imaging studies, which included chest-computed tomography scan and/or positron emission tomography scan, the median tumor size was 4.3 cm (range, 1.0 to 11.6 cm), and cT1-2 stages were more common than cT3 (41 vs. 24). The majority of the patients (60, 92.3%) had clinically evident N2-positive disease, and about half (33, 50.8%) underwent histologic confirmation. Five patients (7.7%) with clinically N2-negative disease were confirmed to have N2 disease based on histological analysis. The procedures for histologic confirmation of N2 disease were endobronchial ultrasound-guided transbronchial needle aspiration in 17 patients, mediastinoscopic biopsy in 11, videoassisted thoracoscopic biopsy in two, endoscopic transesophageal ultrasound guided biopsy in one, bronchoscopic biopsy in one, and open excision of the lymph node in one. Based on all clinical evaluation tools, 43 and 22 patients (66.2% and 33.8%, respectively) were known to have single and multi-station N2 involvement, respectively.

During the median follow-up duration of 18.8 months (range, 1.6 to 173.1 months), 34 patients (52.3%) showed disease progression (Table 2). The most common first treatment failure was distant metastasis, which was observed in 23 patients (34.8%), followed by locoregional progression in 16 (24.6%). Additionally, 12 out of 16 patients with locoregional progression had failure within the RT volume. The most frequent distant metastatic organs were the brain in nine patients, followed by the adrenal gland in four. The median PFS was 18.8 months, and the 2- and 5-year PFS rates were 45.9% and 30.5%, respectively (Fig. 2A). In-field LRC rates at 2 and 5 years were 74.3% and 56.3%, respectively. A total of 39 patients (60.0%) died during the follow-up period. Pulmonary causes such as pneumonia, pneumonitis, and acute respiratory distress syndrome were responsible for seven deaths, which occurred at a median of 4.0 months (range, 2.3 to 8.5 months). There were three intercurrent deaths from hepatocellular carcinoma, myocardial infarction, and gastrointestinal bleeding. The median OS was 28.6 months, and the 2- and 5-year OS rates were 50.1% and 33.3%, respectively (Fig. 2B). Univariate analysis revealed that the cisplatin plus oral etoposide regimen was associated with significantly better PFS and OS (Table 3), and females tended to have a better OS. There were no significant differences in survival outcomes between bimodality groups I and II. Other variables such as cT stage, involvement of multistation lymph nodes, and treatment break did not affect survival outcomes.

Discussion

N2-IIIA NSCLC involves potential heterogeneity in mediastinal lymph node involvement, which could influence the decision regarding the treatment plan among various options. A survey study showed that choice of treatment plan differed according to the extent of mediastinal involvement [7]. In the case of single-node disease, 92% of the oncologists incorporated surgical resection into a treatment plan, while definitive chemoradiation was mostly preferred in the case of bulky multi-station N2 disease. Interestingly, 48% of the treatment plans still included surgery in the second scenario. In addition to the heterogeneity of N2 disease, there might also be heterogeneity in the physician’s treatment plan preference. Among patients who received trimodality therapy for N2-IIIA NSCLC at our institution, 66.8% and 36.6% had clinically evident and multi-station N2 disease, respectively [6].

Our institution has adopted a multidisciplinary approach to management of patients with lung cancer, and tri- or bi-modality treatment showed consistently favorable outcomes. Although not all patients had histological confirmation of involvement of the N2 lymph node in this study, most were found to have clinically evident N2 disease upon imaging analyses, and about one-third of the patients had multi-station N2 disease. Resectability was assessed before and/or during the course of CCRT, in accordance with the multidisciplinary team approach described above. Our rationale for increasing radiation dose to compensate for the unintended treatment break applied in 13 patients in bimodality group I is very difficult to validate based on the current study results. Twenty-one patients in bimodality group I, 13 of whom had treatment break and increased radiation dose, showed similar clinical outcomes to those in bimodality group II (Table 3). Naturally, it is desirable to avoid or shorten the treatment break whenever possible; however, when such a break cannot be avoided, an effort to intensify the boost CCRT seems a reasonable approach.

Trimodality therapy that includes surgical resection following preoperative CCRT in physiologically fit patients with N2-IIIA NSCLC has long been the primary recommendation at SMC, and subsequent clinical outcomes have recently been reported [6]. Definitive bimodality therapy has been recommended to physiologically fit patients who are poor candidates for surgical resection due to either increased surgical risk or patient refusal of trimodality therapy. Direct comparisons of the outcomes following tri- and bimodality therapy might be biased owing to selection bias and heterogeneity in the patient characteristics in this retrospective study. A randomized controlled phase III trial compared the two treatment modalities and determined that the median OS was 23.6 months in patients who underwent surgical resection and 22.2 months in patients who underwent continued radiotherapy (p=0.24), which was similar to the results of the present study [8]. The corresponding PFS were 12.8 and 10.5 months, respectively, in the two treatment groups (p=0.017). Although no survival difference was observed between the two treatment modalities, a survival benefit was observed in patients who received lobectomy after neoadjuvant CCRT (median OS, 33.6 months vs. 21.7 months; p=0.002). Decreased survival in pneumonectomized patients was suggested as the main reason for the limited survival benefit following trimodality treatment. Improved survival after CCRT plus lobectomy and decreased survival after CCRT plus pneumonectomy was also observed in recent studies from our institution and the National Cancer Database [6,9]. Negative survival influence following pneumonectomy has clinical implications in terms of treatment selection in patients with N2-IIIA NSCLC. Pneumonectomy candidates appear to be more suitable for definitive bimodality therapy than trimodality therapy, while candidates who do not require pneumonectomy might benefit from trimodality therapy.

Survival differences between chemotherapy regimens should be interpreted with caution. Treatment results after CCRT with cisplatin plus oral etoposide followed by consolidation chemotherapy were previously reported [10], and the median PFS and 2-year PFS rate were 12.3 months and 40%, respectively. Because more than half of the patients in that study had N3 disease, only a small portion of patients with favorable prognosis should have been included. In addition, the role of the docetaxel-based combination regimen has been widely examined and its effectiveness demonstrated [11-15]. Thus, valid comparison between chemotherapy regimens is not feasible in the current retrospective study. Rather, the role of consolidation chemotherapy should be investigated in the future [15,16]. Because consolidation chemotherapy was rarely applied in the current study, it is still not clear whether further improvement of treatment outcomes is possible from consolidation chemotherapy. A multinational phase III randomized trial that compares CCRT with or without consolidation chemotherapy in inoperable stage III NSCLC was initiated by the authors at SMC [17]. The interim analysis showed a median OS of 20.7 and 21.1 months in the CCRT alone arm and consolidation arm, respectively (p=0.49). In addition, the corresponding median time to progression was 9.0 and 13.9 months, respectively (p=0.19). Long-term results are expected to validate the feasibility and efficacy of consolidation chemotherapy.

Conclusion

It should be noted that the current study has some potential limitations as a result of its retrospective nature, as well as the small number of patients and heterogeneous patient population. As recommended by the current NCCN guideline, definitive bimodality therapy could be applied as a primary treatment in patients with N2-IIIA NSCLC that is unresectable or necessitates pneumonectomy, while trimodality could be considered for candidates that do not need pneumonectomy. Additional efforts to avoid and minimize treatment break should be applied through a multidisciplinary team approach.

NOTES

Conflict of interest relevant to this article was not reported.

Fig. 1.

Treatment flow diagram for patients with N2-positive stage IIIA (N2-IIIA) non-small cell lung cancer (NSCLC).

Fig. 2.

Progression-free survival (A) and overall survival (B) after definitive bimodality concurrent chemoradiotherapy in patients with N2-positive stage IIIA non-small cell lung cancer.

Table 1.

Clinical characteristics

Characteristic	Total (n=65)	Group I (n=21)	Group II (n=44)	p-value
Age (yr)	65 (36-76)	65 (47-76)	63 (36-75)	0.365
Gender				1.000^a)
Male	59 (90.8)	19 (90.5)	40 (90.9)
Female	6 (9.2)	2 (9.5)	4 (9.1)
Smoking history				0.655^a)
Yes	60 (92.3)	19 (90.5)	41 (93.2)
No	5 (7.7)	2 (9.5)	3 (6.8)
FEV₁ (L)	2.44 (0.92-4.26)	2.41 (1.24-3.35)	2.47 (0.92-4.26)	0.411
Histology				0.942
Squamous cell carcinoma	39 (60.0)	13 (61.9)	26 (59.1)
Adenocarcinoma	22 (33.8)	7 (33.3)	15 (34.1)
Others	4 (6.2)	1 (4.8)	3 (6.8)
Tumor size (cm)	4.3 (1.0-11.6)	3.7 (2.0-9.1)	5.8 (1.0-11.6)	0.105
Clinical T classification				0.020
cT1-2	41 (63.1)	9 (42.9)	32 (72.7)
cT3	24 (36.9)	12 (57.1)	12 (27.3)
Extent of N2 disease				0.052
Clinically evident-histologic confirmation	32 (49.2)	10 (47.6)	22 (50.0)
Clinically evident+histologic confirmation	28 (43.1)	7 (33.3)	21 (47.7)
Clinically silent but histologically confirmed	5 (7.7)	4 (19.0)	1 (2.3)
Level of N2 disease				0.952
Single station	43 (66.2)	14 (66.7)	29 (65.9)
Multi-station	22 (33.8)	7 (33.3)	15 (34.1)

Values are presented as median (range) or number (%). FEV₁, forced expiratory volume in 1 second.

^a) Examined by Fisher exact test.

Table 2.

Patterns of first treatment failure

Variable	Total (n=65)	Group I (n=21)	Group II (n=44)
Distant metastasis	18 (27.7)	7 (33.3)	11 (25.0)
Locoregional progression	11 (16.9)	4 (19.0)	7 (15.9)
Local	2	1	1
Regional	6	1	5
Local and regional	3	2	1
Both	5 (7.7)	1 (4.8)	4 (9.1)
Local and distant metastasis	2	1	1
Regional and distant metastasis	3	0	3
Total	34 (52.3)	12 (57.1)	22 (50.0)

Values are presented as number (%).

Table 3.

Prognostic factors affecting survival outcomes upon univariate analysis

Variable	No.	Rates at 2 years
Variable	No.	PFS (%)	p-value	OS (%)	p-value	LRC (%)	p-value
Treatment group			0.748		0.353		0.866
I	21	44.9		53.9		77.1
II	44	46.8		48.6		73.3
Gender			0.831		0.057		0.597
Male	59	45.4		47		73.1
Female	6	50		83.3		83.3
Age (yr)			0.158		0.172		0.089
< 60	21	33.6		36.5		57.8
≥ 60	44	52.5		56.6		82.2
Histology			0.120		0.844		0.702
Squamous cell carcinoma	39	52.2		47.5		69.1
Adenocarcinoma	22	40.3		52.5		80
Others	4	25		75		100
Clinical T			0.602		0.801		0.742
T1-2	41	42.9		51.1		69.2
T3	24	50.1		48.4		81.8
Multistation N2			0.860		0.838		0.831
No	43	43.8		50.3		73.5
Yes	22	50.8		49.7		74.3
Chemotherapy			0.028		0.040		0.237
Taxane+platinum	54	37.1		45.1		64.9
Cisplatin+etoposide	11	80.8		71.6		100
Treatment break			0.636		0.816		0.515
No	52	46.4		49.2		74.8
Yes	13	43.5		55.1		72

PFS, progression-free survival; OS, overall survival; LRC, locoregional control.

REFERENCES

1. Martini N, Kris MG, Ginsberg RJ. The role of multimodality therapy in locoregional non-small cell lung cancer. Surg Oncol Clin N Am. 1997;6:769–91. Article PubMed
2. National Comprehensive Cancer Network. NCCN guidelines version 3, 2014. Non-small cell lung cancer [Internet] . Fort Washington, PA: National Comprehensive Cancer Network; [cited 2014 Jun 9] . Available from: http://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf
3. Ramnath N, Dilling TJ, Harris LJ, Kim AW, Michaud GC, Balekian AA, et al. Treatment of stage III non-small cell lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2013;143(5 Suppl):e314SArticle
4. Fournel P, Robinet G, Thomas P, Souquet PJ, Lena H, Vergnenegre A, et al. Randomized phase III trial of sequential chemoradiotherapy compared with concurrent chemoradiotherapy in locally advanced non-small-cell lung cancer: Groupe Lyon-Saint-Etienne d'Oncologie Thoracique-Groupe Francais de Pneumo-Cancerologie NPC 95-01 Study. J Clin Oncol. 2005;23:5910–7. Article PubMed
5. Curran WJ Jr, Paulus R, Langer CJ, Komaki R, Lee JS, Hauser S, et al. Sequential vs. concurrent chemoradiation for stage III non-small cell lung cancer: randomized phase III trial RTOG 9410. J Natl Cancer Inst. 2011;103:1452–60. Article PubMed PMC
6. Lee H, Ahn YC, Pyo H, Kim B, Oh D, Nam H, et al. Pretreatment clinical mediastinal nodal bulk and extent do not influence survival in N2-positive stage IIIA non-small cell lung cancer patients treated with trimodality therapy. Ann Surg Oncol. 2014;21:2083–90. Article PubMed
7. Tanner NT, Gomez M, Rainwater C, Nietert PJ, Simon GR, Green MR, et al. Physician preferences for management of patients with stage IIIA NSCLC: impact of bulk of nodal disease on therapy selection. J Thorac Oncol. 2012;7:365–9. Article PubMed PMC
8. Albain KS, Swann RS, Rusch VW, Turrisi AT 3rd, Shepherd FA, Smith C, et al. Radiotherapy plus chemotherapy with or without surgical resection for stage III non-small-cell lung cancer: a phase III randomised controlled trial. Lancet. 2009;374:379–86. Article PubMed PMC
9. Koshy M, Fedewa SA, Malik R, Ferguson MK, Vigneswaran WT, Feldman L, et al. Improved survival associated with neoadjuvant chemoradiation in patients with clinical stage IIIA(N2) non-small-cell lung cancer. J Thorac Oncol. 2013;8:915–22. Article PubMed
10. Park J, Ahn YC, Kim H, Lee SH, Park SH, Lee KE, et al. A phase II trial of concurrent chemoradiation therapy followed by consolidation chemotherapy with oral etoposide and cisplatin for locally advanced inoperable non-small cell lung cancers. Lung Cancer. 2003;42:227–35. Article PubMed
11. Scagliotti GV, Turrisi AT 3rd. Docetaxel-based combinedmodality chemoradiotherapy for locally advanced non-small cell lung cancer. Oncologist. 2003;8:361–74. Article PubMed
12. Pillot G, Govindan R. The role of docetaxel in N2 locally advanced non-small-cell lung cancer. Clin Lung Cancer. 2005;7 Suppl 3:S87–92. Article
13. Saloustros E, Georgoulias V. Docetaxel in the treatment of advanced non-small-cell lung cancer. Expert Rev Anticancer Ther. 2008;8:1207–22. Article PubMed
14. Oh IJ, Kim KS, Kim YC, Ban HJ, Kwon YS, Kim YI, et al. A phase III concurrent chemoradiotherapy trial with cisplatin and paclitaxel or docetaxel or gemcitabine in unresectable non-small cell lung cancer: KASLC 0401. Cancer Chemother Pharmacol. 2013;72:1247–54. Article PubMed
15. Saitoh J, Saito Y, Kazumoto T, Kudo S, Yoshida D, Ichikawa A, et al. Concurrent chemoradiotherapy followed by consolidation chemotherapy with bi-weekly docetaxel and carboplatin for stage III unresectable, non-small-cell lung cancer: clinical application of a protocol used in a previous phase II study. Int J Radiat Oncol Biol Phys. 2012;82:1791–6. Article PubMed
16. Eroglu C, Orhan O, Unal D, Dogu GG, Karaca H, Dikilitas M, et al. Concomitant chemoradiotherapy with docetaxel and c isplatin followed by consolidation chemotherapy in locally advanced unresectable non-small cell lung cancer. Ann Thorac Med. 2013;8:109–15. Article PubMed PMC
17. Park K, Ahn Y, Chen M, Cho E, Kim J, Min Y, et al. A multinational phase III randomized trial with or without consolidation chemotherapy using docetaxel and cisplatin after concurrent chemoradiation in inoperable stage III non-small cell lung cancer (CCheIN): interim analysis. J Clin Oncol. 2009;27(15S):7538.Article

Figure & Data

REFERENCES

Citations

Citations to this article as recorded by

Clinical N Staging Subclassification for Stage III-N2 NSCLC Patients Undergoing Trimodality Therapy: A Good Beginning Is Half the Battle
Junghee Lee, Yun Soo Hong, Jin Lee, Genehee Lee, Danbee Kang, Jiyoun Park, Yeong Jeong Jeon, Seong Yong Park, Jong Ho Cho, Yong Soo Choi, Jhingook Kim, Young Mog Shim, Eliseo Guallar, Juhee Cho, Hong Kwan Kim
The Annals of Thoracic Surgery.2025;[Epub] CrossRef
Toxicity of Proton Therapy versus Photon Therapy on Salvage Re-Irradiation for Non-Small Cell Lung Cancer
Kyungmi Yang, Yang-Gun Suh, Hyunju Shin, Hongryull Pyo, Sung Ho Moon, Yong Chan Ahn, Dongryul Oh, Eunah Chung, Kwanghyun Jo, Jae Myoung Noh
Life.2022; 12(2): 292. CrossRef
Salvage proton beam therapy for locoregional recurrence of non-small cell lung cancer
Hyunju Shin, Jae Myoung Noh, Hongryull Pyo, Yong Chan Ahn, Dongryul Oh
Radiation Oncology Journal.2021; 39(1): 24. CrossRef
Experiences of patients with lung cancer receiving concurrent chemo-radiotherapy
Choi Eunsook, Park Sunhee
Clinical Journal of Nursing Care and Practice.2021; 5(1): 015. CrossRef
Prognostic significance of tumor poliovirus receptor and CTLA4 expression in patients with surgically resected non-small-cell lung cancer
Hui You, Yi-Zhong Zhang, Huan-Ling Lai, Dan Li, Yu-Quan Liu, Run-Ze Li, Imran Khan, Wendy Wen-Lun Hsiao, Fu-Gang Duan, Xing-Xing Fan, Xiao-Jun Yao, Ya-Bing Cao, Qi-Biao Wu, Elaine Lai-Han Leung, Mei-Fang Wang
Journal of Cancer Research and Clinical Oncology.2020; 146(6): 1441. CrossRef
Erlotinib as Neoadjuvant Therapy in Stage IIIA (N2) EGFR Mutation-Positive Non-Small Cell Lung Cancer: A Prospective, Single-Arm, Phase II Study
Liwen Xiong, Rong Li, Jiayuan Sun, Yuqing Lou, Weiyan Zhang, Hao Bai, Huiming Wang, Jie Shen, Bo Jing, Chunlei Shi, Hua Zhong, Aiqin Gu, Liyan Jiang, Jianxing Shi, Wentao Fang, Heng Zhao, Jie Zhang, Junyuan Wang, Junyi Ye, Baohui Han
The Oncologist.2019; 24(2): 157. CrossRef
Recurrence dynamics after trimodality therapy (Neoadjuvant concurrent chemoradiotherapy and surgery) in patients with stage IIIA (N2) lung cancer
Junghee Lee, Hong Kwan Kim, Byung Jo Park, Jong Ho Cho, Yong Soo Choi, Jae Ill Zo, Young Mog Shim, Hongryull Pyo, Yong Chan Ahn, Jin Seok Ahn, Myung-Ju Ahn, Keunchil Park, Jhingook Kim
Lung Cancer.2018; 115: 89. CrossRef

PubReader
ePub Link

Cite

CITE: export Copy Download Format; Close

Download Citation

Download a citation file in RIS format that can be imported by all major citation management software, including EndNote, ProCite, RefWorks, and Reference Manager.

Format:

RIS — For EndNote, ProCite, RefWorks, and most other reference management software
BibTeX — For JabRef, BibDesk, and other BibTeX-specific software

Include:

Citation for the content below
Citation and abstract for the content below

Definitive Bimodality Concurrent Chemoradiotherapy in Patients with Inoperable N2-positive Stage IIIA Non-small Cell Lung Cancer

Cancer Res Treat. 2015;47(4):645-652. Published online February 12, 2015

DOI: https://doi.org/10.4143/crt.2014.144

XML Download

Abstract
Introduction
Materials and Methods
Results
Discussion
Conclusion
NOTES
REFERENCES

Clinical Effect of Endosonography on Overall Survival in Patients with Radiological N1 Non–Small Cell Lung Cancer

Definitive Bimodality Concurrent Chemoradiotherapy in Patients with Inoperable N2-positive Stage IIIA Non-small Cell Lung Cancer

Fig. 1. Treatment flow diagram for patients with N2-positive stage IIIA (N2-IIIA) non-small cell lung cancer (NSCLC).

Fig. 2. Progression-free survival (A) and overall survival (B) after definitive bimodality concurrent chemoradiotherapy in patients with N2-positive stage IIIA non-small cell lung cancer.

Fig. 1.

Fig. 2.

Definitive Bimodality Concurrent Chemoradiotherapy in Patients with Inoperable N2-positive Stage IIIA Non-small Cell Lung Cancer

Characteristic	Total (n=65)	Group I (n=21)	Group II (n=44)	p-value
Age (yr)	65 (36-76)	65 (47-76)	63 (36-75)	0.365
Gender				1.000^a)
Male	59 (90.8)	19 (90.5)	40 (90.9)
Female	6 (9.2)	2 (9.5)	4 (9.1)
Smoking history				0.655^a)
Yes	60 (92.3)	19 (90.5)	41 (93.2)
No	5 (7.7)	2 (9.5)	3 (6.8)
FEV₁ (L)	2.44 (0.92-4.26)	2.41 (1.24-3.35)	2.47 (0.92-4.26)	0.411
Histology				0.942
Squamous cell carcinoma	39 (60.0)	13 (61.9)	26 (59.1)
Adenocarcinoma	22 (33.8)	7 (33.3)	15 (34.1)
Others	4 (6.2)	1 (4.8)	3 (6.8)
Tumor size (cm)	4.3 (1.0-11.6)	3.7 (2.0-9.1)	5.8 (1.0-11.6)	0.105
Clinical T classification				0.020
cT1-2	41 (63.1)	9 (42.9)	32 (72.7)
cT3	24 (36.9)	12 (57.1)	12 (27.3)
Extent of N2 disease				0.052
Clinically evident-histologic confirmation	32 (49.2)	10 (47.6)	22 (50.0)
Clinically evident+histologic confirmation	28 (43.1)	7 (33.3)	21 (47.7)
Clinically silent but histologically confirmed	5 (7.7)	4 (19.0)	1 (2.3)
Level of N2 disease				0.952
Single station	43 (66.2)	14 (66.7)	29 (65.9)
Multi-station	22 (33.8)	7 (33.3)	15 (34.1)

Variable	Total (n=65)	Group I (n=21)	Group II (n=44)
Distant metastasis	18 (27.7)	7 (33.3)	11 (25.0)
Locoregional progression	11 (16.9)	4 (19.0)	7 (15.9)
Local	2	1	1
Regional	6	1	5
Local and regional	3	2	1
Both	5 (7.7)	1 (4.8)	4 (9.1)
Local and distant metastasis	2	1	1
Regional and distant metastasis	3	0	3
Total	34 (52.3)	12 (57.1)	22 (50.0)

Variable	No.	Rates at 2 years
Variable	No.	PFS (%)	p-value	OS (%)	p-value	LRC (%)	p-value
Treatment group			0.748		0.353		0.866
I	21	44.9		53.9		77.1
II	44	46.8		48.6		73.3
Gender			0.831		0.057		0.597
Male	59	45.4		47		73.1
Female	6	50		83.3		83.3
Age (yr)			0.158		0.172		0.089
< 60	21	33.6		36.5		57.8
≥ 60	44	52.5		56.6		82.2
Histology			0.120		0.844		0.702
Squamous cell carcinoma	39	52.2		47.5		69.1
Adenocarcinoma	22	40.3		52.5		80
Others	4	25		75		100
Clinical T			0.602		0.801		0.742
T1-2	41	42.9		51.1		69.2
T3	24	50.1		48.4		81.8
Multistation N2			0.860		0.838		0.831
No	43	43.8		50.3		73.5
Yes	22	50.8		49.7		74.3
Chemotherapy			0.028		0.040		0.237
Taxane+platinum	54	37.1		45.1		64.9
Cisplatin+etoposide	11	80.8		71.6		100
Treatment break			0.636		0.816		0.515
No	52	46.4		49.2		74.8
Yes	13	43.5		55.1		72

Table 1. Clinical characteristics

Values are presented as median (range) or number (%). FEV₁, forced expiratory volume in 1 second.

Examined by Fisher exact test.

Table 2. Patterns of first treatment failure

Values are presented as number (%).

Table 3. Prognostic factors affecting survival outcomes upon univariate analysis

PFS, progression-free survival; OS, overall survival; LRC, locoregional control.