Current Update on the Management of Locally Advanced Non-small Cell Lung Cancer

Brain Chang; Clint Park; Hak Choy

doi:10.6058/jlc.2006.5.1.1

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Chang, Park, and Choy: Current Update on the Management of Locally Advanced Non-small Cell Lung Cancer

Original Article

J Lung Cancer 2006;5(1):1-16.

Published online: 18 December 2006

DOI: https://doi.org/10.6058/jlc.2006.5.1.1

Current Update on the Management of Locally Advanced Non-small Cell Lung Cancer

Brain Chang, M.D., Clint Park, M.D., Hak Choy, M.D.

¹Department of Radiation Oncology, UT Southwestern Medical Center, Dallas

Address for correspondence Hak Chov, ΜΌ. Nancy B. and Jake ᄂ Hamon distinguished Chair in Therapeutic Oncology Research Department of Radiation ᄋneology, The University of Texas Southwestern Medical Center, Dallas, 5801 Forest Park Rd, Dallas, Texas 75390-9183 Tel: 214-645-7600 Fax: 214-645-7622 E-mail: Hak.choy@UTSouthwestern.edu

Received 2 January 2006 Accepted 1 February 2006

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.

Abstract

Locally advanced NSCLC is a heterogenous group of bronchogenic malignancies that are traditionally thought to be unresectable without overt distant metastasis or malignant pleural effusion. The mainstay of treatment for this class of diseases until the early 1990s was radiation alone, which resulted in a dismal outcome. The new technologies in radiation therapy (e.g. 3D-CRT) and the shift in paradigm (e.g. omission of ENI) have enabled the dose-escalation, which translated to improved outcome compared to the conventional radiotherapy using 2-D planning. The trials combining chemotherapy with radiotherapy, first sequentially, then concurrently, have changed the standard of care for patients with good functional status to concurrent chemᄋradiation. Some studies have shown survival benefits to adding consolidative systemic therapy with concurrent chemoradiation. We will outline the development of the current treatment standard of locally advanced NSCLC and present selected topics 䴸ndergoing active research to forecast the next generation of NSCLC therapy. (J Lung Cancer 2006;5(1):1-16)

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Fig. 1.

Three-dimensional treatment plan, (A) Coronal section through isᄋcenter of a typical three-dimensional treatment plan isᄋdose distribution. (B) Axial section at 3.5 cm superior to isocenter for the same patient. The planning target volume is outlined in yellow. The patient had T3 NO norismal! cell lung cancer based on disease extension into the right mainstem bronchus. Based on these isodose distributions, the doses were estimated as follows; subcarina, 8,000 cGyæ ispsilateral inferior mediastinum. 4,000 cGy: contralateral inferior mediastinum, 1,000 cGy: superior mediastinum and supraclavicular region 0 Gy.

Fig. 2.

Compared 2-dimensional radiation treatment planning and 3-dimensiᄋnal radiation treatment planning.

Fig. 3.

Tumor is moving by respiration.

Table 1.

Multicenter Phase III Randomized Controlled Trials of Altered Fractionated Radiotherapy

Study	Sequence	Patients	RT dose (Gy)	CT	Fraction size (Gy)/ Schedule	Local-regional 3 yr (%)	Control 5 yr (%)	Median survival (months)	Overall 3 yr (%)	Survival 5 yr (%)	Toxicity (acute) ≥ grade 3 esophaaitis
CHART	tidRT	338	54	N/A	1.5 丁ID	n.r.	n.r.	n.r.	21	n.r.	19
Saunders et al. [34]	qdRT	225	60	N/A	2 QD	n.r.	n.r.	n.r.	13	n.r.	3
ECOG 2597	tidRT	60	57.6	N/A	1.5 TID	n.r.	n.r.	20.3	34	n.r.	25
Belani et al [35]	qdRT	59	64	N/A	2 QD	n.r.	n.r.	14.9	14	n.r.	16
RTOG 9410	CT⟶qdRT	201	60	CDDP/vinblastine	2 QD			14.6	n.r.	10	4
Curran et al. [7]	CT+qdRT	201	60	CDDP/vinblastine	2 QD			17	n.r.	16	23
	CT+bidRT	193	69.6	CDDP/etoposide	1.2 BID			15.1	n.r.	13	46
Cumulative qdRT		284	60~54	N/A	2 QD			14.9	13.2	n.r.	5.7
Cumulative tidRT		398	54 ⟶ 57.6	N/A	1.5 TID			20.3	23	n.r.	20
Cumulative CT⟶qdRT		201	60	CDDP/vinblastine	2 QD			14.6		10	4
Cumulative CT+qdRT		201	60	CDDP/vinblastine	2 QD			17		16	23
Cumulative CT+bidRT		193	69.6	CDDP/etoposide	1.2 BID			15.1		13	46

Table 2.

Multicenter Phase III Randomized Controlled Trials Comparing Sequential Chemoradiation vs. Radiation Alone

Study	Sequence	Patients	RT dose (Gy)	CT	Local-regional 3 yr (%)	Control 5 yr (%)	Median survival (months)	Overall 3 yr (%)	Survival 5 yr (%)	Toxicity (acute) ≥ grade 3 esophaaitis
CALQB 8433	qdRT	77	60	N/A	6	5	9.6	6	6	7
Dillman et al. [47]	CT⟶RT	78	60	CDDP/vinblastine	18	6	13.7	24	17	3
RTOG 8808	qdRT	152	60	N/A	n.r.	n.r.	11.4	11	5	1
Sause et al. [36]	CT⟶RT	152	60	CDDP/vinblastine	n.r.	n.r.	13.8	17	8	1
	bidRT	154	69.9	N/A	n.r.	n.r.	12.3	14	6	3
CEBI 138	qdRT	167	65	N/A	17 (I yr)	17 (1 yr)	10	4	3	3
Le Chevalier et al. [49]	CT⟶RT	165	65	VCPC	15 (1 yr)	15 (1 yr)	12	12	6	5
Cumulative QD-RT		396	60~65	N/A	n.r.	n.r.	10.5	7	4.4	3
Cumulative SEQ		395	60~65	See above	n.r.	n.r.	13	16.2	9	3.1
Cumulative BID-RT		154	69.9	N/A	n.r.	n.r.	12.3	14	6	3

Table 3.

Multicerrter Phase III Randomized Controlled Trials Comparing Concurrent With Sequential Chemoradiotherapy

Study	Sequence	Patients	RT dose (Gy)	CT	Local-regional 3 yr (%)	Control 5 yr (%)	Median survival (months)	Overall 3 yr (%)	Survival 5 yr (%)	Toxicity (acute) ≥ grade 3 esophaaitis
West Japan
Lurig Cancer	CT⟶qdRT	158	56	MVP	n.r.	n.r.	13.3	15	9	2
Group (WJLCG)
Furuse et al. [50]	CT+qdRT	156	56 (split)	MVP	n.r.	n.r.	16.5	22	16	3
RTOG 9410	CT⟶qdRT	201	60	CDDP/vinblastine	n.r.	n.r.	14.6	n.r.	10	4
Curran et al. [7]	CT+qdRT	201	60	CDDP/vinblastine	n.r.	n.r.	17	n.r.	16	23
	CT+bidRT	193	69.6	CDDP/etoposide	n.r.	n.r.	15.1	n.r.	13	46
GLOT-GFPC NPC 95-01	CT⟶qdRT	101	66	CDDP/virorelbine	38	37 (4 yr)	14.5	19	14 (4 yr)	3
Fournel et al. (8)	CT+qdRT⟶CT	100	66	CDDP/etoposide ⟶ CDDP/virorelbine	57	55 (4 yr)	16.3	25	21 (4 yr)	32
Czech republic study	CT⟶qdRT	50	60	CDDP/virorelbine	40%	n.r.	12.9	9.5	n.r.	4
Zatloukal et al. [9]	CT+qdRT	52	60	CDDP/virorelbine	58%	n.r.	16.6	18.6	n.r.	18
Cumulative SEQ	CT⟶qdRT	510	56-66				14			3.2
Cumulative CON-QD	CT+qdRT	509	56-66				16.7			18.1
Cumulative CON-BID	CT+bidRT	193	69.6				15.1			46

Table 4.

Phase 11 Trials Comparing Induction or Consolidation Chemotherapy With Concurrent Chemoradiotherapy

Study	Sequence	Patients	RT dose (Gy)	CT	Local-regional 3 yr (%)	Control 5 yr (%)	Median survival (months)	Overall 3 yr (%)	Survival 5 yr (%)	Toxicity (acute) ≥ grade 3 esophaaitis
CALGB 39801	CT⟶CT+qdRT		66	CBCD/paclitaxel
Vokes et al. [57]	CT+qdRT		66	CBCD/paclitaxel
LAMP	CT⟶qdRT	201	60	CDDP/vinblastine	n.r.	n.r.	14.6	n.r.	10	4
Belani et al. [58]	CT+qdRT	201	60	CDDP/vinblastine	n.r.	n.r.	17	n.r.	16	23
	CT+bidRT	193	69.6	CDDP/etoposide	n.r.	n.r.	15.1	n.r.	13	46
SWOG 9504	CT⟶qdRT	101	66	CDDP/vinorelbine	38	37 (4 yr)	14.5	19	14 (4 yr)	3
Gandara et al. [55]	CT+qdRT⟶CT	100	66	CDDP/etoposide ⟶ CDDP/vinorelbine	57	55 (4 yr)	16.3	25	21 (4 yr)	32
Czech Republic Study	CT⟶qdRT	50	60	CDDP/vinorelbine	58%	n.r.	12.9	9.5	n.r.	4
Zatloukal et al. [9]	CT+qdRT	52	60	CDDP/vinorelbine	40%	n.r.	16.6	18.6	n.r.	18
Cumulative SEQ	CT⟶qdRT	510	56~66				14			3.2
Cumulative CON-QD	CT+qdRT	509	56~66				16.7			18.1
Cumulative CON-BID	CT+bidRT	193	69.6				15.1			46

Table 5.

Selected Chemotherapy Schemes in Multicenter Trials Studying Chemoradiation

Study	Patients	RT dose (Gy)	CT	Fraction (Gy)	Size	Median survival (months)	Toxicity (acute) ≥ arade 3 esophaaitis
RTOG 9410 [7]	CT⟶qdRT	201	60	CDDP/vinblastine	2 QD	14.6	4
CALGB 8433 [46]	CT⟶qdRT	78	60	CDDP/vinblastine	2 QD	13.7	3
RTOG 8808 [36]	CT⟶qdRT	152	60	CDDP/vinblastine	2 QD	13.8	1
CEB1 138 [48]	CT⟶qdRT	165	65	VCPC	2 QD	12	5
WJLCG [6]	CT⟶qdRT	158	56	MVP	2 QD	13.3	2
GLOT-GFPC [8]	CT⟶qdRT	101	66	CDDP/vinorelbine	2 QD	14.5	3
Czech Republic [9]	CT⟶qdRT	50	60	CDDP/vinorelbine	2 QD	12.9	4
LAMP [58]	CT⟶qdRT	201	60	CDDP/vinblastine	2 QD	14.6	4
SWOG 9504 [55]	CT⟶qdRT	101	66	CDDP/vinorelbine	2 QD	14.5	3
RTOG 9410 [7]	CT+qdRT	201	60	CDDP/vinblastine	2 QD	17	23
WJLCG [6]	CT+qdRT	156	56 (split)	MVP	2 QD	16.5	3
GLOT-GFPC [8]	CT+qdRT	100	66	CDDP/etoposide	2 QD	16.3	32
Czech Republic [9]	CT+qdRT	52	60	CDDP/vinorelbine	2 QD	16.6	18
LAMP [58]	CT+qdRT	201	60	CDDP/vinblastine	2 QD	17	23
SWOG 9504 [55]	CT+qdRT	100	66	CDDP/etoposide	2 QD	16.3	32
CALGB 39801 [57]	CT+qdRT	184	66	CBCD/paclitaxel	2 QD	14.1	n.r.
CALGB 8433 [46]	qdRT	77	60	CDDP/vinblastine	2 QD	9.6	7
RTOG 8808 [36]	qdRT	152	60	CDDP/vinblastine	2 QD	11.4	1
CEB1 138 [48)	qdRT	167	65	VCPC	2 QD	10	3
Cumulative	CT-qdRT	1207	56-66		2 QD	13.8	3.3
Cumulative	CT+qdRT	994	56-66		2 QD	16.2	21
Cumulative	qdRT	396	60-65		2 QD	10.5	3

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