The Role of Radiation Therapy in Non-Small Cell Lung Cancer

Majid M. Mohiuddin; Noah C. Choi

doi:10.1055/s-2005-871986

Seminars in Respiratory and Critical Care Medicine, Table of Contents

Semin Respir Crit Care Med 2005; 26(3): 278-288
DOI: 10.1055/s-2005-871986

The Role of Radiation Therapy in Non-Small Cell Lung Cancer

Majid M. Mohiuddin¹ ^, ² , Noah C. Choi¹ ^, ²

¹Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts
²Harvard Medical School, Boston, Massachusetts

Abstract

ABSTRACT

Thoracic irradiation historically plays a strong role in the management of non-small cell lung cancer (NSCLC). Though surgery is the mainstay of early-stage (I and II) disease, adjuvant radiation therapy confers better local control than surgery alone in advanced disease (III). Combining chemotherapy with radiation can help decrease systemic tumor burden and confer an overall survival advantage. Patients with medically inoperable early-stage disease can be treated with radiation alone, and bulky advanced-stage tumors can be treated definitively with platinum-based concurrent chemotherapy and radiation. The success of chemotherapy with radiation together has led to trials of induction treatment for borderline surgical candidates, allowing for downstaging and more complete resection. Local control remains a challenge, and dose escalation as well as more conformal treatment planning studies need to be explored to overcome this problem.

KEYWORDS

Radiation therapy - non-small cell lung cancer - dose escalation - side effects

Full Text

References

REFERENCES

1 Miller K L, Shafman T D, Marks L B. A practical approach to pulmonary risk assessment in the radiotherapy of lung cancer. Semin Radiat Oncol. 2004; 14 298-307
2 Choi N C, Karanek D J, Kazemi H. Physiologic changes in pulmonary function after thoracic radiotherapy for patients with lung cancer and role of regional pulmonary function studies in predicting postradiotherapy pulmonary function before radiotherapy. Cancer Treat Symp. 1985; 2 119-130
3 Rosenman J G, Halle J S, Socinski M A et al.. High-dose conformal radiotherapy for treatment of stage IIIA/IIIB non-small-cell lung cancer: technical issues and results of a phase I/II trial. Int J Radiat Oncol Biol Phys. 2002; 54 348-356
4 Kara M, Sak S D, Orhan D, Yavuzer S. Changing patterns of lung cancer (3/4 in.) 1.9 cm: still a safe length for bronchial resection margin?. Lung Cancer. 2000; 30 161-168
5 Emami B, Mirkovic N, Scott C et al.. The impact of regional nodal radiotherapy (dose/volume) on regional progression and survival in unresectable non-small cell lung cancer: an analysis of RTOG data. Lung Cancer. 2003; 41 207-214
6 Rosenzweig K E, Sim S E, Mychalczak B, Braban L E, Schindelheim R, Leibel S A. Elective nodal irradiation in the treatment of non-small-cell lung cancer with three-dimensional conformal radiation therapy. Int J Radiat Oncol Biol Phys. 2001; 50 681-685
7 Mountain C F. A new international staging system for lung cancer. Chest. 1986; 89 225S-233S
8 Lee W, Daly B D, DiPetrillo T A et al.. Limited resection for non-small cell lung cancer: observed local control with implantation of I-125 brachytherapy seeds. Ann Thorac Surg. 2003; 75 237-242 discussion 242-243
9 Postoperative radiotherapy in non-small-cell lung cancer: systematic review and meta-analysis of individual patient data from nine randomised controlled trials . PORT meta-analysis trialists group. Lancet. 1998; 352 257-263
10 Wang CC Clinical Radiation Oncology. New York; Wiley-Liss 2000
11 Hayakawa K, Mitsuhashi N, Furuta M et al.. High-dose radiation therapy for inoperable non-small cell lung cancer without mediastinal involvement (clinical stage N0, N1). Strahlenther Onkol. 1996; 172 489-495
12 Sibley G S, Jamieson T A, Marks L B, Anscher M S, Prosnitz L R. Radiotherapy alone for medically inoperable stage I non-small-cell lung cancer: the Duke experience. Int J Radiat Oncol Biol Phys. 1998; 40 149-154
13 Saunders M, Dische S, Barrett A, Harvey A, Gibson D, Parmar M. Continuous hyperfractionated accelerated radiotherapy (CHART) versus conventional radiotherapy in non-small-cell lung cancer: a randomised multicentre trial. CHART steering committee. Lancet. 1997; 350 161-165
14 Jeremic B, Shibamoto Y, Acimovic L, Milisavljevic S. Hyperfractionated radiotherapy alone for clinical stage I non-small cell lung cancer. Int J Radiat Oncol Biol Phys. 1997; 38 521-525
15 Uematsu M, Shioda A, Suda A et al.. Computed tomography-guided frameless stereotactic radiotherapy for stage I non-small cell lung cancer: a 5-year experience. Int J Radiat Oncol Biol Phys. 2001; 51 666-670
16 Timmerman R, Papiez L, McGarry R et al.. Extracranial stereotactic radioablation: results of a phase I study in medically inoperable stage I non-small cell lung cancer. Chest. 2003; 124 1946-1955
17 Miyamoto T, Yamamoto N, Koto M, Nishimura H, Tsujii H, Fujisawa T. Heavy-ion therapy for non-small cell lung cancer. Nippon Geka Gakkai Zasshi. 2002; 103 250-255
18 Andre F, Grunenwald D, Pignon J P et al.. Survival of patients with resected N2 non-small-cell lung cancer: evidence for a subclassification and implications. J Clin Oncol. 2000; 18 2981-2989
19 Effects of postoperative mediastinal radiation on completely resected stage II and stage III epidermoid cancer of the lung . The Lung Cancer Study Group. N Engl J Med. 1986; 315 1377-1381
20 Dautzenberg B, Chastang C, Arriagada R et al.. Adjuvant radiotherapy versus combined sequential chemotherapy followed by radiotherapy in the treatment of resected nonsmall cell lung carcinoma: a randomized trial of 267 patients. GETCB (Groupe d’Etude et de Traitement des Cancers Bronchiques). Cancer. 1995; 76 779-786
21 Dautzenberg B, Arriagada R, Chammard A B et al.. A controlled study of postoperative radiotherapy for patients with completely resected nonsmall cell lung carcinoma. Groupe d'Etude et de Traitement des Cancers Bronchiques. Cancer. 1999; 86 265-273
22 Keller S M, Adak S, Wagner H et al.. A randomized trial of postoperative adjuvant therapy in patients with completely resected stage II or IIIA non-small-cell lung cancer. Eastern Cooperative Oncology Group. N Engl J Med. 2000; 343 1217-1222
23 Arriagada R, Bergman B, Dunant A et al.. Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer. N Engl J Med. 2004; 350 351-360
24 Martini N, Flehinger B J, Zaman M B, Beattie Jr E J. Prospective study of 445 lung carcinomas with mediastinal lymph node metastases. J Thorac Cardiovasc Surg. 1980; 80 390-399
25 Pearson F G, DeLarue N C, Ilves R, Todd T R, Cooper J D. Significance of positive superior mediastinal nodes identified at mediastinoscopy in patients with resectable cancer of the lung. J Thorac Cardiovasc Surg. 1982; 83 1-11
26 Roth J A, Fossella F, Komaki R et al.. A randomized trial comparing perioperative chemotherapy and surgery with surgery alone in resectable stage IIIA non-small-cell lung cancer. J Natl Cancer Inst. 1994; 86 673-680
27 Sugarbaker D J, Herndon J, Kohman L J, Krasna M J, Green M R. Results of cancer and leukemia group B protocol 8935: a multiinstitutional phase II trimodality trial for stage IIIA (N2) non-small-cell lung cancer. Cancer and Leukemia Group B Thoracic Surgery Group. J Thorac Cardiovasc Surg. 1995; 109 473-483 discussion 483-485
28 Fleck J, Camargo J, Godoy D et al.. Chemoradiation therapy (CRT) versus chemotherapy (CT) alone as a neo-adjuvant treatment for stage III non-small cell lung cancer (NSCLC): Preliminary report of a phase III prospective randomized trial [abstract 1108]. Proc Am Soc Clin Oncol. 1993; 12 333
29 Choi N C, Carey R W, Daly W et al.. Potential impact on survival of improved tumor downstaging and resection rate by preoperative twice daily radiation and concurrent chemotherapy in stage IIIA non-small cell lung carcinoma. J Clin Oncol. 1997; 15 712-722
30 Albain K S, Rusch V W, Crowley J J et al.. Concurrent cisplatin/etoposide plus chest radiotherapy followed by surgery for stages IIIA (N2) and IIIB non-small-cell lung cancer: mature results of Southwest Oncology Group Phase II Study 8805. J Clin Oncol. 1995; 13 1880-1892
31 Albain K S, Scott C B, Rusch V R et al.. Phase III comparison of concurrent chemotherapy plus radiotherapy (CT/RT) and CT/RT followed by surgical resection for state IIIA(pN2) non-small cell lung cancer (NSCLC): initial results from Intergroup trial 0139 (RTOG 93-09) [abstract 2497]. Proc Am Soc Clin Oncol. 2003; 22 621
32 Choi N C, Doucette J A. Improved survival of patients with unresectable non-small-cell bronchogenic carcinoma by an innovated high-dose en bloc radiotherapeutic approach. Cancer. 1981; 48 101-109
33 Perez C A, Bauer M, Edelstein S, Gillespie B W, Birch R. Impact of tumor control on survival in carcinoma of the lung treated with irradiation. Int J Radiat Oncol Biol Phys. 1986; 12 539-547
34 Dillman R O, Seagren S L, Propert K J et al.. A randomized trial of induction chemotherapy plus high-dose radiation versus radiation alone in stage III non-small-cell lung cancer. N Engl J Med. 1990; 323 940-945
35 Dillman R O, Herndon J, Seagren S L, Eaton Jr W L, Green M R. Improved survival in stage III non-small-cell lung cancer: seven-year follow-up of Cancer and Leukemia Group B (CALGB) 8433 trial. J Natl Cancer Inst. 1996; 88 1210-1215
36 Sause W, Kolesar P, Taylor S IV et al.. Final results of phase III trial in regionally advanced unresectable non-small cell lung cancer: Radiation Therapy Oncology Group, Eastern Cooperative Oncology Group, and Southwest Oncology Group. Chest. 2000; 117 358-364
37 Schaake-Koning C, van den Bogaert W, Dalesio O et al.. Effects of concomitant cisplatin and radiotherapy on inoperable non-small-cell lung cancer. N Engl J Med. 1992; 326 524-530
38 Arriagada R, Le Chevalier T, Quoix E et al.. ASTRO (American Society for Therapeutic Radiology and Oncology) plenary: effect of chemotherapy on locally advanced non-small cell lung carcinoma: a randomized study of 353 patients. GETCB (Groupe d’Etude et Traitement des Cancers Bronchiques), FNCLCC (Federation Nationale des Centres de Lutte Contre le Cancer) and the CEBI trialists. Int J Radiat Oncol Biol Phys. 1991; 20 1183-1190
39 Furuse K, Fukuoka M, Kawahara M et al.. Phase III study of concurrent versus sequential thoracic radiotherapy in combination with mitomycin, vindesine, and cisplatin in unresectable stage III non-small-cell lung cancer. J Clin Oncol. 1999; 17 2692-2699
40 Kubota K, Furuse K, Kawahara M et al.. Role of radiotherapy in combined modality treatment of locally advanced non-small-cell lung cancer. J Clin Oncol. 1994; 12 1547-1552
41 Belani C P, Wang W, Johnson D H. Induction chemotherapy followed by standard thoracic radiotherapy (std RT) vs. hyperfractionated accelerated radiotherapy (HART) for patients with unresectable stage III A&B non-small cell lung cancer (NSCLC): phase III study of the Eastern Cooperative Oncology Group (ECOG 2597) [abstract 2500]. Proc Am Soc Clin Oncol. 2003; 22 622
42 Choy H, Curran W J, Scott C B et al.. Preliminary report of locally advanced multimodality protocol (LAMP): ACR 427: A randomized phase II study of three chemo-radiation regimens with paclitaxel, carboplatin, and thoracic radiation (TRT) for patients with locally advanced non-small cell lung cancer (LA-NSCLC) [abstract 1160]. Proc Am Soc Clin Oncol. 2002; 21 291
43 Pancoast H K. Importance of careful roentgen ray investigations of apical chest tumors. JAMA. 1924; 83 1407-1411
44 Pancoast H K. Superior pulmonary sulcus tumor: tumor characterized by pain, Horner’s syndrome, destruction of bone and atrophy of hand muscles. JAMA. 1932; 99 1391-1396
45 Chardack W M, MacCallum J D. Pancoast tumor: five-year survival without recurrence or metastases following radical resection and postoperative irradiation. J Thorac Surg. 1956; 31 535-542
46 Shaw R R, Paulson D L, Kee J L. Treatment of the superior sulcus tumor by irradiation followed by resection. Ann Surg. 1961; 154 29-40
47 Hagan M P, Choi N C, Mathisen D J, Wain J C, Wright C D, Grillo H C. Superior sulcus lung tumors: impact of local control on survival. J Thorac Cardiovasc Surg. 1999; 117 1086-1094
48 Rusch V W, Giroux D J, Kraut M J et al.. Induction chemoradiation and surgical resection for non-small cell lung carcinomas of the superior sulcus: initial results of Southwest Oncology Group trial 9416 (Intergroup trial 0160). J Thorac Cardiovasc Surg. 2001; 121 472-483
49 Sonett J R, Suntharalingam M, Edelman M J et al.. Pulmonary resection after curative intent radiotherapy (> 59 Gy) and concurrent chemotherapy in non-small-cell lung cancer. Ann Thorac Surg. 2004; 78 1200-1205 discussion 1206
50 Tong D, Gillick L, Hendrickson F R. The palliation of symptomatic osseous metastases: final results of the study by the Radiation Therapy Oncology Group. Cancer. 1982; 50 893-899
51 Rubin P, Johnston C J, Williams J P, McDonald S, Finkelstein J N. A perpetual cascade of cytokines postirradiation leads to pulmonary fibrosis. Int J Radiat Oncol Biol Phys. 1995; 33 99-109
52 Roach III M, Gandara D R, Yuo H S et al.. Radiation pneumonitis following combined modality therapy for lung cancer: analysis of prognostic factors. J Clin Oncol. 1995; 13 2606-2612
53 Inoue A, Saijo Y, Maemondo M et al.. Severe acute interstitial pneumonia and gefitinib. Lancet. 2003; 361 137-139
54 Taghian A G, Assaad S I, Niemierko A et al.. Risk of pneumonitis in breast cancer patients treated with radiation therapy and combination chemotherapy with paclitaxel. J Natl Cancer Inst. 2001; 93 1806-1811
55 Cutillas J R, Rodriguez E G, Vinals N B. Chemotherapy-induced pulmonary toxicity in lung cancer management. Oncologia. 2001; 4 183-195
56 Johansson S, Bjermer L, Franzen L, Henriksson R. Effects of ongoing smoking on the development of radiation-induced pneumonitis in breast cancer and oesophagus cancer patients. Radiother Oncol. 1998; 49 41-47
57 Kohno N, Hamada H, Fujioka S, Hiwada K, Yamakido M, Akiyama M. Circulating antigen KL-6 and lactate dehydrogenase for monitoring irradiated patients with lung cancer. Chest. 1992; 102 117-122
58 Antonadou D. Radiotherapy or chemotherapy followed by radiotherapy with or without amifostine in locally advanced lung cancer. Semin Radiat Oncol. 2002; 12 50-58
59 Werner-Wasik M, Langer C, Movsas B. Randomized phase II study of amifostine mucosal protection by either subcutaneous injection or rapid IV bolus for patients with inoperable stage II-IIIA/B or stage IV non-small cell lung cancer with oligometastases receiving concurrent radiochemotherapy with carboplatin and paclitaxel followed by optional consolidative chemotherapy: a follow-up study after RTOG 98-01. Semin Oncol. 2004; 31 47-51
60 Ozturk B, Egehan I, Atavci S, Kitapci M. Pentoxifylline in prevention of radiation-induced lung toxicity in patients with breast and lung cancer: a double-blind randomized trial. Int J Radiat Oncol Biol Phys. 2004; 58 213-219
61 Werner-Wasik M, Pequignot E, Leeper D, Hauck W, Curran W. Predictors of severe esophagitis include use of concurrent chemotherapy, but not the length of irradiated esophagus: a multivariate analysis of patients with lung cancer treated with nonoperative therapy. Int J Radiat Oncol Biol Phys. 2000; 48 689-696

Majid MohiuddinM.D.

Department of Radiation Oncology, Massachusetts General Hospital

Harvard Medical School, 100 Blossom St.

Cox 3, Boston, MA 02114

Email: mmohiuddin@partners.org