Toxicity and patterns of failure of adaptive/ablative proton therapy for early-stage, medically inoperable non-small cell lung cancer.
OBJECTIVE
To analyze the toxicity and patterns of failure of proton therapy given in ablative doses for medically inoperable early-stage non-small cell lung cancer (NSCLC).


METHODS
Eighteen patients with medically inoperable T1N0M0 (central location) or T2-3N0M0 (any location) NSCLC were treated with proton therapy at 87.5 Gy (relative biological effectiveness) at 2.5 Gy /fraction in this Phase I/II study. All patients underwent treatment simulation with four-dimensional CT; internal gross tumor volumes were delineated on maximal intensity projection images and modified by visual verification of the target volume in 10 breathing phases. The internal gross tumor volumes with maximal intensity projection density was used to design compensators and apertures to account for tumor motion. Therapy consisted of passively scattered protons. All patients underwent repeat four-dimensional CT simulations during treatment to assess the need for adaptive replanning.


RESULTS
At a median follow-up time of 16.3 months (range, 4.8-36.3 months), no patient had experienced Grade 4 or 5 toxicity. The most common adverse effect was dermatitis (Grade 2, 67%; Grade 3, 17%), followed by Grade 2 fatigue (44%), Grade 2 pneumonitis (11%), Grade 2 esophagitis (6%), and Grade 2 chest wall pain (6%). Rates of local control were 88.9%, regional lymph node failure 11.1%, and distant metastasis 27.8%. Twelve patients (67%) were still alive at the last follow-up; five had died of metastatic disease and one of preexisting cardiac disease.


CONCLUSIONS
Proton therapy to ablative doses is well tolerated and produces promising local control rates for medically inoperable early-stage NSCLC.
Department of Radiation Oncology, The University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA. jychang@mdanderson.org
Joe Y
JY
Chang
Ritsuko
R
Komaki
Hong Y
HY
Wen
Beth
B
De Gracia
Jaques B
JB
Bluett
Mary F
MF
McAleer
Stephen G
SG
Swisher
Michael
M
Gillin
Radhe
R
Mohan
James D
JD
Cox
D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D005260:Female; D005500:Follow-Up Studies; D056973:Four-Dimensional Computed Tomography; D006801:Humans; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D009068:Movement; D009367:Neoplasm Staging; D058958:Organs at Risk / Q000528:radiation effects; D011446:Prospective Studies; D061766:Proton Therapy; D011522:Protons / Q000009:adverse effects; D011832:Radiation Injuries / Q000209:etiology / Q000473:pathology; D011879:Radiotherapy Dosage; D011880:Radiotherapy Planning, Computer-Assisted / Q000379:methods; D012062:Relative Biological Effectiveness; D012119:Respiration; D017211:Treatment Failure; D047368:Tumor Burden
D011522:Protons
Int J Radiat Oncol Biol Phys. 2005 Feb 1;61(2):318-28
15667949
Int J Radiat Oncol Biol Phys. 2006 Apr 1;64(5):1589-95
16580508
Chest. 2004 Oct;126(4):1198-203
15486383
Int J Radiat Oncol Biol Phys. 2006 May 1;65(1):107-11
16458447
Int J Radiat Oncol Biol Phys. 2007 Mar 1;67(3):906-14
17293240
Phys Med Biol. 2008 Jun 21;53(12):3343-64
18523345
Int J Radiat Oncol Biol Phys. 2008 Dec 1;72(5):1385-95
18486357
Semin Radiat Oncol. 2010 Jul;20(3):171-7
20652085
J Thorac Oncol. 2007 Jul;2(7 Suppl 3):S94-100
17603311
Int J Radiat Oncol Biol Phys. 1993 Oct 20;27(3):517-23
8226143
Int J Radiat Oncol Biol Phys. 2006 Jul 15;65(4):1087-96
16682145
Int J Radiat Oncol Biol Phys. 2005 Dec 1;63(5):1427-31
16169670
J Clin Oncol. 2006 Oct 20;24(30):4833-9
17050868
Lung Cancer. 2009 Oct;66(1):89-93
19168260
Int J Radiat Oncol Biol Phys. 2006 Sep 1;66(1):117-25
16765528
Int J Radiat Oncol Biol Phys. 2005 Nov 15;63(4):1010-5
16115740
Int J Radiat Oncol Biol Phys. 2001 Apr 1;49(5):1429-38
11286851
Int J Radiat Oncol Biol Phys. 2008 Nov 15;72(4):967-71
18954709
Int J Radiat Oncol Biol Phys. 2003 May 1;56(1):7-13
12694818
Int J Radiat Oncol Biol Phys. 2007 Jul 1;68(3):786-93
17379439
Int J Radiat Oncol Biol Phys. 2010 Jun 1;77(2):357-66
19660879
Int J Radiat Oncol Biol Phys. 1993 Oct 20;27(3):507-16
8226142
CA Cancer J Clin. 2008 Mar-Apr;58(2):71-96
18287387