- Email: [email protected]
CT-guided permanent brachytherapy for patients with medically inoperable early-stage non-small cell lung cancer (NSCLC)
Lung Cancer (2008) 61, 209—213
available at www.sciencedirect.com
journal homepage: www.elsevier.com/locate/lungcan
CT-guided permanent brachytherapy for patients with medically inoperable early-stage non-small cell lung cancer (NSCLC) Rafael Mart´ınez-Monge a,∗, Mar´ıa Pagola a, Isabel Vivas b, Jos´ e Mar´ıa L´ opez-Picazo a a
Department of Oncology, Cl´ınica Universitaria de Navarra, University of Navarra, Avda P´ıo XII s/n, Pamplona, Navarre, Spain b Department of Radiology, Cl´ınica Universitaria de Navarra, University of Navarra, Avda P´ıo XII s/n, Pamplona, Navarre, Spain Received 25 October 2007; received in revised form 12 December 2007; accepted 18 December 2007
KEYWORDS Lung cancer; Medically inoperable; CT-guided; Brachytherapy; Early-stage; Iodine-125; Palladium-103
Summary Seven patients with early stage T1N0M0 NSCLC who had medical contraindications for surgical resection were treated with CT-guided percutaneous implantation of 103 Pd or 125 I seeds. After the procedure, two patients developed pneumothorax and hemo/pneumothorax that was managed with aspirative drainage. One patient developed a focal pneumonitis 3 months after the procedure. After a median follow-up of 13 months (4.6—41.0+ months), no patient has developed local or regional failure. © 2008 Elsevier Ireland Ltd. All rights reserved.
1. Introduction Surgical resection remains the mainstay of therapy for the vast majority of the patients with early stage non-small cell lung cancer (NSCLC) [1]. However, some patients who are technically operable cannot tolerate the operative procedure and the expected reduction in lung function after resection [2]. The management of these patients who are unfit for surgery is still controversial, although many are referred for radiation therapy [3]. Establishment of radiation guidelines for the management of these frail patients is
∗
Corresponding author. Tel.: +34 948 255400; fax: +34 948 255500. E-mail address: [email protected] (R. Mart´ınez-Monge).
crucial for a number of reasons. First, improvements in medical care and technology are expected to lead to an increase in mean life expectancy that will result in a doubling of the number of people older than 65 years living with lung cancer by 2050 [4,5]. In addition, the number of patients diagnosed at an early stage will probably increase due to the implementation of computed tomography-driven screening programs [6]. At the present time, the type and regimen of radiation therapy to be used in this patient category is undefined because no randomized trials comparing different regimens are available [3,7,8]. Standard or 3D external beam radiation therapy (EBRT), when given at tumoricidal doses, still carries a considerable risk of lung damage that can be prohibitive in patients with a limited respiratory function.
0169-5002/$ — see front matter © 2008 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.lungcan.2007.12.016
210
R. Mart´ınez-Monge et al.
In addition to the conventional radiation techniques, other emerging newer radiation modalities such as CTguided brachytherapy or stereotactic fractionated external beam radiation therapy are being developed for the treatment of patients who are not suitable for surgical resection. These techniques provide a better lung tissue sparing and have the advantage of a shorter treatment time. We recently reported our preliminary results in the management of stage T1N0M0 medically inoperable NSCLC [9] with CT-guided 103 Pd brachytherapy. That previous report has been expanded with the accrual of more patients and longer follow-up.
2. Methods and materials Seven patients, 5 men and 2 women with histologically confirmed NSCLC stage T1N0M0 [10] and an average age of 80 years (range 75—92), were treated with CT-guided permanent interstitial brachytherapy (PIB) at the Cl´ınica Universitaria, University of Navarra, Spain from 2000 to 2007. In addition to advanced age, all the patients presented with severe comorbidities that made them unfit for a major surgical procedure (Table 1). The details of the CT-guided brachytherapy program have been described previously [9]. Briefly, baseline evaluation included detailed medical history, physical examination, CT scan of the chest and upper abdomen, bone scan, brain MRI,
Table 1
and PET scan. The patients finally selected for CT-guided PIB were additionally evaluated with chest CT to confirm the percutaneous accessibility of the lesion and the ideal patient positioning to avoid bony interference. The CT images were also used to perform a preplanning dosimetric study that determined the number of needle trajectories, the number of seeds, and the total activity to be implanted. Palladium103 or 125 I seeds were implanted to deliver a minimum tumor dose of 125 or 145 Gy, respectively. Doses were prescribed at the clinical target volume (CTV) that was arbitrarily defined as the gross tumor volume (GTV) plus a 5 mm margin [11]. No EBRT was added. The choice of radioisotope was determined by availability, due to the shortage of 103 Pd in Europe after 2005. The first four patients were treated with 103 Pd and the last three with 125 I seeds. All the brachytherapy implants were performed in an standard CT room under general anesthesia. This allowed patient immobilization and limited lung motion, decreasing the risk of pneumothorax. CT imaging determined the coordinates of the skin entry point and permitted adjustment of depth and angle of needle placement. Mini-Mick or standard 20 cm Mick needles were used. After target volume determination, interstitial needles (20 cm long, 16-gauge) were inserted into the tumor at an interspacing of approximately 0.5 cm. The median number of needles used was 5 (range 4—8). A relatively small number of needle passages were chosen to minimize the risk of pneumothorax, although this created an uneven dosimetric distribution. The 125 I or
Patient characteristics
No.
Histology
Age
Gender
Location
Co-morbidities
Pulmonary Function
1
Large cell, anaplastic
86
Male
Peripheral, RLLa
COPD Multiorganic diabetes mellitus Parkinson’s disease
FEV1 = 0.8 L FEV1 /FVC = n/a DLCO = n/a
2
Non-small cell lung cancer
60
Male
Central, RULb
End-stage liver cirrhosis
FEV1 = 1.8 L FEV1 /FVC = 38% DLCO = 32%
3
Squamous cell carcinoma
81
Male
Peripheral, LULc
Radiation fibrosis and surgical scarringd
FEV1 = 1.7 L FEV1 /FVC = 54% DLCO = 51%
4
Squamous cell carcinoma
80
Male
Peripheral, RUL
Diabetes mellitus Hypertension Aortic aneurysm Chronic kidney failure
FEV1 = 2.1 L FEV1 /FVC = 65% DLCO = 69%
5
Squamous cell carcinoma
75
Male
Peripheral, LUL
Myastenia gravis Synchronous prostate cancer
FEV1 = 1.4 L FEV1 /FVC = 75% DLCO = 69%
6
Non-small cell lung cancer Squamous cell carcinoma
92
Female
Peripheral, LLLe
Synchronous breast cancer
n/a
75
Female
Peripheral, RUL
Liver transplantation recipient Alpha-1 antitrypsin defficiency
FEV1 = 0.8 L FEV1 /FVC = 44% DLCO = 38%
7
a b c d e
Right lower lobe. Right upper lobe. Left upper lobe. Prior treatment with surgery and radiation for another primary NSCLC in 1992. Left lower lobe.
CT-guided permanent brachytherapy for patients Table 2
211
Implant characteristics
No. 1 2 3 4 5 6 7
Tumor diameter (cm) 1.0 0.7 3.0 1.0 1.8 1.9 1.4
Activity/seed (U)
Radioisotope
No. of seeds
No. of needles
2.5 2.5 2.5 2.5 0.48 0.55 0.54
103
30 50 50 35 45 45 45
5 5 4 8 5 6 8
Pd Pd 103 Pd 103 Pd 125 I 125 I 125 I 103
Fig. 1 Preimplant CT scan (left). Postimplant CT scan obtained 3 months after implantation showing tumor shrinkage and brachytherapy seeds in place.
103
Pd seeds were inserted through each needle using the Mick applicator. The median number of seeds was 45 (range 30—50) with an average activity of 2.51 U for 103 Pd seeds and 0.53 U for 125 I seeds (Table 2). The overall length of the procedure, including anesthesia, averaged 2.5 h. No patient was considered unfit for anesthesia. Once the implant was completed, a final CT scan was obtained for postplanning. Fig. 1 shows the pre- and postimplant CT obtained in patient number 6.
3. Results One patient with a bullous lung developed a pneumothorax that required drainage for 5 days. Another patient developed a combined pneumothorax and hemothorax (780 cm3 ) and required drainage as well. A third patient with myasthenia gravis required hospital admission due to a focal pneumonitis/respiratory infection 3 months after the implant procedure. The other 4 patients did not have any immediate or delayed complications. After a median follow-up of 13 months (4.6—41.0+ months) no patient has developed local or regional failure. Two patients died at 4 and 13 months of liver failure and stroke, respectively; five patients remain alive, one with disease. Among the five patients alive at last follow-up, one has developed a new contralateral second primary lung tumor at 8 months and is alive with
disease at 41.0 months, and 4 remain alive without disease at a median of 13.5 months (range 6.5—27.8) (Table 3).
4. Discussion While PIB has been used with some success in the intraoperative treatment of unresectable, residual, or medically inoperable NSCLC since the 1940s [12—14], its use in a percu-
Table 3 No. 1 2 3 4 5 6 7
Outcome
Acute complications
Late complications
Pneumotorax Pneumonitis/ infection Pneumo/ hemothorax
Status
F/up (months)
DFDa DFDb AWD NED NED
13.0 4.7 41.0 27.8 16.0
NED NED
11.2 6.5
NED: no evidence of disease; AWD: alive with disease; DFD: dead free of disease. a Died of stroke. b Died of liver failure.
212 taneous CT-guided approach is merely anecdotal [9,15,16]. This fact may be explained in part by the lack of tradition even in the most experienced brachytherapy centers, the small number of suitable candidates that probably stands for less than 20% of those referred for radical radiation due to a poor surgical risk and the fear of acute complications associated with the procedure. This small study shows that none of the seven patients treated developed local or loco-regional failure. Although the observation period is limited, due in part to the short life expectancy related to the pre-existing comorbid conditions, this excellent local control outcome can be explained by the small volume of the tumors treated and the very high doses of radiation delivered by PIB. The median tumor diameter of the patients treated in the present study was 1.4 cm (range 0.7—3.0), which corresponds to a median tumor volume of 11.5 cm3 . Hof et al. [17] in a study of stereotatic body radiotherapy (SRS) reported no local recurrences in a group of 12 patients with tumors smaller than 12 cm3 treated with single dose (19—30 Gy) SRS. Two patients developed pneumothorax or hemothorax. Although these patients had a poor baseline respiratory function, no significants effects were noted because pneumothorax was diagnosed during the implantation procedure and was immediately resolved with the patient closely monitored under general anesthesia. A dose-effect relationship has been well established for various human malignancies including NSCLC, and the dose-effect resulting from PIB should also be considered when accounting for the excellent control results observed. The median doses to the CTV (GTV + 0.5 cm) were 128 Gy for 103 Pd and 144 Gy for 125 I, and the median doses to the GTV were 187 Gy for 103 Pd and 217 Gy for 125 I. Different single or fractionated SRS studies have noted a significant increase in local control after biological effective doses (BED) of 90—100 Gy [17—19]. Although the BED obtained with either hypofractionated SRS or PIB cannot be directly compared due to the different patterns of dose delivery, current radiobiological principles suggest that the PIB doses used in the present study are well beyond that range. Future CT-guided PIB studies should be compared with other highly selective radiation techniques such as SRS. A recent report by Hof et al. [17] described the treatment of patients with Stage I and II NSCLC with single dose (19—30 Gy) SRS. Local control rates at 1, 2, and 3 years were 89.5, 67.9, and 67.9%, respectively. An earlier phase I trial reported by McGarry et al. [20] used fractionated SRS in a dose escalation trial beginning at 24 Gy in 3 fractions and increasing dose levels in 6 Gy steps. Four of 19 patients with T1 lesions experienced local failure. Although the results obtained with CT-guided PIB in the present study compare favorably with those reported by several SRS trials [17—19], the numbers are too small to allow a formal comparison. Finally, there were some patients in the group who had a short survival. These patients might have never become symptomatic for lung cancer and therefore, this kind of aggressive interventional treatment would not have been justified. An improved patient selection is mandatory when more experience is gained with PIB.
R. Mart´ınez-Monge et al.
5. Conclusions CT-guided PIB is an effective treatment for patients with medically inoperable stage I NSCLC. The complications associated with the procedure can be managed conservatively.
References [1] National Comprehensive Cancer Network. Practice Guidelines in Oncology. v. 2; 2007. [2] Beckles MA, Spiro SG, Colice GL, Rudd RM. The physiologic evaluation of patients with lung cancer being considered for resectional surgery. Chest 2003;123(Suppl. 1 (January)):105S—14S. [3] Rowell NP, Williams CJ. Radical radiotherapy for stage I/II non-small cell lung cancer in patients not sufficiently fit for or declining surgery (medically inoperable): a systematic review. Thorax 2001;56(8 (August)):628— 38. [4] Hurria A, Kris MG. Management of lung cancer in older adults. CA Cancer J Clin 2003;53(6 (November—December)):325— 41. [5] Simmonds MA. Cancer statistics, 2003: further decrease in mortality rate, increase in persons living with cancer. CA Cancer J Clin 2003;53(1 (January—February)):4. [6] Henschke CI, Yankelevitz DF, Libby DM, Pasmantier MW, Smith JP, Miettinen OS. Survival of patients with stage I lung cancer detected on CT screening. N Engl J Med 2006;355(17):1763—71. [7] Graham PH, Gebski VJ, Langlands AO. Radical radiotherapy for early nonsmall cell lung cancer. Int J Radiat Oncol Biol Phys 1995;31:261—6. [8] Jeremic B, Classen J, Bamberg M. Radiotherapy alone in technically operable, medically inoperable, early-stage (I/II) non-small-cell lung cancer. Int J Radiat Oncol Biol Phys 2002;54(1 (September)):119—30. [9] Martinez-Monge R, Garran C, Vivas I, Lopez-Picazo JM. Percutaneous CT-guided 103Pd implantation for the medically inoperable patient with T1N0M0 non-small cell lung cancer: a case report. Brachytherapy 2004;3(3):179—81. [10] AJCC Cancer Staging Manual, 6th ed. http://www.cancerstaging.net; 2003. [11] International Commission on Radiation Units and Measurements. Prescribing, recording and reporting photon beam therapy. ICRU Report 62. Bethesda, MD: International Commission on Radiation Units and Measurements, 1999. [12] Lee W, Daly BD, DiPetrillo TA, Morelli DM, Neuschatz AC, Morr J, 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(1):237—42. [13] Santos R, Colonias A, Parda D, Trombetta M, Maley RH, Macherey R, et al. Comparison between sublobar resection and 125Iodine brachytherapy after sublobar resection in highrisk patients with Stage I non-small-cell lung cancer. Surgery 2003;134(4):691—7. [14] Hilaris BS, Mastoras DA. Contemporary brachytherapy approaches in non-small-cell lung cancer. J Surg Oncol 1998;69(4):258—64. [15] Heelan RT, Hilaris BS, Anderson LL, Nori D, Martini N, Watson RC, et al. Lung tumors: percutaneous implantation of I-125 sources with CT treatment planning. Radiology 1987;164(3):735—40. [16] Sider L, Mittal BB, Nemcek Jr AA, Bobba VS. CT-guided placement of iodine-125 seeds for unresectable carcinoma of the lung. J Comput Assist Tomogr 1988;12(3):515—7. [17] Hof H, Muenter M, Oetzel D, Hoess A, Debus J, Herfarth K. Stereotactic single-dose radiotherapy (radiosurgery)
CT-guided permanent brachytherapy for patients of early stage nonsmall-cell lung cancer (NSCLC). Cancer 2007;110(1):148—55. [18] Onishi H, Araki T, Shirato H, Nagata Y, Hiraoka M, Gomi K, et al. Stereotactic hypofractionated high-dose irradiation for stage I nonsmall cell lung carcinoma—–clinical outcomes in 245 subjects in a Japanese multinstitutional study. Cancer 2004;101(7):1623—31.
213 [19] Wulf J, Baier K, Mueller G, Flentje MP. Dose-response in stereotactic irradiation of lung tumors. Radiother Oncol 2005;77(1):83—7. [20] McGarry RC, Papiez L, Williams M, Whitford T, Timmerman RD. Stereotactic body radiation therapy of early-stage non-smallcell lung carcinoma: phase I study. Int J Radiat Oncol Biol Phys 2005;63(4):1010—5.
available at www.sciencedirect.com
journal homepage: www.elsevier.com/locate/lungcan
CT-guided permanent brachytherapy for patients with medically inoperable early-stage non-small cell lung cancer (NSCLC) Rafael Mart´ınez-Monge a,∗, Mar´ıa Pagola a, Isabel Vivas b, Jos´ e Mar´ıa L´ opez-Picazo a a
Department of Oncology, Cl´ınica Universitaria de Navarra, University of Navarra, Avda P´ıo XII s/n, Pamplona, Navarre, Spain b Department of Radiology, Cl´ınica Universitaria de Navarra, University of Navarra, Avda P´ıo XII s/n, Pamplona, Navarre, Spain Received 25 October 2007; received in revised form 12 December 2007; accepted 18 December 2007
KEYWORDS Lung cancer; Medically inoperable; CT-guided; Brachytherapy; Early-stage; Iodine-125; Palladium-103
Summary Seven patients with early stage T1N0M0 NSCLC who had medical contraindications for surgical resection were treated with CT-guided percutaneous implantation of 103 Pd or 125 I seeds. After the procedure, two patients developed pneumothorax and hemo/pneumothorax that was managed with aspirative drainage. One patient developed a focal pneumonitis 3 months after the procedure. After a median follow-up of 13 months (4.6—41.0+ months), no patient has developed local or regional failure. © 2008 Elsevier Ireland Ltd. All rights reserved.
1. Introduction Surgical resection remains the mainstay of therapy for the vast majority of the patients with early stage non-small cell lung cancer (NSCLC) [1]. However, some patients who are technically operable cannot tolerate the operative procedure and the expected reduction in lung function after resection [2]. The management of these patients who are unfit for surgery is still controversial, although many are referred for radiation therapy [3]. Establishment of radiation guidelines for the management of these frail patients is
∗
Corresponding author. Tel.: +34 948 255400; fax: +34 948 255500. E-mail address: [email protected] (R. Mart´ınez-Monge).
crucial for a number of reasons. First, improvements in medical care and technology are expected to lead to an increase in mean life expectancy that will result in a doubling of the number of people older than 65 years living with lung cancer by 2050 [4,5]. In addition, the number of patients diagnosed at an early stage will probably increase due to the implementation of computed tomography-driven screening programs [6]. At the present time, the type and regimen of radiation therapy to be used in this patient category is undefined because no randomized trials comparing different regimens are available [3,7,8]. Standard or 3D external beam radiation therapy (EBRT), when given at tumoricidal doses, still carries a considerable risk of lung damage that can be prohibitive in patients with a limited respiratory function.
0169-5002/$ — see front matter © 2008 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.lungcan.2007.12.016
210
R. Mart´ınez-Monge et al.
In addition to the conventional radiation techniques, other emerging newer radiation modalities such as CTguided brachytherapy or stereotactic fractionated external beam radiation therapy are being developed for the treatment of patients who are not suitable for surgical resection. These techniques provide a better lung tissue sparing and have the advantage of a shorter treatment time. We recently reported our preliminary results in the management of stage T1N0M0 medically inoperable NSCLC [9] with CT-guided 103 Pd brachytherapy. That previous report has been expanded with the accrual of more patients and longer follow-up.
2. Methods and materials Seven patients, 5 men and 2 women with histologically confirmed NSCLC stage T1N0M0 [10] and an average age of 80 years (range 75—92), were treated with CT-guided permanent interstitial brachytherapy (PIB) at the Cl´ınica Universitaria, University of Navarra, Spain from 2000 to 2007. In addition to advanced age, all the patients presented with severe comorbidities that made them unfit for a major surgical procedure (Table 1). The details of the CT-guided brachytherapy program have been described previously [9]. Briefly, baseline evaluation included detailed medical history, physical examination, CT scan of the chest and upper abdomen, bone scan, brain MRI,
Table 1
and PET scan. The patients finally selected for CT-guided PIB were additionally evaluated with chest CT to confirm the percutaneous accessibility of the lesion and the ideal patient positioning to avoid bony interference. The CT images were also used to perform a preplanning dosimetric study that determined the number of needle trajectories, the number of seeds, and the total activity to be implanted. Palladium103 or 125 I seeds were implanted to deliver a minimum tumor dose of 125 or 145 Gy, respectively. Doses were prescribed at the clinical target volume (CTV) that was arbitrarily defined as the gross tumor volume (GTV) plus a 5 mm margin [11]. No EBRT was added. The choice of radioisotope was determined by availability, due to the shortage of 103 Pd in Europe after 2005. The first four patients were treated with 103 Pd and the last three with 125 I seeds. All the brachytherapy implants were performed in an standard CT room under general anesthesia. This allowed patient immobilization and limited lung motion, decreasing the risk of pneumothorax. CT imaging determined the coordinates of the skin entry point and permitted adjustment of depth and angle of needle placement. Mini-Mick or standard 20 cm Mick needles were used. After target volume determination, interstitial needles (20 cm long, 16-gauge) were inserted into the tumor at an interspacing of approximately 0.5 cm. The median number of needles used was 5 (range 4—8). A relatively small number of needle passages were chosen to minimize the risk of pneumothorax, although this created an uneven dosimetric distribution. The 125 I or
Patient characteristics
No.
Histology
Age
Gender
Location
Co-morbidities
Pulmonary Function
1
Large cell, anaplastic
86
Male
Peripheral, RLLa
COPD Multiorganic diabetes mellitus Parkinson’s disease
FEV1 = 0.8 L FEV1 /FVC = n/a DLCO = n/a
2
Non-small cell lung cancer
60
Male
Central, RULb
End-stage liver cirrhosis
FEV1 = 1.8 L FEV1 /FVC = 38% DLCO = 32%
3
Squamous cell carcinoma
81
Male
Peripheral, LULc
Radiation fibrosis and surgical scarringd
FEV1 = 1.7 L FEV1 /FVC = 54% DLCO = 51%
4
Squamous cell carcinoma
80
Male
Peripheral, RUL
Diabetes mellitus Hypertension Aortic aneurysm Chronic kidney failure
FEV1 = 2.1 L FEV1 /FVC = 65% DLCO = 69%
5
Squamous cell carcinoma
75
Male
Peripheral, LUL
Myastenia gravis Synchronous prostate cancer
FEV1 = 1.4 L FEV1 /FVC = 75% DLCO = 69%
6
Non-small cell lung cancer Squamous cell carcinoma
92
Female
Peripheral, LLLe
Synchronous breast cancer
n/a
75
Female
Peripheral, RUL
Liver transplantation recipient Alpha-1 antitrypsin defficiency
FEV1 = 0.8 L FEV1 /FVC = 44% DLCO = 38%
7
a b c d e
Right lower lobe. Right upper lobe. Left upper lobe. Prior treatment with surgery and radiation for another primary NSCLC in 1992. Left lower lobe.
CT-guided permanent brachytherapy for patients Table 2
211
Implant characteristics
No. 1 2 3 4 5 6 7
Tumor diameter (cm) 1.0 0.7 3.0 1.0 1.8 1.9 1.4
Activity/seed (U)
Radioisotope
No. of seeds
No. of needles
2.5 2.5 2.5 2.5 0.48 0.55 0.54
103
30 50 50 35 45 45 45
5 5 4 8 5 6 8
Pd Pd 103 Pd 103 Pd 125 I 125 I 125 I 103
Fig. 1 Preimplant CT scan (left). Postimplant CT scan obtained 3 months after implantation showing tumor shrinkage and brachytherapy seeds in place.
103
Pd seeds were inserted through each needle using the Mick applicator. The median number of seeds was 45 (range 30—50) with an average activity of 2.51 U for 103 Pd seeds and 0.53 U for 125 I seeds (Table 2). The overall length of the procedure, including anesthesia, averaged 2.5 h. No patient was considered unfit for anesthesia. Once the implant was completed, a final CT scan was obtained for postplanning. Fig. 1 shows the pre- and postimplant CT obtained in patient number 6.
3. Results One patient with a bullous lung developed a pneumothorax that required drainage for 5 days. Another patient developed a combined pneumothorax and hemothorax (780 cm3 ) and required drainage as well. A third patient with myasthenia gravis required hospital admission due to a focal pneumonitis/respiratory infection 3 months after the implant procedure. The other 4 patients did not have any immediate or delayed complications. After a median follow-up of 13 months (4.6—41.0+ months) no patient has developed local or regional failure. Two patients died at 4 and 13 months of liver failure and stroke, respectively; five patients remain alive, one with disease. Among the five patients alive at last follow-up, one has developed a new contralateral second primary lung tumor at 8 months and is alive with
disease at 41.0 months, and 4 remain alive without disease at a median of 13.5 months (range 6.5—27.8) (Table 3).
4. Discussion While PIB has been used with some success in the intraoperative treatment of unresectable, residual, or medically inoperable NSCLC since the 1940s [12—14], its use in a percu-
Table 3 No. 1 2 3 4 5 6 7
Outcome
Acute complications
Late complications
Pneumotorax Pneumonitis/ infection Pneumo/ hemothorax
Status
F/up (months)
DFDa DFDb AWD NED NED
13.0 4.7 41.0 27.8 16.0
NED NED
11.2 6.5
NED: no evidence of disease; AWD: alive with disease; DFD: dead free of disease. a Died of stroke. b Died of liver failure.
212 taneous CT-guided approach is merely anecdotal [9,15,16]. This fact may be explained in part by the lack of tradition even in the most experienced brachytherapy centers, the small number of suitable candidates that probably stands for less than 20% of those referred for radical radiation due to a poor surgical risk and the fear of acute complications associated with the procedure. This small study shows that none of the seven patients treated developed local or loco-regional failure. Although the observation period is limited, due in part to the short life expectancy related to the pre-existing comorbid conditions, this excellent local control outcome can be explained by the small volume of the tumors treated and the very high doses of radiation delivered by PIB. The median tumor diameter of the patients treated in the present study was 1.4 cm (range 0.7—3.0), which corresponds to a median tumor volume of 11.5 cm3 . Hof et al. [17] in a study of stereotatic body radiotherapy (SRS) reported no local recurrences in a group of 12 patients with tumors smaller than 12 cm3 treated with single dose (19—30 Gy) SRS. Two patients developed pneumothorax or hemothorax. Although these patients had a poor baseline respiratory function, no significants effects were noted because pneumothorax was diagnosed during the implantation procedure and was immediately resolved with the patient closely monitored under general anesthesia. A dose-effect relationship has been well established for various human malignancies including NSCLC, and the dose-effect resulting from PIB should also be considered when accounting for the excellent control results observed. The median doses to the CTV (GTV + 0.5 cm) were 128 Gy for 103 Pd and 144 Gy for 125 I, and the median doses to the GTV were 187 Gy for 103 Pd and 217 Gy for 125 I. Different single or fractionated SRS studies have noted a significant increase in local control after biological effective doses (BED) of 90—100 Gy [17—19]. Although the BED obtained with either hypofractionated SRS or PIB cannot be directly compared due to the different patterns of dose delivery, current radiobiological principles suggest that the PIB doses used in the present study are well beyond that range. Future CT-guided PIB studies should be compared with other highly selective radiation techniques such as SRS. A recent report by Hof et al. [17] described the treatment of patients with Stage I and II NSCLC with single dose (19—30 Gy) SRS. Local control rates at 1, 2, and 3 years were 89.5, 67.9, and 67.9%, respectively. An earlier phase I trial reported by McGarry et al. [20] used fractionated SRS in a dose escalation trial beginning at 24 Gy in 3 fractions and increasing dose levels in 6 Gy steps. Four of 19 patients with T1 lesions experienced local failure. Although the results obtained with CT-guided PIB in the present study compare favorably with those reported by several SRS trials [17—19], the numbers are too small to allow a formal comparison. Finally, there were some patients in the group who had a short survival. These patients might have never become symptomatic for lung cancer and therefore, this kind of aggressive interventional treatment would not have been justified. An improved patient selection is mandatory when more experience is gained with PIB.
R. Mart´ınez-Monge et al.
5. Conclusions CT-guided PIB is an effective treatment for patients with medically inoperable stage I NSCLC. The complications associated with the procedure can be managed conservatively.
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