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  Table of Contents  
ORIGINAL ARTICLE
Year : 2017  |  Volume : 54  |  Issue : 1  |  Page : 301-304
 

Stereotactic body radiation therapy for early-stage primary lung cancer, is an active breath coordinator necessary? An audit from a tertiary cancer care center


1 Department of Radiation Oncology, Amrita Institute of Medical Sciences, Amrita University, Kochi, Kerala, India
2 Department of Radiation Physics, Amrita Institute of Medical Sciences, Amrita University, Kochi, Kerala, India
3 Department of Biostatistics, Amrita Institute of Medical Sciences, Amrita University, Kochi, Kerala, India

Date of Web Publication1-Dec-2017

Correspondence Address:
R Madhavan
Department of Radiation Oncology, Amrita Institute of Medical Sciences, Amrita University, Kochi, Kerala
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijc.IJC_230_17

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 » Abstract 

CONTEXT: The hypofractionated stereotactic body radiation therapy (SBRT) has emerged as a safe and effective treatment modality for early-stage nonsmall cell lung carcinoma. AIMS: An audit SBRT in primary lung cancer treated in our center with and without an active breath coordinator (ABC) was undertaken to evaluate its impact on target volumes and clinical outcomes. SETTINGS AND DESIGN: This was an observational study. MATERIALS AND METHODS: Nine patients with lung carcinoma were treated from January 2014 to August 2016. Five patients were simulated using ABC and four patients with free breathing. Volumetric modulated arc therapy plans were generated using Monaco treatment planning software. Three patients were treated with a dose of 54 Gy in three fractions and six patients with a dose of 48 Gy in four fractions. STATISTICAL ANALYSIS USED: The statistical analysis was performed using Kaplan–Meier survival. RESULTS: The mean planning target volumes (PTV) in ABC and free breathing groups were 42.19cc and 60.17cc, respectively. The mean volume of lung receiving 20, 10, and 5 Gy (V20, V10and V5) in ABC group were 5.37cc, 10.49cc, and 18.45cc whereas in free breathing 6.63cc, 12.74cc, and 20.64cc, respectively. At a median follow-up of 18 months, there were three local recurrences. No significant toxicity occurred in our series. CONCLUSION: Our initial results show that SBRT is well tolerated with good local control. Although the PTV volume and irradiated normal lung volume was higher in this group compared to ABC group, this did not translate to any added clinical toxicity.


Keywords: Active breath coordinator, carcinoma lung, stereotactic body radiation therapy


How to cite this article:
Madhavan R, Renilmon P S, Nair H M, Lal A, Nair S S, Unnikrishnan U G, Makuny D. Stereotactic body radiation therapy for early-stage primary lung cancer, is an active breath coordinator necessary? An audit from a tertiary cancer care center. Indian J Cancer 2017;54:301-4

How to cite this URL:
Madhavan R, Renilmon P S, Nair H M, Lal A, Nair S S, Unnikrishnan U G, Makuny D. Stereotactic body radiation therapy for early-stage primary lung cancer, is an active breath coordinator necessary? An audit from a tertiary cancer care center. Indian J Cancer [serial online] 2017 [cited 2020 Mar 31];54:301-4. Available from: http://www.indianjcancer.com/text.asp?2017/54/1/301/219571



 » Introduction Top


Conventionally, stage I nonsmall cell lung carcinoma (NSCLC) is treated using surgical resection with a 60%–70% 5 years overall survival (OS).[1] The hypofractionated stereotactic body radiation therapy (SBRT) has emerged as a safe and effective treatment modality for NSCLC in recent years with tumor control rates at 3 years of up to 90%.[2],[3] SBRT involves delivery of large doses in few fractions using high precision technology. SBRT provides local control similar to surgical resection.[4],[5],[6]

The delivery of such high doses without under dosing the tumor or overdosing normal tissues requires accurate delineation of planning target volume (PTV). One major source of uncertainty in PTV delineation is due to tumor motion during respiration. Immobilization of moving target can be done by respiratory gating using an active breath coordinator (ABC). An alternative way is to use a four-dimensional (4D) computed tomography (CT) simulator to assess the respiratory movement and give a margin to the target volume. We present an audit of SBRT in primary lung cancer cases treated with and without ABC in our cancer institute. An evaluation of the impact of ABC on target volumes and clinical outcomes was also done in this study.


 » Materials and Methods Top


Nine patients were treated with SBRT from January 2014 to August 2016. All patients were having early-stage primary lung adenocarcinoma. All patients had a positron emission tomography (PET) CT staging before treatment. The cases were discussed in multidisciplinary pulmonary tumor board before treatment and got approval for SBRT. The patients were also informed about the concept, methodology, and rationale of this treatment. These patients were either medically inoperable or refused surgery. Each patient was immobilized using a vacloc and SBRT body frame localizer. The patient position was supine with arms above the head. CT simulation was done in supine position using 4D CT simulator GE OPTIMA 500W. Five patients were simulated using ABC and four patients without ABC under free breathing. The CT slice thickness was 1.25 mm, and entire lung was scanned. For patients using ABC, training was given for 3 days. The picture of ABC is given in [Figure 1].
Figure 1: Patient with active breath coordinator during computed tomography simulation. Patient characteristics of nine patients with early-stage primary lung cancer treated with stereotactic body radiation therapy. Tumor characteristics of nine patients with early-stage primary lung cancer treated with stereotactic body radiation therapy. Dosimetric details of nine patients with early-stage primary lung cancer treated with stereotactic body radiation therapy

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For free breathing after contouring gross tumor volume (GTV) using lung window, an internal target volume (ITV) was created using maximum intensity projection generated by 4D simulator. PTV was generated by 3 mm uniform expansion of ITV. For cases with ABC, PTV was generated by 5 mm expansion in axial and 10 mm expansion in craniocaudal axis of GTV. No nodal irradiation was attempted. Critical structures such as combined lung, heart, spinal cord, esophagus, great vessels, trachea, carina, and primary and secondary bronchi were contoured. Volumetric modulated arc therapy (VMAT) plans were generated using Monaco 5.10.02 treatment planning software. Three patients were treated with a dose of 54 Gy in three fractions, and six patients were treated with a dose of 48 Gy in four fractions. At least 90% of prescription dose was covering the entire PTV. The doses to all critical structures were limited within tolerance. All plans were delivered using two arcs in each fraction. The VMAT plans are shown in [Figure 2].
Figure 2: Volumetric modulated arc therapy plans for early-stage primary lung cancer

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All patients were treated using 6 MV photons with Elekta Synergy Linear Accelerator. A cone beam CT (CBCT) verification using kilovoltage on board imaging system was done before radiation therapy. The images from CBCT scan were registered with planning CT scan using automatic soft-tissue match. The resulting three-dimensional matching was verified, and corrections are applied if necessary. The corrections of resulting discrepancies were made by remote controlled couch shift in all directions. In principal, all patients were treated on consecutive days. No chemotherapy was administered before or during radiotherapy.

Initial follow-up was done 4 weeks after the completion of treatment. Toxicity was assessed using Common Toxicity Criteria version 4. Response assessment was done after 3 months with CT scan using Response Evaluation Criteria in Solid Tumors criteria.[7] Complete response indicated that tumor has completely disappeared or replaced by fibrous tissue. Partial response was defined as ≥30% reduction in maximum cross-sectional diameter. Local failure was defined as 25% increase in primary lesion size. PET imaging was only obtained for patients with subsequent CT evidence of local enlargement or suspicious metastatic disease. Thereafter, routine clinical follow-up was done every 3 months along with chest X-ray. In case of doubt, further imaging in the form of CT or PET is obtained. For those patients who were unable to attend the clinical follow-up at our center, telephonic consultation was done. All dosimetric data were abstracted from planning software. All reported lung doses were that of combined lung minus PTV. Lung V5(volume of lung receiving 5 Gy), V10(volume of lung receiving 10 Gy), and V20(VOLUME OF LUNG RECEiving 20 Gy) were assessed and recorded. Statistical analysis was done using SPSS software version 20. Kaplan–Meier actuarial analysis was employed.


 » Results Top


All patients completed treatment without obvious complaints. Characteristics of nine patients are shown in [Table 1]. The tumor characteristics are shown in [Table 2]. SBRT dosimetric characteristics are shown in [Table 3]. The median duration of follow-up was 18 months.
Table 1: Patient characteristics (n=9)

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Table 2: Tumor characteristics (n=9)

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Table 3: Stereotactic body radiation therapy dosimetric characteristics (n=9)

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At reassessment, CT scan after 3 months, there were five complete responses, two partial responses, and two stable diseases. A PET-CT scan showing complete response is given in [Figure 3]. At a median follow-up of 18 months, there were three local recurrences. The median time of local recurrence postradiation was 8 months. Out of three local recurrences, two patients were in ABC group, developed distant metastases also and died. All locally recurrent patients received salvage chemotherapy. The median OS is 28 months (95% confidence interval [CI] 20.5–35.5). The median disease-free survival (DFS) is 27 months (95% CI 19.5–35.5). The Kaplan–Meier curve showing OS and DFS are given in [Figure 4]a and [Figure 4]b. No grade 2 or higher acute and late toxicity occurred in our series.
Figure 3: Positron emission tomography image showing complete response after stereotactic body radiation therapy in early-stage primary lung cancer

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Figure 4: (a) Overall survival of patients treated with stereotactic body radiation therapy in early-stage primary lung cancer. (b) Disease-free survival of patients treated with stereotactic body radiation therapy in early-stage primary lung cancer

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 » Discussion Top


SBRT is an emerging technique in early-stage lung carcinoma with improved tumor control and less toxicity compared with conventional radiation therapy. The poor local control rates with conventional radiotherapy have been attributed to doses that are too low for tumor control. Mehta et al. provided a detailed theoretical analysis of NSCLC responses to radiotherapy and concluded that higher biologically effective doses (BED) administered during a short period is essential for successful local control of lung tumors.[8] SBRT typically uses 3–5 fractions with a total dose of 48–60 Gy. This approach substantially decreases overall treatment time from several weeks of conventional radiotherapy schedule to a few days offering important advantage to the patient. Although various fractionation schedules are undergoing evaluation around the globe, the BED of frequently used SBRT dose schedules has been set a little above 100 Gy. In our study, we used two fractionation schedules 54 Gy in three fractions and 48 Gy in four fractions.

Since lymph nodal stations are not electively treated in SBRT N0 status in patients had to be confirmed. The sensitivity and specificity for staging mediastinum in NSCLC are superior with PET (sensitivity 85%, specificity 90%) compared to CT (sensitivity 61%, specificity 79%). Hence, all patients in our group had undergone PET-CT staging before SBRT.[9]

A surgical resection is considered the standard of care for early-stage NSCLC. However, many patients will not undergo surgery due to old age and comorbidities. Onishi et al. published data of 245 patients with stage I NSCLC treated with SBRT technique. With a median 24 months follow-up, they had a 3-year OS of 56% and 3-year cause-specific survival of 78%.[10] Toxicity profiles proved favorable with <5% of patients experiencing grade 2 or greater pulmonary, esophageal or dermatologic toxicity. Nagata reports similar outcomes treating 45 patients with SBRT, including 3-year OS of 83% for stage IA and 72% for stage IB.[11] In our audit with a median follow-up of 18 months, the 2 years OS is 75%. The 2 years DFS is also 75%. Whitson et al. found 3 years OS rates of 87.2% and 81.6% in video-assisted thoracoscopic lobectomy and open thoracotomy, respectively.[12] However, we cannot conclude that the SBRT is equivalent to surgery because most of the SBRT data are from retrospective studies. There are no randomized control trials comparing surgery and SBRT available. The patients included in SBRT series usually have worst prognostic factors compared to surgery. In addition, the median age of patients treated in surgical series is 10 years less than that of SBRT patients. Hence, it is reasonable to infer that SBRT results are comparable to surgical series reported.

The toxicities related to SBRT for larger tumors are not yet well described. The usual toxicities encountered include radiation pneumonitis, bronchial stenosis or necrosis, esophageal injury, rib fractures, and injury to brachial plexus.[13] The parameters known to influence radiation pneumonitis after conventional radiation are lung volume receiving 20, 10, and 5 Gy.[14],[15],[16] Usually, radiation pneumonitis is uncommon after SBRT. In our series also, no significant grade 2 or higher acute or late toxicities occurred. Although our follow-up data are complete, a key limitation of our study is short follow-up period. However, a median follow-up of 24 months is sufficient for the detection of clinical radiation pneumonitis as previous studies have demonstrated its onset 5 months post-SBRT.[17]

ABC provides noninvasive, internal immobilization of anatomies affected by respiratory motion. It includes digital spirometry connected to computer controlled valve. In this technique, respiratory motion is immobilized repeatedly in a reproducible manner for a period of time that can be comfortably tolerated by the patient. Moderate deep inspiration breath holds at 75%–80% of maximum inspiratory capacity is desirable. Radiation will be delivered only during the breath hold. This improves target localization and helps clinicians to decrease the PTV margins. The disadvantages of ABC technique is it can be tiring for the patient. Only those patients who can hold breath for >15 s can be taken up for this technique. In addition, the radiation therapists have to give training to the patients.

4D CT data are generated by a continuous motion model for treatment planning in lung radiotherapy. It provides full range of respiratory movement for tumor and normal structures. Here, CT data are used to depict the extent of motion of the target and incorporate this motion as part of PTV. This is deemed as a passive approach and will increase the target volume to be irradiated compared to ABC technique where the target volume is reduced by arresting tumor motion at a specific stage of respiration. This target volume increase will lead to increase in normal lung tissue irradiated and will lead to higher normal tissue complication probability. The advantage is patient compliance is better as there is no need of any respiratory breath hold. In our study also, the free breathing group had higher PTV volume and higher normal lung doses. However, this has not translated to any increase in lung toxicity.


 » Conclusion Top


SBRT is a safer and noninvasive radical treatment option for early-stage NSCLCs. Long-term chronic toxicity remains unclear. A longer and larger follow-up of SBRT is needed. Free breathing technique is more patient friendly than ABC. Although the PTV volume and irradiated normal lung volume was higher in this group compared to ABC group, this did not translate to any added clinical toxicity.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
 » References Top

1.
Williams DE, Pairolero PC, Davis CS, Bernatz PE, Payne WS, Taylor WF, et al. Survival of patients surgically treated for stage I lung cancer. J Thorac Cardiovasc Surg 1995;109:120-9.  Back to cited text no. 1
    
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Zimmermann FB, Geinitz H, Schill S, Thamm R, Nieder C, Schratzenstaller U, et al. Stereotactic hypofractionated radiotherapy for stage I non small cell lung cancer. Lung Cancer 2005;48:107-14.  Back to cited text no. 2
    
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McGarry RC, Papiez L, Williams M, Whitford T, Timmerman RD. Stereotactic body radiation therapy of early-stage non-small-cell lung carcinoma: Phase I study. Int J Radiat Oncol Biol Phys 2005;63:1010-5.  Back to cited text no. 3
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Timmerman R, Paulus R, Galvin J, Michalski J, Straube W, Bradley J, et al. Stereotactic body radiation therapy for inoperable early stage lung cancer. JAMA2010;303:1070-6.  Back to cited text no. 5
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Lagerwaard FJ, Verstegen NE, Haasbeek CJ, Slotman BJ, Paul MA, Smit EF, et al. Outcomes of stereotactic ablative radiotherapy in patients with potentially operable stage I non-small cell lung cancer. Int J Radiat Oncol Biol Phys 2012;83:348-53.  Back to cited text no. 6
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Therasse P, Arbuck SG, Eisenhauer EA, Eisenhauer EA, Wanders J, Kaplan RS, et al. New guidelines to evaluate the response to treatment in solid tumors. J Natl Cancer Inst 2000;92:205-16.  Back to cited text no. 7
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Mehta M, Scrimger R, Mackie R, Paliwal B, Chappell R, Fowler J. A new approach to dose escalation in non-small-cell lung cancer. Int J Radiat Oncol Biol Phys 2001;49:23-33.  Back to cited text no. 8
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Gould MK, Kuschner WG, Rydzak CE, Maclean CC, Demas AN, Shigemitsu H, et al. Test performance of positron emission tomography and computed tomography for mediastinal staging in patients with non-small-cell lung cancer: A meta-analysis. Ann Intern Med 2003;139:879-92.  Back to cited text no. 9
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Onishi H, Araki T, Shirato H, Nagata Y, Hiraoka M, Gomi K, et al. Stereotactic hypofractionated high dose irradiation for stage I non small cell lung carcinoma: Clinical outcomes in 245 subjects in a Japanese multi institutional study. Cancer 2004;101:1623-31.  Back to cited text no. 10
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Nagata Y, Takayama K, Matsuo Y, Norihisa Y, Mizowaki T, Sakamoto T, et al. Clinical outcomes of a phase I/II study of 48 Gy of stereotactic body radiotherapy in 4 fractions for primary lung cancer using a stereotactic body frame. Int J Radiat Oncol Biol Phys 2005;63:1427-31.  Back to cited text no. 11
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Whitson BA, Groth SS, Duval SJ, Swanson SJ, Maddaus MA. Surgery for early-stage non-small cell lung cancer: A systematic review of the video-assisted thoracoscopic surgery versus thoracotomy approaches to lobectomy. Ann Thorac Surg 2008;86:2008-16.  Back to cited text no. 12
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Chi A, Liao Z, Nguyen NP, Xu J, Stea B, Komaki R. Systemic review of patterns of failure following stereotactic body radiation therapy in early stage non small cell lung cancer: Clinical implication. Radiother Oncol 2010;94:1-11.  Back to cited text no. 13
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Fay M, Tan A, Fisher R, Mac Manus M, Wirth A, Ball D. Dose-volume histogram analysis as predictor of radiation pneumonitis in primary lung cancer patients treated with radiotherapy. Int J Radiat Oncol Biol Phys 2005;61:1355-63.  Back to cited text no. 14
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Seppenwoolde Y, Lebesque JV, de Jaeger K, Belderbos JS, Boersma LJ, Schilstra C, et al. Comparing different NTCP models that predict the incidence of radiation pneumonitis. Normal tissue complication probability. Int J Radiat Oncol Biol Phys 2003;55:724-35.  Back to cited text no. 15
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Yamashita H, Nakagawa K, Nakamura N, Koyanagi H, Tago M, Igaki H, et al. Exceptionally high incidence of symptomatic grade 2-5 radiation pneumonitis after stereotactic radiation therapy for lung tumors. Radiat Oncol 2007;2:21.  Back to cited text no. 17
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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

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