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ORIGINAL ARTICLE
Year : 2016  |  Volume : 12  |  Issue : 1  |  Page : 47-52

Comparison of the gross tumor volume in end-expiration/end-inspiration (2 Phase) and summated all phase volume captured in four-dimensional computed tomography in carcinoma lung patients


1 Department of Medical Physics, International Oncology Center, Fortis Hospital, Noida, NCR; Department of BioMedical, Shobhit University, Meerut, Uttar Pradesh, India
2 Department of Medical Physics, International Oncology Center, Fortis Hospital, Noida, NCR, India
3 Department of Radiation Oncology, Fortis Memorial and Research Institute, Gurgaon, Haryana, India
4 Department of Radiation Oncology, International Oncology Center, Fortis Hospital, Noida, NCR, India
5 Department of Radiation Oncology, Montefi ore Medical Centre, New York, USA
6 Department of BioMedical, Shobhit University, Meerut, Uttar Pradesh, India

Date of Web Publication13-Apr-2016

Correspondence Address:
Pramod Kumar Sharma
Department of Medical Physics, International Oncology Center, Fortis Hospital, Sector 62, Noida - 201 301, Uttar Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.159088

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 > Abstract 

Purpose: The aim of this study was to compare the delineation and treatment planning of 2 Phase based (end-expiration and end-inspiration) internal gross tumor volume (IGTV) with 10-phase based (four-dimensional [4D]) IGTV.
Materials and Methods: Patients with lung tumors at different sites were selected for the study. The location of the tumor in Groups A, B, C were at the upper lobe (attached to the chest wall), middle lobe, and lower lobe, respectively. We contoured the GTV on each of the 10 respiratory phases of the 4D computed tomography (4DCT) data set. The combination of these GTVs produced the IGTV “All Phases.” GTV was also generated on the extreme respiratory phases. The combination of these two GTVs produced IGTV “2 Phases.” Treatment planning was done, and dose to organs at risks (OARs) were compared in both cases.
Results: The average volume of IGTV “2 Phases” and IGTV “All Phases” for Group A were nearly same. However, for Group B and Group C, IGTV “2 Phases” were smaller than the IGTV “All Phases.” Lung-GTV doses were less in “exp-insp” phases than in “4DCT” for Groups B, C, whereas it was same for “expiration-inspiration” and “4DCT” in Patient A.
Conclusion: Patients with tumor upper lobe tumor have no difference in tumor coverage and OARs sparing in the 2 Phase and all phases but middle lobe and lower lobe have a greater excursion during respiration and hence greater all phases IGTV.

Keywords: Four-dimensional computed tomography, lung tumors, motion management, phases


How to cite this article:
Sharma PK, Srivastava R, Munshi A, Chomal M, Saini G, Garg M, Manjhi J, Rai D V. Comparison of the gross tumor volume in end-expiration/end-inspiration (2 Phase) and summated all phase volume captured in four-dimensional computed tomography in carcinoma lung patients. J Can Res Ther 2016;12:47-52

How to cite this URL:
Sharma PK, Srivastava R, Munshi A, Chomal M, Saini G, Garg M, Manjhi J, Rai D V. Comparison of the gross tumor volume in end-expiration/end-inspiration (2 Phase) and summated all phase volume captured in four-dimensional computed tomography in carcinoma lung patients. J Can Res Ther [serial online] 2016 [cited 2021 Jan 16];12:47-52. Available from: https://www.cancerjournal.net/text.asp?2016/12/1/47/159088




 > Introduction Top


Lung cancer remains one of the most common causes of cancer death. Radiotherapy (RT) is a cornerstone in the management of locally advanced lung cancer patients. The respiratory motion is an important serious source of error for RT in many patients of nonsmall-cell lung cancer (NSCLC).[1],[2] The consequent intrafraction-motion is an issue that is becoming increasingly important.[3] To account for this motion in the normal course RT treatment planning, a large margin needs to apply to the tumor.[4],[5] These excessive volumes result in excessive lung tissue irradiation with the risk of causing an increased chance of radiation pneumonitis and also restrict the ability of dose escalation.[6],[7],[8],[9] Therefore, integration of other technologies such as respiratory gated RT and cone-beam computed tomography (CBCT) verification of patient set-up are important components of intensity modulated radiotherapy (IMRT) and image-guided radiotherapy (IGRT) of the lung.[1],[2],[3]

Several recent publications have addressed the issue of tumor motion in target delineation of lung tumors and the consequent impact on dosimetry.[10] However, the possibility of doing a 2 Phase scan in the treatment of lung cancers has not been explored by investigators. The present study was aimed to do a comparison of the gross tumor volume (GTV) in end-expiration/end-inspiration (2 Phase) and summated all phase volume captured in four-dimensional CT (4DCT) in carcinoma lung patients.


 > Materials and Methods Top


For this study, lung cancer patients for RT planning were divided into three groups on the basis of the location of the tumor. Each group contained two patients of similar tumor location.





  • Group A: Tumor located at left upper lobe (attached to the chest wall)
  • Group B: Tumor located at the right middle lobe
  • Group C: Tumor located at left lower lobe.


TNM staging of all patients was tabulated in [Table 1].
Table 1: TNM staging for all three groups of patients

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Acquisition of computed tomography scans

For each patient, three CT scans were acquired. The first CT scan was acquired in end-inspiration (EI 0% phase). EI scan has taken by asking the patient to breathe in and hold throughout the scan. The second scan was acquired in the end-expiration (EE 50% phase) phases of the respiratory cycle (breath out and holding it throughout the scan). The third CT study set was a 4DCT, which was split in 10 respiratory phases (0%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, and 90%). All scans were done using IV contrast in order to delineate tumor accurately. All the study sets (EI, EE, and 4D) which included 12 sets (10 in 4DCT and one in EI and one in EE) CT study sets were imported in Eclipse ® treatment planning system (V11 Varian Medical System). EE CT scan was co-registered with EI CT scan and with each of the 10 phase scans of 4DCT study.

Contouring of structures

A CT structure set was created in EE CT scan, and all the target structures and organs at risks (OARs) were delineated in EE CT structure set. GTVEE (GTV) was contoured on the EE CT structure set. GTVEI was delineated on EE CT structure set by blending EI CT scan with EE CT scan. GTVEE and GTVEI were combined to create an internal GTV (IGTV2 Phases) in EE CT structure. Furthermore, 10 GTVs of 10 respiratory phases were contoured on EE CT structure set with the help of registered 10 CT study sets of the 4DCT data set. These 10 GTVs of 4DCT scan were combined on EE CT structure set to generate IGTVAll Phases.

The clinical target volume was expanded uniformly by 6 mm for each patient to create ITV2 Phases and ITVAllPhases. PTV2 Phases and PTVAllPhases were created by giving 3 mm volume expansion around their respective ITVs as shown in [Figure 1]. OARs including lungs, heart, spine, and esophagus were delineated for all patients on EE CT structure set with the help of registered EI scan and 4DCT scan.
Figure 1: Internal gross tumor volumes comparison of “2 Phases” and “All Phases” in all three lobes

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We compared an IGTV which was generated by combining GTVs drawn involuntary end-expiration and end-inspiration breath hold phases (IGTV2 Phases) and that obtained by combining GTVs drawn in all 10 phases (IGTVAll Phases) in patients. This exercise was repeated for all patients. The dosimetric comparison was done among Group A, Group B, and Group C of lung patients.

Plan generation and dose prescription

Our department is equipped with Varian Trilogy Linear Accelerator with 6 and 15 MV photons beam and High Definition MLC with 120 leaves. The prescribed dose for all patients was 60 Grays (Gy) in 30 fractions. Hybrid treatment plans were generated on EE CT structure set using Eclipse ® treatment planning system (V11 Varian Medical System) for both PTVs (PTV2 Phases and PTVAllPhases) up to 15 fractions with AP PA technique and remaining 15 fractions with 7 beam inverse IMRT technique.

The treatment plans named as Plan2 Phases and PlanAll Phases were compared for each patient for their PTV coverages and OARs sparing.

Radiation Therapy Oncology Group (RTOG) Conformity Index (C.I.), Oliver moderate dose homogeneity index (H.I.), Paddick dose gradient index (G.I.) were calculated from Plan Sum2 Phases and Plan SumAll Phases of each patient of each group and tabulated in [Table 1]. Doses to lung, heart, esophagus, and spine were evaluated in terms of their mean and volume doses.

RTOG C.I. = PI/TV

Oliver dose H.I. = D95%/D5%

Paddick G.I. = PI50%/TV

Where,

PI was the volume of the prescription isodose line

PI50% was the volume of 50% of the prescription isodose line

TV is the PTV volume.

D5% is the dose received by the 5% volume of the PTV

D95% is the dose received by the 95% volume of the PTV

[Table 2] gives the OAR doses for “All Phases” (4DCT) and “2 Phases” (end-expiration inspiration) scan for all three groups of patients.
Table 2: PTV dose indices for all phases (4DCT) and 2 phases (end-expiration inspiration) scan for all three groups of patients

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Single tailed paired Student's t-test had been applied between “Plan2 Phases” and “PlanAllPhases” in all three groups, to check the statistical significance between the groups.


 > Results Top


The difference between the volume of IGTV2 Phases and IGTVAll Phases for Group A patients was not statistically significant. IGTV2 Phases was found to be smaller than IGTVAll Phases in patients of Group B and Group C [Figure 1] and the difference in the values were statistically significant (P < 0.05) [Table 2].

In PlanAllPhases, the differences in the values C.I., H.I., and G.I. were not statistically significant for all three pairs (Group A vs. Group B, Group B vs. Group C, Group A vs. Group C) [Table 2].

In Plan2 PhasesC.I. and G.I. were found to be better in Group B patients than in Group C patients and the difference in the values obtained of C.I. and G.I. were found statistically significant (P < 0.05) in pair Group B versus Group C [Figure 2].
Figure 2: Planning target volume coverage with 95% isodose of upper lobe tumor, middle lobe lung tumor, and lower lobe tumor for both the phases

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Normal lung mean doses were significantly lower in Plan2 Phases than in PlanAll Phases for Group B (P < 0.05) and Group C (P < 0.05) patients. The mean doses were comparable in both the plans for Group A (P > 0.05) patients. Normal lung V5 (volume receiving 5 Gy dose), V10 (volume receiving 10 Gy dose), and V20 (volume receiving 20 Gy dose) were found to be lesser in Plan2 Phases as compared to PlanAll Phases for Groups B and C patients. The difference in the values was statistically significant in both the groups (P < 0.05). The mean dose to the heart and V25, V30 was significantly lower in Plan2 Phases as compared to PlanAll Phases in Group B patients [Table 3]. For Group A patients, there was no significant difference in V5, V10, V20, values in both the plans.
Table 3: OAR doses for all phases (4DCT) and 2 Phases (end-expiration inspiration) scan for all three groups of patients

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The data validation have been done for all three lobes using Sun Nuclear Arc Check Phantom with its “Respiratory Motion Sim” Software. Group A (upper lobe) result shows there is no significant difference in the DVHs of “2 Phases” and “All Phases” IGTVs in their “3DVH” software analysis whereas Group B (middle lobe) and Group C (lower lobe) result reveal a significant difference in IGTVs of “2 Phases” and “All Phases.”


 > Discussion Top


Lung cancer is the leading cause of cancer death in the world with an overall 5 years survival rate of approximately 15%. The physiological respiratory motion of primary lung tumors may reduce the chances of obtaining an optimal local control rate after RT. Strategies employing dose escalation require some form of motion control. Respiratory motion is an important serious source of error for RT of NSCLC in many patients, and the integration of other technologies such as respiratory gated RT and CBCT verification of patient set-up are important components of IMRT and IGRT of the lung.[11],[12]

The desired imaging modality for simulation, especially for targets, which are likely to be in a state of motion during treatment is a 4DCT. This special modality captures the desired area not as a snapshot in time but as a real-time scan of the patient while he or she is lying down and thus gives a dynamic image of the moving target. In gating, one uses only a particular phase (10%, 20% etc.) to plan the treatment schedule.

Several approaches are available for aiming at correcting for tumor motion potentially leading to a better conformity of RT.[13],[14],[15],[16] These include synchronizing the beam-on/beam-off time with respiratory motion (gating), holding the patient in a particular phase of breath and treating in a breath hold phase or targeting the tumor in all the phases of the respiratory cycle (tumor tracking). In addition, a 4DCT also enables to generate Maximum Intensity Projection images.[13] These images are the summation of the tumor position in all phases of the respiratory cycle.

These patients were planned by hybrid technique as per the departmental protocol. The basis behind that protocol is the fact that IMRT alone for cancer lung results in higher low dose volumes of the normal lung (e.g., v5 and v15).

The idea behind the hybrid planning is to spare maximum lung with AP-PA technique. However, AP-PA field arrangement can be delivered up to the limit of spinal tolerance dose only, Hence we delivered 30 Gy with AP-PA technique in which the spine gets a maximum dose of up to 33 Gy and the remaining 30 Gy dose to the tumor is delivered by IMRT technique. This limits further dose to the spine to a maximum of 10 Gy over and above already delivered and also keeps the lung doses low. Therefore, by this hybrid technique we can restrict low dose volume to lung and also limit maximum spine dose (Dmax) to 42 Gy.

We employed a special technique of “2 Phases” and compared it with the conventional 4D scan in our patients. Our aim was to see differences in volumes and dosimetry between these two modalities. Our study compared C.I., H.I., and G.I. and found that these parameters were similar for “2 Phases” and “All Phases” scans in Groups A, B, and C. In “All Phases” scan, the values of C.I., H.I., and G.I. were comparable in all three groups.

The “2 Phases” technique has the potential to be a suitable alternative to centers lacking a regular 4DCT scanner. In our study, however, we found that “2 Phases”-based approaches to IGTV delineation significantly underestimated the IGTV in middle lobe patients. The underestimation was there in lower lobe tumors as well, albeit to a lesser extent. Even though the patient number is small, it implies that a significant amount of the tumor volume could be missed in an individual patient. It is therefore, advisable to use the “2 Phases” technique with caution in middle and lower lobe tumors.

Similarly, the reduced mean doses to the lung seen in Group B and Group C in “2 Phases” plans are likely to be a result of the smaller PTV in “2 Phases” plans as compared to a larger PTV for “All Phases” plans.

All existing studies in the literature relate to 4DCT scans and to subsequently employed technique of 4D treatment.[17],[18],[19] We are not aware of any other study in literature that addresses this critical issue. Our study, however, is not without pitfalls. An intrinsic fallacy of the “2 Phases” technique is the subjectivity of the patient in taking and leaving the breath and the timing of the scan. This variation can cause displacement of the tumor position. Nevertheless, this study has given critical leads and has the potential to extend the concept of 4D treatments even to the centers lacking a 4D scanner. Further work on refining the “2 Phases” technique can make perhaps make it more appropriate for middle and lower lobe tumors.


 > Conclusion Top


To summarize, our study shows the patients with a tumor in upper lobe have no difference in tumor coverage and OARs sparing in the end-expiration inspiration and 4DCT. However, tumors in middle lobe and lower lobe have a greater excursion during respiration and hence greater “All Phases” IGTV. At present, based on the findings of our study, while a “2 Phases” scan is good enough for upper lobe tumors, we suggest performing a 4D scan and end-expiration inspiration scan both for middle and lower lobe categories of patients in order to include the entire tumor excursion due to breathing.

 
 > References Top

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Perez CA, Bauer M, Edelstein S, Gillespie BW, Birch R. Impact of tumor control on survival in carcinoma of the lung treated with irradiation. Int J Radiat Oncol Biol Phys 1986;12:539-47.  Back to cited text no. 1
    
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Rosenman JG, Halle JS, Socinski MA, Deschesne K, Moore DT, Johnson H, 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;54:348-56.  Back to cited text no. 2
    
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Paoli J, Rosenzweig KE, Yorke E, Hanley J, Mah D, Mageras GS, et al. Comparison of different phases of respiration in the treatment of lung cancer: Implications for gated treatment (abstract). Int J Radiat Oncol Biol Phys 1999;45:386-7.  Back to cited text no. 3
    
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Munshi A, Budrukkar A. Hypofractionated radiation therapy in breast cancer: A revolutionary breakthrough or a long way to go? J Clin Oncol 2007;25:458-9.  Back to cited text no. 7
    
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Hayden AJ, Rains M, Tiver K. Deep inspiration breath hold technique reduces heart dose from radiotherapy for left-sided breast cancer. J Med Imaging Radiat Oncol 2012;56:464-72.  Back to cited text no. 8
    
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Swanson T, Grills IS, Ye H, Entwistle A, Teahan M, Letts N, et al. Six-year experience routinely using moderate deep inspiration breath-hold for the reduction of cardiac dose in left-sided breast irradiation for patients with early-stage or locally advanced breast cancer. Am J Clin Oncol 2013;36:24-30.  Back to cited text no. 9
    
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Hanley J, Debois MM, Mah D, Mageras GS, Raben A, Rosenzweig K, et al. Deep inspiration breath-hold technique for lung tumors: The potential value of target immobilization and reduced lung density in dose escalation. Int J Radiat Oncol Biol Phys 1999;45:603-11.  Back to cited text no. 11
    
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Muirhead R, McNee SG, Featherstone C, Moore K, Muscat S. Use of Maximum Intensity Projections (MIPs) for target outlining in 4DCT radiotherapy planning. J Thorac Oncol 2008;3:1433-8.  Back to cited text no. 13
    
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Wong VY, Tung SY, Ng AW, Li FA, Leung JO. Real-time monitoring and control on deep inspiration breath-hold for lung cancer radiotherapy – Combination of ABC and external marker tracking. Med Phys 2010;37:4673-83.  Back to cited text no. 14
    
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Barnes EA, Murray BR, Robinson DM, Underwood LJ, Hanson J, Roa WH. Dosimetric evaluation of lung tumor immobilization using breath hold at deep inspiration. Int J Radiat Oncol Biol Phys 2001;50:1091-8.  Back to cited text no. 15
    
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Kimura T, Murakami Y, Kenjo M, Kaneyasu Y, Wadasaki K, Ito K, et al. Interbreath-hold reproducibility of lung tumour position and reduction of the internal target volume using a voluntary breath-hold method with spirometer during stereotactic radiotherapy for lung tumours. Br J Radiol 2007;80:355-61.  Back to cited text no. 16
    
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Yoshitake T, Shioyama Y, Nakamura K, Ohga S, Nonoshita T, Ohnishi K, et al. A clinical evaluation of visual feedback-guided breath-hold reproducibility of tumor location. Phys Med Biol 2009;54:7171-82.  Back to cited text no. 17
    
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Mageras GS, Yorke E, Rosenzweig K, Braban L, Keatley E, Ford E, et al. Fluoroscopic evaluation of diaphragmatic motion reduction with a respiratory gated radiotherapy system. J Appl Clin Med Phys 2001;2:191-200.  Back to cited text no. 18
    
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Mah D, Hanley J, Rosenzweig KE, Yorke E, Braban L, Ling CC, et al. Technical aspects of the deep inspiration breath-hold technique in the treatment of thoracic cancer. Int J Radiat Oncol Biol Phys 2000;48:1175-85.  Back to cited text no. 19
    


    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

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