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ORIGINAL ARTICLE
Year : 2017  |  Volume : 54  |  Issue : 1  |  Page : 155-160
 

Actual gains in dosimetry and treatment delivery efficiency from volumetric modulated arc radiotherapy for inoperable, locally advanced lung cancer over five-field forward-planned intensity-modulated radiotherapy


1 Department of Radiation Oncology, Tata Medical Centre, Kolkata, West Bengal, India
2 Department of Medical Physics, Tata Medical Centre, Kolkata, West Bengal, India
3 Department of Medical Statistics, Tata Medical Centre, Kolkata, West Bengal, India

Date of Web Publication1-Dec-2017

Correspondence Address:
Dr. R K Shrimali
Department of Radiation Oncology, Tata Medical Centre, Kolkata, West Bengal
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijc.IJC_79_17

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 » Abstract 

AIMS: Volumetric modulated arc radiotherapy (VMAT) is used for inoperable, locally advanced nonsmall cell lung cancer, where three-dimensional conformal radiotherapy (3D-CRT) cannot yield an acceptable plan. METHODS: The planning and treatment data were prospectively collected on the first 18 patients treated using VMAT plans. We analyzed the actual dosimetric gain and impact on treatment, compared with complex multisegment 3D-CRT (five-field forward-planned intensity-modulated radiotherapy [IMRT]) that were generated for treatment. Proportion of planning target volume (PTV) receiving 95% dose (PTV-V95%) conformity index (CI), conformity number (CN), dose homogeneity index (DHI), monitor units (MUs), and treatment time were also analyzed. RESULTS: The PTV coverage (PTV-V95%) was improved from a median of 91.41% for 5-F forward-IMRT to 98.25% for VMAT (P < 0.001). The CI improved with a mean of 1.12 for VMAT and 1.31 for 5-F forward-IMRT (P < 0.001). The mean DHI improved from 1.15 for forward-IMRT to 1.08 for VMAT (P < 0.001). The mean CN improved from 0.62 for forward-IMRT to 0.87 for VMAT (P < 0.001). No significant increase in the low-dose bath (V5, V10 and mean lung dose) to the lung was seen. Significantly higher number of MUs (P < 0.001) and shorter treatment delivery times (P = 0.03) were seen with VMAT. CONCLUSION: VMAT resulted in improvement in target volume coverage, demonstrated by PTV-V95%, CI, CN, and DHI, without any increase in the low-dose bath to the lung. For conventional fractionation, VMAT requires more MUs (P < 0.001) but has a shorter treatment delivery time (P = 0.03) per fraction.


Keywords: Forward-planned intensity-modulated radiotherapy, intensity-modulated radiotherapy, lung cancer, radiotherapy, volumetric modulated arc radiotherapy


How to cite this article:
Shrimali R K, Arunsingh M, Reddy G D, Mandal S, Arun B, Prasath S, Sinha S, Mallick I, Achari R, Chatterjee S. Actual gains in dosimetry and treatment delivery efficiency from volumetric modulated arc radiotherapy for inoperable, locally advanced lung cancer over five-field forward-planned intensity-modulated radiotherapy. Indian J Cancer 2017;54:155-60

How to cite this URL:
Shrimali R K, Arunsingh M, Reddy G D, Mandal S, Arun B, Prasath S, Sinha S, Mallick I, Achari R, Chatterjee S. Actual gains in dosimetry and treatment delivery efficiency from volumetric modulated arc radiotherapy for inoperable, locally advanced lung cancer over five-field forward-planned intensity-modulated radiotherapy. Indian J Cancer [serial online] 2017 [cited 2020 Apr 5];54:155-60. Available from: http://www.indianjcancer.com/text.asp?2017/54/1/155/219601



 » Introduction Top


Lung cancer is a leading cause of cancer death across the world.[1],[2],[3] A majority of patients with nonsmall cell lung cancer (NSCLC) in India present with locally advanced (Stage IIIb; AJCC Cancer Staging Manual, 7th Edition, 2010) and metastatic (Stage IV) disease.[4],[5],[6] Radical radiotherapy combined with chemotherapy given with curative intent is the primary treatment option for most patients with Stage III disease; however, the survival remains poor with a 3-year survival rate of 24%.[7] The radiotherapy strategies that aim to improve local control and survival of these patients with inoperable, locally advanced NSCLC include dose escalation, altered fractionation, individualized radiotherapy administration, and advanced modern radiotherapy techniques such as intensity-modulated radiotherapy (IMRT) or volumetric modulated arc radiotherapy (VMAT).[8],[9]

IMRT is well established as an advanced form of highly conformal radiotherapy (CRT) where the intensity of the beam is varied across its profile. This allows carefully sculpted dose distributions and steeper dose gradients with narrower margins than previously possible. VMAT is based on a similar inverse planning process but allows continuous delivery of radiation in a moving arc by simultaneously varying the gantry rotation speed, positions of the multileaf collimator (MLC), and dose rate. VMAT is increasingly being used because of shorter treatment times.[10],[11],[12] IMRT or VMAT has been shown to decrease the dose to the spinal cord and normal lung tissue and to improve tumor coverage.[13],[14],[15],[16],[17] The proportion of whole lung excluding planning target volume (PTV) (whole lung volume − PTV) receiving a dose of at least 20 Gy (V20) expressed as percentage and the mean lung dose (MLD) expressed in Gy are established predictors of lung toxicity, and it is aimed to keep them below 32%–35% and 20 Gy, respectively.[18],[19],[20] In locally advanced disease, the dose constraints to organs at risk (OAR) may be impossible to meet with adequate PTV coverage using with three-dimensional CRT (3D-CRT) planning, and until recently many of these patients often received palliative radiotherapy.[17],[18],[19],[20],[21]

Numerous retrospective series have been published showing improved local control rates with IMRT for NSCLC.[22],[23],[24],[25] We had reviewed the published evidence including various guidelines, recommendations, and reports for the practice and documentation of IMRT pertaining to lung cancer, before implementing this practice at our center.[26],[27],[28],[29],[30]

The current study is not a typical planning study but aims to review our initial planning and treatment experience with patients with inoperable, locally advanced NSCLC. These patients were planned with multisegment 3D-CRT (five-field forward-planned IMRT), which was routine for NSCLC with large tumor volumes or complex shapes, before deciding that VMAT plans were necessary. This was because it provided better PTV coverage while maintaining satisfactory OAR constraints. We also describe the planning methods used and analyze the actual dosimetric gain and the impact on treatment efficiency from VMAT compared to five-field forward-IMRT.


 » Methods Top


Patient selection

The first 18 patients with inoperable, locally advanced NSCLC, who were treated with VMAT at our center, were included in this prospectively planned study. They were treated with VMAT plans from March 2012 to May 2014. These patients were initially planned using 3D-CRT and found to be unsuitable for a radical dose of radiotherapy, based on established dose constraints to the OARs and PTV coverage parameters. Our standard practice was to create a 3D-conformal plan using three or four fields. If the dose volume parameters for tumor coverage were not met or OAR dose was too high, a forward-planned multisegment five-field plan was generated. In all of the patients, multisegment 3D-CRT using five-field and numerous subfields were attempted multiple times (ranging from 3 to 6 times) before a decision was made in favor of a VMAT plan. The most optimal forward-IMRT plan (after review by a radiation oncologist and a physicist) was selected for each patient, prior to attempting a VMAT plan. Therefore, this was not a typical planning study where alternative plans are created in hindsight for academic comparison.

Treatment planning

Standard (helical) and slow (axial) computed tomography (CT) scans were acquired in quick succession, with the patient lying in treatment position at the same sitting. The gross tumor volume was delineated on the slow scan to obtain the tumor encompassing volume including the entire motion envelope to yield the internal target volume (ITV). Information from staging positron emission tomography (PET) using fluorodeoxyglucose was used to inform and help tumor and involved lymph node (or ITV) delineation. However, the PET images were not fused with planning images or directly used for planning. The clinical target volume (CTV) was obtained by a margin of 5 mm for subclinical extension, around the ITV, where appropriate. The PTV was defined by a margin of 1 cm around the CTV and 1.3 cm in the craniocaudal direction to account for organ and tumor motion and setup errors. The CTV and PTV margins were decided as per the European Organization for Research and Treatment of Cancer guidelines.[19],[20] The spinal cord and lung were outlined as OARs, and esophagus and heart were contoured for dose evaluation purposes. The aim of planning was to ensure that the PTV received coverage of 95%–107% for a prescribed dose of 60 Gy in 30 fractions. A satisfactory target volume (TV) coverage for treatment was defined as V95% of ≥95% (95% of the PTV should receive a dose equal to or higher than 95% of the prescription dose) and a V107% of 1 cc or less (a maximum of 1 cc of the PTV should receive a dose >107% of the prescribed dose). Our dose criteria for OARs are summarized in [Table 1].
Table 1: Dose constraints for organs at risk

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The eclipse treatment planning system (version 10.0.42, Varian Medical Systems, Palo Alto, CA, USA) was used to generate all the plans. The typical planning process used for forward-IMRT and for VMAT for lung cancers used by the authors has been described in an earlier publication.[30] Identical planning objectives and dose constraints for OAR were used for both types of plans.

The multisegment 3D-CRT (forward-IMRT) plans comprised 5 beam angles were optimized according to target localization. Most of the beams were made to enter through the ipsilateral lung, and off-cord beam arrangements were used wherever possible. With this technique, the 5 beams were used with varying gantry angles, differential weighting, and different apertures shaped with high-definition MLC. Thirty-two pairs of MLC used had a thickness of 2.5 mm, and the remaining 28 pairs had a thickness of 5 mm. The MLC were set to cover at least 5 mm more than the PTV margins. The plans were normalized at the isocenter, which was placed in the tumor region of the PTV, avoiding bone, or air cavity. The multisegment plan was achieved by manually adding subfields with various weights and evaluating the dose distribution. In each nonautomated iteration of the process, the planner introduced changes to revise the plan, producing multiple subfields. Each multisegment 3D-CRT plan had an average of about ten subfields, and the minimum number of monitor units (MUs) for each subfield was 4. The plans were optimized to meet the dose constraints for the TVs and the OAR. A 3D dose matrix was computed with 3D treatment planning software. With fixed dose rate, energy, and fixed subfield size in the treatment machine, the MUs were calculated. The final dose calculations were performed using an analytic anisotropic algorithm (AAA). The best multisegment five-field forward-IMRT plan for each patient that was closest to meeting the target doses and OAR constraints was also identified by the treating radiation oncologist and archived on our system. A comparative analysis was carried out between the best multisegment 3D-CRT (forward-IMRT) plan that was achieved and the VMAT plan that was actually used to treat the patients as identical planning objectives and dose constraints were used for both types of plans.

For VMAT (RapidArc), the progressive resolution algorithm was used for dose-volume optimization where MLC positions, dose rate (fluence output), and gantry rotation speed are simultaneously optimized in five levels with increasing resolution to fulfill the desired objectives.[31] Multiresolution dose calculation algorithm was used for fast dose estimation during optimization. The final dose calculation was performed using AAA at a grid size of 2.5 mm. Each VMAT plan comprised 2–4 (full or partial) arcs. The full arcs often had skipped angles (arcs restricted by avoidance sectors). The collimator angle, for a VMAT plan, ranged from 20° to 45° in either direction.[31]

Data and statistical analysis

To compare the VMAT and multisegment forward-IMRT plans, the dose distributions and the dose-volume histograms were generated and evaluated in accordance with the dose constraints in [Table 1]. The comparison and analysis were carried out by a physicist, a physician, and a statistician with a focus on TV coverage indices and OAR constraints. Conformity index (CI), conformity number (CN), and dose homogeneity index (DHI) have been computed based on the equations as described in [Table 2].
Table 2: Formulae for the indices used for plan quality evaluation

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The CI was first proposed by the Radiation Therapy Oncology Group (RTOG) in the year 1993 for the evaluation of stereotactic radiotherapy plans and was also described in report 62 of the International Commission on Radiation Units and Measurements (ICRU).[32],[33],[34],[37] It is defined as the ratio of the volume delineated by the reference isodose (RI) and the TV. This RI is defined by the RTOG as the prescription isodose. A CI equal to 1 would represent absolute conformation. With traditional 3D-CRT, the CI of between 1 and 2 is considered satisfactory.[35],[36],[37] However, the CI as defined by RTOG, although widely used in studies, fails to account for the degree of spatial intersection of the two volumes. It is possible to have a CI of 1 while the PTV and prescribed isodose volume, although measured to be equal, are separated from each other. As this is merely a ratio of two different volumes, it must be combined with visual assessment of the entire treatment plan including dosimetry and dose-volume histograms.[34]

However, the CN is a product of two ratios, where the first ratio defines the quality of coverage of the TV and the second ratio defines the volume of healthy normal tissue covered by the prescription isodose (i.e. receiving a dose greater than or equal to the prescribed dose). This number (CN) takes into account the irradiation of both TV as well as the delineated normal tissues. This number ranges from 0 to 1, where 1 represents the ideal situation.[34],[35]

Duration of time taken by planners for each of these plans was not recorded prospectively, and therefore could not be analyzed. The MUs and beam-on times were computed and compared. The treatment delivery time of the multisegment 3D-CRT plans was obtained by treatment delivery to a phantom and was compared with treatment delivery time for VMAT obtained from the actual radiotherapy treatments.

We compared the two different radiotherapy modalities (RapidArc and multisegment forward-IMRT) to see if there was a statistically significant difference for each of the parameters (V-95%, PTV-V95%, DHI, CN, CI, MLD [PTV], V20, V10, V5, max spinal cord dose) between VMAT and multisegment forward-IMRT. As the VMAT plan was used to treat each of these 18 patients and the best forward-IMRT plan achieved was saved for each patient, we have paired data. As the sample size was 18, the two-tailed Wilcoxon signed-rank test was used instead of the paired t-test. Differences were reported to be statistically significant at P ≤ 0.05.


 » Results Top


Tumor and lung volume details are presented in [Table 3]. Each VMAT plan comprised 2–4 arcs with a median beam-on time was about 3 min. The median of the computed beam-on time for the forward-IMRT plans was 2.98 min and for VMAT was 2.62 min. The MU delivered for VMAT plans was significantly higher at 655.0 compared to 286.6 MUs calculated for the forward-IMRT plans (P< 0.001).
Table 3: Tumour and lung volume characteristics

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Planning target volume coverage

The total volume of tissue receiving >95% of the prescribed dose (within the 95% isodose lines) was significantly higher for forward-IMRT with a median value of 1044 cc compared to 874.5 cc (P< 0.001). The TV coverage (assessed by PTV-V95%) was seen to improve significantly with VMAT as seen in [Table 4]. The improvement in CN was significant with a mean of 0.87 with VMAT when compared with 0.62 for multisegment 3D-CRT. The CI also showed a significant improvement with VMAT. [Figure 1] and [Figure 2] illustrate some examples of improvement in tumor coverage and conformity by VMAT from our patient series. As mentioned earlier, this was because the planners and physicists had manually created the most acceptable five-field forward-IMRT plan that could potentially be delivered. This often meant that the safety of the patient (in terms of maximum spinal cord doses and lung doses) was weighted more important than better target coverage for large- or complex-shaped tumors, examples are seen in [Figure 1] and [Figure 2]. The dose distribution was also found to be better with VMAT with less heterogeneity within the TV as evaluated using DHI. The median DHI improved from 1.15 for forward-IMRT to 1.08 for VMAT.
Figure 1: Better TV and tumour coverage in the second (VMAT) plan; suboptimal coverage of the TV to meet the dose constraints for the spinal canal in the first plan

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Figure 2: Better conformity in the second (VMAT) plan; poorly conforming high dose volume treating much more normal tissue outside the planning target volume in the first plan

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Table 4: Analysis of comparison of volumetric modulated arc radiotherapy with five-field multisegment forward-intensity-modulated radiotherapy

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Organs at risk sparing

The VMAT plan satisfied the OARs constraints by improving the mean of the MLD and mean of the maximum spinal cord dose, while maintaining satisfactory PTV coverage and made radical radiotherapy with curative intent possible. The outcome of the analysis between the two different types of radiotherapy plans is displayed in [Table 4]. A statistically significant difference was seen for CI, CN, DHI, MU, beam-on time, and total treatment time between the VMAT and the forward-IMRT group as displayed in [Table 4]. For other parameters, the difference between the groups was statistically not significant. The worsening in these lung dose parameters was also statistically not significant.


 » Discussion Top


On comparison with five-field forward-IMRT, VMAT was shown to improve the TV coverage in the current study, without any worsening of the doses to the relevant normal tissues. In addition, VMAT was associated with a nonsignificant trend toward improvement in the MLD and maximum spinal cord dose, and a slight worsening in V10 and V5, which was not unexpected and other reported studies have shown similar results.[14],[15] The CI and the CN were found to be significantly improved. The DHI was not a major endpoint for our analysis but was computed to see if there was any significant impact on this as a result of using VMAT. The DHI was shown to have improved significantly with VMAT compared to the forward-IMRT plans (P< 0.001).

Numerous planning studies have reported the dosimetric benefits of IMRT and VMAT when compared to 3D-CRT.[13],[14],[15],[16],[17] Previous planning studies have shown improvement in V20 from IMRT ranging from 8% to 15% over 3D-CRT.[14],[15],[16] However, in our study, the improvement in OARs dosimetry is not statistically or clinically significant for the reasons described below. Retrospective clinical series for NSCLC have been reported to show improved local control rates with IMRT.[22],[23],[24],[25]

The current study is important because it is based on prospective data from planning, plan evaluation, and clinical decision-making. The TVs in this study were large and had complex shapes in these patients with Stage III NSCLC. For these more advanced cases (N2 and N3 disease), our starting default solution is a manually created multisegment five-field forward-IMRT, conformed using MLC. It was retrospectively discovered that the PTV coverage was typically compromised by the planners and physicists in the forward-IMRT plans to ensure that the normal lung doses and maximum spinal cord doses were kept within the acceptable range [Figure 1] and [Figure 2]. At the time of planning, they believed that these plans would be used for treating these patients; therefore, the dose constraints for spinal cord and normal lung were strictly adhered to.

For VMAT planning, we made use of both partial arcs and/or full arcs with or without skipped angles (arcs restricted by avoidance sectors) for optimal lung sparing using the method previously described as restricted modular arcs by Rosca et al.[38] The planned MUs for treatment delivery have been shown to be fewer with VMAT when compared with static IMRT.[11],[39],[40] However, as in the current study, it may be greater when VMAT plans are compared with complex 3D-CRT (or forward-IMRT). Overall time on the treatment couch has also been reported to be shorter with VMAT (mostly reported in other tumor sites) when compared with static IMRT,[11],[39] although the beam-on time may be longer as seen in locally advanced lung cancer setting in the current study.

VMAT planning algorithms depend on delineation of TVs (including PTV) and OARs to create a plan with the best combination of accurately conformed beams. The planning and dosimetry software provides the dose-distribution on each axial slice of the CT volume but does not indicate or quantify the TV coverage or the conformity of the entire plan. Two-dimensional radiotherapy and 3D-CRT plans are often evaluated by visual analysis of dosimetry on each axial slice of the CT planning scan dataset. However, overall understanding of more complex plans such as IMRT/VMAT makes dose-volume histograms essential as a detailed comparison between several plans to choose the most desired plan may be difficult.[34]

As the ITV was delineated on a slow CT scan to obtain the tumor encompassing volume including the entire motion envelope, the impact of interplay due to tumor motion should be fairly small. Several studies have shown that the dosimetric impact of interplay in conventionally fractionated (with 30 fractions or more) IMRT treatment was <1% as the effects of interplay are probably blurred or “washed out.”[41],[42],[43] The challenges and benefits of IMRT for lung cancer have been discussed by the authors in an earlier publication.[30]

VMAT allows more patients to receive radical doses of radiotherapy in patients with lung cancer, with good PTV coverage. The TV coverage indices (PTV-V95%, CI, and CN) are important geometric parameters, although it is yet to be seen whether they are associated with local disease control or survival. Further studies are required to assess the impact of VMAT on toxicity, local control, and survival and to correlate with these indices, in patients with inoperable, locally advanced lung cancer.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
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    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]

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