A study to see the difference in doses received to tumour and normal organs in patients undergoing prostate radiotherapy by two different techniques Volumetric modulated Arc Therapy (VMAT)and Intensity Modulated radiotherapy(IMRT).
- Conditions
- DIAGNOSED CASE OF CA PROSTATE, ELIGIBLE FOR RADICAL RADIOTHERAPY
- Registration Number
- CTRI/2011/11/002121
- Lead Sponsor
- MedantaThe Medicity
- Brief Summary
**VOLUMETRIC MODULATED ARC THERAPY FOR PROSTATE RADIOTHERAPY:**
**IS THERE ANY SCOPE FOR DOSE ESCALATION ?**
**Introduction:**
Three-dimensional conformal radiotherapy (3D-CRT) has traditionally been the standard modality for external beam RT for prostate cancer. Randomized controlled trials using this technique have demonstrated improved prostate-specific antigen control with dose escalation, but at the cost of increasing toxicity (1,2). This increased toxicity can be circumvented by treating less of the surrounding normal tissue, using techniques such as intensity-modulated RT (IMRT). The potential downsides of IMRT include the increased time required for RT delivery and increased monitor units (MU) needed, resulting in a greater integral body dose (3). Volumetric modulated arc therapy (VMAT) is a novel form of IMRT optimization that allows the radiation dose to be accurately and efficiently delivered in a single 360 gantry rotation (4). With this technique, a full 360 of beam directions are available for optimization. Compared with IMRT, the potential advantages of VMAT include a large reduction in treatment time and a concomitant reduction in the number of MUs required to deliver a given fraction size.
**Aims and Objectives:**
1. To quantitatively compare IMRT and VMAT techniques with regards to dosimetric quality and treatment delivery efficiency in the treatment of prostate cancers eligible to receive RT without violating the organ-at-risk constraints (OARs), and
2. To evaluate the Normal tissue complication probability (NTCP) and Tumor control probability (TCP) by dose escalation with VMAT in terms of target coverage and sparing of organs at risk.
**Materials and Methods:**
Thirty prostate cancer patients will be included in this retrospective study to evaluate VMAT and IMRT planning for the radical radiotherapy in carcinoma prostate. Eligibility crteria for patients will be:
1. Histologically proven prostate adenocarcinoma
2. Clinical stage T1-T3, N0-N1, M0 (Patients beyond T1-T2c will be taken after complete androgen blockade for 2 months
3. No prior radical surgery or cryosurgery for prostate cancer
Monaco (ver. 2.03.01) planning system has been used to generate IMRT and the same will be utilzed for VMAT planning using identical optimization objectives. A dosimetric evaluation will be done to compare target coverage, integral dose and sparing of OARs between the two treatment plans. The time required to deliver each plan will be also be measured for each case. The time measured for IMRT and VMAT will include both the beam on time and the gantry rotation time between subsequent beams or arcs. Patients will be assessed for acute rectal and bladder toxicity as per criteria laid down in CTCAE v 4.0 (5).
*Radiotherpy planning:*
All patient have undergone multislice contrast computed tomography(CT) simulation in the supine position with full bladder and empty rectum as per department protocol at 3.0 mm thickness. Organs at risk included are rectum, bladder, penile bulb and femoral heads. The rectum was contoured from the anus to rectosigmoid and the femoral heads were contoured to the level of the ischial tuberosities. The normal tissue was defined as the patient’s volume included in the CT dataset minus the PTV volume. The prostate contours used for the study were denoted as the clinical target volume (CTV). The PTV72 was generated by adding a 10-mm margin to the CTV in all dimensions, except posteriorly where a 6-mm margin was used and was prescribed to a dose of 7,200 cGy in 36 fractions. The same volume will be prescribed to a dose of 7800cGy in 39 fractions (PTV78) for the dose escalation study. The seminal vesicles will be intended to receive 5400cGy in 27 fractions (PTV 54). The regional lymphnodes will be planned for 4500cGy in 25 fractions only if there was more than 15% risk of involvement as per Roach’s estimates/Partin’s Nomogram (6,7) (PTV45). Prescription dose will be delivered to an International Commission on Radiation Units and Measurements report 62 reference point in the PTV, with ≥98% of the PTV covered by 95% of the prescribed dose and to keep the maximal point dose at ≤ 107%. The primary dose constraints will be determined using a Radiation Therapy Oncology Group protocol (8) (Table 1).
| | | | | |
| --- | --- | --- | --- | --- |
|**Normal organ limit**
**No more than 15% volume receives dose that exceeds**
**No more than 25% volume receives dose that exceeds**
**No more than 35% volume receives dose that exceeds**
**No more than 50% volume receives dose that exceeds**
|**Bladder Constraints**
80Gy
75Gy
70Gy
65Gy
|**Rectum Constraints**
75Gy
70Gy
65Gy
60Gy
|**Penile bulb**
Mean Dose ≤ 52.5Gy
To better test the normal tissue-sparing capacity of IMRT and VMAT, more stringent secondary dose constraints will be evaluated (Table 2).
| | |
| --- | --- |
|**Structure**
|**Rectum**
V70Gy ≤5%
|V40Gy ≤25%
|V20Gy ≤50%
|**Bladder**
V40Gy ≤25%
|V20Gy ≤50%
|**Femoral Heads**
V40Gy ≤50%
The treatment plans so far have been generated using seven field IMRT consisting seven coplanar beams, at gantry angles of 0, 55, 105, 155, 205, 255, and 305. The VMAT plans will consist of a single arc, starting at a gantry angle of 179 and rotating clockwise through 358 to stop at a gantry angle of 181. For both techniques, the final dose calculation will be performed using the Monte carlo algorithm. The same planning protocol will be used for PTV78 with similar dose PTV 54 and PTV 45 and same dose constraints to OARs.
*Plan evaluation:*
For all patients, cumulative dose-volume histograms and dosimetric parameters will be calculated and compared for the PTV and OARs. In addition, dose distributions among PTVs and OARs will be evaluated on each axial computed tomography slices, and the number of MUs required to deliver a 2-Gy fraction will be calculated for each plan. For PTV the following data will be as be reported: PTV coverage (Prescription dose Dp, D2%, D50% D98%, V95 and V107). The dose conformity index (9) will be calculated as: Planning isodose volume (volume included in 95% isodose)/volume of PTV. Inhomogeneity within the PTV will be be calculated as (D5%-D95%)/ Dmean, where Dn% is the minimal dose delivered to the percentage of volume of the prostate (9). For OARs, the maximum point dose (Dmax), the mean dose, and appropriate values of VxGy (volume receiving at least × Gy) will be scored. Similar parameters will be utilized for evaluation of VMAT plans. Also, the normal tissue integral dose (NTID) will be calculated as the product of the mean dose and the volume of normal tissue, excluding the PTV, inside the scanned region. The probability of uncomplicated local control(P+) will be computed using the tumor control probability (TCP) (10,11) and normal tissuecomplication probability(NTCP) (12-14) with the formula:TCP.(1-NTCPOARs) (10) for both IMRT and VMAT plans. To aid in the interpretation of the dose distributions in the CTV, PTV, and OARs, the concept of equivalent uniform dose (EUD) will be used.
where vi is volume receiving NTDi. The volume dependence parameter was n = 0.12 for the rectum and n = 0.5 for the bladder (14).
*Statistical analysis:*
The Wilcoxon matched-pair signed-rank test will be used to compare the results among the IMRT, and VMAT plans. The threshold for statistical significance will be p ≤0.05.
Technical features of treatments will be reported in terms of main delivery parameters (field and control point (CP) size, MU, MU/deg and MU/Gy, Dose Rate (DR), Gantry Speed (GS), Collimator angle, beam-on-time).
**References:**
1. Peeters ST, Heemsbergen WD, Koper PC, et al. Dose-response in radiotherapy for localized prostate cancer: Results of the Dutch multicenter randomized phase III trial comparing 68 Gy of radiotherapy with 78 Gy. J Clin Oncol 2006;24:1990–1996.
2. Pollack A, Zagars GK, Smith LG, et al. Preliminary results of a randomized radiotherapy dose-escalation study comparing 70 Gy with 78 Gy for prostate cancer. J Clin Oncol 2000;18: 3904–3911.
3. Hall EJ, Wuu C-S. Radiation-induced second cancers: The impact of 3D-CRT and IMRT. Int J Radiat Oncol Biol Phys 2003; 56:83–88.
4. Otto K. Volumetric modulated arc therapy: IMRT in a single gantry arc. Med Phys 2008;35:310–317.
5. Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 Published: May 28, 2009 (v4.02: Sept. 15, 2009), National Institutes of Health, National Cancer Institute.
6. Roach M. Equations for predicting the pathologic stage of men with localized prostate cancer using the preoperative prostate specific antigen. J Urol 1993;150:1923-924.
7. Partin AW, Yoo J, Carter HB, et al. The use of prostate specific antigen, clinical stage and Gleason score to predict pathological stage in men with localized prostate cancer. J Urol 1993;150:110-114.
8. Radiation Therapy Oncology Group. RTOG 0415: A phase III randomized study of hypofractionated 3D-CRT/IMRT versus conventionally fractionated 3D-CRT/IMRT in patients with favorable risk prostate cancer. Available from: [http://www.rtog](http://www.rtog/). org/members/protocols/0415/0415.pdf. Accessed March 28, 2008.
9. Mock U, Georg D, Bogner J, et al. Treatment planning comparison of conventional, 3D conformal, and intensity-modulated photon (IMRT) and proton therapy for paranasal sinus carcinoma. Int J Radiat Ooncol Biol Phys 2004;58:147–154.
10. De Meerleer GO, Vakaet LA, De Gersem WR, et al. Radiotherapy of prostate cancer with or without intensity modulated beams: A planning comparison. Int J Radiat Oncol Biol Phys 2000;47:639–648.
11. Webb S, Nahum AE. A model for calculating tumour control probability in radiotherapy including the effects of inhomogeneous distributions of dose and clonogenic cell density. Phys Med Biol 1993;38:653–666.
12. Lyman JT. Complication probability as assessed from dose– volume histograms. Radiat Res Suppl 1985;8(S13):19.
13. Kutcher GJ, Burman C. Calculation of complication probability factors for non-uniform normal tissue irradiation: The effective volume method. Int J RadiatOncol Biol Phys 1989;16:1623–1630.
14. Burman C, Kutcher GJ, Emami B, et al. Fitting of normal tissue tolerance data to an analytic function. Int J Radiat Oncol BiolPhys 1991;21:123–135.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Open to Recruitment
- Sex
- Male
- Target Recruitment
- 30
- Histologically proven prostate adenocarcinoma 2.
- Clinical stage T1-T3, N0-N1, M0 (Patients beyond T1-T2c will be taken after complete androgen blockade for 2 months 3.
- No prior radical surgery or cryosurgery for prostate cancer.
Not provided
Study & Design
- Study Type
- Observational
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method To quantitatively compare IMRT and VMAT techniques with regards to dosimetric quality and treatment delivery efficiency in the treatment of prostate cancers eligible to receive RT without violating the organ-at-risk constraints (OARs) To quantitatively compare IMRT and VMAT techniques with regards to dosimetric quality and treatment delivery efficiency in the treatment of prostate cancers eligible to receive RT without violating the organ-at-risk constraints (OARs)
- Secondary Outcome Measures
Name Time Method To evaluate the Normal tissue complication probability (NTCP) and Tumor control probability (TCP) by dose escalation with VMAT in terms of target coverage and sparing of organs at risk. One year.
Trial Locations
- Locations (1)
MEDANTA-THE MEDICITY, SECTOR 38, GURGAON
🇮🇳Gurgaon, HARYANA, India
MEDANTA-THE MEDICITY, SECTOR 38, GURGAON🇮🇳Gurgaon, HARYANA, IndiaDR TEJINDER KATARIAPrincipal investigator919810643131tejinder.kataria@medanta.org