Swamidas V. Jamema

A treatment planning study comparing volumetric arc modulation with RapidArc and fixed field IMRT for cervix uteri radiotherapy

PURPOSE A treatment planning study was performed to evaluate the performance of the novel volumetric modulated single arc radiotherapy on cervix uteri cancer patients. Conventional fixed field IMRT was used as benchmark. METHODS AND MATERIALS CT datasets of eight patients were included in the study. Plans were optimised with the aim to assess organs at risk and healthy tissue sparing while enforcing highly conformal target coverage. Planning objectives for PTV were: maximum significant dose lower than 52.5 Gy and minimum significant dose higher than 47.5 Gy. For organs at risk, the median and maximum doses were constrained to be lower than 30 (rectum), 35 (bladder) and 25 Gy (small bowel) and 47.5 Gy; additional objectives were set on various volume thresholds. Plans were evaluated on parameters derived from dose volume histograms and on NTCP estimates. Peripheral doses at 5, 10 and 15 cm from the PTV surface were recorded to assess the low-level dose bath. The MU and delivery time were scored to measure expected treatment efficiency. RESULTS Both RapidArc and IMRT resulted in equivalent target coverage but RapidArc had an improved homogeneity (D(5%)-D(95%) = 3.5 +/- 0.6 Gy for RapidArc and 4.3 +/- 0.8 Gy for IMRT) and conformity index (CI(90%) = 1.30 +/- 0.06 for RapidArc and 1.41 +/- 0.15 for IMRT). On rectum the mean dose was reduced by about 6 Gy (10 Gy for the rectum fraction not included in the PTV). Similar trends were observed for the various dose levels with reductions ranging from approximately 3 to 14.4 Gy. For the bladder, RapidArc allowed a reduction of mean dose ranging from approximately 4 to 6Gy and a reduction from approximately 3 to 9 Gy w.r.t. IMRT. Similar trends but with smaller absolute differences were observed for the small bowel and left and right femur. NTCP calculations on bladder and rectum confirmed the DVH data with a potential relative reduction ranging from 30 to 70% from IMRT to RapidArc. The healthy tissue was significantly less irradiated in the medium to high dose regions (from 20 to 30 Gy) and the integral dose reduction with RapidArc was about 12% compared to IMRT. Concerning peripheral dose, the relative difference between IMRT and RapidArc was of 9 +/- 2%, 43 +/- 11% and 36 +/- 5% at 5, 10 and 15 cm from the PTV surface, respectively. The MU/Gy from RapidArc was 245 +/- 17 corresponding to an expected average beam on time of 73 +/- 10 s per fractions of 2 Gy. IMRT plans presented higher values with an average of MU/Gy = 479 +/- 63. CONCLUSION RapidArc was investigated for cervix uteri cancer showing significant improvements in organs at risk and healthy tissue sparing with uncompromised target coverage leading to better conformal avoidance of treatments w.r.t. conventional IMRT. This, in combination with the confirmed short delivery time, can lead to clinically significant advances in the management of this highly aggressive cancer type. Clinical protocols are now advised to evaluate prospectively the potential benefit observed at the planning level.

A multicentre comparison of the dosimetric impact of inter- and intra-fractional anatomical variations in fractionated cervix cancer brachytherapy

Background and purpose To compare the dosimetric impact of organ and target variations relative to the applicator for intracavitary brachytherapy by a multicentre analysis with different application techniques and fractionation schemes. Material and methods DVH data from 363 image/contour sets (120 patients, 6 institutions) were included for 1–6 fractions per patient, with imaging intervals ranging from several hours to ∼20 days. Variations between images acquired within one (intra-application) or between consecutive applicator insertions (inter-application) were evaluated. Dose plans based on a reference MR or CT image series were superimposed onto subsequent image sets and D2cm3 for the bladder, rectum and sigmoid and D90 for HR CTV were recorded. Results For the whole sample, the systematic dosimetric variations for all organs at risk, i.e. mean variations of D2cm3, were found to be minor (<5%), while random variations, i.e. standard deviations were found to be high due to large variations in individual cases. The D2cm3 variations (mean ± 1SD) were 0.6 ± 19.5%, 4.1 ± 21.7% and 1.6 ± 26.8%, for the bladder, rectum and sigmoid. For HR CTV, the variations of D90 were found to be −1.1 ± 13.1% for the whole sample. Grouping of the results by intra- and inter-application variations showed that random uncertainties for bladder and sigmoid were 3–7% larger when re-implanting the applicator for individual fractions. No statistically significant differences between the two groups were detected in dosimetric variations for the HR CTV. Using 20% uncertainty of physical dose for OAR and 10% for HR CTV, the effects on total treatment dose for a 4 fraction HDR schedule at clinically relevant dose levels were found to be 4–8 Gy EQD2 for OAR and 3 Gy EQD2 for HR CTV. Conclusions Substantial variations occur in fractionated cervix cancer BT with higher impact close to clinical threshold levels. The treatment approach has to balance uncertainties for individual cases against the use of repetitive imaging, adaptive planning and dose delivery.

Inter-application variation of dose and spatial location of D 2 cm 3 volumes of OARs during MR image based cervix brachytherapy

PURPOSE Evaluation of Inter-application variation of doses and spatial location of D(2cm(3)) volumes of OARs during MR-image based cervix brachytherapy. MATERIALS AND METHODS Twenty-seven patients treated with EMBRACE protocol were analyzed. Every patient had two applications, one week apart. For each application patient had undergone MR-imaging (MR-1 and MR-2), volume delineation, reconstruction, treatment planning (plan-1 and plan-2) and dose evaluation. Both the image series were then co-registered with applicator as the reference coordinate system (Eclipse planning system v8.6.14). Inter-application dose, volume and spatial location of D(2cm(3)) variation were evaluated. RESULTS The largest inter-application systematic and random dose variations were observed for sigmoid as compared to rectum and bladder. The mean (±SD) of the relative D(2cm(3)) variations were 0.6(±15.1)%, 0.9(±13.1)% and 11.9(±37.5)% for rectum, bladder and sigmoid respectively. The overlap of D(2cm(3)) volumes was more than 50% in 16(59%), 8(30%) and 3(11%) patients for rectum, bladder and sigmoid, respectively. CONCLUSION The 2cm(3) volumes between the applications/fractions are quite stable in topography for bladder and rectum, and hence the current practice of cumulative addition of D(2cm(3)) dose is expected to be valid for bladder and rectum. For sigmoid, significant topographical changes were seen, which need further validation in a larger patient population and in multi-centric settings.

Comparison of DVH parameters and loading patterns of standard loading, manual and inverse optimization for intracavitary brachytherapy on a subset of tandem/ovoid cases.

PURPOSE Comparison of inverse planning with the standard clinical plan and with the manually optimized plan based on dose-volume parameters and loading patterns. MATERIALS AND METHODS Twenty-eight patients who underwent MRI based HDR brachytherapy for cervix cancer were selected for this study. Three plans were calculated for each patient: (1) standard loading, (2) manual optimized, and (3) inverse optimized. Dosimetric outcomes from these plans were compared based on dose-volume parameters. The ratio of Total Reference Air Kerma of ovoid to tandem (TRAK(O/T)) was used to compare the loading patterns. RESULTS The volume of HR CTV ranged from 9-68 cc with a mean of 41(±16.2) cc. Mean V100 for standard, manual optimized and inverse plans was found to be not significant (p=0.35, 0.38, 0.4). Dose to bladder (7.8±1.6 Gy) and sigmoid (5.6±1.4 Gy) was high for standard plans; Manual optimization reduced the dose to bladder (7.1±1.7 Gy p=0.006) and sigmoid (4.5±1.0 Gy p=0.005) without compromising the HR CTV coverage. The inverse plan resulted in a significant reduction to bladder dose (6.5±1.4 Gy, p=0.002). TRAK was found to be 0.49(±0.02), 0.44(±0.04) and 0.40(±0.04) cGy m(-2) for the standard loading, manual optimized and inverse plans, respectively. It was observed that TRAK(O/T) was 0.82(±0.05), 1.7(±1.04) and 1.41(±0.93) for standard loading, manual optimized and inverse plans, respectively, while this ratio was 1 for the traditional loading pattern. CONCLUSIONS Inverse planning offers good sparing of critical structures without compromising the target coverage. The average loading pattern of the whole patient cohort deviates from the standard Fletcher loading pattern.

Dosimetric evaluation of rectum and bladder using image-based CT planning and orthogonal radiographs with ICRU 38 recommendations in intracavitary brachytherapy

The purpose is to compare CT-based dosimetry with International Commission on Radiation Units and Measurements (ICRU 38) bladder and rectum reference points in patients of carcinoma of uterine cervix treated with intracavitary brachytherapy (ICA). Twenty-two consecutive patients were evaluated. Orthogonal radiographs and CT images were acquired and transferred to PLATO planning system. Bladder and rectal reference points were identified according to ICRU 38 recommendations. Dosimetry was carried out based on Manchester system. Patient treatment was done using 192Iridium high dose rate (HDR) remote after-loading machine based on the conventional radiograph-based dosimetry. ICRU rectal and bladder point doses from the radiograph plans were compared with D2, dose received by 2 cm3 of the organ receiving maximum dose from CT plan. V2, volume of organ receiving dose more than the ICRU reference point, was evaluated. The mean (±standard deviation) volume of rectum and bladder was 60 (±28) cm3 and 138 (±41) cm3 respectively. The mean reference volume in radiograph and CT plan was 105 (±7) cm3 and 107 (±7) cm3 respectively. It was found that 6 (±4) cm3 of rectum and 16 (±10) cm3 of bladder received dose more than the prescription dose. V2 of rectum and bladder was 7 (±1.7) cm3 and 20.8 (±6) cm3 respectively. Mean D2 of rectum and bladder was found to be 1.11 (±0.2) and 1.56 (±0.6) times the mean ICRU reference points respectively. This dosimteric study suggests that comparison of orthogonal X-ray-based and CT-based HDR ICA planning is feasible. ICRU rectal point dose correlates well with maximum rectal dose, while ICRU bladder point underestimates the maximum bladder dose.

Uncertainties of deformable image registration for dose accumulation of high-dose regions in bladder and rectum in locally advanced cervical cancer

PURPOSE To compare the dose accumulation for bladder and rectum by deformable image registration (DIR) and direct addition (DA) of dose volume histogram parameters in magnetic resonance image-guided adaptive brachytherapy (IGABT). Two DIR algorithms, contour- and intensity-based, also have been analyzed. METHODS AND MATERIALS Patients (n = 21) treated with IGABT for carcinoma cervix under the IntErnational study on MRI-guided BRachytherapy in locally Advanced CErvical cancer protocol were analyzed. Each patient underwent two HDR-BT applications, 1-week apart with two fractions of 7 Gy each delivered per application. For each application, magnetic resonance imaging, volume delineation, reconstruction, treatment planning (BT1 and BT2), and dose evaluation were carried out. BT1 and BT2 images were registered using an intensity-based DIR, followed by deformable dose accumulation (DDA), which was then compared with DA. To compare the intensity-based DIR to other DIR approaches, nine patients were further evaluated using an in-house contour-based DIR algorithm for bladder dose accumulation. RESULTS Mean (±standard deviation; range) percentage variation between DA and DDA was found to be 2.4% (±3.3;-1.8, 11.5) and 5.2% (±5.1;-1.7, 16.5) for the rectum and bladder, respectively. The differences between the DA and DDA were found to be statistically significant for both rectum (p = 0.008) and bladder (p = 0.0003). Intensity-based DIR algorithm resulted in a larger mean deviation between DDA and DA as compared with contour-based DIR, although statistically insignificant (p = 0.32). The difference between DDA and DA was 2.4 ± 2.0% and 1.3 ± 1.2%, for intensity- and contour-based DIR, respectively. CONCLUSIONS DA of dose volume histogram parameters provides a good estimate to the dose to the organs at risk; DIR based on image intensities may lead to systematic underestimation of dose due to implausible DIR.

Performance characterization of siemens primus linear accelerator under small monitor unit and small segments for the implementation of step-and-shoot intensity-modulated radiotherapy.

Implementation of step-and-shoot intensity-modulated radiotherapy (IMRT) needs careful understanding of the accelerator start-up characteristic to ensure accurate and precise delivery of radiation dose to patient. The dosimetric characteristic of a Siemens Primus linear accelerator (LA) which delivers 6 and 18 MV x-rays at the dose rate of 300 and 500 monitor unit (MU) per minutes (min) respectively was studied under the condition of small MU ranging from 1 to 100. Dose monitor linearity was studied at different dose calibration parameter (D1_C0) by measuring ionization at 10 cm depth in a solid water phantom using a 0.6 cc ionization chamber. Monitor unit stability was studied from different intensity modulated (IM) groups comprising various combinations of MU per field and number of fields. Stability of beam flatness and symmetry was investigated under normal and IMRT mode for 20×20 cm2 field under small MU using a 2D Profiler kept isocentrically at 5 cm depth. Inter segment response was investigated form 1 to 10 MU by measuring the dose per MU from various IM groups, each consisting of four segments with inter-segment separation of 2 cm. In the range 1-4 MU, the dose linearity error was more than 5% (max −32% at 1 MU) for 6 MV x-rays at factory calibrated D1_C0 value of 6000. The dose linearity error was reduced to −10.95% at 1 MU, within −3% for 2 and 3 MU and ±1% for MU ≥4 when the D1_C0 was subsequently tuned at 4500. For 18 MV x-rays, the dose linearity error at factory calibrated D1_C0 value of 4400 was within ±1% for MU ≥3 with maximum of −13.5 observed at 1 MU. For both the beam energies and MU/field ≥4, the stability of monitor unit tested for different IM groups was within ±1% of the dose from the normal treatment field. This variation increases to −2.6% for 6 MV and −2.7% for 18 MV x-rays for 2 MU/field. No significant variation was observed in the stability of beam profile measured from normal and IMRT mode. The beam flatness was within 3% for 6 MV x-rays and more than 3% (Max 3.5%) for 18 MV x-rays at lesser irradiation time ≤3 MU. The beam stability improves with the increase in irradiation time. Both the beam energies show very good symmetry (≤2%) at all irradiation time. For all the three segment sizes studied, the nonlinearity was observed at smaller MU/segment in both the energies. When the MU/segment is ≥4, all segment size shows fairly linear relation with dose/MU. The smaller segment size shows larger nonlinearity at smaller MU/segment and become more linear at larger MU/segment. Based on our study, we conclude that the Primus LA from Siemens installed at our hospital is ideally suited for step-and-shoot IMRT preferably for radiation ON time ≥4MU per segment.

Whole abdomen radiation therapy in ovarian cancers: a comparison between fixed beam and volumetric arc based intensity modulation.

PurposeA study was performed to assess dosimetric characteristics of volumetric modulated arcs (RapidArc, RA) and fixed field intensity modulated therapy (IMRT) for Whole Abdomen Radiotherapy (WAR) after ovarian cancer.Methods and MaterialsPlans for IMRT and RA were optimised for 5 patients prescribing 25 Gy to the whole abdomen (PTV_WAR) and 45 Gy to the pelvis and pelvic nodes (PTV_Pelvis) with Simultaneous Integrated Boost (SIB) technique. Plans were investigated for 6 MV (RA6, IMRT6) and 15 MV (RA15, IMRT15) photons. Objectives were: for both PTVs V90% > 95%, for PTV_Pelvis: Dmax < 105%; for organs at risk, maximal sparing was required. The MU and delivery time measured treatment efficiency. Pre-treatment Quality assurance was scored with Gamma Agreement Index (GAI) with 3% and 3 mm thresholds.ResultsIMRT and RapidArc resulted comparable for target coverage. For PTV_WAR, V90% was 99.8 ± 0.2% and 93.4 ± 7.3% for IMRT6 and IMRT15, and 98.4 ± 1.7 and 98.6 ± 0.9% for RA6 and RA15. Target coverage resulted improved for PTV_Pelvis. Dose homogeneity resulted slightly improved by RA (Uniformity was defined as U5-95% = D5%-D95%/Dmean). U5-95% for PTV_WAR was 0.34 ± 0.05 and 0.32 ± 0.06 (IMRT6 and IMRT15), 0.30 ± 0.03 and 0.26 ± 0.04 (RA6 and RA15); for PTV_Pelvis, it resulted equal to 0.1 for all techniques. For organs at risk, small differences were observed between the techniques. MU resulted 3130 ± 221 (IMRT6), 2841 ± 318 (IMRT15), 538 ± 29 (RA6), 635 ± 139 (RA15); the average measured treatment time was 18.0 ± 0.8 and 17.4 ± 2.2 minutes (IMRT6 and IMRT15) and 4.8 ± 0.2 (RA6 and RA15). GAIIMRT6 = 97.3 ± 2.6%, GAIIMRT15 = 94.4 ± 2.1%, GAIRA6 = 98.7 ± 1.0% and GAIRA15 = 95.7 ± 3.7%.ConclusionRapidArc showed to be a solution to WAR treatments offering good dosimetric features with significant logistic improvements compared to IMRT.

Treatment outcome with low-dose-rate interstitial brachytherapy in early-stage oral tongue cancers

PURPOSE Although radical radiotherapy is known to be equally effective for early-stage oral tongue cancers (T1-2 N0) with the added advantage of organ and function preservation, surgery remains the preferred treatment. We present outcome of patients treated with brachytherapy (BT) either radical or boost. MATERIALS AND METHODS Fifty-seven patients (T1/T2 31/26) were studied. Seventeen patients (30%) were treated with radical BT (50-67 Gy) while 40 (70%) with external beam radiation therapy (EBRT) + BT (36-56 Gy + 15-38 Gy]. Low-dose-rate (LDR) BT was delivered with 192 Ir wires, using plastic bead technique with varied dose rates (<60 cGy/h in 29 patients, 60-90 cGy/h in 17, and >90 cGy/h in 11). RESULTS The overall local control (LCR) was achieved in 59.7% (34/57) patients. LCR for T1 and T2 was 67.8% and 50%, respectively. A total of 23 patients had failures [local: 20 (T1: 8; T2: 12 patients), node: 5 (T1:2; T2: 3), and local + nodal: 3]. Overall 5-year disease-free survival and overall survival (OAS) were 51% and 67%, respectively and those for T1 and T2 was 64.5/77.4% and 38.5/54% respectively (P = 0.002). All 16 patients were salvaged. Median survival after salvage treatment was 13.5 months (6-100 months). Soft tissue necrosis was observed in 12.3% (7/57) and osteoradionecrosis in two patients. CONCLUSION BT, as an integral part of radical radiation therapy in early-stage tongue cancers, appears to be an effective alternative treatment modality with preservation of the organ and function without jeopardizing the outcome.

Comparison of IPSA with dose-point optimization and manual optimization for interstitial template brachytherapy for gynecologic cancers

PURPOSE To compare inverse planning simulated annealing (IPSA) algorithm with the dose-point optimized (DPO) plan and manual/graphically optimized (GrO) plan for interstitial template brachytherapy for gynecologic cancers. METHODS AND MATERIALS The data set of 10 consecutive patients was selected for this dosimetric study. For each patient, three plans were calculated: DPO, GrO, and IPSA. Dose-volume parameters from the three plans were compared to analyze the dosimetric outcome. RESULTS Coverage of the clinical target volume (CTV) with GrO plan and IPSA algorithm was significantly better (mean V(100) of 88.8% and 89.1%; p=0.006) as compared with DPO plan (83.7%; p=0.62). Similarly, mean D(90) was same in both GrO plan and IPSA, 3.96±0.23 and 3.96±0.15Gy, respectively. DPO plans were homogeneous with homogeneity index being 0.82 as compared with 0.68±0.05 of GrO plan and 0.71±0.04 of IPSA. However, IPSA resulted in high conformity with conformity index of 0.78 as compared with 0.72 (p=0.001) and 0.68 (p≤0.001) for GrO and DPO plans, respectively. The dose to rectum (3.3±1.06Gy) and bladder (3.17±0.5Gy) was generally high for DPO plan. GrO plan reduced the dose to the rectum (2.91±0.63; p=0.011) and bladder (2.89±0.63Gy; p=0.003) significantly. IPSA resulted in a further reduction of the dose to rectum (2.79±0.67Gy; p=0.046) and bladder (2.81±0.67Gy; p=0.035), however with no statistical significance as compared with GrO plan. CONCLUSION IPSA resulted in significant sparing of normal tissues without compromising CTV coverage as compared with DPO plan. However, IPSA did not show any significant improvement either in CTV coverage or in normal tissue sparing as compared with GrO plan. IPSA was found to be superior in terms of homogeneity and conformity as compared with GrO plan.