Siji Nojin Paul

Predictors of Grade 3 or Higher Late Bowel Toxicity in Patients Undergoing Pelvic Radiation for Cervical Cancer: Results From a Prospective Study

PURPOSE The present study investigates relationship between dose-volume parameters and severe bowel toxicity after postoperative radiation treatment (PORT) for cervical cancer. METHODS AND MATERIALS From June 2010 to December 2012, a total of 71 patients undergoing PORT were included. Small bowel (SB) and large bowel (LB) loops were contoured 2 cm above the target volume. The volume of SB and LB that received 15 Gy, 30 Gy, and 40 Gy was calculated (V15 SB, V15 LB, V30 SB, V30 LB, V40 SB, V 40 LB). On follow-up, bowel toxicity was scored using Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. A reciever operating characteristic (ROC) curve identified volume thresholds that predicted for grade 3 or higher toxicity with highest specificity. All data was dichotomized across these identified cut-off values. Univariate and multivariate analysis was performed using SPSS, version 15. RESULTS The median patient age was 47 years (range, 35-65 years). Of the 71 patients, 46 received image-guided intensity modulated radiation therapy, and 25 received conformal radiation (50 Gy in 25 fractions for 5 weeks). Overall, 63 of 71 patients received concurrent chemotherapy. On a median follow-up of 18 months (range, 8-29 months), grade 2 or higher bowel toxicity was seen in 22 of 71 patients (30.9%) and grade 3 or higher bowel toxicity was seen in 9 patients (12.6%). On univariate analysis, V15 SB <275 cc (P=.01), V30 SB <190 cc (P=.02), V40 SB <150 cc (P=.01), and V15 LB <250 cc (P=.03), and V40 LB <90 cc (P=.04) predicted for absence of grade 3 or higher toxicity. No other patient- or treatment-related factors were statistically significant. On multivariate analysis, only V15 SB (P=.002) and V15 LB (P=.03) were statistically significant. CONCLUSIONS V 15 Gy SB and LB are independent predictors of late grade 3 or higher toxicity. Restricting V15 SB and V15 LB to <275 cc and <250 cc can reduce grade 3 or higher toxicity to less than 5%.

Use of tomotherapy in treatment of synchronous bilateral breast cancer: dosimetric comparison study

OBJECTIVE Synchronous malignancy in both breasts is a rare incidence. The present study aims at dosimetric comparison of conventional bitangential radiotherapy (RT) technique with conventional [field-in-field (FIF)] and rotational [Helical TomoTherapy(®) and TomoDirect™ (TD); Accuray Inc., Sunnyvale, CA] intensity-modulated RT for patients with synchronous bilateral breast cancer (SBBC). METHODS CT data sets of 10 patients with SBBC were selected for the present study. RT was planned for all patients on both sides to whole breast and/or chest wall using the above-mentioned techniques. Six females with breast conservation on at least one side also had a composite plan along with tumour bed (TB) boost using sequential electrons for bitangential and FIF techniques or sequential helical tomotherapy (HT) boost (for TD) or simultaneous integrated boost (SIB) for HT. RESULTS All techniques produced acceptable target coverage. The hotspot was significantly lower with FIF technique and HT but higher with TD. For the organs at risk doses, HT resulted in significant reduction of the higher dose volumes. Similarly, TD resulted in significant reduction of the mean dose to the heart and total lung by reducing the lower dose volumes. All techniques of delivering boost to the TB were comparable in terms of target coverage. HT-SIB markedly reduced mean doses to the total lung and heart by specifically lowering the higher dose volumes. CONCLUSION This study demonstrates the cardiac and pulmonary sparing ability of tomotherapy in the setting of SBBC. ADVANCES IN KNOWLEDGE This is the first study demonstrating feasibility of treatment of SBBC using tomotherapy.

Protocol for a phase III randomised trial of image-guided intensity modulated radiotherapy (IG-IMRT) and conventional radiotherapy for late small bowel toxicity reduction after postoperative adjuvant radiation in Ca cervix

Introduction External beam radiation followed by vaginal brachytherapy (±chemotherapy) leads to reduction in the risk of local recurrence and improves progression-free survival in patients with adverse risk factors following Wertheims hysterectomy albeit at the risk of late bowel toxicity. Intensity Modulated Radiotherapy (IMRT) results in reduction in bowel doses and has potential to reduce late morbidity, however, needs to be confirmed prospectively in a randomised trial. The present randomised trial tests reduction if any in late small bowel toxicity with the use of IMRT in postoperative setting. Methods and analysis Patients more than 18 years of age who need adjuvant (chemo) radiation will be eligible. Patients with residual pelvic or para-aortic nodal disease, history of multiple abdominal surgeries or any other medical bowel condition will be excluded. The trial will randomise patients into standard radiation or IMRT. The primary aim is to compare differences in late grades II–IV bowel toxicity between the two arms. The secondary aims of the study focus on evaluating correlation of dose–volume parameters and late toxicity and quality of life. The trial is planned as a multicentre randomised study. The trial is designed to detect a 13% difference in late grades II–IV bowel toxicity with an α of 0.05 and β of 0.80. A total of 240 patients will be required to demonstrate the aforesaid difference. Ethics and dissemination The trial is approved by institutional ethics review board and will be routinely monitored as per standard guidelines. The study results will be disseminated via peer reviewed scientific journals, conference presentations and submission to regulatory authorities. Registration The trial is registered with clinicaltrials.gov (NCT 01279135).

Predictors of late bowel toxicity using three different methods of contouring in patients undergoing post-operative radiation for cervical cancer

OBJECTIVE This study investigates the correlation between dose-volume histogram derived from three bowel contouring methods and late toxicity in patients undergoing post-operative radiation therapy (PORT) for cervical cancer. METHODS From June 2010 to May 2013, 103 patients undergoing PORT were included. Three different contouring methods were used: (a) individual small bowel (SB) and large bowel (LB) loops, (b) total bowel (TB; including SB and LB) and (c) peritoneal cavity (PC). The volume of SB, LB, TB and PC receiving 15, 30 and 40 Gy was calculated. Acute and late bowel toxicities were scored using Common Terminology Criteria for Adverse events v. 3.0. Receiver operating characteristic curve identified thresholds predicting late toxicity with the highest specificity. All data were dichotomized across these thresholds. Univariate and multivariate analyses were performed using SPSS(®) v. 20 (IBM Corporation, Armonk, NY; formerly SPSS Inc., Chicago, IL). RESULTS On univariate analysis, V30 PC ≥ 900 cm(3) (p = 0.01), V40 PC ≥ 750 cm(3) (p = 0.03) and V40 TB ≥ 280 cm(3) (p = 0.03) and use of concurrent chemotherapy (p = 0.03) predicted grade ≥II acute toxicity. On multivariate analysis, use of concurrent chemotherapy [odds ratio (OR) 3.5, 95% confidence interval (CI) 1.1-11.1, p = 0.03] and V30 PC ≥ 900 cm(3) (OR 2.3, 95% CI 1-5.5, p = 0.05) predicted acute grade ≥II toxicity. On univariate analysis for late toxicity, SB (V30 ≥ 190 cm(3), p = 0.009; V40 ≥ 150 cm(3), p = 0.03), LB (V15 ≥ 250 cm(3), p = 0.04), V40 PC (V40 ≥ 750 cm(3), p = 0.001) and presence of acute grade ≥III toxicity (p = 0.006), treatment technique (three-dimensional conformal radiation or intensity modulated radiotherapy, p = 0.02) predicted more than or equal to grade ll late bowel toxicity. On multivariate analysis, only body mass index ≥25 kg m(-2) (OR 7.3, 95% CI 1.6-31.6, p = 0.008) and presence of acute grade III toxicity predicted toxicity (OR 5.1, 95% CI 1.4-18.1, p = 0.007). CONCLUSION V30 PC ≥ 900 cm(3) and use of concurrent chemotherapy independently predicts acute toxicity. Presence of acute grade ≥III toxicity independently predicts late toxicity. Minimizing dose to PC subvolumes can therefore reduce both acute and late toxicities. ADVANCES IN KNOWLEDGE Study establishes PC thresholds that can minimize both acute and late bowel toxicities.

Vaginal displacement during course of adjuvant radiation for cervical cancer: results from a prospective IG-IMRT study

OBJECTIVE To compare internal target volume (ITV) generated using population-based displacements (ITV_study) with empty and full bladder scan fusion (ITV_EBFB) for organ-at-risk (OAR) doses during adjuvant intensity-modulated radiation therapy (IMRT) for cervical cancer. METHODS From January 2011 to October 2012, patients undergoing IMRT were included. CT simulation was carried out after inserting vault markers. Planning target volume (PTV)_EBFB received 50 Gy per 25 fractions. Pre-treatment megavoltage CT (MVCT) was performed. MVCTs were registered using bony landmarks with Day 1 MVCT. Displacement of the centre of mass of markers was measured along each axis. Directional ITV was calculated using mean ± 2 standard deviations (SDs) (ITV_study). Replanning was performed using PTV study, and OAR doses were compared with PTV_EBFB using Wilcoxon test. RESULTS A total of 348/386 data sets were evaluable for 16 patients. The median vaginal displacement was 1.2 mm (SD, 1.3 mm), 4.0 mm (SD, 3.5 mm) and 2.8 mm (SD, 3.3 mm) in the mediolateral, superoinferior and anteroposterior directions, respectively. The ITV margins were 4.1, 10.3 and 10.6 mm. ITV_study and ITV_EBFB were 115.2 cm(3) (87.7-152.2 cm(3)) and 151 cm(3) (95.7-277.1 cm(3)) (p < 0.0001), respectively. PTV_study and PTV_EBFB were 814 and 881 cm(3) (p < 0.0001), respectively. Median doses to the bladder were lower with the PTV_study (46.2 Gy vs 43.2 Gy; p = 0.0001), and a similar trend was observed in the volume of the small bowel receiving 40 Gy (68.2 vs 60.1 cm(3); p = 0.09). CONCLUSION Population-based PTV margins can lead to reduction in OAR doses. ADVANCES IN KNOWLEDGE Population-based ITV may reduce OAR doses while executing adjuvant IMRT for cervical cancer.

Intensity modulated radiation therapy (IMRT) is not superior to three-dimensional conformal radiation (3DCRT) for adjuvant gastric radiation: A matched pair analysis

AIMS To compare three-dimensional conformal radiation (3DCRT) and Intensity Modulated Radiation Therapy (IG-IMRT) for adjuvant gastric irradiation. SUBJECTS AND METHODS From Jan 2010-Aug 2013, all patients undergoing 3DCRT and IG-IMRT were included. Systemic chemotherapy included 1 cycle before and 2 cycles after chemoradiation. Planning Target Volume (PTV) received 45 Gy/25 fractions/5 weeks with concurrent capcetabine 825 mg/m2 bid. Matched pair analysis was performed to evaluate imbalance in two cohorts if any. Common Toxicity Criteria for Adverse Event (CTCAE) vs 3.0 was used to record gastrointestinal (GI), hematological (HL), and renal toxicity during treatment and follow-up. Patterns of recurrence were documented. Mann-Whitney U test was used for statistical comparison. RESULTS Of the 51 patients, 26 received 3DCRT and 25 IMRT. IMRT led to decrease in dose received by right and left kidney (12.4 Gy and 7.1 Gy and 29 Gy vs 8.2 Gy; P<0.001). Overall, 17.6% and 19.6% patients had grade II GI and HL toxicity and 3.9% and 5.9% had grade III GI and HL toxicity. No difference was observed in acute grade II-V GI or HL toxicity (11.5% vs 24%, P=0.07; 7.6% vs 20% P=0.20) or late GI, HL, or renal toxicity between 3DCRT and IMRT. No difference was observed in patterns of local relapse (11.5% vs 12%, P=0.14) or overall survival (39% and 38% (P=0.97)) between 3DCRT and IMRT. CONCLUSIONS 3DCRT and IMRT are equivalent in terms of toxicity and local control.

Multi-catheter interstitial brachytherapy for partial breast irradiation: an audit of implant quality based on dosimetric evaluation comparing intra-operative versus post-operative placement

Purpose The use of multicatheter interstitial brachytherapy (MIB) for accelerated partial breast irradiation (APBI) in early breast cancer (EBC) patients outside the trial setting has increased. Hence, there is a need to critically evaluate implant quality. Moreover, there is a scarcity of reports using an open cavity technique. We report the dosimetric indices of open and closed cavity MIB techniques. Material and methods The dosimetric parameters of 60 EBC patients treated with MIB (open and closed cavity) who underwent three dimensional, computerized tomography (CT) based planning for APBI from November 2011 to July 2015 were evaluated. Coverage Index (CI), Dose Homogeneity Index (DHI), Conformity Index (COIN), Plan Quality Index (PQI), and Dose Non-uniformity Index (DNR) were assessed. Results Forty-one patients underwent open cavity and 19 patients underwent closed cavity placement of brachytherapy catheters. The median number of planes was 4 and median number of needles was 20. Median dose was 34 Gy with dose per fraction of 3.4 Gy, given twice a day, 6 hours apart. The D90 of the cavity and clinical target volume (CTV) were 105% and 89%, respectively. The median doses to the surgical clips were greater than 100%. The median CI of the cavity and CTV was 0.96 and 0.82, respectively. The DHI and COIN index of the CTV was 0.73 and 0.67. There were no significant differences in the dosimetric parameters based on whether the technique was done open or closed. Conclusions Critical evaluation of the dosimetric parameters of MIB-APBI is important for optimal results. While the open and closed techniques have similar dosimetry, our institutional preference is for an open technique which eases the procedure due to direct visualization of the tumor cavity.

Incidental Dose to Pelvic Nodal Regions in Prostate-Only Radiotherapy.

Objectives: Pelvic lymph nodal regions receive an incidental dose from conformal treatment of the prostate. This study was conducted to investigate the doses received by the different pelvic nodal regions with varying techniques used for prostate radiotherapy. Methods and Materials: Twenty patients of high-risk node-negative prostate cancer treated with intensity-modulated radiotherapy to the prostate alone were studied. Replanning was done for intensity-modulated radiotherapy, 3-dimensional conformal treatment, and 2-dimensional conventional radiotherapy with additional delineation of the pelvic nodal regions, namely, common iliac (upper and lower), presacral, internal iliac, obturator, and external iliac. Dose–volume parameters such as Dmean, D100%, D66%, D33%, V40, and V50 to each of the nodal regions were estimated for all patients. Results: The obturator nodes received the highest dose among all nodal regions. The mean dose received by obturator nodal region was 44, 29, and 22 Gy from 2-dimensional conventional radiotherapy, 3-dimensional conformal treatment, and intensity-modulated radiotherapy, respectively. The mean dose was significantly higher when compared between 2-dimensional conventional radiotherapy and 3-dimensional conformal treatment (P < .001), 2-dimensional conventional radiotherapy and intensity-modulated radiotherapy (P < .001), and 3-dimensional conformal treatment and intensity-modulated radiotherapy (P < .001). The D33% of the obturator region was 64, 39, and 37 Gy from 2-dimensional conventional radiotherapy, 3-dimensional conformal treatment, and intensity-modulated radiotherapy, respectively. The dose received by all other pelvic nodal regions was low and not clinically relevant. Conclusion: The incidental dose received by obturator regions is significant especially with 2-dimensional conventional radiotherapy and 3-dimensional conformal treatment techniques as used in the trials studying elective pelvic nodal irradiation. However, with intensity-modulated radiotherapy, this dose is lower, making elective pelvic irradiation more relevant. Advances in Knowledge: This study highlights that incidental dose received by obturator regions is significant especially with 2-dimensional conventional radiotherapy and 3-dimensional conformal treatment techniques.

Characterization of commercial MOSFET detectors and their feasibility for in-vivo HDR brachytherapy

AIM The present study was to investigate the use of MOSFET as an vivo dosimeter for the application of Ir-192 HDR brachytherapy treatments. MATERIAL AND METHODS MOSFET was characterized for dose linearity in the range of 50-1000 cGy, depth dose dependence from 2 to 7 cm, angular dependence. Signal fading was checked for two weeks. RESULT AND DISCUSSION Dose linearity was found to be within 2% in the dose range (50-1000 cGy). The response varied within 8.07% for detector-source distance of 2-7 cm. The response of MOSFET with the epoxy side facing the source (0 degree) is the highest and the lowest response was observed at 90 and 270 degrees. Signal was stable during the study period. CONCLUSION The detector showed high dose linearity and insignificant fading. But due to angular and depth dependence, care should be taken and corrections must be applied for clinical dosimetry.

Commissioning and validation of commercial deformable image registration software for adaptive contouring

PURPOSE To report the commissioning and validation of deformable image registration(DIR) software for adaptive contouring. METHODS DIR (SmartAdapt®v13.6) was validated using two methods namely contour propagation accuracy and landmark tracking, using physical phantoms and clinical images of various disease sites. Five in-house made phantoms with various known deformations and a set of 10 virtual phantoms were used. Displacement in lateral, anterio-posterior (AP) and superior-inferior (SI) direction were evaluated for various organs and compared with the ground truth. Four clinical sites namely, brain (n = 5), HN (n = 9), cervix (n = 18) and prostate (n = 23) were used. Organs were manually delineated by a radiation oncologist, compared with the deformable image registration (DIR) generated contours. 3D slicer v4.5.0.1 was used to analyze Dice Similarity Co-efficient (DSC), shift in centre of mass (COM) and Hausdorff distances Hf95%/avg. RESULTS Mean (SD) DSC, Hf95% (mm), Hfavg (mm) and COM of all the phantoms 1-5 were 0.84 (0.2) mm, 5.1 (7.4) mm, 1.6 (2.2) mm, and 1.6 (0.2) mm respectively. Phantom-5 had the largest deformation as compared to phantoms 1-4, and hence had suboptimal indices. The virtual phantom resulted in consistent results for all the ROIs investigated. Contours propagated for brain patients were better with a high DSC score (0.91 (0.04)) as compared to other sites (HN: 0.84, prostate: 0.81 and cervix 0.77). A similar trend was seen in other indices too. The accuracy of propagated contours is limited for complex deformations that include large volume and shape change of bladder and rectum respectively. Visual validation of the propagated contours is recommended for clinical implementation. CONCLUSION The DIR algorithm was commissioned and validated for adaptive contouring.