Automatic segmentation of magnetic resonance images for high-dose-rate cervical cancer brachytherapy using deep learning.

PURPOSE: Magnetic resonance (MR) imaging is the gold standard in image-guided brachytherapy (IGBT) due to its superior soft-tissue contrast for target and organs-at-risk (OARs) delineation. Accurate and fast segmentation of MR images are very important for high-quality IGBT treatment planning. The purpose of this work is to implement and evaluate deep learning (DL) models for the automatic segmentation of targets and OARs in MR image-based high-dose-rate (HDR) brachytherapy for cervical cancer. METHODS: A 2D DL model using residual neural network architecture (ResNet50) was developed to contour the targets (gross tumor volume (GTV), high-risk clinical target volume (HR CTV), and intermediate-risk clinical target volume (IR CTV)) and OARs (bladder, rectum, sigmoid, and small intestine) automatically on axial MR slices of HDR brachytherapy patients. Furthermore, two additional 2D DL models using sagittal and coronal images were also developed. A 2.5D model was generated by combining the outputs from axial, sagittal, and coronal DL models. Similarly, a 2D and 2.5D DL models were also generated for the inception residual neural network (InceptionResNetv2 (InRN)) architecture. The geometric (Dice similarity coefficient (DSCs) and 95th percentile of Hausdorff distance (HD)) and dosimetric accuracy of 2D (axial only) and 2.5D (axial + sagittal + coronal) DL model generated contours were calculated and compared. RESULTS: The mean (range) DSCs of ResNet50 across all contours were 0.674 (0.05-0.96) and 0.715 (0.26-0.96) for the 2D and 2.5D models, respectively. For InRN, these were 0.676 (0.11-0.96) and 0.723 (0.35-0.97) for the 2D and 2.5D models, respectively. The mean HD of ResNet50 across all contours was 15.6 mm (1.8-69 mm) and 12.1 mm (1.7-44 mm) for the 2D and 2.5D models, respectively. The similar results for InRN were 15.4 mm (2-68 mm) and 10.3 mm (2.7-39 mm) for the 2D and 2.5D models, respectively. The dosimetric parameters (D90) of GTV and HR CTV for manually contoured plans matched better with the 2.5D model (p > 0.6) and the results from the 2D model were slightly lower (p < 0.08). On the other hand, the IR CTV doses (D90) for all of the models were slightly lower (2D: -1.3 to -1.5 Gy and 2.5D: -0.5 to -0.6 Gy) and the differences were statistically significant for the 2D model (2D: p < 0.000002 and 2.5D: p > 0.06). In case of OARs, the 2.5D model segmentations resulted in closer dosimetry than 2D models (2D: p = 0.07-0.91 and 2.5D: p = 0.16-1.0). CONCLUSIONS: The 2.5D DL models outperformed their respective 2D models for the automatic contouring of targets and OARs in MR image-based HDR brachytherapy for cervical cancer. The InceptionResNetv2 model performed slightly better than ResNet50.

Late Toxicity After Adjuvant Conventional Radiation Versus Image-Guided Intensity-Modulated Radiotherapy for Cervical Cancer (PARCER): A Randomized Controlled Trial.

PURPOSE: Postoperative Adjuvant Radiation in Cervical Cancer (PARCER), a phase III randomized trial, compared late toxicity after image-guided intensity-modulated radiotherapy (IG-IMRT) with three-dimensional conformal radiation therapy (3D-CRT) in women with cervical cancer undergoing postoperative radiation. METHODS: Patients were randomly assigned to receive either IG-IMRT or 3D-CRT after stratification for the type of hysterectomy and use of concurrent chemotherapy. The primary end point was 3-year grade ≥ 2 late GI toxicity assessed using Common Toxicity Criteria for Adverse Events v 3.0 and estimated using time-to-event, intention-to-treat analysis, with a study level type I error of 0.05 and a nominal α of .047 after accounting for one interim analysis. Secondary end points included acute toxicity, health-related quality of life, and pelvic relapse-free, disease-free, and overall survival. RESULTS: Between 2011 and 2019, 300 patients were randomly assigned (IG-IMRT 151 and 3D-CRT 149). At a median follow-up of 46 (interquartile range, 20-72) months, the 3-year cumulative incidence of grade ≥ 2 late GI toxicity in the IG-IMRT and 3D-CRT arms were 21.1% versus 42.4% (hazard ratio [HR] 0.46; 95% CI, 0.29 to 0.73; P < .001). The cumulative incidence of grade ≥ 2 any late toxicity was 28.1% versus 48.9% (HR 0.50; 95% CI, 0.33 to 0.76; P < .001), respectively. Patients reported reduced diarrhea (P = .04), improved appetite (P = .008), and lesser bowel symptoms (P = .002) with IG-IMRT. However, no difference was observed in the time by treatment interaction. The 3-year pelvic relapse-free survival and disease-free survival in the IG-IMRT versus the 3D-CRT arm were 81.8% versus 84% (HR 1.17; 95% CI, 0.68 to 1.99; P = .55) and 76.9% versus 81.2% (HR 1.03; 95% CI, 0.62 to 1.71; P = .89), respectively. CONCLUSION: IG-IMRT results in reduced toxicity with no difference in disease outcomes.

Implementation of a visual feedback system for motion management during radiation therapy.

PURPOSE: To describe the details of an in-house video goggles feedback system assembled from several commercially available components. The objective of this paper is to share our experience with this system, provide details on the equipment needed, system assembly, patient set up and user settings on some components. MATERIALS AND METHODS: The system consisted of goggles (FPView3DHD, ITV, USA), RJ45(Registered Jack) to Digital Visual Interface (DVI) converter (Tripplite), DVI to HDMI converters, Local Area Network(LAN) cable, HDMI and power extender cables. The video coaching system was implemented both in CT simulator (GE Discovery)) and in treatment delivery machine True Beam v2.1 Varian Medical Systems (VMS, Palo Alto), which was integrated with respiratory motion management (RPM V 1.7.5) system. RESULTS: The video feedback system is in clinical use since Aug 2017, so far, we have treated 13 patients, with approximately 150 fractions. The performance of the device was found to be satisfactory. All the patients were coached for DIBH and the usage of the goggles, which includes wearing the goggles, display details of the monitor, and the threshold levels of the breathing wave cycle. The patients understand the instructions very well and hence regulate the breathing cycle, which improves the treatment accuracy and efficiency. CONCLUSION: Video feedback system for motion management, for patients undergoing radiotherapy was implemented successfully both in CT simulator and in linear accelerator.

MRI- and PET-Guided Interstitial Brachytherapy for Postsurgical Vaginal Recurrences of Cervical Cancer: Results of Phase II Study.

PURPOSE: This phase II study evaluated the utility of magnetic resonance imaging (MRI) and positron emission tomography for planning radiation and brachytherapy in patients with postsurgical recurrence of cervical cancer. METHODS AND MATERIALS: The study (NCT01391065) recruited patients with residual or recurrent disease after hysterectomy. Patients underwent baseline T2 weighted (T2W) MRI, 18F-flouro-deoxyglucose (18F-FDG), 18F-flouro thymidine (18F-FLT) and 18F-flouromisonidazole (18F-F Miso) positron emission tomography (PET) and received external radiation (50 Gy/25 fractions for 5 weeks) and weekly cisplatin (40 mg/m2). MRI was performed at brachytherapy and used for delineation of clinical target volume (CTV). Patients with parametrial disease at baseline received interstitial brachytherapy (16-20 Gy/4-5 fractions) and those with vaginal disease received intracavitary brachytherapy (12-14 Gy/2-4 fractions). Kaplan-Meier analysis was performed to evaluate locoregional relapse, disease free survival, and overall survival. Common Toxicity Criteria for adverse event reporting (CTCAE) v4.1 was used for toxicity scoring and European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questtionaire Core 30 (QLQC-30) and Cx 24 for quality-of-life reporting. RESULTS: Between January 2011 and February 2016, 60 patients were included, of which 50 received study treatment. The mean gross tumor volume on T2 W MR was 20 (IQR 3.6-90) cc. The metabolic tumor volume was 15 (interquartile range [IQR] 2.1-56.1) cc. The median FLT volume was 10 (IQR 0-48) cc. A total of 8 patients had 18-F F Miso uptake. The median CTV at brachytherapy was 38 (12-85) cc. The median CTVD90 and D 98 was 71 (53-74) and 74 (53-74) Gy. At a median follow-up of 60 (5-93) months, the 5-year local control, disease free survival, and overall survival were 84%, 73%, and 74.5%, respectively. Grade III and IV proctitis and cystitis were observed in 4% and 2% of patients. On multivariate analysis baseline tumor volume, on T2 W MR impacted disease free (91% vs 65%, P = .03) and overall survival (96% vs 77%, P = .06). CONCLUSIONS: Image-guided assisted radiation and brachytherapy are associated with good to excellent local control and survival in patients with vaginal recurrences of cervical cancer.

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.

Should molecular subtype be recommended as one of the selection criteria for accelerated partial breast irradiation? Preliminary results from an Asian cohort.

PURPOSE: The purpose of this study was to report clinical outcomes in patients treated with accelerated partial breast irradiation (APBI), stratified as per molecular subtype and American Society for Therapeutic Radiology and Oncology/Groupe Européen de Curiethérapie and European Society for Radiotherapy & Oncology (ASTRO/GEC-ESTRO) patient selection criteria in order to determine whether molecular subtype should be recommended as one of the selection criteria for APBI. MATERIAL AND METHODS: 157 early-stage breast cancers patients, treated with APBI using multi-catheter interstitial brachytherapy with ≥ 6 months follow-up were included. Molecular subtype was assigned based on estrogen/progesterone receptor (ER/PR), Her2neu and tumor grade. Patients were stratified into ASTRO and GEC-ESTRO risk groups, as per updated ASTRO consensus statement (CS) and GEC-ESTRO recommendation, respectively. The Kaplan-Meier method was used to calculate the time to event data of clinical outcomes. RESULTS: With a median follow-up of 35 months, local control (LC) and locoregional control (LRC) were not significantly different among the different molecular subtypes (p = 0.19, p = 0.41, respectively). None of the APBI guidelines predicted risk of local or locoregional recurrence. Re-analyzing the data by replacing ER status with molecular subtype in the ASTRO-CS did not show any significant difference in LC/LRC across the various categories. Her2neu subtype was associated with significantly lower disease-free survival, cause specific survival, and overall survival than the luminal subtypes. CONCLUSIONS: None of the mentioned APBI guidelines predicted local or locoregional recurrence risk in our study population. Additional follow-up will be needed to recommend inclusion of molecular subtype (or at least HER2 receptor status) in the patient selection criteria for APBI.

First clinical report of helical tomotherapy with simultaneous integrated boost for synchronous bilateral breast cancer.

OBJECTIVE: Radiotherapy (RT) for synchronous bilateral breast cancer (SBBC) is technically very challenging. This study reports the clinical feasibility, dosimetry and safety of helical tomotherapy (HT) with simultaneous integrated boost (SIB) in patients treated with adjuvant radiotherapy for SBBC. METHODS: 21 women with SBBC treated with HT from January 2013 to June 2016 were retrospectively evaluated. Radiation lung toxicity was assessed using pulmonary function test (PFT) and high-resolution computerized tomography scan (HRCT) scan at baseline and 1 yearpost-RT in 18 patients. Survival was calculated using Kaplan-Meier curves. Significance of the difference between pre- and post-RT PFT values was assessed using paired t-test. RESULTS: The dose prescription was 50Gy to the breast, chest wall or regional nodes and 61Gy to the tumour bed as SIB, delivered in 25 fractions. Dosimetric outcome was excellent both for target volumes and normal tissues. Acute skin and oesophageal toxicities were minimal. Symptomatic radiation-induced pnuemonitis was not observed. Subclinical radiological Grade I-II changes were apparent in 14 patients. Only one patient developed Grade III radiological change whereas no change was documented for three patients. PFTs did not show any significant change in any of the measured parameters. At a median follow-up of 25 months, 3-year disease-free survival, overall survival and loco-regional control were 65.6%, 83.3% and 85.7% respectively. CONCLUSION: Women with SBBC can be safely treated with HT and this is not associated with adverse short- to intermediate term radiation toxicity. Advances in knowledge: This is the first report that establishes the safety of HT for adjuvant RT using SIB technique in SBBC.

Dose-volume correlation of cumulative vaginal doses and late toxicity after adjuvant external radiation and brachytherapy for cervical cancer.

PURPOSE: To investigate dose-response relationship between vaginal doses and long-term morbidity. METHODS AND MATERIALS: Patients receiving adjuvant pelvic (chemo) radiation and brachytherapy for cervical cancer from January 2011 to December 2014 were included. Baseline vaginal length was determined clinically and from imaging at BT planning. Dose points were defined along mucosa and at 5 mm depth at 12, 3, 6, and 9 'o' clock positions at every 2 cm from apex to introitus. Cumulative equivalent doses in 2 Gy were calculated. Vaginal stenosis was reported in reference to baseline length according to CTCAE version 3.0. Receiver operator characteristics curve was used to identify dose thresholds for univariate and multivariate analysis. RESULTS: Overall, 78 women with median age of 49 (32-71) years were included. The median dose at vaginal apex mucosa and 5 mm depth was 118 Gy3 (78-198) and 81 Gy3 (70-149) respectively. At median follow-up of 36 (18-60) months, vaginal stenosis ≥25%, and grade ≥ II telangiectasia was observed in 33.3% and 45.7%, respectively. On receiver operator characteristics analysis, apical mucosal dose >142 Gy3 and recto-vaginal point dose >86 Gy3 predicted for stenosis on univariate (p = 0.02, p = 0.06) and multivariate analysis (p = 0.04). The probability of stenosis increased from 32% at 70 Gy3, 38% at 80 Gy3, and 45% at 90 Gy3 rectovaginal point dose. No correlation was observed between vaginal doses and telangiectasia and vaginal stenosis and sexual quality of life. CONCLUSION: Vaginal apex mucosal dose >142 Gy3 independently predicts for vaginal stenosis.

Interobserver Variability in the Delineation of Gross Tumour Volume and Specified Organs-at-risk During IMRT for Head and Neck Cancers and the Impact of FDG-PET/CT on Such Variability at the Primary Site.

PURPOSE: To assess interobserver variability (IOV) in the delineation of structures during intensity-modulated radiation therapy for head and neck squamous cell carcinoma and the impact of fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) on such variability at the primary site. METHODS: Three experienced head-neck radiation oncologists, blinded to each other, delineated the primary site gross tumour volume (GTV) and specified organs-at-risk (OARs) viz parotid gland, spinal cord, and cochlea in 10 patients with pharyngolaryngeal cancers suited for definitive intensity-modulated radiation therapy. IOV was assessed by concordance index (CI), Dice similarity coefficient (DSC), and Fleiss' kappa. Subsequently, the observers refined their corresponding GTVs incorporating information from FDG-PET/CT. The impact of FDG-PET/CT on variability of GTV was assessed by comparing the overlap indices with and without FDG-PET/CT using paired 't' test. RESULTS: There was moderate IOV in the delineation of GTV as evidenced by mean CI, DSC, and Fleiss' kappa of 0.41, 0.57, and 0.56, respectively. The use of FDG-PET/CT improved consistency of target volume delineation with resultant improvement in the overlap indices (mean CI, DSC, and Fleiss' kappa of 0.54, 0.69, and 0.69, respectively) that was statistically significant (P < .001). There was good agreement between the three observers for delineation of spinal cord and parotid glands. Concordance was worst for the cochlea. CONCLUSION: This study demonstrates the presence of moderate IOV between three experienced head and neck radiation oncologists in an academic institutional setting for the delineation of GTV. The use of FDG-PET/CT for target volume delineation results in significant reduction of such variability.

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.

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.

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.

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.

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.

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%.

Evaluation of quality indices during multifractionated pelvic interstitial brachytherapy for cervical cancer.

PURPOSE: To evaluate the impact of needle displacements on quality indices during multifractionated pelvic interstitial brachytherapy (IBT). METHODS AND MATERIALS: Patients undergoing boost IBT were included. Postprocedure planning and verification CT scans were obtained. Three-dimensional needle displacements were measured. Clinical target volume and organ at risk were delineated. Coverage index (CI), dose homogeneity index (DHI), dose nonuniformity ratio (DNR), V170, V200, V250, and dose received by 2cc of organs at risk were obtained at baseline. The displacements were simulated by shifting dwell positions, and dose point optimized and graphically optimized plans were generated. Wilcoxon test determined statistical significance of differences in quality indices. RESULTS: Fifteen patients were included and received five fractions of IBT over 3 days. Maximum displacements were observed in caudal direction (average, 19.1mm). At baseline, CI of 0.94 (range, 0.91-0.99), DHI of 0.90 (range, 0.80-0.94), and DNR of 0.10 (range, 0.05-0.10) were attained. The CI, DHI, and DNR in Day 3 dose point optimized plans were 0.76 (range, 0.4-0.99), 0.76 (range, 0.40-0.94), and 0.23 (range, 0.06-0.64), respectively. The difference in CI, DHI, and DNR between baseline and Day 3 dose point optimized plans was statistically significant (p = 0.002, 0.007, and 0.001, respectively). Day 3 graphically optimized plans were superior to Day 3 dose point optimized plans (CI, 0.82 vs. 0.76; p = 0.01). Graphically optimized could however improve CI without compromise in DHI, DNR, V170, V200, and V250 only in patients wherein caudal displacements ≤15mm. CONCLUSIONS: Caudal needle displacements during multifractionated IBT cause significant deterioration of quality indices. Replanning with graphically optimized and/or needle repositioning maybe required for maintaining the quality of IBT.

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 Wertheim's 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 ß 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).

Can irradiation of potential cancer stem-cell niche in the subventricular zone influence survival in patients with newly diagnosed glioblastoma?

Glioblastoma progenitor or stem cells residing in the stem-cell niche in the subventricular zones (SVZ) can initiate or promote tumorigenesis. They can also migrate throughout the brain, resulting in disease progression. Irradiation of potential cancer stem-cell niche in the SVZ may influence survival. To analyze radiotherapy dose-volume parameters to the SVZ that correlate with survival in adequately treated patients with newly diagnosed glioblastoma, 40 adults with histopathologically proven supratentorial glioblastoma with available baseline imaging treated with postoperative conventionally fractionated focal conformal radiotherapy plus chemotherapy, available radiotherapy planning dataset, and documented event of progression or death or minimum 6-month follow-up were included in this retrospective study. Dose-volume parameters to the SVZ were extracted from treatment planning system and analyzed in relation to survival outcomes. Mean ipsilateral and contralateral SVZ volumes were 5.6 and 6.4 cc, respectively. With median follow-up of 15 months (interquartile range 12-18 months), median [95 % confidence interval (CI)] progression-free survival (PFS) and overall survival (OAS) was 11 months (95 % CI 8.9-13.0 months) and 17 months (95 % CI 11.6-22.4 months), respectively. Older age (>50 years), poor recursive partitioning analysis (RPA) class, and higher than median of mean contralateral SVZ dose were associated with significantly worse PFS and OAS. Multivariate analysis identified RPA class, Karnofsky performance status, and mean ipsilateral SVZ dose as independent predictors of survival. Increasing mean dose to the ipsilateral SVZ was associated with significantly improved OAS. Irradiation of potential cancer stem-cell niche influences survival outcomes in patients with newly diagnosed glioblastoma.

Quality assurance of multifractionated pelvic interstitial brachytherapy for postoperative recurrences of cervical cancers: a prospective study.

PURPOSE: To evaluate three-dimensional needle displacements during multifractionated interstitial brachytherapy (BT) for cervical cancers. METHODS AND MATERIALS: Patients scheduled to undergo pelvic interstitial BT for postoperative and or postradiation vault recurrences were included from November 2009 to December 2010. All procedures were performed under spinal anesthesia. Postprocedure BT planning CT scans were obtained with patients in supine position with arms on the chest (interslice thickness of 3 mm). Thereafter, verification CT was repeated at every alternate fraction. Needle displacements were measured in reference to a relocatable bony point. The mean cranial, caudal, anteroposterior, and mediolateral displacements were recorded. Statistical significance of mean interfraction displacements was evaluated with Wilcoxon Test. RESULTS: Twenty patients were included. Seventeen received boost BT (20 Gy/5 fractions/3 days) after external radiation, three received radical BT alone (36 Gy/9 fractions/5-8 days). An average of three scans (range, 2-3) were available per patient, and 357 needle displacements were analyzed. For the entire study cohort, the average of mean needle displacement was 2.5 mm (range, 0-7.4), 17.4 mm (range, 0-27.9), 1.7 mm (range, 0-6.7), 2.1 mm (range, 0-9.5), 1.7 mm (range, 0-9.3), and 0.6 mm (range, 0-7.8) in cranial, caudal, anterior, posterior, right, and left directions, respectively. The mean displacement in the caudal direction was higher between Days 1 and 2 than that between Days 2 and 3 (13.4 mm vs. 3.8 mm; p = 0.01). The average caudal displacements were no different between reirradiation and boost cohort (15.2 vs. 17.8 mm). CONCLUSIONS: Clinically significant caudal displacements occur during multifractionated pelvic brachytherapy. Optimal margins need to be incorporated while preplanning brachytherapy to account for interfraction displacements.