Reena Phurailatpam

Three-dimensional conformal radiotherapy (3D-CRT) versus intensity modulated radiation therapy (IMRT) in squamous cell carcinoma of the head and neck: A randomized controlled trial

PURPOSE To compare three-dimensional conformal radiotherapy (3D-CRT) with intensity modulated radiation therapy (IMRT) in curative-intent irradiation of head-neck squamous cell carcinoma (HNSCC). METHODS Previously untreated patients with biopsy-proven squamous carcinoma of oropharynx, larynx, or hypopharynx (T1-3, N0-2b) were randomly assigned using computer-generated permuted-block design to either 3D-CRT or IMRT, with incidence of physician-rated Radiation Therapy Oncology Group (RTOG) grade 2 or worse acute salivary gland toxicity as primary end-point. RESULTS Between 2005 and 2008, 60 patients randomly allocated to either 3D-CRT (n=28 patients) or IMRT (n=32) were included and analyzed on an intention-to-treat basis. The proportion [95% confidence intervals (CI)] of patients with RTOG grade 2 or worse acute salivary gland toxicity was significantly lesser in the IMRT arm [19 of 32 patients (59%, 95%CI: 42-75%)] as compared to 3D-CRT [25 of 28 patients (89%, 95%CI: 72-97%; p=0.009)]. Late xerostomia and subcutaneous fibrosis were also significantly lesser with IMRT. There was significant recovery of salivary function over time in patients treated with IMRT (p-value for trend=0.0036). At 3-years, there were no significant differences in loco-regional control or survival between the two arms. CONCLUSION IMRT significantly reduces the incidence and severity of xerostomia compared to 3D-CRT in curative-intent irradiation of HNSCC.

High-precision radiotherapy for craniospinal irradiation: evaluation of three-dimensional conformal radiotherapy, intensity-modulated radiation therapy and helical TomoTherapy

This study aimed to establish the feasibility of intensity-modulated radiation therapy (IMRT) in craniospinal irradiation (CSI) using conventional linear accelerator (IMRT_LA) and compare it dosimetrically with helical TomoTherapy (IMRT_Tomo) and three-dimensional conformal radiotherapy (3DCRT). CT datasets of four previously treated patients with medulloblastoma were used to generate 3DCRT, IMRT_LA and IMRT_Tomo plans. A CSI dose of 35 Gy was prescribed to the planning target volume (PTV). IMRT_LA plans for tall patients were generated using an intensity feathering technique. All plans were compared dosimetrically using standardised parameters. The mean volume of each PTV receiving at least 95% of the prescribed dose (V(95%)) was >98% for all plans. All plans resulted in a comparable dose homogeneity index (DHI) for PTV_brain. For PTV_spine, IMRT_Tomo achieved the highest mean DHI of 0.96, compared with 0.91 for IMRT_LA and 0.84 for 3DCRT. The best dose conformity index was achieved by IMRT_Tomo for PTV_brain (0.96) and IMRT_LA for PTV_spine (0.83). The IMRT_Tomo plan was superior in terms of reduction of the maximum, mean and integral doses to almost all organs at risk (OARs). It also reduced the volume of each OAR irradiated to various dose levels, except for the lowest dose volume. The beam-on time was significantly longer in IMRT_Tomo. In conclusion, IMRT_Tomo for CSI is technically easier and potentially dosimetrically favourable compared with IMRT_LA and 3DCRT. IMRT for CSI can also be realised on a conventional linear accelerator even for spinal lengths exceeding maximum allowable field sizes. The longer beam-on time in IMRT_Tomo raises concerns about intrafraction motion and whole-body integral doses.

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%.

Encouraging Early Clinical Outcomes With Helical Tomotherapy–Based Image-Guided Intensity-Modulated Radiation Therapy for Residual, Recurrent, and/or Progressive Benign/Low-Grade Intracranial Tumors: A Comprehensive Evaluation

PURPOSE To report early clinical outcomes of helical tomotherapy (HT)-based image-guided intensity-modulated radiation therapy (IMRT) in brain tumors of varying shape, size, and location. MATERIALS AND METHODS Patients with residual, recurrent, and/or progressive low-grade intracranial and skull-base tumors were treated on a prospective protocol of HT-based IMRT and followed clinicoradiologically. Standardized metrics were used for plan evaluation and outcome analysis. RESULTS Twenty-seven patients with 30 lesions were treated to a median radiotherapy dose of 54 Gy in 30 fractions. All HT plans resulted in excellent target volume coverage with steep dose-gradients. The mean (standard deviation) dose homogeneity index and conformity index was 0.07 (0.05) and 0.71 (0.08) respectively. At first response assessment, 20 of 30 lesions were stable, whereas 9 showed partial regression. One patient with a recurrent clival chordoma though neurologically stable showed imaging-defined progression, whereas another patient with stable disease on serial imaging had sustained neurologic worsening. With a median follow-up of 19 months (interquartile range, 11-26 months), the 2-year clinicoradiological progression-free survival and overall survival was 93.3% and 100% respectively. CONCLUSIONS Careful selection of radiotherapy technique is warranted for benign/low-grade brain tumors to achieve durable local control with minimum long-term morbidity. Large or complex-shaped tumors benefit most from IMRT. Our early clinical experience of HT-based IMRT for brain tumors has been encouraging.

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.

Assessment of Three-dimensional Set-up Errors using Megavoltage Computed Tomography (MVCT) during Image-guided Intensity-modulated Radiation Therapy (IMRT) for Craniospinal Irradiation (CSI) on Helical Tomotherapy (HT)

The purpose of this study was to assess three-dimensional (3D) set-up errors using megavoltage computed tomography (MVCT) during image-guided intensity-modulated radiation therapy (IMRT) for supine craniospinal irradiation (CSI) on helical tomotherapy (HT). Patients were immobilized in a customized 4-clamp thermoplastic head mask with or without whole-body vacuum cradle. Set-up was based primarily on a set of cranial fiducial markers. MVCT scans were acquired and co-registered with planning scan separately at three different levels (brain, upper, and lower spine) at every fraction. Only translational displacements were analysed, wherein positive sign denotes deviation in anterior, left, and superior direction; while negative sign denotes deviation in posterior, right, and inferior direction. Mean displacements, systematic, and random errors of the study population were calculated at all three levels separately. Local residual uncertainty of the upper and lower spine was also derived assuming perfect co-registration of the skull. Set-up margins for clinical target volume (CTV) to planning target volume (PTV) were derived at these three levels separately using published margin recipes. Data from 1868 co-registrations in 674 fractions on 33 patients was included. The mean displacements in the lateral, longitudinal, and vertical directions were −1.21, −1.36, and 1.38 mm; −1.25, −0.34, and 0.65 mm; and −1.47, −2.78, and 0.22 mm for the brain; upper spine; and lumbar spine respectively. The corresponding 3D vector of displacement was 2.28; 1.45; and 3.15 mm respectively. There was a distinct systematic trend towards increasing inaccuracy from the brain towards the lower spine. Using Stroom’s formula, the minimum recommended CTV to PTV margins in absence of daily image-guidance were 6.5; 7.0; and 9.5 mm for the brain; upper spine; and lower spine respectively. This increased to 7.5; 8.5; and 11.5 mm using van Herk’s formula. Subset and sensitivity analyses could not identify any factor predictive of increased inaccuracy. Residual uncertainty of the spinal column was lesser after daily co-registration referenced to the skull, suggesting that smaller set-up margins maybe appropriate while using daily image-guidance with an online correction protocol. Daily MVCT imaging during supine CSI on HT provides volumetric verification of the set-up process. There is substantial site-dependent variability in translational displacements that increases systematically from brain towards the lower spine with implications for differential set-up -margins for the brain, upper, and lower spine.

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.