Vellaiyan Subramani

Early Clinical Outcomes and Toxicity of Intensity Modulated Versus Conventional Pelvic Radiation Therapy for Locally Advanced Cervix Carcinoma: A Prospective Randomized Study

PURPOSE To evaluate the toxicity and clinical outcome in patients with locally advanced cervical cancer (LACC) treated with whole pelvic conventional radiation therapy (WP-CRT) versus intensity modulated radiation therapy (WP-IMRT). METHODS AND MATERIALS Between January 2010 and January 2012, 44 patients with International Federation of Gynecology and Obstetrics (FIGO 2009) stage IIB-IIIB squamous cell carcinoma of the cervix were randomized to receive 50.4 Gy in 28 fractions delivered via either WP-CRT or WP-IMRT with concurrent weekly cisplatin 40 mg/m(2). Acute toxicity was graded according to the Common Terminology Criteria for Adverse Events, version 3.0, and late toxicity was graded according to the Radiation Therapy Oncology Group system. The primary and secondary endpoints were acute gastrointestinal toxicity and disease-free survival, respectively. RESULTS Of 44 patients, 22 patients received WP-CRT and 22 received WP-IMRT. In the WP-CRT arm, 13 patients had stage IIB disease and 9 had stage IIIB disease; in the IMRT arm, 12 patients had stage IIB disease and 10 had stage IIIB disease. The median follow-up time in the WP-CRT arm was 21.7 months (range, 10.7-37.4 months), and in the WP-IMRT arm it was 21.6 months (range, 7.7-34.4 months). At 27 months, disease-free survival was 79.4% in the WP-CRT group versus 60% in the WP-IMRT group (P=.651), and overall survival was 76% in the WP-CRT group versus 85.7% in the WP-IMRT group (P=.645). Patients in the WP-IMRT arm experienced significantly fewer grade ≥2 acute gastrointestinal toxicities (31.8% vs 63.6%, P=.034) and grade ≥3 gastrointestinal toxicities (4.5% vs 27.3%, P=.047) than did patients receiving WP-CRT and had less chronic gastrointestinal toxicity (13.6% vs 50%, P=.011). CONCLUSION WP-IMRT is associated with significantly less toxicity compared with WP-CRT and has a comparable clinical outcome. Further studies with larger sample sizes and longer follow-up times are warranted to justify its use in routine clinical practice.

Use of transrectal ultrasound for high dose rate interstitial brachytherapy for patients of carcinoma of uterine cervix

OBJECTIVE Transrectal ultrasound (TRUS) has been widely used for guiding prostate implants, but not much for interstitial brachytherapy (IBT) of cervix cancer. The aim of our study is to report our experience with TRUS guided high dose rate (HDR) IBT in patients with carcinoma of uterine cervix. METHODS During the year 2005-2006, 25 patients of cervical cancer not suitable for intracavitary radiotherapy (ICRT), were enrolled in this prospective study. We used B-K Medical USG machine (Falcon 2101) equipped with a TRUS probe (8658) having a transducer of 7.5 MHz for IBT. Post procedure, a CT scan was done for verification of needle position and treatment planning. Two weekly sessions of HDR IBT of 8-10 Gy each were given after pelvic external beam radiation therapy. RESULTS A total of 40 IBT procedures were performed in 25 patients. Average duration of implant procedure was 50 minutes. There was no uterine perforation in any of 11 patients in whom central tandem was used. CT scan did not show needle perforation of bladder/rectum in any of the patients. During perioperative period, only 1 procedure (2.5%) was associated with hematuria which stopped within 6 hours. Severe late toxicity was observed in 3 (12%) patients. Overall pelvic control rate was 64%. CONCLUSION Our experience suggests that TRUS is a practical and effective imaging device for guiding the IBT procedure of cervical cancer patients. It helps in accurate placements of needles thus avoiding the injury to normal pelvic structures.

High Dose Rate Interstitial Brachytherapy using Two Weekly Sessions of 10 Gy Each for Patients with Locally Advanced Cervical Carcinoma

PURPOSE To evaluate the feasibility of high-dose rate interstitial brachytherapy (HDR-IBT) using two weekly sessions of 10 Gy in combination to pelvic external beam radiation therapy (EBRT) for patients with locally advanced cervical carcinoma. METHODS AND MATERIALS Between the year 2005 and 2007, 42 patients with locally advanced cervical carcinoma (International Federation of Gynecology and Obstetrics Stage IIB-IVA), not suitable for intracavitary radiotherapy after completing EBRT, were enrolled in this prospective study. Two weekly sessions of HDR-IBT with 10 Gy each were delivered 1 week after pelvic EBRT. Various parameters studied for evaluating the feasibility were procedure-related complications, delayed radiation toxicity, and recurrence-free survival. RESULTS International Federation of Gynecology and Obstetrics stage distribution of patients was as follows: Stage IIB (10), Stage IIIB (27), and Stage IVA (5). A total of 84 HDR-IBT procedures were performed in these 42 patients. Each session of brachytherapy treatment (from needle insertion to removal of template) was completed in less than 4 h. Frequency of various procedure-related complications were as follows: hematuria (3.5%), deep vein thrombosis (0%), and visceral puncture (0%). Overall delayed radiation toxicity (Grade III-IV) was 9%. Median followup was 23 months. The 3-y overall survival for all stages was 47% and the 3-y recurrence-free survival for stage IIB, IIIB, and IVA was 67%, 34%, and 20%, respectively. CONCLUSION Our clinical results have shown that weekly HDR-IBT schedule (10 Gy × 2) is associated with low toxicity, decent local control, and survival rates thereby proving its clinical feasibility.

Pulsed-dose-rate intracavitary brachytherapy for cervical carcinoma: the AIIMS experience.

Objective:The aim of present study was to analyze the results of pulsed-dose-rate (PDR) brachytherapy in patients with cervical carcinoma treated at our center. Methods:From September 2003 to September 2005, 48 patients with histopathologically proved cervical carcinoma, stages IB to IVA, were treated with PDR intracavitary radiotherapy (ICRT) and pelvic irradiation at our center. Radiotherapy consisted of whole pelvis external beam radiation therapy (EBRT) with a dose of 40 Gy in 22 fractions over 4.5 weeks followed by 10 Gy in 5 fractions over 1 week with midline shielding. Weekly chemotherapy (Cisplatin, 40 mg/m2) was administered during the course of EBRT to suitable patients. After an interval of 1 to 2 weeks, a single session of standard ICRT application was done to deliver a dose of 27 Gy to point A by PDR (hourly pulse, 70 cGy). Results:Median age was 50 years (range: 30–65). FIGO stage distribution of the patients was as follows: stage IB, 6; stage IIA, 1; stage IIB, 15; stage IIIB, 25; and stage IVA, 1. Follow-up period ranged from 3 to 50 months (median: 15 months). Ten patients had disease recurrence (5 each in stage IIB and stage IIIB). Eight patients had pelvic failure, 1 had bone metastases, and 1 had supraclavicular node metastases. Overall grades III to IV late toxicity rate at 50 months was 6%. For the median follow-up period of 15 months, the actuarial recurrence-free survival in stages I to II was 82% and stages III to IV was 78%. Conclusion:Our results reveal that PDR ICRT in combination with pelvic EBRT provides excellent pelvic disease control, survival, and low radiation related morbidity rate in the patients with cervical carcinoma.

Comparative Evaluation of Two-dimensional Radiography and Three Dimensional Computed Tomography Based Dose-volume Parameters for High-dose-rate Intracavitary Brachytherapy of Cervical Cancer: A Prospective Study

BACKGROUND Dosimetric comparison of two dimensional (2D) radiography and three-dimensional computed tomography (3D-CT) based dose distributions with high-dose-rate (HDR) intracavitry radiotherapy (ICRT) for carcinoma cervix, in terms of target coverage and doses to bladder and rectum. MATERIALS AND METHODS Sixty four sessions of HDR ICRT were performed in 22 patients. External beam radiotherapy to pelvis at a dose of 50 Gray in 27 fractions followed by HDR ICRT, 21 Grays to point A in 3 sessions, one week apart was planned . All patients underwent 2D-orthogonal and 3D-CT simulation for each session. Treatment plans were generated using 2D-orthogonal images and dose prescription was made at point A. 3D plans were generated using 3D-CT images after delineating target volume and organs at risk. Comparative evaluation of 2D and 3D treatment planning was made for each session in terms of target coverage (dose received by 90%, 95% and 100% of the target volume: D90, D95 and D100 respectively) and doses to bladder and rectum: ICRU-38 bladder and rectum point dose in 2D planning and dose to 0.1cc, 1cc, 2cc, 5cc, and 10cc of bladder and rectum in 3D planning. RESULTS Mean doses received by 100% and 90% of the target volume were 4.24 ± 0.63 and 4.9 ± 0.56 Gy respectively. Doses received by 0.1cc, 1cc and 2cc volume of bladder were 2.88 ± 0.72, 2.5 ± 0.65 and 2.2 ± 0.57 times more than the ICRU bladder reference point. Similarly, doses received by 0.1cc, 1cc and 2cc of rectum were 1.80 ± 0.5, 1.48 ± 0.41 and 1.35 ± 0.37 times higher than ICRU rectal reference point. CONCLUSIONS Dosimetric comparative evaluation of 2D and 3D CT based treatment planning for the same brachytherapy session demonstrates underestimation of OAR doses and overestimation of target coverage in 2D treatment planning.

MAGAT gel and EBT2 film‐based dosimetry for evaluating source plugging‐based treatment plan in Gamma Knife stereotactic radiosurgery

This work illustrates a procedure to assess the overall accuracy associated with Gamma Knife treatment planning using plugging. The main role of source plugging or blocking is to create dose falloff in the junction between a target and a critical structure. We report the use of MAGAT gel dosimeter for verification of an experimental treatment plan based on plugging. The polymer gel contained in a head‐sized glass container simulated all major aspects of the treatment process of Gamma Knife radiosurgery. The 3D dose distribution recorded in the gel dosimeter was read using a 1.5T MRI scanner. Scanning protocol was: CPMG pulse sequence with 8 equidistant echoes, TR=7 s, echo step=14 ms, pixel size=0.5 mm x 0.5 mm, and slice thickness of 2 mm. Using a calibration relationship between absorbed dose and spin‐spin relaxation rate (R2), we converted R2 images to dose images. Volumetric dose comparison between treatment planning system (TPS) and gel measurement was accomplished using an in‐house MATLAB‐based program. The isodose overlay of the measured and computed dose distribution on axial planes was in close agreement. Gamma index analysis of 3D data showed more than 94% voxel pass rate for different tolerance criteria of 3%/2 mm, 3%/1 mm and 2%/2 mm. Film dosimetry with GAFCHROMIC EBT 2 film was also performed to compare the results with the calculated TPS dose. Gamma index analysis of film measurement for the same tolerance criteria used for gel measurement evaluation showed more than 95% voxel pass rate. Verification of gamma plan calculated dose on account of shield is not part of acceptance testing of Leksell Gamma Knife (LGK). Through this study we accomplished a volumetric comparison of dose distributions measured with a polymer gel dosimeter and Leksell GammaPlan (LGP) calculations for plans using plugging. We propose gel dosimeter as a quality assurance (QA) tool for verification of plug‐based planning. PACS number: 87.53.Ly, 87.55.‐x, 87.56.N‐

Indigenously developed multipurpose acrylic head phantom for verification of IMRT using film and gel dosimetry

The purpose of this study was to validate the newly designed acrylic phantom for routine dosimetric purpose in radiotherapy. The phantom can be used to evaluate and compare the calculated dose and measured dose using film and gel dosimetric methods. In this study, a doughnut‐shaped planning target volume (8.54 cm3) and inner organ at risk (0.353 cm3) were delineated for an IMRT test plan using the X‐ray CT image of the phantom. The phantom consists of acrylic slabs which are integrated to form a human head with a hole in the middle where several dosimetric inserts can be positioned for measurement. An inverse planning with nine coplanar intensity‐modulated fields was created using Pinnacle TPS. For the film analysis, EBT2 film, flatbed scanner, in‐house developed MATLAB codes and ImageJ software were used. The 3D dose distribution recorded in the MAGAT gel dosimeter was read using a 1.5 T MRI scanner. Scanning parameters were CPMG pulse sequence with 8 equidistant echoes, TR=5600, echo step=22 ms, pixel size=0.5 times 0.5, slice thickness=2 mm. Using a calibration relationship between absorbed dose and spin‐spin relaxation rate (R2), R2 images were converted to dose images. The dose comparison was accomplished using in‐house MATLAB‐based graphical user interface named “IMRT3DCMP”. For gel measurement dose grid from the TPS was extracted and compared with the measured dose grid of the gel. Gamma index analysis of film measurement for the tolerance criteria of 2%/2 mm, 1%/1 mm showed more than 90% voxels pass rate. Gamma index analysis of 3D gel measurement data showed more than 90% voxels pass rate for different tolerance criteria of 2%/2 mm and 1%/1 mm. Overall both 2D and 3D measurement were in close agreement with the Pinnacle TPS calculated dose. The phantom designed is cost‐effective and the results are promising, but further investigation is required to validate the phantom with other 3D conformal techniques for dosimetric purpose. PACS numbers: 87.53.Kn, 87.55.km, 87.56.N‐

Multi-isocentric 4π volumetric-modulated arc therapy approach for head and neck cancer

Abstract Objectives To explore the feasibility of multi‐isocentric 4π volumetric‐modulated arc therapy (MI4π‐VMAT) for the complex targets of head and neck cancers. Methods Twenty‐five previously treated patients of HNC underwent re‐planning to improve the dose distributions with either coplanar VMAT technique (CP‐VMAT) or noncoplanar MI4π‐VMAT plans. The latter, involving 3–6 noncoplanar arcs and 2–3 isocenters were re‐optimized using the same priorities and objectives. Dosimetric comparison on standard metrics from dose‐volume histograms was performed to appraise relative merits of the two techniques. Pretreatment quality assurance was performed with IMRT phantoms to assess deliverability and accuracy of the MI4π‐VMAT plans. The gamma agreement index (GAI) analysis with criteria of 3 mm distance to agreement (DTA) and 3% dose difference (DD) was applied. Results CP‐VMAT and MI4π‐VMAT plans achieved the same degree of coverage for all target volumes related to near‐to‐minimum and near‐to‐maximum doses. MI4π‐VΜΑΤ plans resulted in an improved sparing of organs at risk. The average mean dose reduction to the parotids, larynx, oral cavity, and pharyngeal muscles were 3 Gy, 4 Gy, 5 Gy, and 4.3 Gy, respectively. The average maximum dose reduction to the brain stem, spinal cord, and oral cavity was 6.0 Gy, 3.8 Gy, and 2.4 Gy. Pretreatment QA results showed that plans can be reliably delivered with mean gamma agreement index of 97.0 ± 1.1%. Conclusions MI4π‐VMAT plans allowed to decrease the dose‐volume‐metrics for relevant OAR and results are reliable from a dosimetric standpoint. Early clinical experience has begun and future studies will report treatment outcome.