Low-dose radiation therapy for COVID-19 pneumonia: a pilot study.

OBJECTIVES: The World Health Organization (WHO) has declared coronavirus disease 2019 (COVID-19) as pandemic in March 2020. Currently there is no specific effective treatment for COVID-19. The major cause of death in COVID-19 is severe pneumonia leading to respiratory failure. Radiation in low doses (<100 cGy) has been known for its anti-inflammatory effect and therefore, low dose radiation therapy (LDRT) to lungs can potentially mitigate the severity of pneumonia and reduce mortality. We conducted a pilot trial to study the feasibility and clinical efficacy of LDRT to lungs in the management of patients with COVID-19. METHODS: From June to Aug 2020, we enrolled 10 patients with COVID-19 having moderate to severe risk disease [National Early Warning Score (NEWS) of ≥5]. Patients were treated as per the standard COVID-19 management guidelines along with LDRT to both lungs with a dose of 70cGy in single fraction. Response assessment was done based on the clinical parameters using the NEWS. RESULTS: All patients completed the prescribed treatment. Nine patients had complete clinical recovery mostly within a period ranging from 3 to 7 days. One patient, who was a known hypertensive, showed clinical deterioration and died 24 days after LDRT. No patients showed the signs of acute radiation toxicity. CONCLUSION: The results of our pilot study suggest that LDRT is feasible in COVID-19 patients having moderate to severe disease. Its clinical efficacy may be tested by conducting randomized controlled trials. ADVANCES IN KNOWLEDGE: LDRT has shown promising results in COVID-19 pneumonia and should be researched further through randomized controlled trials.

Auto-segmentation of head and neck organs at risk in radiotherapy and its dependence on anatomic similarity

PURPOSE: The aim is to study the dependence of deformable based auto-segmentation of head and neck organs-at-risks (OAR) on anatomy matching for a single atlas based system and generate an acceptable set of contours. METHODS: A sample of ten patients in neutral neck position and three atlas sets consisting of ten patients each in different head and neck positions were utilized to generate three scenarios representing poor, average and perfect anatomy matching respectively and auto-segmentation was carried out for each scenario. Brainstem, larynx, mandible, cervical oesophagus, oral cavity, pharyngeal muscles, parotids, spinal cord, and trachea were the structures selected for the study. Automatic and oncologist reference contours were compared using the dice similarity index (DSI), Hausdroff distance and variation in the centre of mass (COM). RESULTS: The mean DSI scores for brainstem was good irrespective of the anatomy matching scenarios. The scores for mandible, oral cavity, larynx, parotids, spinal cord, and trachea were unacceptable with poor matching but improved with enhanced bony matching whereas cervical oesophagus and pharyngeal muscles had less than acceptable scores for even perfect matching scenario. HD value and variation in COM decreased with better matching for all the structures. CONCLUSION: Improved anatomy matching resulted in better segmentation. At least a similar setup can help generate an acceptable set of automatic contours in systems employing single atlas method. Automatic contours from average matching scenario were acceptable for most structures. Importance should be given to head and neck position during atlas generation for a single atlas based system.

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

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.

Dosimetric comparison of head and neck cancer patients planned with multivendor volumetric modulated arc therapy technology.

AIM: Purpose of this study is to dosimetrically compare head and neck (H and N) cancer patients planned with multivendor volumetric modulated arc therapy (VMAT) technology. VMAT treatment planning can be done using biological (treatment planning system [TPSB]: Monaco) or physical (TPSP: Eclipse)-based cost function optimization techniques. Planning and dosimetric comparisons were done in both techniques for H and N cases. MATERIALS AND METHODS: Twenty H and N patients were retrospectively selected for this study. VMAT plans were generated using TPSP (V11.0) and TPSB (V3.0) TPS. A total dose of 66 Gy (planning target volume 1 [PTV1]) and 60 Gy (PTV2) were prescribed to primary and nodal target volumes. Clinical planning objectives were achieved by both the optimization techniques. Dosimetric parameters were calculated for PTVs, and quantitative analyses were performed for critical organs. Monitor units were compared between two TPSs, and gamma analysis was performed between I'matriXX measured and TPS calculated. RESULTS: Clinically, acceptable VMAT plans showed comparable dose distributions between TPSB and TPSP optimization techniques. Comparison of mean dose, homogeneity index, and conformity index for PTV1 showed no statistical difference (P - 0.922, 0.096, and 0.097); however, in PTV2 statistically significant difference was observed (P - 0.024, 0.008, and 0.002) between TPSB and TPSP. TPSB optimization showed statistically significant superiority for spinal cord and brainstem (D1% P - 0.0078, 0.00002) whereas improved parotid sparing was observed in TPSP optimization (mean dose P - 0.00205). Gamma analysis illustrated that both systems could produce clinically deliverable plans. CONCLUSION: VMAT plans by TPSP and TPSB offered clinically acceptable dose distributions. TPSB-based optimization showed enhanced sparing of serial organs whereas TPSP-based optimization showed superior sparing of parallel organs.

Is 5 mm MMLC suitable for VMAT-based lung SBRT? A dosimetric comparison with 2.5 mm HDMLC using RTOG-0813 treatment planning criteria for both conventional and high-dose flattening filter-free photon beams.

The aim of this study is to assess the suitability of 5 mm millennium multileaf collimator (MMLC) for volumetric-modulated arc therapy (VMAT)-based lung stereotactic body radiotherapy (SBRT). Thirty lung SBRT patient treatment plans along with their planning target volumes (ranging from 2.01 cc to 150.11 cc) were transferred to an inhomogeneous lung phantom and retrospectively planned using VMAT technique, along with the high definition multileaf collimator (HDMLC) and MMLC systems. The plans were evaluated using Radiation Therapy Oncology Group (RTOG-0813) treatment planning criteria for target coverage, normal tissue sparing, and treatment efficiency for both the MMLC and HDMLC systems using flat and flattening filter-free (FFF) photon beams. Irrespective of the target volumes, both the MLC systems were able to satisfy the RTOG-0813 treatment planning criteria without having any major deviation. Dose conformity was marginally better with HDMLC. The average conformity index (CI) value was found to be 1.069 ± 0.034 and 1.075 ± 0.0380 for HDMLC and MMLC plans, respectively. For the 6 MV FFF beams, the plan was slightly more conformal, with the average CI values of 1.063 ± 0.029 and 1.073 ± 0.033 for the HDMLC and MMLC plans, respectively. The high dose spillage was the maximum for 2 cc volume set (3% for HDMLC and 3.1% for MMLC). In the case of low dose spillage, both the MLCs were within the protocol of no deviation, except for the 2 cc volume set. The results from this study revealed that VMAT-based lung SBRT using 5 mm MMLC satisfies the RTOG-0813 treatment planning criteria for the studied target size and shapes.

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.

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.

Critical appraisal of the accuracy of Acuros-XB and Anisotropic Analytical Algorithm compared to measurement and calculations with the compass system in the delivery of RapidArc clinical plans.

BACKGROUND: The accuracy of the two dose calculation engines available for RapidArc planning (both released for clinical use) is investigated in comparison to the COMPASS data. METHODS: Two dose calculation algorithms (Acuros-XB and Anisotropic Analytic Algorithm (AAA)) were used to calculate RA plans and compared to calculations with the Collapsed Cone Convolution algorithm (CC) from the COMPASS system (IBA Dosimetry). CC calculations, performed on patient data, are based on experimental fluence measurements with a 2D array of ion chambers mounted on the linac head. The study was conducted on clinical cases treated with RA. Five cases for each of the following groups were included: Brain, Head and Neck, Thorax, Pelvis and stereotactic body radiation therapy for hypo-fractionated treatments with small fields. COMPASS measurements were performed with the iMatrixx-2D array. RapidArc plans were optimized for delivery using 6MV photons from a Clinac-iX (Varian, Palo Alto, USA). RESULTS: For almost all parameters, the better agreement was between Acuros-XB and COMPASS independently from the anatomical site and fractionation. The same result was obtained from the mean dose difference per organ with Acuros-CC average differences below 0.5% while for AAA-CC data, average deviations exceeded 0.5% and in the case of the pelvis 1%. Relevance of observed differences determined with the 3D gamma analysis resulted in a pass rate exceeding 99.5% for Acuros-CC and exceeding 97.5% for AAA-CC. CONCLUSIONS: This study demonstrated that i) a good agreement exists between COMPASS-CC calculations based on measured fluences with respect to dose distributions obtained with both Acuros-XB and AAA algorithms; ii) 3D dose distributions reconstructed from actual delivery coincide very precisely with the planned data; iii) a slight preference in favor of Acuros-XB was observed suggesting the preference for this algorithm in clinical applications.

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 = 0.5mm × 0.5mm, 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.

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.

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.

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/m) 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.

Characterization of responses and comparison of calibration factor for commercial MOSFET detectors.

A commercial metal oxide silicon field effect transistor (MOSFET) dosimeter of model TN502-RD has been characterized for its linearity, reproducibility, field size dependency, dose rate dependency, and angular dependency for Cobalt-60 (60Co), 6-MV, and 15-MV beam energies. The performance of the MOSFET clearly shows that it is highly reproducible, independent of field size and dose rate. Furthermore, MOSFET has a very high degree of linearity, with r-value>0.9 for all 3 energies. The calibration factor for 2 similar MOSFET detectors of model TN502-RD were also estimated and compared for all 3 energies. The calibration factor between the 2 similar MOSFET detectors shows a variation of about 1.8% for 60Co and 15 MV, and for 6 MV it shows variation of about 2.5%, indicating that calibration should be done whenever a new MOSFET is used. However, the detector shows considerable angular dependency of about 8.8% variation. This may be due to the variation in radiation sensitivity between flat and bubble sides of the MOSFET, and indicates that positional care must be taken while using MOSFET for stereotactic radiosurgery and stereotactic radiotherapy dosimetric applications.