Low-dose radiotherapy for COVID 19: A radioimmunological perspective.

The world is fighting the onslaught of COVID 19 for the last 10 months, ever since the first case was reported in December 2019 in Wuhan, China. Now, it has spread to over 200 countries. COVID 19-associated respiratory syndrome is causing a lot of mortality and morbidity. There are reports suggesting that the complications and ARDS associated with COVID 19 is an immune response reaction. The cytokine storm associated with severe cases of COVID 19 acts as a cause of death in many sick patients. It has been shown that COVID 19 is associated with a peculiar immune profile: Decrease in CD3, CD4, CD8, natural killer cell and B-cells; Rise in interleukin (IL)-4, IL-6 and tumor necrosis factor (TNF) alpha; Decrease in IL-10; Decrease in interferon-gamma. Low-dose radiotherapy (LDRT) immunosuppressive features resulting from M2 macrophage phenotype activation, increase in IL-10, transforming growth factor beta, a decrease in IL-6, TNF alpha and an increase in CD3, CD4, and CD8 T cell counts may negate the harmful effects of cytokine release syndrome. Literature review shows that radiation was previously used to treat viral pneumonia with a good success rate. This practice was discontinued in view of the availability of effective antibiotics and antivirals. As there are no scientifically proven treatment for severe COVID 19-associated respiratory distress today, it is prudent that we understand the benefits of LDRT at this critical juncture and take rational decisions to treat the same. This article provides an radioimmunological rationale for the treatment of immune crisis mediated complications in severe cases of COVID 19.

Performance of a deformable image registration algorithm for CT and cone beam CT using physical multi-density geometric and digital anatomic phantoms.

PURPOSE: To study the accuracy of deformable registration algorithm for CT and cone beam CT (CBCT) using a combination of physical and digital phantoms. MATERIALS AND METHODS: The physical phantoms consisted of objects over a range of electron densities, shape and sizes. The system was tested for simple and complex scenarios including performance in the presence of metallic artefacts. Clinically present deformations were simulated using a set of five geometric and anatomic virtual phantoms. RESULTS: The system could not account for large changes in size, shape and Hounsfield units. Deformations of low intensity structures and small objects were highly inaccurate, and errors were prominent for volume reduction scenario than volume growth. The presence of artefacts did alter the performance of the algorithm. Objects of low density and that close to artefacts were affected the most. Overall, deformations to CBCT were poor. In virtual phantoms, the system could not handle gas pockets and deformation errors in inverse direction were higher than that in forward direction. CONCLUSION: The algorithm was tested for several non-clinical and clinical scenarios. The performance was acceptable for realistic and clinically present deformations. However, it is necessary to tread cautiously for structures with small volumes and large reductions in volume.

Low Dose Radiation Therapy for COVID-19 Pneumonia: A Pilot Study

BackgroundThe World Health Organization (WHO) has declared coronavirus disease 2019 (COVID-19) as pandemic in March 2020. Currently there is no vaccine or 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. MethodsFrom 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. ResultsAll patients completed the prescribed treatment. Nine patients had complete clinical recovery mostly within a period ranging from 3-7 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. ConclusionResults of our study (90% response rate) suggest the feasibility and clinical effectiveness of LDRT in COVID-19 patients having moderate to severe risk disease. This mandates a randomized controlled trial to establish the clinical efficacy of LDRT in COVID-19 pneumonia.

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.

Commissioning of portal dosimetry using a novel method for flattening filter-free photon beam in a nontrue beam linear accelerator.

AIM: The aim of this study is to commission and validate the portal dosimetry (PD) system using an indirect method for flattening filter free (FFF) photon beam of the upgraded c-series linear accelerator. BACKGROUND: Varian Medical System clinacs with amorphous-silicon portal imager panel (aSi-1000) do not have PD for FFF beams. Recently, our c-series linear accelerator was upgraded to deliver 6MV FFF (6MVFFF) photon beam with the highest dose rate of 1400 monitor unit (MU)/min. The study, therefore, focuses on the commissioning and validation of PD for the 6MVFFF beam. MATERIALS AND METHODS: An indirect method was implemented to predict the portal dose for FFF beam in Eclipse as the treatment planning system does not have direct prediction algorithm for FFF beam (version. 11). Dosimetrical characteristics of aSi-electronic portal imaging device (EPID) were evaluated for 6MVFFF beam and validation of PD for 6MVFFF beam was performed for open fields along with pretreatment quality assurance of intensity-modulated radiation therapy (IMRT), volumetric-modulated arc therapy (VMAT), and stereotactic radiosurgery (SRS) techniques for 30 patients planned with 6MVFFF beam. RESULTS: ASi-EPID saturates between 100 and 130 cm source to detector distance (SDD) for 6MVFFF beam and resolved at more than 140 cm SDD. The squared correlation coefficient (R2) for MU linearity was found to be 1 (R2 = 1), and instantaneous dose response linearity at different SDD's was found to be 0.999 (R2 = 0.999) for the 6MVFFF beam. Maximum gamma area index (GAI) for 3% dose difference and 3 mm distance-to-agreement criteria for IMRT, VMAT, and SRS/stereotactic radiotherapy plans was 97.9% ± 0.3%, 96.3% ± 0.5%, and 98.2% ± 0.2%, respectively. CONCLUSION: The results reveal that this novel method can be used to commission portal dosimetry for 6MVFFF beam as it is a convenient, faster, and accurate method.

Application of aSi-kVCBCT for Volume Assessment and Dose Estimation: An Offline Adaptive Study for Prostate Radiotherapy

Objective: The purpose of this study is to develop a method to estimate the dose using amorphous silicon detector panel cone beam computed tomography (aSi-kVCBCT) for the OARs and targets in prostate radiotherapy and to compare with the actual planned dose. Methods: The aSi-kVCBCT is used widely in radiotherapy to verify the patient position before treatment. The advancement in aSi-kVCBCT combined with adaptive software allows us to verify the dose distribution in daily acquired CBCT images. CBCT images from 10 patients undergoing radical prostate radiotherapy were included in this study. Patients received total dose of 65Gy in 25 fractions using volumetric modulated arc therapy (VMAT). aSi-kVCBCT scans were acquired before daily treatment and exported to smart adapt software for image adaptation. The planning CT is adapted to daily aSi-kVCBCT images in terms of HU mapping. The primary VMAT plans were copied on to the adapted planning CT images and dose was calculated using Anisotropic Analytic Algorithm (AAA). The DVH is then used to evaluate the volume changes of organs at risk (OAR), the actual dose received by OARs, CTV and PTV during a single fraction. Results: The normalized volume of the bladder and rectum ranged from 0.70­1.66 and 0.70­1.16 respectively. The cumulative mean Sorensen­Dice coefficient values of bladder and rectum were 0.89±0.04 and 0.79±0.06 respectively. The maximum dose differences for CTV and PTV were 2.5% and -4.7% and minimum were 0.1% and 0.1% respectively. Conclusion: The adapted planning CT obtained from daily imaging using aSi-kVCBCT and SmartAdapt® can be used as an effective tool to estimate the volume changes and dose difference in prostate radiotherapy.

Feasibility of offline head & neck adaptive radiotherapy using deformed planning CT electron density mapping on weekly cone beam computed tomography.

OBJECTIVE: The purpose of the study was to use deformable mapping of planning CT (pCT) electron density values on weekly cone-beam CT (CBCT) to quantify the anatomical changes and determine the dose-volume relationship in offline adaptive volumetric-modulated arc therapy. METHODS: 10 patients treated with RapidArc plans who had weekly CBCTs were selected retrospectively. The pCT was deformed to weekly CBCTs and the deformed contours were checked for any discrepancies. Clinical target volume 66 Gy and 60 Gy (CTV66 and CTV60), parotids and spinal cord were the structures selected for analysis. Volume reduction and dice similarity index (DSI) were determined. Hybrid RapidArc plans were created and the cumulative dose-volume histograms for selected structures were analyzed. RESULTS: Results showed a mean volume reduction of 18.82 ± 6.08% and 18.22 ± 6.1% for Clinical target volume 66 Gy and 60 Gy (CTV66 and CTV60), respectively, and their corresponding DSI values were 0.94 ± 0.03 and 0.95 ± 0.01. Mean volume reductions of left and right parotids were 32.79 ± 10.28% and 29.46 ± 8.78%, respectively, and their corresponding mean DSI values were 0.90 ± 0.05 and 0.89 ± 0.05. The cumulative mean dose difference for Planning target volume 66 Gy (PTV66) was -1.35 ± 1.71% and for Planning target volume 60 Gy (PTV60), it was -0.69 ± 1.37%. Spinal cord doses varied for all patients over the course. CONCLUSION: The results from the study showed that it is clinically feasible to estimate the dose-volume relationship using deformed pCT. Monitoring of patient anatomic changes and incorporating patient-specific replanning strategy are necessary to avoid critical structure complications. Advances in knowledge: Deformable mapping of pCT electron density values on weekly CBCTs has been performed to establish the volumetric and dosimetric changes. The anatomical changes differ among the patients and hence, the choice for adaptive radiotherapy should be strictly patient specific rather than time specific.

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

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.