Dosimetric Comparision of Coplanar versus Noncoplanar Volumetric Modulated Arc Therapy for Treatment of Bilateral Breast Cancers.

Introduction: The purpose of this study was to compare the dosimetric parameters of volumetric modulated arc therapy (VMAT) treatment plans using coplanar and noncoplanar beams in patients with bilateral breast cancer/s (BBCs) in terms of organ at risk sparing and target volume coverage. The hypothesis was to test whether VMAT with noncoplanar beams can result in lesser dose delivery to critical organs such as heart and lung, which will result in lesser overall toxicity. Materials and Methods: Data of nine BBC cases treated at our hospital were retrieved. Computed tomography simulation data of these cases was used to generate noncoplanar VMAT plans and the parameters were compared with standard VMAT coplanar plans. Contouring was done using radiation therapy oncology group guidelines. Forty-five Gray in 25 fractions was planned followed by 10 Gy in five fractions boost in breast conservation cases. Results: No significant difference in planning target volume (PTV) coverage was found for the right breast/chestwall (P = 0.940), left breast/chestwall (P = 0.872), and in the total PTV (P = 0.929). Noncoplanar beams resulted in better cardiac sparing in terms of Dmean heart. The difference in mean dose was >1 Gy (8.80 ± 0.28 - 7.28 ± 0.33, P < 0.001). The Dmean, V20 and V30 values for total lung slightly favor noncoplanar beams, although there was no statistically significant difference. The average monitor units (MUs) were similar for coplanar plans (1515 MU) and noncoplanar plans (1455 MU), but the overall treatment time was higher in noncoplanar plans due to more complex setup and beam arrangement. For noncoplanar VMAT plans, the mean conformity index was slightly better although the homogeneity indices were similar. Conclusion: VMAT plans with noncoplanar beam arrangements had significant dosimetric advantages in terms of sparing of critical organs, that is Dmean of heart doses with almost equivalent lung doses and equally good target coverage. Larger studies with clinical implications need to be considered to validate this data.

Prospective evaluation of dose-escalated preoperative concurrent chemo-radiation with image guided-IMRT in locally advanced rectal cancers.

Purpose: To analyse the safety and efficacy of neoadjuvant chemoradiation (NACRT) with dose-escalated image-guided intensity modulated radiation therapy (IG-IMRT) in locally advanced (T3/4; T1-4N1-2) rectal cancers (LARCs). Materials and methods: Twenty patients with the diagnosis of LARC were recruited in this prospective interventional single-arm study treated by IG-IMRT with 45 Gray (Gy) in 25 fractions to elective nodal volumes and 55 Gy in 25 fractions to the gross primary and nodal disease with concurrent capecitabine 825 mg/m2 twice daily on radiotherapy days. Patients underwent total mesorectal excision 6-8 weeks post completion of NACRT followed by adjuvant chemotherapy (Capecitabine and oxaliplatin every 3 weekly for 6-8 cycles). Primary end point was acute toxicity assessment and secondary end points were pathological complete response (pCR) and loco-regional control (LRC). Results: Clinical T stage was T3:T4 in 19:1 and clinical N0:N1: N2 in 2:7:11 patients, respectively. With a median follow up of 21.2 months (13.8-25.6 months), 18 of 20 (90%) patients received the full course of treatment. Tumour and nodal downstaging was achieved in 78% and 84% of patients, respectively. pCR and overall complete response (defined as pCR and near CR) was achieved in 22.2% and 44.4% of patients, respectively. 2 (10%) patients completed NACRT, and achieved complete clinical response but refused surgery. Adjuvant chemotherapy course was completed by 17/18 (94.5%) patients. Grade 3 toxicities were observed in 2 (10%) patients during NACRT. All patients were disease-free at the time of the last follow up. Conclusion: Dose-escalation of NACRT therapy with IG-IMRT in LARC patients offers decent rates of pCR and overall response with excellent LRC and acceptable toxicities.

Dosimetric assessment of the mono and dual-isocentric VMAT technique based on flattening filter-free beams for SBRT with non-contiguous spinal targets.

The study aimed to evaluate the planning characteristics of spinal stereotactic body radiotherapy (SBRT) using mono- and dual-isocentric volumetrically modulated arc therapy (VMAT) techniques. The dosimetric indices were compared between different beam arrangement techniques for spinal SBRT planning, including spinal cord avoidance, planning target volume (PTV) dose coverage, conformity, homogeneity, and gradient index. A total of 8 PTVs were contoured on RANDO phantom computed tomography (CT) images, with 4 PTVs per section of the spine (thoracic and lumbar). VMAT plans for each PTV were generated using 4 different beam arrangement techniques with a 6-MV FFF photon beam, two of which were mono-isocentric (MI) and 2 of which were dual-isocentric (DI). Dose calculations for all plans were performed using the Acuros XB algorithm. The study found that when non-contiguous spinal lesions are widely spaced, it may be more effective to use 4-Arcs DI to generate a better homogeneity index and gradient index, whereas 2-Arcs MI was beneficial for closely spaced lesions. Furthermore, the use of more arcs with a dual isocenter reduced the volume of partial cord receiving 10 Gy (V10Gy), maximum dose to 0.03 cc of partial cord (D0.03cc), and monitor units (MUs). The results showed that DI has a higher plan quality than MI for treating non-contiguous spine SBRT, with better homogeneity and a lower dose to the spinal cord, as well as comparable tumor coverage, delivery accuracy, and adequate tumour coverage. 4-Arcs DI had the sharpest dose falloff and achieved the lowest overall spinal cord doses at the expense of twice the treatment time as 2Arcs-MI. These results could help figure out which VMAT beam arrangements are best for treating non-contiguous spinal tumors.

Correlation of PD-L1 expression with toxicities and response in oropharyngeal cancers treated with definitive chemoradiotherapy.

Introduction: The programmed death receptor ligand 1 (PD-L1) is a cell-surface glycoprotein expressed in tumour cells (TCs) and is also upregulated in tumour infiltrating lymphocytes. The effect of PD-L1 expression on TCs and tumour-infiltrating lymphocytes (TILs) on acute radiation toxicity and response in oropharyngeal squamous cell carcinoma treated with concurrent chemoradiotherapy is less known. Material and methods: Squamous cell carcinoma of oropharynx with stage II-IVA (AJCC 8th) were recruited in this prospective observational study. Definitive radiation therapy (RT) of 70 Gray in 35 fractions at 2 Gray per fraction, 5 fractions a week in 2 phases was delivered with concurrent chemotherapy (cisplatin 40 mg/m2 weekly). Patients were assessed weekly for acute toxicities with Radiation Therapy Oncology Group criteria. Response assessment was done at 3 months post RT according to World Health Organization response assessment criteria. The programmed death receptor ligand 1 expression in TCs and TILs was correlated with acute toxicity and survival. Results: Of 51 patients, 20 (39.2%) had PD-L1 expression in TCs and 18 (35.3%) in TILs. Patients with PD-L1 expression in TCs had fewer grade ≥ 3 oral mucositis (25% vs. 58%; p = 0.02) and grade ≥ 3 dysphagia (25% vs. 55%; p = 0.046). The programmed death receptor ligand 1-tumour infiltrating lymphocytes positives had lower ≥ 3 grade oral mucositis (22% vs. 58%; p = 0.02) and ≥ 3 grade dysphagia (17% vs. 58%; p = 0.007). Two-year overall and progression-free survival rate for the PD-L1-tumour-positive vs. PD-L1-tumour-negative group was not different (p > 0.5). Conclusions: Positive PD-L1 expression is associated with fewer acute radiation toxicities, and this could be used as a potential biomarker.

Development and validation of an indigenous, radiobiological model-based tumor control probability and normal tissue complication probability estimation software for routine plan evaluation in clinics.

Purpose: Development and validation of a simple and convenient computational program in MATLAB environment for estimating the tumor control probability (TCP) and the normal tissue complication probability (NTCP), as a decision support system for routine plan evaluation. Materials and Methods: We developed an in-house software using MATLAB 2016b (Mathworks) for estimating TCP and NTCP named as RBMODELV1. The program contains Niemierko free equivalent uniform dose (EUD) program code provided in authors research article. For rest of radiobiological (RB) models in the software separate coding is performed. The program accepts cumulative dose-volume histogram file in (.txt) format containing two columns dose and volume. A set of two RB parameters were prepared, default and user-dependent in excel sheet named as RBDATA. We cross-validated results of RBMODELV1 software with BioSuite software for Poisson's TCP model and Lyman-Kutcher-Burman (LKB) model. A set of total 20 patient's data of head and neck site took under study and respective TCP and NTCP calculated by all the RB models and compared. Results: This is the first study in which we tried to establish correlation between the mean doses (EUD) received by parallel structure (parotid gland and oral cavity) and predicted percentage of NTCP values. It is found that mean dose in the range of 35-40 Gy for parotid gland can result in more than 50% NTCP predicted by all four RB models. Similarly oral cavity receiving mean dose in the range of 53-58 Gy can results in more than 35% NTCP predicted by all the four models. There is <3% variation observed between TCP calculated by BioSuite and RBMODELV1 software and <4% variation observed between predicted NTCP for parotid gland and oral cavity OAR from LKB model by both the software. Conclusion: We created simple software RBMODELV1 which can be used as a research tool as well as decision support system.

Non-Invasive characterisation of renal stones using dual energy CT: A method to differentiate calcium stones.

BACKGROUND: Non-invasive DECT based characterization of renal stones using their effective atomic number (Zeff) and the electron density (ρe) in patients. AIM: This paper aims to develop a method for in-vivo characterization of renal stone. Differentiation of renal stones in-vivo especially sub types of calcium stones have very important advantage for better judgement of treatment modality. MATERIALS AND METHODS: 50 extracted renal stones were scanned ex-vivo using dual energy CT scanner. A method was developed to characterize these renal stones using effective atomic number and electron density obtained from dual energy CT data. The method and formulation developed in ex-vivo experiments was applied in in-vivo study of 50 randomly selected patients of renal stones who underwent dual energy CT scan. RESULTS: The developed method was able to characterize Calcium Oxalate Monohydrate (COM) and the combination of COM and Calcium Oxalate Dihydrate (COD) stones non-invasively in patients with a sensitivity of 81% and 83%respectively. The method was also capable of differentiating Uric, Cystine and mixed stones with the sensitivity of 100, 100 and 85.71% respectively. CONCLUSION: The developed dual energy CT based method was capable of differentiating sub types of calcium stones which is not differentiable on single energy or dual energy CT images.

Dosimetric evaluation of different planning techniques based on flattening filter-free beams for central and peripheral lung stereotactic body radiotherapy.

This study aimed to dosimetrically compare and evaluate the flattening filter-free (FFF) photon beam-based three-dimensional conformal radiotherapy (3DCRT), intensity-modulated radiation therapy (IMRT), and volumetric modulated arc therapy (VMAT) for lung stereotactic body radiotherapy (SBRT). RANDO phantom computed tomography (CT) images were used for treatment planning. Gross tumor volumes (GTVs) were delineated in the central and peripheral lung locations. Planning target volumes (PTVs) was determined by adding a 5 mm margin to the GTV. 3DCRT, IMRT, and VMAT plans were generated using a 6-MV FFF photon beam. Dose calculations for all plans were performed using the anisotropic analytical algorithm (AAA) and Acuros XB algorithms. The accuracy of the algorithms was validated using the dose measured in a CIRS thorax phantom. The conformity index (CI), high dose volume (HDV), low dose location (D2cm), and homogeneity index (HI) improved with FFF-VMAT compared to FFF-IMRT and FFF-3DCRT, while low dose volume (R50%) and gradient index (GI) showed improvement with FFF-3DCRT. Compared with FFF-3DCRT, a drastic decrease in the mean treatment time (TT) value was observed with FFF-VMAT for different lung sites between 57.09% and 60.39%, while with FFF-IMRT it increased between 10.78% and 17.49%. The dose calculation with Acuros XB was found to be superior to that of AAA. Based on the comparison of dosimetric indices in this study, FFF-VMAT provides a superior treatment plan to FFF-IMRT and FFF-3DCRT in the treatment of peripheral and central lung PTVs. This study suggests that Acuros XB is a more accurate algorithm than AAA in the lung region.

Radiotherapy plan evaluation indices: A dosimetrical suitability check.

PURPOSE: To classify the available plan evaluation indices and compare the dosimetric suitability of these indices. MATERIALS AND METHODS: Available published plan evaluation indices were categorized. Conformity index (CI) into two groups, one group contains those CI formulas which do not consider critical structure and other group contains those CI formulas which consider planning target volume (PTV) coverage, normal tissue and critical structure sparing simultaneously. Various homogeneity index (HI) formulas extracted from literature. Structure data sets of 25 patients were taken under consideration comprising of various sites. For each patient, two plans were created using Volumetric Arc Therapy technique. First type of plan (Plan-A) were generated considering all tissue objectives for targets and Organ at Risks (OARs) whereas second type of plan (Plan-B) were generated considering only targets tissue objectives and excluding OARs tissue objectives during plan optimization and dose calculation. Planning evaluation parameters were compared between Plan-A and Plan-B. RESULTS: CI calculated by various formulas in two different scenarios presented <2% variation. Any commonly used CI formula failed to differentiate the two different planning situations. On comparison between HI of two different scenario, it is observed that there are four formulas of HI which showed negligible variation but two formulae: S-index and HI (D) showed marginal variation. It is also observed that when OARs are removed from optimization dose homogeneity improved which is specifically pointed by sigma index formula. CONCLUSION: CI, which has assimilated the presence of OAR in their formulation, shows more reliability in plan evaluation. Sigma index was found to be more efficient formula while evaluating homogeneity of a treatment plan.

Dosimetry of a 6 MV flattening filter-free small photon beam using various detectors.

The present study aimed to dosimetrically evaluate the small-fields of a 6 MV flattening filter-free (FFF) photon beam using different detectors.The 6 MV FFF photon beam was used for measurement of output factor, depth dose, and beam profile of small-fields of sizes 0.6 cm × 0.6 cm to 6.0 cm × 6.0 cm. The five detectors used were SNC125c, PinPoint, EDGE, EBT3, and TLD-100. All measurements were performed as per the International Atomic Energy Agency TRS 483 protocol. Output factors measured using different detectors as direct reading ratios showed significant variation for the smallest fields, whereas after correcting them according to TRS 483, all sets of output factors were nearly compatible with each other when measurement uncertainty was also considered. The beam profile measured using SNC125c showed the largest penumbra for all field sizes, whereas the smallest was recorded with EDGE. Compared with that of EBT3, the surface dose was found to be much higher for all the other detectors. PinPoint, EBT3, TLD-100, and EDGE were found to be the detector of choice for small-field output factor measurements; however, PinPoint needs special attention when used for the smallest field size (0.6 cm × 0.6 cm). EDGE and EBT3 are optimal for measuring beam profiles. EBT3, PinPoint, and EDGE can be selected for depth dose measurements, and EBT3 is suitable for surface dose estimation.

Patterns of failure and clinical outcomes of post-operative buccal mucosa cancers treated with adjuvant ipsilateral radiotherapy.

PURPOSE: Adjuvant radiotherapy (RT) in buccal mucosa cancers is guided by histopathological factors. The decision to treat ipsilateral or bilateral draining lymph node is on physician discretion and guidelines do not have a defined indication regarding this. We aimed to analyze the failure patterns and survival in buccal mucosa cancers treated with adjuvant ipsilateral RT. MATERIALS AND METHODS: One hundred sixteen cases of post-operative buccal mucosa cancers-pT3 or more, node positive, close margins (1-5 mm), lymphovascular invasion positive, perineural invasion positive, depth of invasion >4 mm-treated with RT to primary and ipsilateral nodes from May 2013 to May 2019 were retrospectively analyzed. Patients were treated to a dose of 60-66 Gy (44 Gy in the first phase and a coned down boost of 16-22 Gy in the second phase) with three-dimensional conformal radiotherapy on a linear accelerator. Primary end point was to assess control rates and secondary end point was to evaluate the overall survival (OS) and disease-free survival (DFS) outcomes. RESULTS: Median age was 46 years with male; female ratio of 110:6. The edition of the American Joint Committee on Cancer stage distributions were I (3.4%), II (34.4%), III (24.1%), and IV (37.9%). At a median follow-up of 22 months, crude rates of local failure, regional failure, and contralateral neck failure were 9.4%, 10.3%, and 3.4%, respectively. The 2-year contralateral neck control rate was 94.9%. Pathological positive node portended poorer OS (86.6% vs. 68.6%; p = 0.015) and DFS (86.5% vs. 74.9%; p = 0.01). CONCLUSION: Incidence of contralateral recurrence with ipsilateral irradiation in buccal mucosa cancers is low with descent survival outcomes, particularly in node negative cases.

Development of a Method to Determine Electron Density and Effective Atomic Number of High Atomic Number Solid Materials Using Dual-Energy Computed Tomography.

AIM: This study aims to develop a method using dual-energy computed tomography (DECT) to determine the effective atomic number and electron density of substances. MATERIALS AND METHODS: Ten chemical substances of pure analytical grade were obtained from various manufacturers. These chemicals were pelletized using a hydraulic press. These pellets were scanned using DECT. A relation was obtained for the pellet's atomic number and electron density with their CT number or Hounsfield unit (HU) values. Calibration coefficients were determined. Five new chemical pellets were scanned, and their effective atomic number and electron densities were determined using the calibration coefficients to test the efficacy of the calibration method. RESULTS: The results obtained for effective atomic number and electron density from the HU number of DECT images were within ±5% and ±3%, respectively, of their actual values. CONCLUSIONS: DECT can be used as an effective tool for determining the effective atomic number and electron density of high atomic number substance.

Non-invasive characterization of coronary artery atherosclerotic plaque using dual energy CT: Explanation in ex-vivo samples.

PURPOSE: In this study non-calcified plaque composition is evaluated by Dual Energy CT (DECT). Energy Dispersive X-ray Spectroscopy (EDS) has been used to study the Plaque composition. An attempt has been made to explain the DECT results with EDS analysis. METHODS: Thirty-two ex-vivo human cadaver coronary artery samples were scanned by DECT and data was evaluated to calculate their effective atomic number and electron density (Zeff & ρe) by inversion method. Result of DECT was compared with pathology to assess their differentiating capability. The EDS study was used to explain DECT outcome. RESULTS: DECT study was able to differentiate vulnerable plaque from stable with 87% accuracy (area under the curve (AUC):0.85 [95% confidence interval {CI}:0.73-0.98}] and Kappa Coefficient (KC):0.75 with respect to pathology. EDS revealed significant compositional difference in vulnerable and stable plaque at p < .05. The weight percentage of higher atomic number elements like F, Na, Mg, S, Si, P, Cl, K and Ca was found to be slightly more in vulnerable plaques as compared to a stable plaque. EDS also revealed a significantly increased weight percentage of nitrogen in stable plaques. CONCLUSIONS: The EDS results were able to explain the outcomes of DECT study. This study conclusively explains the physics of DECT as a tool to assess the nature of non-calcified plaques as vulnerable and stable. The method proposed in this study allows for differentiation between vulnerable and stable plaque using DECT.