Verification of an optimizer algorithm by the beam delivery evaluation of intensity-modulated arc therapy plans

Background In the case of dynamic radiotherapy plans, the fractionation schemes can have dosimetric effects. Our goal was to define the effect of the fraction dose on the plan quality and the beam delivery. Materials and methods Treatment plans were created for 5 early-stage lung cancer patients with different dose schedules. The planned total dose was 60 Gy, fraction dose was 2 Gy, 3 Gy, 5 Gy, 12 Gy and 20 Gy. Additionally renormalized plans were created by changing the prescribed fraction dose after optimization. The dosimetric parameters and the beam delivery parameters were collected to define the plan quality and the complexity of the treatment plans. The accuracy of dose delivery was verified with dose measurements using electronic portal imaging device (EPID). Results The plan quality was independent from the used fractionation scheme. The fraction dose could be changed safely after the optimization, the delivery accuracy of the treatment plans with changed prescribed dose was not lower. According to EPID based measurements, the high fraction dose and dose rate caused the saturation of the detector, which lowered the gamma passing rate. The aperture complexity score, the gantry speed and the dose rate changes were not predicting factors for the gamma passing rate values. Conclusions The plan quality and the delivery accuracy are independent from the fraction dose, moreover the fraction dose can be changed safely after the dose optimization. The saturation effect of the EPID has to be considered when the action limits of the quality assurance system are defined.

Comparison of sliding window and field-in-field techniques for tangential whole breast irradiation using the Halcyon and Synergy Agility systems

Background To implement a tangential treatment technique for whole breast irradiation using the Varian Halcyon and to compare it with Elekta Synergy Agility plans. Methods For 20 patients two comparable treatment plans with respect to dose coverage and normal tissue sparing were generated. Tangential field-in-field treatment plans (Pinnacle/Synergy) were replanned using the sliding window technique (Eclipse/Halcyon). Plan specific QA was performed using the portal Dosimetry and the ArcCHECK phantom. Imaging and treatment dose were evaluated for treatment delivery on both systems using a modified CIRS Phantom. Results The mean number of monitor units for a fraction dose of 2.67 Gy was 515 MUs and 260 MUs for Halcyon and Synergy Agility plans, respectively. The homogeneity index and dose coverage were similar for both treatment units. The plan specific QA showed good agreement between measured and calculated plans. All Halcyon plans passed portal dosimetry QA (3%/2 mm) with 100% points passing and ArcCheck QA (3%/2 mm) with 99.5%. Measurement of the cumulated treatment and imaging dose with the CIRS phantom resulted in lower dose to the contralateral breast for the Halcyon plans. Conclusions For the Varian Halcyon a plan quality similar to the Elekta Synergy device was achieved. For the Halcyon plans the dose contribution from the treatment fields to the contralateral breast was even lower due to less interleaf transmission of the Halcyon MLC and a lower contribution of scattered dose from the collimator system.

Prognostic factors in elderly patients with T1 glottic cancer treated with radiotherapy

The aim of the study was the evaluation of the effectiveness of radiotherapy in elderly T1 glottic cancer patients and prognostic factors with particular focus on comorbidities. Five-year overall survival, disease-specific survival, and local control rates were 63%, 92%, and 93%, respectively. Multivariate analysis showed that the following factors had statistically significant impact on local relapse risk and cancer death risk: diabetes, underweight, and fraction dose of 2 Gy. High number of comorbidities, high CCI, and underweight negatively influenced overall survival. A retrospective analysis was performed in a group of 131 T1N0M0 glottic cancer patients aged 70 and above treated with irradiation at the National Institute of Oncology in Cracow between 1977 and 2007. In the analyzed group men prevailed (92%) of mean age of 74 years. Each patient was diagnosed with at least one comorbidity with the following comorbid conditions being most frequent: hypertension, ischemic heart disease, and chronic obstructive pulmonary disease. In the studied group, the effect of comorbidities on overall survival was evaluated using Charlson Comorbidity Index (CCI). Twenty five (19%) patients showed underweight. All patients were irradiated once daily, 5 days a week, to a total dose of 60–70 Gy with a fraction dose of 2 or 2.5 Gy. Radiotherapy is an effective treatment modality in elderly T1 glottic cancer patients. Diabetes as comorbidity, underweight, and conventional dose fractionation decrease the probability of curative effect of radiotherapy in this group of patients, while high number of comorbidities diminishes the probability of long-term survival.

Long Term Arm and Shoulder Toxicities in Breast Cancer Patients Receiving Hypofractionated Radiation Therapy

Aim: The purpose of this study is to evaluate the late toxicities in hypo fractionated radiation schedule in breast cancer patients with regional nodal irradiation (RNI), limited to axilla and supraclavicular regions. Late effects on arm and shoulder were noted as follows: skin edema (lymphedema), restricted shoulder movements (brachial plexus injury) and localised pain.Material and Methods: In this study we randomly enrolled 100 breast cancer post mastectomy cases in the year 2018. All cases were previously asymptomatic after surgery. They were prospectively treated with hypo fractionated local and regional nodal irradiation by 2.67 gray / fraction dose, total 15 fractions (total dose-40 gray). Evaluation was done at 12 months after completion of radiation therapy. Assessment was done by RTOG, LENT- SOMA scales. Results: Significant lymphedema was observed in 17 (17%) cases. Restricted arm mobility was seen in 14 (14%) of patients. Pain (moderate/severe) in arm and shoulder was most commonly seen, in 25 (25%) cases. Conclusions: As hypo fractionated regimes in breast cancer treatment have become new standard; its late term effects are significant and comparable to other conventional radiation therapy regimes. These studies need further and longer duration of evaluation.

Comparison of Sliding Window and Field-In-Field Techniques For Tangential Whole Breast Irradiation Using The Halcyon and Synergy Agility Systems

Background: To develop a tangential treatment technique for whole breast irradiation using the Varian Halcyon and to compare it with Elekta Synergy Agility plans.Methods: For 20 patients two comparable treatment plans with respect to dose coverage and normal tissue sparing were generated. Tangential field-in-field treatment plans (Pinnacle/Synergy) were replanned using the sliding window technique (Eclipse/Halcyon). Plan specific QA was performed using the portal Dosimetry and the ArcCHECK phantom. Imaging and treatment dose were evaluated for treatment delivery on both systems using a modified CIRS Phantom.Results: The mean number of monitor units for a fraction dose of 2.67 Gy was 515 MUs and 260 MUs for Halcyon and Synergy Agility plans, respectively. The homogeneity index and dose coverage were similar for both treatment units. The plan specific QA showed good agreement between measured and calculated plans. All Halcyon plans passed portal dosimetry QA (3%/2 mm) with 100% points passing and ArcCheck QA (3%/2 mm) with 99.5%. Measurement of the treatment and imaging dose with the CIRS phantom resulted in lower dose to the contralateral breast for the Halcyon plans.Conclusions: For the Varian Halcyon a plan quality similar to the Elekta Synergy device was achieved. For the Halcyon plans the dose contribution from the treatment fields to the contralateral breast was even lower due to less interleaf transmission of the Halcyon MLC and a contribution of scattered dose from the collimator system.

Anti-inflammatory Effect of the Alkaloid-rich Fraction of Landolphia owarensis

Background: Plants have several chemical compounds acclaimed to be responsible for the pharmacological actions produced when herbal products are administered to biological systems.Objectives: This study was designed to investigate the anti-inflammatory effect of the alkaloid-rich fraction of the ethanol leaf extract of Landolphia owariensis.Methods: Qualitative phytochemical analyses were carried on the crude extract using standard methods. The alkaloid-rich fraction was obtained from the crude ethanol extract, using the classical acid/base shake-up method and the obtained fraction tested positive to Dragendorf’s reagent. Oral acute toxicity was evaluated by OECD method (No 423). Anti-inflammatory effect of the fraction was evaluated using xylene-induce ear oedema and carrageenan-induced paw inflammation in mice at doses of 100, 200 and 400 mg/kg.Results: Phytochemical screening revealed presence of alkaloids, flavonoids, tannins, saponins, steroids/terpenes and glycosides. Acute toxicity studies showed no adverse symptoms of toxicity during the 14-day observation period and no mortality was recorded, thus the LD50 was estimated to be greater than 2000 mg/kg. The alkaloid-rich fraction dose-dependently inhibited inflammation induced by xylene and carrageenan. In the xylene test, the fraction produced significant inhibition of 41.70 % at 400 mg/kg (p ≤ 0.05) while in the carrageenan test 55.69 % significant inhibition (p ≤ 0.001) was recorded with 400 mg/kg at 60 mins after induction of inflammation.Conclusion: This study showed the anti-inflammatory potentials of the alkaloid-rich fraction of Landophia owariensis.

IR-Surviving NSCLC Cells Exhibit Different Patterns of Molecular and Cellular Reactions Relating to the Multifraction Irradiation Regimen and p53-Family Proteins Expression

Radiotherapy is a primary treatment modality for patients with unresectable non-small cell lung cancer (NSCLC). Tumor heterogeneity still poses the central question of cancer radioresistance, whether the presence of a particular cell population inside a tumor undergoing a selective outgrowth during radio- and chemotherapy give rise to metastasis and tumor recurrence. In this study, we examined the impact of two different multifraction X-ray radiation exposure (MFR) regimens, fraction dose escalation (FDE) in the split course and the conventional hypofractionation (HF), on the phenotypic and molecular signatures of four MFR-surviving NSCLC cell sublines derived from parental A549 (p53 wild-type) and H1299 (p53-null) cells, namely A549FR/A549HR, H1299FR/H1299HR cells. We demonstrate that sublines surviving different MFR regimens in a total dose of 60 Gy significantly diverge in their molecular traits related to irradiation regimen and p53 status. The observed changes regarding radiosensitivity, transformation, proliferation, metabolic activity, partial epithelial-to-mesenchymal transition (EMT) program activation and 1D confined migratory behavior (wound healing). For the first time, we demonstrated that MFR exposure led to the significant decrease in the expression of p63 and p73, the p53-family members, in p53null cells, which correlated with the increase in cell polyploidy. We could not find significant differences in FRA1 expression between parental cells and their sublines that survived after any MFR regimen regardless of p53 status. In our study, the FDE regimen probably causes partial EMT program activation in MFR-survived NSCLC cells through either Vimentin upregulation in p53null or an aberrant N-cadherin upregulation in p53wt cells. The HF regimen likely less influences the EMT activation irrespectively of the p53 status of MFR-survived NSCLC cells. Our data highlight that both MFR regimens caused overall higher cell transformation of p53null H1299FR and H1299HR cells than their parental H1299 cells. Moreover, our results indicate that the FDE regimen raised the radioresistance and transformation of MFR-surviving NSCLC cells irrespectively of their p53 status, though the HF regimen demonstrated a similar effect on p53null NSCLC cells only. Our data once again emphasize that NSCLC therapy approaches should become more personalized according to radiation therapy (RT) regimen, tumor histology, and molecular status of critical proteins.

Field in Field Technique (FIF) Technique With Intra-fractionally Modulated Junction Shifts for Cranio-spinal Irradiation (FSI) Planning With 3D-CRT.

Background To plan craniospinal irradiation (CSI) with ‘‘field-in-field’’ (FIF) homogenization technique in combination with daily, intra-fractional modulation of the field junctions, to minimize the possibility of spinal cord overdose. Photon-based techniques for CSI may result in dose inhomogeneity within the treatment volume and usually require a weekly manual shift of the field junctions to minimize the possibility of spinal cord overdose. Nowadays FIF technique is used to feather out the dose inhomogeneity caused by multiple fields. We have started using this technique after acquiring advanced technology machines in recent years. Methods and Materials: 16 patients treated with 3D-CRT for CSI were retrospectively chosen for analysis. These patients were treated during 2016–2017. Contouring of PTV and OAR were done and planning done on Eclipse TM TPS (Varian). These patients were planned with Lateral cranio-cervical fields and posterior spinal fields using a forward-planned, FIF technique. Field junctions were automatically modulated and custom-weighted for maximal homogeneity within each treatment fraction. Dose volume histogram (DVH) was used for analysis of results. A corresponding plan without FIF technique was planned and maximum dose at the junction was noted for each patient with both plans and the readings were evaluated. Results Plan inhomogeneity improved with FIF technique. It provided consistent dose delivery during each fraction of treatment across the junctions. The maximum doses calculated at the junction were higher in the CSI plans without FIF compared to those with FIF technique. Conclusion This paper hence proves that FIF technique is better in planning CSI.

Visual light perceptions caused by medical linear accelerator: Findings of machine-learning algorithms in a prospective questionnaire-based case–control study

This study aimed to investigate the possible incidence of visual light perceptions (VLPs) during radiation therapy (RT). We analyzed whether VLPs could be affected by differences in the radiation energy, prescription doses, age, sex, or RT locations, and whether all VLPs were caused by radiation. From November 2016 to August 2018, a total of 101 patients who underwent head-and-neck or brain RT were screened. After receiving RT, questionnaires were completed, and the subjects were interviewed. Random forests (RF), a tree-based machine learning algorithm, and logistic regression (LR) analyses were compared by the area under the curve (AUC), and the algorithm that achieved the highest AUC was selected. The dataset sample was based on treatment with non-human units, and a total of 293 treatment fields from 78 patients were analyzed. VLPs were detected only in 122 of the 293 exposure portals (40.16%). The dataset was randomly divided into 80% and 20% as the training set and test set, respectively. In the test set, RF achieved an AUC of 0.888, whereas LR achieved an AUC of 0.773. In this study, the retina fraction dose was the most important continuous variable and had a positive effect on VLP. Age was the most important categorical variable. In conclusion, the visual light perception phenomenon by the human body during RT is induced by radiation rather than being a self-suggested hallucination or induced by phosphenes.