Effect of statistical uncertainty on Monaco Monte-Carlo dose calculation

Purpose: The aim of this study is to evaluate influence of statistical uncertainty on Monte-Carlo dose calculation of Monaco 5.11 treatment planning system (TPS).Methods: Phantom with contoured C-Shape structure set was downloaded from AAPM website provided with TG119 report. VMAT plan was created for C-Shape test case using Monaco TPS for 6 MV Elekta Versa-HD linear-accelerator. Dose prescription and constraints were as per TG119. After optimizations, C-Shape plan was calculated with different statistical-uncertainty (i) 0.5%, 1.0%, 3.0% and 5.0% per control point and (ii) 0.5%, 1.0%, 3.0% and 5.0% per calculation. Base plan was calculated with 0.5% per control point.Results: Variations in PTV doses for different statistical-uncertainties with respect to 0.5% per control point were within PTV-D95: 82 cGy(1.64%); PTV-D10: 14.8 cGy(0.28%); Core-D10: 3.7 cGy(0.15%). MU required to deliver a plan (920 MU) were observed same with different statistical-uncertainty. Calculation time increases with decrease in statistical-uncertainty due to more number of histories. 2D-Gamma pass rate was ranging from 98.1% to 98.9% for analyzed statistical-uncertainties. Statistical-uncertainty 0.5% per control point showed higher Gamma pass-rate (98.9%).Conclusion: Minor variation (<1.64%) in dose volume parameters was observed with different statistical-uncertainties, whereas Monitor unit remain same. 3.0% per control point and 0.5% per calculation resulted in almost similar results and found optimal with reasonable calculation time in terms of plan quality and delivery accuracy (gamma pass-rate)

IL-2 and IL-12 in thyroid cancer: Clinical implication

Purpose: The roles of IL-2 and IL-12, in different malignancies have been looked for since years. But very few studies have elucidated their role in thyroid tumorigenesis. Hence, present study sought to explore their utility in thyroid cancer, mainly the papillary thyroid cancer (PTC).Methods: A total of 67 patients with benign thyroid diseases, 106 with thyroid cancer and 67 healthy individuals were included in the study. Circulating levels of IL-2 and IL-12 were estimated by ELISA from all patients and controls. Protein expression of both interleukins was determined using immunohistochemistry. The results were statistically analysed using SPSS software.Results: Serum IL-12 exhibited good discriminatory efficacy between patients with benign thyroid diseases and healthy individuals. IL-2 and IL-12 levels could efficiently differentiate PTC and anaplastic thyroid cancer (ATC) patients from healthy individuals. Additionally, IL-12 showed good discriminating efficacy between PTC and benign thyroid disease patients and IL-2 well discriminated ATC patients from benign thyroid diseases. IL-2 was significantly higher in patients having unilateral tumors (P=0.006) while, IL-12 was significantly higher in patients with smaller tumor size (P=0.036) and early stage disease (P=0.008). The cytokine protein expressions in benign thyroid tissues and carcinoma did not differ significantly. IL-12 expression was significantly higher in male patients (P=0.042) and unilateral tumors (P=0.031).Kaplan-Meier survival analysis revealed that nuclear IL-2 expression was able to predict disease free survival and overall survival (OS) in subgroup of PTC patients having multifocal tumors and only OS in patients having bilateral tumors. Moreover, higher IL-12 immunoreactivity was a significant predictor of shorter OS in PTC patients treated with surgery alone.Conclusion: Serologic determination of IL-2 and IL-12 may help in validating indeterminate FNAC results and disclose diagnostic difference between benign and malignant thyroid diseases. However, a large cohort study is mandatory to establish a defined cut off for such discrimination

A method for an external quality audit programme in radiosurgery with TLDs and radiochromic film

Purpose: Radiosurgery is a high-precision technique that delivers a single highly conformed dose to a stereotactically localized target in most cases. This study proposes a simple and reliable postal quality assurance (QA) phantom for use in an independent evaluation.Methods: Two important parameters were verified, including the dosimetric precision of the treatment planning system, by comparing the absorbed dose measured in the target volume using different dosimeters (i.e., radiochromic film and thermoluminescence dosimeters) calibrated against a small volume ion chamber. The head phantom and the instruction sheets were extensively tested and sent by mail to selected institutions. The institutions were chosen according to the type of linear accelerator they had. The three institutions chosen had different radiosurgery systems for the delivery of treatment and the planning system. The objective was to understand whether our system would be applicable to different radiosurgery delivery systems.Results: A comparison between the TPS plan and the measurement plan using the radiochromic film showed that the gamma pass rate was more than 90% for a gamma criteria of 2 mm/2%. In the worst case scenario, the disagreement with TLD measurements at position 1 arose because the highest dose gradient occurred in that region. The other positions measured with thermoluminescence dosimeters (TLDs) varied by less than 3% from the calculated dose.Conclusion: The overall results were very encouraging and suggest that the proposed phantom may be used as a postal system as part of an independent QA tool for radiosurgery

A single center study of cancer patients with chronic kidney disease

Purpose: It is clinically understood that chronic kidney disease (CKD) and cancer are interrelated. Yet, few studies measure how renal outcomes vary according to common malignancies and common therapeutic agents. We report the incidence and the nature of CKD among cancer patients from a single institution.Methods: A retrospective chart review of cancer patients managed in the onconephrology clinic at the Moffitt Cancer Center from 05/01/2015 to 07/31/2016 was conducted. Patients with kidney injury were included in this study. Renal function was recorded at three-month follow-up intervals for 15-month duration.Results: Out of the total 88 patients with median age of 68 years, 63 patients (~ 72%) were diagnosed with chronic kidney disease (CKD), whereas the remaining had acute kidney injury. Kidney cancer and multiple myeloma represented the single malignancies with the largest proportion of CKD with 12 patients each (~14% each). Patients with kidney cancer had a mean creatinine of (2.35, 1.74 SD) mg/dl compared to patients without kidney cancer with creatinine (1.97, 1.07 SD) mg/dl. Abdominal cancers represented the highest frequency category of malignancies in this sample (n = 38), and about 32 (84%) of these patients had CKD. About 80% of patients with genitourinary cancers (n = 27) had CKD. In terms of prescribed chemotherapeutic agents, patients treated with tyrosine kinase inhibitors had a lower average estimated glomerular filtration rate (28.37, 9.86 SD) mL/min/1.73 m2 compared to other chemotherapeutic agents, though this was weakly significant (p-value = 0.07). Similar renal outcomes per malignancy and chemotherapy are reported.Conclusion: This group of patients demonstrated the frequency of chronic kidney disease differs depending on the type of malignancy or chemotherapy. A multidisciplinary approach involving oncologists and nephrologists should be adopted to prevent further renal damage from cancer and its therapies

Association between tumor response and change in EQ5D-3L quality of life among cancer patients

Purpose: The primary aim in cancer treatment is to provide excellent tumor response while maintaining the most acceptable quality of life. The relationship of QoL to tumor response has not yet been well discussed. This study determines the association between the change in the QoL from baseline to one (1) year follow-up and tumor response among patients enrolled in the ASEAN Cost in Oncology (ACTION) study.Methods: Pooled data from the ACTION study was reviewed. Associations between demographics, cancer type, and tumor response were analyzed.Results: Of the qualified profiles (412 / 742), breast cancer (42.2%), colorectal (21.8%), and head neck (10%) are still most common. Of these cases, 126 (30.6%) were metastatic on presentation. Demographic data showed female sex having better tumor response. More importantly, tumor response was significantly associated with improvement in QoL: complete or partial response was associated with improvement in QoL (p = .000) while progressive disease related to worse situations. The general pattern seen above was reflected in female breast cancer cases, colon and rectal cancer, and other malignant neoplasms.Conclusion: Improvement in QoL was significantly associated with better tumor response. This trend was similar for breast cancer, colorectal cancer and other malignancies. The use of universal measures of health like the EQ5D 3L may be used to quantify improvements in QoL with several limitations: 1) cultural differences should be established and 2) limitations in quantifying precise changes in QoL. The utilization of more culturally adept QoL measures may address this problem. Similarly, the use of secondary data may limit the results in this study. Prospective studies specifically addressing the objectives may improve results

Intraocular breast metastasis: a case report

Breast cancer accounts for approximately 16% of all newly diagnosed cancer cases in the Philippines. Among these, 5% are metastatic at presentation. The eye is an atypical location for metastatic spread from breast cancer. A 53-year-old Filipino female presented with a breast mass with concomitant blurring of vision. Further work-up showed invasive ductal carcinoma with bone metastasis. Ophthalmologic examination showed an intraocular mass with associated exudation and retinal detachment, which explained the blurring of vision. Chemotherapy for the breast cancer subsequently reduced tumor mass of both breast and eye, with progression of both after first line chemotherapy. Clinicians should be wary of patients presenting with a known primary mass lesion with associated ophthalmologic complaints. The possibility of metastatic disease in these patients should warrant ophthalmologic screening to possibly prevent the deterioration of the quality of life of these patients

Design and development of an add-on automated multi-leaf collimator for telecobalt therapy machine and study of its characteristics

Purpose: The purpose of the paper is to present the design, development and dosimetric characteristics of an automated Multi-leaf collimator (MLC) integrated along with an inexpensive Treatment Planning System (ROPS), developed for existing telecobalt units as an add-on without making any modifications to the treatment machine.Method: The prototype MLC design consists of 28 tungsten alloy leaves (14 leaf pairs) having a mass density of 18 g cm-3. Each of the leaves projects 10 mm width at the isocenter, which is at 80 cm from the source. The automation has been achieved with a dedicated linear actuator for each leaf. Radiochromic films and IC PROFILER™ (Sun Nuclear Corporation, Melbourne, FL) were used for the measurement of beam profiles and the profiles were analyzed to arrive at radiation field width, beam flatness, symmetry and beam penumbra.Results: The prototype MLC can define radiation fields of up to 14 × 14 cm² within the prescribed tolerance values of 2 mm. The flatness and symmetry were found to be within the prescribed tolerance value of 3%. The penumbra for a 10 × 10 cm² field size is 9.5 mm which is less than the generally acceptable value of 12 mm for a telecobalt machine. The maximum leakage through the leaf ends in closed condition was observed to be 7.3% which is less than the values reported for other MLCs designed for medical linear accelerators.Conclusion: It is concluded that dosimetric parameters and the leakage radiation of the prototype MLC are well below their recommended tolerance values. The MLC can be used for carrying out conformal radiotherapy with existing telecobalt machines

5-FU resistant colorectal cancer cells possess improved invasiveness and βIII-tubulin expression

Purpose: Elevated bIII-tubulin levels are associated with resistance to a broad spectrum of drugs in different carcinomas and are associated with poor prognosis of different epithelial cancers. 5-Fluorouracil (5-FU) is a widely used standard drug in chemotherapeutic regimens for colorectal cancer treatment, although the resistance to 5-FU is a major obstacle to successful therapy. The aim of the study was to compare the invasive and adhesion properties and the expression levels of bIII-tubulin in a 5-Fluorouracil (5-FU)-resistant colorectal cancer (CRC) cell line HCT116 and parental cells.Methods: The 5-FU-resistant cell line was established by continuous stepwise selection with increasing concentrations of 5-FU. Cell viability and properties were evaluated using MTT, adhesion and transwell invasion assays respectively. The expression of bIII-tubulin was revealed by immunoblot and immunofluorescence.Results: The derivative line is 25-fold resistant to 5-FU and characterized by altered cell morphology, twice as many cells of the 5-FU-resistant line fail to adhere than is the case for the parental cell line and were characterized by enhanced invasiveness, accompanied by increased bIII-tubulin expression. In addition, we found that loss of bIII-tubulin expression was correlated with loss of 5-FU resistance.Conclusion: Our results indicate that even though 5-FU does not target microtubules, there appears to be a correlation between bIII-tubulin expression and resistance to 5-FU and that this is particularly important with regard to invasiveness. These findings indicate a possible contribution of bIII-tubulin to 5-FU resistance in vivo.

The efficacy of the quercetin analogue LY294002 in immortalized cancer cell lines is related to the oxygenic and metabolic status of cells

Purpose: LY294002, a promising drug for chemotherapy, suppresses the activity of Phosphatidylinositol 3-Kinase (PI3K) which is pivotal to a number of processes such as proliferation, metabolism, and apoptosis. The compound has, however, been seen to have very variable efficacy in vivo.Methods: Proliferation and viability of two immortalized cells with divergent bioenergetic profiles was determined using crystal violet staining, and the 3-(4, 5-dimethylthiazol-2yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay. Oxygen consumption rates were determined using MitoXpress-Xtra probes, and lactate generation was assessed with pH-Xtra probe and BM-lactate strips. Immunoblotting was performed with phospho-Akt-Ser 473 and Akt-pan primary antibodies.Results: U87 cells were shown to have a glycolytic metabolism, whereas RD cells exhibited a more aerobic metabolism. In both lines, hypoxia was shown to increase lactate production, and LY294002 reduced lactate production. The drug decreased cell proliferation and viability under all conditions, but the effect was greatest in U87 cells under normoxic conditions.Conclusion: Metabolic analysis showed a link between a glycolytic cell status and LY294002 induced cell death. However, in both cell lines the drug was also less effective under hypoxic conditions, as would be found in a tumour in vivo. Furthermore, in the presence of LY294002 the phosphorylation status of Akt, a target of PI3K, was found to be related to both the mechanism of cell respiration, and the oxygenic status of the cells

Clinical implementation of IMRT step and shoot with simultaneous integrated boost for breast cancer: A dosimetric comparison of planning techniques

Purpose: Radiotherapy post-lumpectomy with two coplanar tangent beams is the standard treatment for women with early stage breast cancer. Despite the use of wedges as tissue compensators, the resultant plans often contains a significant dose gradient and 'hot spots' in excess of 15% or more of prescribed dose. In recent years a field-in-field (FIF) dose-compensation technique, which use two standard tangent fields and one or two (rarely three) small beams within these, was developed. It allows to obtain a more uniform dose throughout the target volume in the majority of cases but not in all. This study presents our experience to develop optimal intensity modulated radiation therapy (IMRT) techniques to be applied clinically in those cases where the traditional technique with two tangent fields or its variant field in field (FIF) are unable to achieve a satisfactory planning target volumes (PTVs) coverage and dose objectives to the organs at risk (OARs). Methods: We investigated two pure IMRT plans (named 3F-IMRT and 4F-IMRT) and a hybrid one (H-IMRT). Treatment plans were performed for 7 left-sided and 4 right-sided breasts using simultaneously integrated boost (SIB) planned technique with inverse optimization. Results were compared with those obtained with FIF technique. Dose prescribed was 45 Gy/20 fractions to the breast and 50 Gy /20 fractions to the lumpectomy cavity delivered in 5 fr/week. Dose–volume histograms were generated and parameters as target dose coverage, conformity and homogeneity as well as OARs dose distribution were analyzed. Finally the secondary cancer risk to contralateral breast due to radiation was evaluated as a further parameter for the choice of the optimal plan. Results: Compared to the FIF, the three IMRT plans provided the same target coverage and a better dose conformation, but a worst dose homogeneity of the boost target. The volume of the OARs, receiving higher doses than 15 Gy was reduced but was increased the volume receiving low doses. This causes the increase of the risk of radiation induced cancer, especially for the contralateral breast. For this organ, the highest value of the excess absolute risk (EAR) was associated to the 4F-IMRT, while the lower, to the FIF. Conclusion: The intensity-modulated radiation therapy techniques 5F-IMRT and 4F-IMRT were the best to be applied clinically in those cases, where the traditional technique of irradiation of the breast is unable to achieve the PTVs coverage and dose objectives to the OARs. However, all the IMRT techniques showed an increased volume of healthy tissues receiving low doses, so they should not be used in extensive manner and in particular should be avoided in the cases of young women due to the excess of risk to develop a secondary cancer