International Journal of Cancer Therapy and Oncology
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Cone beam computed tomography: An accurate imaging technique in comparison with orthogonal portal imaging in intensity-modulated radiotherapy for prostate cancer
Get PDFPurpose: Various factors cause geometric uncertainties during prostate radiotherapy, including interfractional and intrafractional patient motions, organ motion, and daily setup errors. This may lead to increased normal tissue complications when a high dose to the prostate is administered. More-accurate treatment delivery is possible with daily imaging and localization of the prostate. This study aims to measure the shift of the prostate by using kilovoltage (kV) cone beam computed tomography (CBCT) after position verification by kV orthogonal portal imaging (OPI).Methods: Position verification in 10 patients with prostate cancer was performed by using OPI followed by CBCT before treatment delivery in 25 sessions per patient. In each session, OPI was performed by using an on-board imaging (OBI) system and pelvic bone-to-pelvic bone matching was performed. After applying the noted shift by using OPI, CBCT was performed by using the OBI system and prostate-to-prostate matching was performed. The isocenter shifts along all three translational directions in both techniques were combined into a three-dimensional (3-D) iso-displacement vector (IDV).Results: The mean (SD) IDV (in centimeters) calculated during the 250 imaging sessions was 0.931 (0.598, median 0.825) for OPI and 0.515 (336, median 0.43) for CBCT, p-value was less than 0.0001 which shows extremely statistical significant difference.Conclusion: Even after bone-to-bone matching by using OPI, a significant shift in prostate was observed on CBCT. This study concludes that imaging with CBCT provides a more accurate prostate localization than the OPI technique. Hence, CBCT should be chosen as the preferred imaging technique
Application of therapeutic drug monitoring of imatinib for individual treatment of gastrointestinal stromal tumor
Get PDFMany molecular target agents are continuously administered at fixed dosages. Imatinib, which can control the growth of a gastrointestinal stromal tumor, is administrated at 400 mg/day. However, many patients cannot continue treatment because of adverse events, such as neutropenia. To obtain the best therapeutic response while maintaining quality of life, individualization should be considered. Study participants were gastrointestinal stromal tumor patients who required treatment with imatinib. Therapeutic drug monitoring was conducted using high-performance liquid chromatography. In our study, the trough (lowest) concentration that a drug reaches before the next dose is administered differed among patients. The grades of adverse events also differed individually. Moreover, the dosage that was necessary to shrink gastrointestinal stromal tumor differed in cases by cases. Dosage was modified according to the balance between blood concentration and therapeutic responses in order to minimize adverse events for individual patients, and to maximize the effect as the responses differed among patients. It was shown that based on therapeutic drug monitoring, individualization enabled the patients who may not normally continue the typical treatment to tolerate imatinib. According to the therapeutic drug monitoring, individualization of dosage of imatinib could improve the patients’ outcomes in both ends, therapeutic and adeverse responses.
Uncertainties in the relative biological effectiveness of therapeutic proton beams associated with bias towards high doses per fraction in radiobiological experiments
Get PDFMost data supporting the widely accepted relative biological effectiveness (RBE) value of 1.1 for therapeutic proton beams are from radiobiological experiments with relatively high doses per fraction. The purpose of this study was to estimate bias in RBE that differences in dose levels between these experiments and proton radiotherapy treatments may cause. The linear quadratic model was applied to calculate, using prior experimental data, RBE variations with dose and a/b ratio for doses delivered in a standard fractionation regimen. The results suggest that the RBE measured at relatively high doses per fraction typical for a radiobiological experiment underestimates the RBE of proton radiotherapy with a standard fractionation. The bias increases with decreasing radiation dose and decreasing a/b ratio, suggesting that, if differences in dose levels are not accounted for, there may be a large underestimation of biological effects in late-responding tissues exposed to low doses of radiation
DVH Analysis of Cobalt-60 treatment plans incorporating a recently developed MLC
Get PDFPurpose: The aim of this investigation was to measure the gain in DVH indices when the recently developed MLC was used for Cobalt-60 treatments.Methods: A prototype multileaf collimator (MLC) that was retrofitted to telecobalt-60 therapy machine was reported and is currently proposed for clinical trials in our institution. Ten patients’ plans that were previously planned through an ECLIPSE® treatment planning system and were treated with open beams from Cobalt-60 machine were imported into Radiation Oncology Planning System [ROPS] and the dose calculations and dose volume histogram (DVH) analysis were performed. The plans were re-planned using the Cobalt-MLC, a feature available in the ROPS planning system. The DVH analysis consisted of conformity index (CI), homogeneity index (HI) and conformation number (CN). The results of this study are presented in this paper. The analysis specifically aimed at measuring the gain in these indices when the MLC was compared with open beams.Results: DVH Comparison of ten sites using open and Cobalt MLC fields showed that the use of MLC results in reduced normal tissue dose, while maintaining the GTV dose. Lower value of CI for normal structures was observed demonstrating the sparing of critical organs when MLC was used. The index HI was studied to show the significance of hot spots outside the PTV. Hot spots were observed even with MLC beams for some cases due to less number of fields.Conclusion: It has been demonstrated through DVH analysis that the use of the recently developed MLC for Cobalt Teletherapy machine results in benefit for the treatment of patients
A dosimetric dnalysis of flattening-filter-free mode linear accelerator-based stereotactic body radiation therapy and HDR brachytherapy for prostate cancer
Get PDFPurpose: Prior studies have reported that linear accelerator (LINAC)-based stereotactic body radiation therapy (SBRT) plans for prostate cancer are unable to achieve comparable intraprostatic doses to high-dose-rate brachytherapy (HDR). However, the utilization of flattening-filter-free (FFF) beams provides superior dose distributions compared with flattened beams. The purpose of this study was to test the feasibility of achieving the high intraprostatic doses observed in HDR by utilizing LINAC - based SBRT with FFF beams.Methods: We randomly selected 10 patients with localized prostate cancer previously treated at our institution in 2013. FFF-mode LINAC-based SBRT and simulated HDR (using virtual HDR catheters) plans were generated for each patient. The planning target volume (PTV) V100, V125, V150 and V200 values were compared between the two plans using the two-sided paired samples t-test.Results: Regarding the PTV coverage, the mean V100 was slightly higher for SBRT at 96.47% compared with 94.68% for HDR (p = 0.003). The V125 (61.69% versus 66.51%, p = 0.004) and V200 (15.06% versus 19.66%, p < 0.001) were slightly lower for SBRT. There were no significant differences in V150 between the two plans (47.59% versus 49.8%, p = 0.375). Rectal and bladder dosimetry were also comparable between the two modalities, though the rectal maximum dose was lower in the SBRT plan (99.6% versus 103.66%, p = 0.006) and the dose to 15cc of bladder was lower in the HDR plan (96.34% versus 78.18%, p = 0.005).Conclusion: Utilization of FFF mode LINAC-based SBRT allows for achievable dosimetry that is very similar to high dose rate brachytherapy. Further studies are warranted regarding the safety and efficacy of this modality.
Statistical evaluation of dosimetric differences changes between the Modified Batho's density correction method and the Anisotropic Analytical Algorithm for clinical practice
Get PDFPurpose: The aim of this work was to assess and to quantify, for clinical practice, the differences in computed doses using two types of dose calculation algorithm for the heterogeneity correction including target volumes and organs at risk (OARs).Methods: 35 patients having lung, breast, spine, head & neck, brain and pelvic tumors, were studied. For each patient, 2 treatment plans were generated. In plan 1, the dose was calculated using the Modified Batho's (MB) density correction method integrated in the Pencil Beam Convolution algorithm. In plan 2, the dose was calculated using the Anisotropic Analytical Algorithm (AAA). To compare the two plans a dosimetric analysis was carried out including cumulative and differential dose volume histograms (DVH), coverage index, and conformity index. Wilcoxon signed rank and Spearman’s tests were used to calculate p-values and correlation coefficients (r), respectively. Bootstrap simulation with 1000 random samplings was used to calculate the 95% confidence interval (95% CI).Results: The analysis of DVH showed that the AAA method calculated significantly higher doses for OARs for all cancer sites and lower doses for target volumes, especially for targets located in lung, with p < 0.05. The data demonstrated a strong correlation between MB and AAA for all cancer sites with r > 0.9.Conclusion: This study confirms that using the AAA integrated into Eclipse® TPS, the calculated dose will be increased to OARs, and reduced to target volumes. Thus, when changing from the MB algorithm to AAA, attention should be paid to avoid any bias of over/under estimating the dose given by AAA and to hold discussions between physicists and oncologists regarding any necessary modification in the prescription method
Dosimetric analysis of 3D-conformal radiotherapy and intensity modulated radiotherapy for treatment of advanced stage cervical cancer: A comparative study
Get PDFPurpose: The purpose of this study is to analyze the dosimetric parameters of three dimensional conformal radiotherapy (3DCRT), intensity modulated radiotherapy (IMRT) with seven and nine fields (7F-IMRT, 9F-IMRT) in selected advanced stage cervical cancer cases.Methods: Fifteen cases of cervical cancer (IIB to IIIB) were selected for retrospective analysis. All the cases were previously treated with 3DCRT technique with prescribed dose of 50 Gy in 25 fractions. For this study, plans with seven fields IMRT and nine fields IMRT were generated for all patients following Radiation Therapy Oncology Group (RTOG) guidelines. The plans were compared on the basis of planning target volume (PTV) coverage (dose to 1%, 5%, 95% and 99% of target), maximum dose and mean dose to organs at risk (OARs) and also doses at different volumes of OARs. Apart from this, uniformity index (UI), homogeneity index (HI), conformity index (CI) and dose spillage index (R50%) were also calculated with respect to PTV coverage.Results: The average dose value of PTV coverage for all three techniques were comparable and all the DVH indices for 7field IMRT (UI (1.04±0.01), HI (0.07 ±0.02), CI (0.75±0.03) and R50% (4.47±0.36)) were better than 3DCRT and 9F-IMRT techniques. All OAR doses were significantly reduced in 7F- IMRT compared to 3DCRT and 9F- IMRT. The target volumes ranged from 769.2 ml to 1375.6 ml with average target volume of 1071.9 ml (SD: 205.38 ml).Conclusion: This study showed that significant dose reduction to OARs could be achieved with seven field IMRT plans by maintaining the PTV coverage compared to 3DCRT or 9F- IMRT for treating cervical cancer in advanced stages particularly from IIB to IIIB
Dosimetric study of RapidArc plans and conventional intensity modulated radiotherapy for prostate cancer involving seminal vesicles and pelvis lymph nodes
Get PDFPurpose: The main purpose of this study is to (1) identify the continual diversity between conventional fixed field intensity modulation radiotherapy (IMRT) and RapidArc (RA) for high-risk prostate cancer; and (2) determine potential benefits and drawbacks of using for this type of treatment.Methods: A cohort of 20 prostate cases including prostate, seminal vesicles and pelvic lymph nodes was selected for this study. The primary planning target volume (PTVP) and boost planning target volume (PTVB) were contoured. The total prescription dose was 75.6 Gy (45 Gy to PTVP and an additional 21.6 Gy to PTVB). Two plans were generated for each PTV: multiple 7-fields for IMRT and two arcs for RA.Results: A Sigma index (IMRT: 2.75 ± 0.581; RA: 2.8 ± 0.738) for PTVP and (IMRT: 2.0 ± 0.484; RA: 2.1 ± 0.464) for PTVB indicated similar dose homogeneity inside the PTV. Conformity index (IMRT: 0.96 ± 0.047; RA: 0.95 ± 0.059) for PTVP and (IMRT: 0.97 ± 0.015; RA: 0.96 ± 0.014) for PTVB was comparable for both the techniques. IMRT offered lower mean dose to organ at risks (OARs) compared to RA plans. Normal tissue integral dose in IMRT plan resulted 0.87% lower than RA plans. All the plans displayed significant increase (2.50 times for PTVP and 1.72 for PTBB) in the average number of necessary monitor units (MUs) with IMRT beam. Treatment delivery time of RA was 2 ‒ 6 minutes shorter than IMRT treatment.Conclusion: For PTV including pelvic lymph nodes, seminal vesicles and prostate, IMRT offered a greater degree of OARs sparing. For PTV including seminal vesicles and prostate, RA with two arcs provided comparable plan with IMRT. RA also improved the treatment efficiency due to smaller number of MUs required
Dose-to-medium vs. dose-to-water: Dosimetric evaluation of head and neck VMAT cases using Monaco treatment planning system
Get PDFPurpose: In this paper, we evaluate the dosimetric differences between absorbed dose to water and absorbed dose to medium in Monte Carlo (MC)-based calculations used for radiation therapy treatment plans.Methods: Thirty-four treated Head and Neck simultaneously integrated boost cases were analyzed retrospectively. All of them were planned by Monaco treatment planning system (TPS), calculated and reviewed on absorbed dose to medium (Dm) calculations and treated in Elekta Versa HD LINAC. Absorbed dose to medium Dm was converted to absorbed dose to water Dw in Monaco treatment planning system using the procedure based on stopping power ratios and the Bragg-Gray cavity theory. Dosimetric parameters were then compared and analyzed with respect to absorbed dose to medium (Dm) calculations for multiple planning target volumes (PTVs) and critical organs such as brainstem, spinal cord, left and right lens, left and right parotids, larynx, left and right middle ear and lips.Results: It was found that mean and minimum Dw (i.e. Dw mean and Dw min) of organs at risk did not differ much (hardly differing by 0.8-2%) with respect to those of the absorbed dose to medium. However maximum Dw (i.e. Dw max) in case of lips, left and right middle ear were found to differ more than 4% with respect to Dm max. For serial organs brainstem and spinal cord, maximum dose Dw max were found to vary around 1% and 2%, respectively, with respect to absorbed dose to medium dose calculation. In case of PTVs, the mean percentages variation of Dw min and Dw mean were found to be less than 1 %, although the variation of maximum Dw was found to be high around 5-7% with respect to that of Dm.Conclusion: The comparative analysis of dosimetric parameters in the present study shows that the selection of either Dm or Dw in Monaco planning system is less likely to produce any significant clinical effect in tumor control and to the damage of organs at risk
Notch Signalling as a Therapeutic Target in Cancer
No full textNotch signalling is a conserved developmental pathway involved, inter alia, in cell-fate decision, morphogenesis and tissue patterning. Extensive research has linked this pathways with a variety of malignancies, cancer stem cell renewal, induction of epithelial-to-mesenchymal transition and tumor angiogenesis. These data indicate that Notch can act as both a tumor suppressor and an oncoprotein, depending upon cellular context and identify it as a potential therapeutic target in cancer treatment. This review discusses the implications of Notch in a number of hematologic and solid malignancies and some of the currently available inhibitors developed against this pathway as potential cancer therapeutics.