Increase In Tumor Control Probability Research Articles

Dosimetry comparison and evaluation of 3D and IMRT for left breast cancer radiotherapy techniques treated at ain wazein medical village hospital in Lebanon

Breast cancer patients undergoing radiation therapy can be treated using the 3D conformal or VMAT techniques. For both plans, the doses received by the target and the organs at risk are determined and compared with protocols recommended for the safety of the patients. CT simulations of 10 women with left breast cancer were used for a 3D conformal and VMAT treatment plans in the radiotherapy department of Ain Wazein Medical Village Hospital (AWMV) utilizing Monaco Treatment Planning system using Collapsed-cone and Monte Carlo algorithms respectively. The total prescribed dose to the PTV was 50 Gy in 25 fractions each 2 Gy. The dosimetric parameters obtained were mean, D95%, and homogeneity index for PTV; mean dose and max doses for the heart; the V20% for the left and the right lungs. All values of this retrospective study were analysed and compared to the normal tissue maximum dose tolerance. VMAT plans resulted in significantly better coverage for the target volume concepts as compared with 3D-CRT (D95: 97% vs. 82%, p-value = 0.002; Dmean 4953 cGy in 3D-CRT vs. 5093 cGy in VMAT, p-value = 0.01). The left lung (V20:28.44% with 3D-CRT vs. 21.93 with VMAT, p-value = 0.02). For the heart (Dmax = 4919 cGy in 3D-CRT vs. 4617 cGy in VMAT, p-value = 0.07). For the right lung (V20 was 0.12% in 3D-CRT vs. 0.52% in VMAT with p-value = 0.008). Even though the p-value was significant for the 3D conformal technique, the dose for both techniques was very low and non-significant to have a risk in the organ. The VMAT technique with correct target volume delineation allowed a significant dose escalation and an increase in Tumor Control Probability (TCP). VMAT resulted in an improved sparing of OARs as compared with 3D-CRT at equivalent dose levels.

“A comparative study using conventional concomitant chemoradiotherapy (using cisplatin-based chemotherapy) with accelerated (six fractions a week) chemoradiotherapy in inoperable or nonresectable locally advanced non-small cell lung cancers:” A prospective randomized trial

Context: The conventional concomitant chemoradiotherapy (CCRT) is the standard treatment for locally advanced non-small cell lung cancer. Accelerated CCRT results in shortening of overall treatment time which can contribute in controlling accelerated tumor repopulation. The increase in tumor control probability (TCP) can be expected with no or little effect on late normal tissue injury for a given total dose. Aim: The aim of this study was to compare the disease response, toxicity profile, quality of life (QoL), and overall survival in accelerated versus conventional CCRT. Subjects and Methods: Total 42 patients were randomized into two groups – study group (n = 21): Accelerated CCRT, radiation was given as 6 fractions per week (60 Gy/5 weeks/30#) with injection cisplatin 20 mg/m2 intravenous (iv) days 1–5 and days 29–33 + injection etoposide 50 mg/m2 iv days 1–5 and days 29–33 and control group (n = 21): Conventional CCRT, radiation was given as 5 fractions per week (60 Gy/6 weeks/30#) along with the same chemotherapy. External beam radiation therapy was delivered by cobalt-60 machines. Results: The overall response rate (complete and partial response) for all patients was 66.6%. In the control group, it was 66.2%, and in the study group, it was 66.6%. Grade ≥II pulmonary, hematological, and esophageal toxicities were seen in 57%, 43%, and 24% in patients of the control group and 53%, 53%, and 33% in the study group, respectively. In QoL analysis, maximum improvement was noted for hemoptysis, arm/shoulder pain, dyspnea, and chest pain in both the groups. Statistical Analysis Used: The data were analyzed by Student's t-test and Chi-square test. P

The potential for increased tumor control probability in non–small cell lung cancer with a hypofractionated integrated boost to the gross tumor volume

Treatment outcomes in locally advanced non–small cell lung cancer (NSCLC) to date have been poor, with normal tissue toxicity often limiting the dose that can be delivered to the tumor. Treatment intensification in NSCLC via targeted dose escalation with modern delivery techniques may offer the potential for a significant increase in tumor control probability (TCP) without a clinically significant increase in organ-at-risk (OAR) toxicity. In this planning study, 20 patients were re-planned with a volumetric modulated arc therapy (VMAT) and an inhomogeneous dose distribution with iteratively escalated doses to the gross tumor volume (iGTV) (composite GTV across multiple 4-dimensional computed tomography [4DCT] phases) in a series of 20 fraction regimes. For each plan OAR doses, target coverage and predicted TCPs were collected and compared with homogenous 3-dimensional (3D) and VMAT plans, as well as with each other. In 70% of patients, it was possible to escalate to 75 Gy in 20 fractions within OAR tolerances, opening the possibility of treating these patients to a biological effective dose (BED) of 103.1 Gy10. This planning study forms the basis of a clinical trial INTENSE (Inhomogeneous Targeted Dose Escalation in Non-Small CEll Lung Cancer), CTRIAL 15-47.

Quantifying the Combined Effect of Radiation Therapy and Hyperthermia in Terms of Equivalent Dose Distributions

To develop a method to quantify the therapeutic effect of radiosensitization by hyperthermia; to this end, a numerical method was proposed to convert radiation therapy dose distributions with hyperthermia to equivalent dose distributions without hyperthermia. Clinical intensity modulated radiation therapy plans were created for 15 prostate cancer cases. To simulate a clinically relevant heterogeneous temperature distribution, hyperthermia treatment planning was performed for heating with the AMC-8 system. The temperature-dependent parameters α (Gy(-1)) and β (Gy(-2)) of the linear-quadratic model for prostate cancer were estimated from the literature. No thermal enhancement was assumed for normal tissue. The intensity modulated radiation therapy plans and temperature distributions were exported to our in-house-developed radiation therapy treatment planning system, APlan, and equivalent dose distributions without hyperthermia were calculated voxel by voxel using the linear-quadratic model. The planned average tumor temperatures T90, T50, and T10 in the planning target volume were 40.5°C, 41.6°C, and 42.4°C, respectively. The planned minimum, mean, and maximum radiation therapy doses were 62.9 Gy, 76.0 Gy, and 81.0 Gy, respectively. Adding hyperthermia yielded an equivalent dose distribution with an extended 95% isodose level. The equivalent minimum, mean, and maximum doses reflecting the radiosensitization by hyperthermia were 70.3 Gy, 86.3 Gy, and 93.6 Gy, respectively, for a linear increase of α with temperature. This can be considered similar to a dose escalation with a substantial increase in tumor control probability for high-risk prostate carcinoma. A model to quantify the effect of combined radiation therapy and hyperthermia in terms of equivalent dose distributions was presented. This model is particularly instructive to estimate the potential effects of interaction from different treatment modalities.

Dose Escalation for Locally Advanced Lung Cancer Using Adaptive Radiation Therapy With Simultaneous Integrated Volume-Adapted Boost

To test the feasibility of a planned phase 1 study of image-guided adaptive radiation therapy in locally advanced lung cancer. Weekly 4-dimensional fan beam computed tomographs (4D FBCT) of 10 lung cancer patients undergoing concurrent chemoradiation therapy were used to simulate adaptive radiation therapy: After an initial intensity modulated radiation therapy plan (0-30 Gy/2 Gy), adaptive replanning was performed on week 2 (30-50 Gy/2 Gy) and week 4 scans (50-66 Gy/2 Gy) to adjust for volume and shape changes of primary tumors and lymph nodes. Week 2 and 4 clinical target volumes (CTV) were deformably warped from the initial planning scan to adjust for anatomical changes. On the week 4 scan, a simultaneous integrated volume-adapted boost was created to the shrunken primary tumor with dose increases in 5 0.4-Gy steps from 66 Gy to 82 Gy in 2 scenarios: plan A, lung isotoxicity; plan B, normal tissue tolerance. Cumulative dose was assessed by deformably mapping and accumulating biologically equivalent dose normalized to 2 Gy-fractions (EQD2). The 82-Gy level was achieved in 1 in 10 patients in scenario A, resulting in a 13.4-Gy EQD2 increase and a 22.1% increase in tumor control probability (TCP) compared to the 66-Gy plan. In scenario B, 2 patients reached the 82-Gy level with a 13.9 Gy EQD2 and 23.4% TCP increase. The tested image-guided adaptive radiation therapy strategy enabled relevant increases in EQD2 and TCP. Normal tissue was often dose limiting, indicating a need to modify the present study design before clinical implementation.

Risk-Adaptive Volumetric Modulated Arc Therapy Using Biological Objective Functions for Subvolume Boosting in Radiotherapy

Objectives. Simultaneous integrated boost (SIB) for prostate cancer allows increases in tumor control probability while respecting normal tissue dose constraints. Biological optimization functions that optimize based on treatment outcome can be used to create SIB prostate plans. This study investigates the feasibility of biologically optimized volumetric modulated arc therapy (VMAT) for SIB prostate radiotherapy. Methods. Five prostate cancer patients with diffusion-weighted MR images were selected for analysis. A two-step VMAT optimization was performed, which consisted of an initial biological optimization of a static gantry angle delivery followed by conversion of the static delivery to a single arc VMAT plan. A dosimetric analysis was performed on the resulting plans. Results. The VMAT plans resulted in a ΔEUD between the prostate and the boost volume of between 15.1 Gy and 20.3 Gy. Rectal volumes receiving 75.6 Gy ranged from 4.5 to 9.9%. Expected rectal normal tissue complication probabilities were between 8.6% and 21.4%. Maximum bladder doses ranged from 73.6 Gy to 75.8 Gy. Estimated treatment time was 120 s or less. Conclusions. The presented biological optimization method resulted in deliverable VMAT plans that achieved sufficient modulation for SIB without violating rectal and bladder dose constraints. Advances in knowledge. This study presents a method for creating simultaneous integrated boost VMAT treatments using biological outcome objective functions.

SU‐D‐BRB‐04: A Monte Carlo Based Approach to Electron Beam Treatment Planning

Purpose: Electron radiotherapy (RT) offers a number of advantages over photons. The high surface dose, combined with a rapid dose fall‐off beyond the target volume presents a net increase in tumor control probability and decreases the normal tissue complication for superficial tumors. The current techniques involving electron RT are more seldom used than photon therapy due to the complexity of the electron transport involved and greater error in planning accuracy. Electron treatments are normally delivered clinically without previously calculated dose distributions. Our current research aims to use Monte Carlo (MC) methods to model clinical electron beams in order to accurately calculate electron beam dose distributions in patients. In addition to this, electron output factors can be quickly calculated, reducing the need for a clinical measurement. Methods: The present work is incorporated into a research MC calculation system: McGill Monte Carlo Treatment Planning (MMCTP) system. MMCTP streamlines the calculation of output factors for various electron beam energies and applicator sizes. Measurements of PDDs, profiles and output factors in addition to 2D EBT‐2 GAFCHROMIC measurements in heterogeneous phantoms were obtained to commission the electron beam model. Results: Forty‐nine output factors were measured and calculated. The mean percentage difference between measured and calculated was 1.35% with a maximum of 3.27%. The mean error and calculation time of the calculations were found to be 1.64% and 2 hours respectively. A dose difference of 3% and distance‐to‐agreement of 3 mm were used to compare two dimensional dose maps using the gamma method, yielding a good outcome. Conclusions: The use of MC for electron TP will provide more accurate treatments and yield greater knowledge of the electron dose distribution within the patient. The calculation of output factors could invoke a clinical time saving of up to 1 hour per patient.

SU‐E‐T‐14: Predicted Biological Effectiveness of Treatments Delivered Using Dynamic MLC IMRT versus VMAT

Purpose: Intensity Modulated Radiation Therapy (IMRT) is an effective method of maximizing dose conformity while minimizing damage to healthy tissue. The spatial effects of IMRT are commonly used as a technique to evaluate treatment quality. However, the use of spatial information alone neglects that cell survival is directly related to the temporal dose deposition. This study uses the linear quadratic (LQ) model, with the Lea‐Catcheside dose protraction factor in order to investigate the change in biological effectiveness between IMRT modalities, including sliding window (DMLC) and volumetric modulated arc therapy (VMAT). Methods: The dose‐time relationship was measured using Lucite phantom and an ion chamber. Measurements were taken for both prostate and head/neck plans. A specific coordinate was chosen in the tumor and the dose rate was measured as a function of time. The temporal dose deposition was used to calculate the dose protraction factor and the effective total dose (ETD) with varying repair half‐times and α/β ratios. The biological effectiveness was further studied using a Poisson model of tumor control probability (TCP). Results: Switching from VMAT to DMLC, for both the prostate and head/neck treatments, revealed a drop in the biological effects. A comparison of the DMLC and VMAT techniques showed a percentage loss of ETD for both anatomical sites. Differences in the protraction factor for DMLC and VMAT also contributed to a shift in the TCP model. The tumor control results revealed an overall increase in tumor control probability for VMAT compared to DMLC Conclusions: Comparing DMLC and VMAT techniques demonstrates that temporal dose deposition is an important characteristic in determining the biological effects from different treatment modalities. Although uncertainties in biological parameters prevents clinical application of these results this study still illustrates that the shorter treatment times characteristic of VMAT plans is preferable to the longer DMLC plans.

Improvement in tumour control probability with active breathing control and dose escalation: A modelling study

Introduction The prognosis from non-small cell lung cancer remains poor, even in those patients suitable for radical radiotherapy. The ability of radiotherapy to achieve local control is hampered by the sensitivity of normal structures to irradiation at the high tumour doses needed. This study aimed to look at the potential gain in tumour control probability from dose escalation facilitated by moderate deep inspiration breath-hold. Method The data from 28 patients, recruited into two separate studies were used. These patients underwent planning with and without the use of moderate deep inspiration breath-hold with an active breathing control (ABC) device. Whilst maintaining the mean lung dose (MLD) at the level of the conventional plan, the ABC plan dose was theoretically escalated to a maximum of 84 Gy, constrained by usual normal tissue tolerances. Calculations were performed using data for both lungs and for the ipsilateral lung only. Resulting local progression-free survival at 30 months was calculated using a standard logistic model. Results The prescription dose could be escalated from 64 Gy to a mean of 73.7 ± 6.5 Gy without margin reduction, which represents a statistically significant increase in tumour control probability from 0.15 ± 0.01 to 0.29 ± 0.11 ( p < 0.0001). The results were not statistically different whether both lungs or just the ipsilateral lung was used for calculations. Conclusion A near-doubling of tumour control probability is possible with modest dose escalation, which can be achieved with no extra increase in lung dose if deep inspiration breath-hold techniques are used.

Hypoxia Dose Painting by Numbers: A Planning Study

To investigate the feasibility of different hypoxia dose painting strategies in head-and-neck radiotherapy; the potential benefit was limited by the stipulation of isotoxicity with respect to the conventional intensity-modulated radiotherapy (IMRT) treatment. Thirteen head-and-neck cancer patients were included into the planning study. For each patient, three different treatment plans were created: a conventional IMRT plan, an additional uniform dose escalation (uniDE) of 10% to the fluorodeoxyglucose (FDG)-positive volume, and a plan in which dose painting by numbers (DPBN) was implemented. Dose painting by numbers was realized according to a map of dose-escalation factors calculated from dynamic [(18)F]-fluoromisonidazole (FMISO) positron emission tomography data. Both dose-escalation approaches were shown to be feasible under the constraint of limiting normal tissue doses to the level of conventional IMRT. For DPBN, the prescriptions could be fulfilled in larger regions of the target than for uniDE. Fluorodeoxyglucose-positive volumes had sizes up to 94 cm(3). In contrast, regions receiving comparable dose levels with DPBN presented volumes in the range of 0-2.7 cm(3). Overtreatment of the target was observed with uniDE in most of the cases, whereas some regions did not receive the required dose to overcome hypoxia-induced radiation insensitivity. Tumor control probability increased from 55.9% with conventional IMRT to 57.7% for the uniDE method in the patient group. For DPBN, a potential increase in tumor control probability from 55.9% to 70.2% was determined. Therefore, DPBN seems to result in higher benefits for the patients. Dose painting by numbers delivers the dose more effectively than an additional uniform boost to the FDG-positive area. If hypoxia could be adequately quantified with a simple imaging technique like FMISO positron emission tomography, DPBN in head-and-neck cancer could substantially increase tumor control.

On the possible increase in local tumour control probability for gliomas exhibiting low dose hyper-radiosensitivity using a pulsed schedule

Using modelling, we have developed a treatment strategy for gliomas exhibiting low dose hyper-radiosensitivity (HRS) that employs both a reduced dose-rate and pulsed treatment dose delivery. The model exploits the low dose hypersensitivity observed in some glioma cell lines at low radiation doses. We show, based on in vitro data, that a pulsed delivery of external beam radiation therapy could yield significant increases in local control. We therefore propose a pulsed delivery scheme for the treatment of gliomas in which the daily treatment fraction is delivered using 0.20 Gy pulses, separated by three minutes for a time-averaged dose-rate of 0.0667 Gy/min. The dose per pulse of 0.2 Gy is near or below the transition dose observed in vitro for four of the five glioma cell lines we have studied. Using five established glioma cell lines our modelling demonstrates that our pulsed delivery scheme yields a substantial increase in tumour control probability (TCP).

Prediction of normal tissue response and individualization of doses in radiotherapy

In this work we estimate the therapeutic gain that could be obtained using a radiotherapy programme in which doses were based on a radiosensitivity test that was able to predict the final response of normal tissues to radiation for each particular patient. To date, no good radiosensitivity assay has been demonstrated and by way of example we use an assay based on initial DNA damage. The individualized programme we propose is based on an increase in the dose delivered to patients showing a resistant behaviour to radiation and on the adoption of alternative programmes or a careful monitoring of those patients in whom an excessive reaction is expected. To quantify the results produced by the individualization programme, both analytical and Monte Carlo simulation methods are used. The increase in tumour control probability obtained by means of this individualization strongly depends on the dose-response curve for the particular tumour. In certain cases, this enhancement can be marked, and 40% of the patients considered in this work could attain more than 10% increase in tumour control probability. The quantitative estimations in this study indicate the need to seek a predictive assay of radiosensitivity, for both normal and tumour tissue response, in order to develop individualized treatment protocols.

A quantitative treatment planning study evaluating the potential of dose escalation in conformal radiotherapy of the oesophagus

Background and purpose: This study aims to evaluate the reduction in radiation dose to normal thoracic structures through the use of conformal radiotherapy techniques in the treatment of oesophageal cancer, and to quantify the resultant potential for dose escalation. Materials and methods: Three different CT-derived treatment plans were created and compared for each of ten patients. A two-phase treatment with conventional straight-edged fields and standard blocks (CV2), a two-phase conformal plan (CF2), and a three-phase conformal plan where the third phase was delivered to the gross tumour only (CF3), were considered for each patient. Escalated dose levels were determined for techniques CF2 and CF3, which by virtue of the conformal field shaping, did not increase the mean lung dose. The resulting increase in tumour control probability (TCP) was estimated. Results: A two-phase conformal technique (CF2) reduced the volume of lung irradiated to 18 Gy from 19.7±11.8 (1 SD) to 17.1±12.3% ( P=0.004), and reduced the normal tissue complication probability (NTCP) from 2.4±4.0 to 0.7±1.6% ( P=0.02) for a standard prescribed dose of 55 Gy. Consequently, technique CF2 permitted a target dose of 59.1±3.2 Gy without increasing the mean lung dose. Technique CF3 facilitated a prescribed dose of 60.7±4.3 Gy to the target, the additional 5 Gy increasing the TCP from 53.1±5.5 to 68.9±4.1%. When the spinal cord tolerance was raised from 45 to 48 Gy, technique CF3 allowed 63.6±4.l Gy to be delivered to the target, thereby increasing the TCP to 78.1±3.2%. Conclusions: Conformal radiotherapy techniques offer the potential for a 5–10 Gy escalation in dose delivered to the oesophagus, without increasing the mean lung dose. This is expected to increase local tumour control by 15–25%.

Interactions between ascorbic acid and the radiation of bone marrow, skin, and tumor

In studies of isotransplants of a murine fibrosarcoma, FSaII, ascorbic acid administered 50 min before whole-body radiation significantly increased the dose of radiation required to cause a fatal radiation syndrome and the dose of radiation required to obtain skin desquamation. A single intraperitoneal dose of 4.5 g/kg body wt was not cytotoxic and did not affect the radiation dose required to control 50% of tumors or to achieve remissions. The mechanism of this differential radiomodification of normal tissue sensitivity and tumor tissue response is unclear. The data suggest that after high-dose ascorbic acid the radiation dose given to cancer patients could be increased without increasing acute complications but with an expected increase in tumor-control probability. However, only acute radiation reaction endpoints have been studied. Application of these findings to humans must therefore await further studies confirming that late reacting tissues are similarly protected by ascorbic acid.