To prospectively study acute rectal and urinary reactions from three-dimensional conformal external beam radiotherapy for localized prostate cancer comparing two hypofractionation regimens with ...standard fractionation (standard). The hypofractionation regimens were designed to avoid more late reactions in the hypofractionation groups than in the standard group, with the advantage of one-half as many treatment sessions.
A total of 56 nonrandomized patients chose hypofractionation delivered at 3 (n = 22) or 3.15 (n = 34) Gy/fraction, 4 d/wk, to a total dose of 60 or 63 Gy within 5 weeks. A total of 74 patients were contemporarily treated with standard fractionation at 2 Gy/fraction, 5 d/wk, to a total dose of 76 to 80 Gy.
The differences within patients without complications were not statistically significant in the three groups. However, for acute complications of Grade 2 or worse, the Hypo3.15 group had significantly greater (p = 0.001) complication rates (50%) compared with the standard group (17%). The incidence of patients without acute rectal complications was significantly lower for the Hypo3.15 group compared with the Hypo3 and standard groups. The incidence of rectal Grade 2 or greater complications was correspondingly significantly greater for the Hypo3.15 group than for the Hypo3 and standard groups (p < 0.001). The incidence of patients with urinary complications was not significantly different among the three groups.
Acute rectal reactions were more frequent and intense in the Hypo3.15 group than in the Hypo3 and standard groups. In our study, 60 Gy at 3 Gy/fraction within 5 weeks resulted in acute toxicity similar to that after standard fractionation.
In 1989 the British Journal of Radiology published a review proposing the term biologically effective dose (BED), based on linear quadratic cell survival in radiobiology. It aimed to indicate ...quantitatively the biological effect of any radiotherapy treatment, taking account of changes in dose-per-fraction or dose rate, total dose and (the new factor) overall time. How has it done so far? Acceptable clinical results have been generally reported using BED, and it is in increasing use, although sometimes mistaken for "biologically equivalent dose", from which it differs by large factors, as explained here. The continuously bending nature of the linear quadratic curve has been questioned but BED has worked well for comparing treatments in many modalities, including some with large fractions. Two important improvements occurred in the BED formula. First, in 1999, high linear energy transfer (LET) radiation was included; second, in 2003, when time parameters for acute mucosal tolerance were proposed, optimum overall times could then be "triangulated" to optimise tumour BED and cell kill. This occurs only when both early and late BEDs meet their full constraints simultaneously. New methods of dose delivery (intensity modulated radiation therapy, stereotactic body radiation therapy, protons, tomotherapy, rapid arc and cyberknife) use a few large fractions and obviously oppose well-known fractionation schedules. Careful biological modelling is required to balance the differing trends of fraction size and local dose gradient, as explained in the discussion "How Fractionation Really Works". BED is now used for dose escalation studies, radiochemotherapy, brachytherapy, high-LET particle beams, radionuclide-targeted therapy, and for quantifying any treatments using ionising radiation.
Optimum fractionation in radiotherapy occurs when tumor control is improved without enhancement of complications. The main influence on choice of overall time, total dose and fraction size is ...biological: the proliferation status of tumors. For rapidly proliferating tumors, shorter schedules than 6 to 8 weeks are necessary. Optimum overall time is similar to Tk, the time after beginning cytotoxic treatment when rapid proliferation in tumors starts: 21 to 35 days in head and neck tumors. These, and non-small cell lung tumors, have a clonogenic cell doubling time during radiotherapy of about 3 days. New developments in designing optimum schedules for such tumors are presented: carefully regulated hypofractionation (CRH). For slowly proliferating tumors, especially prostate adenocarcinoma, intracellular repair is large, so larger doses per fraction will be necessary. New evidence is presented showing that their f g ratio may indeed be lower than 3 Gy. For an entirely different reason from that above, hypofractionation should be tested.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
The purpose of this study was to examine the reliability and validity of the Toolkit After-Death Bereaved Family Member Interview to measure quality of care at the end of life from the unique ...perspective of family members. The survey included proposed problem scores (a count of the opportunity to improve the quality of care) and scales. Data were collected through a retrospective telephone survey with a family member who was interviewed between 3 and 6 months after the death of the patient. The setting was an outpatient hospice service, a consortium of nursing homes, and a hospital in New England. One hundred fifty-six family members from across these settings participated. The 8 proposed domains of care, as represented by problem scores or scales, were based on a conceptual model of patient-focused, family-centered medical care. The survey design emphasized face validity in order to provide actionable information to health care providers. A correlational and factor analysis was undertaken of the 8 proposed problem scores or scales. Cronbach's alpha scores varied from 0.58 to 0.87, with two problem scores (each of which had only 3 survey items) having a low alpha of 0.58. The mean item-to-total correlations for the other problem scores varied from 0.36 to 0.69, and the mean item-to-item correlations were between 0.32 and 0.70. The proposed problem scores or scales, with the exception of closure and advance care planning, demonstrated a moderate correlation (i.e., from 0.44 to 0.52) with the overall rating of satisfaction (as measured by a five-point, “excellent” to “poor” scale). Family members of persons who died with hospice service reported fewer problems in each of the six domains of medical care, gave a higher rating of the quality of care, and reported higher self-efficacy in caring for their loved ones. These results indicate that 7 of the 8 proposed problem scores or scales demonstrated psychometric properties that warrant further testing. The domain of closure demonstrated a poor correlation with overall satisfaction and requires further work. This survey could provide information to help guide quality improvement efforts to enhance the care of the dying.
To examine the fractionation effect of stereotactic body radiation therapy with a heterogeneous dose distribution.
Derived from the linear quadratic formula with measurements from a hypothetical 2-cm ...radiosurgical tumor, the threshold percentage was defined as (α/β(tissue)/α/β(tumor)), the balance α/β ratio was defined as (prescription dose/tissue tolerance*α/β(tumor)), and the balance dose was defined as (tissue tolerance/threshold percentage).
With increasing fractions and equivalent peripheral dose to the target, the biological equivalent dose of "hot spots" in a target decreases. The relative biological equivalent doses of serial organs decrease only when the relative percentage of its dose to the prescription dose is above the threshold percentage. The volume of parallel organs at risk decreases only when the tumor's α/β ratio is above the balance α/β ratio and the prescription dose is lower than balance dose.
The potential benefits of fractionation in stereotactic body radiation therapy depend on the complex interplay between the total dose, α/β ratios, and dose differences between the target and the surrounding normal tissues.
Starting in 2002, the Radiation Therapy Oncology Group in North America began the process of developing multicenter prospective trials in lung cancer using Stereotactic Body Radiation Therapy (SBRT). ...Much of the work was based on the prospective single institution trials from Indiana University that had been presented and published. In late 2004, RTOG 0236 using SBRT for medically inoperable patients with clinical stage I non-small cell lung cancer (NSCLC) was activated for accrual. Prior to activation, representatives from the Lung, Image-Guided Therapy, Physics, and Radiobiology Committees met on regular occasions to design the multicenter study and quality assurance measures. SBRT is not a black box, and the essence of the therapy had to be distilled via guidelines. Issues related to patient selection, method of dosimetry construction, equipment requirements, motion assessments and control, site accreditation, data exchange, and follow-up policies were worked out by compromise and consensus. RTOG 0236 has nearly completed its accrual. The Lung Committee has initiated the development of several other trials, each building on the last, to investigate the therapy in central tumors, in combinations with systemic therapy, in operable patients, and in lung metastases patients. The guidelines developed for RTOG 0236 will be refined to take advantage of more modern innovations including heterogeneity corrections and intensity modulation when appropriate. The development of RTOG 0618 using SBRT in operable patients with early stage NSCLC is a testament to both the enthusiasm from already published works and prospective multicenter clinical testing using SBRT techniques.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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