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Biomedical subjects

Michael Goitein

Publications and source records attributed to Michael Goitein.

10 recordsLinked to original sources
PubMed2007

Secondary carcinogenesis in patients treated with radiation: a review of data on radiation-induced cancers in human, non-human primate, canine and rodent subjects.

Concern for risk of radiation-induced cancer is growing with the increasing number of cancer patients surviving long term. This study examined data on radiation transformation of mammalian cells in vitro and on the risk of an increased cancer incidence after irradiation of mice, dogs, monkeys, atomic bomb survivors, occupationally exposed persons, and patients treated with radiation. Transformation of cells lines in vitro increased linearly with dose from approximately 1 to approximately 4-5 Gy. At <0.1 Gy, transformation was not increased in all studies. Dose-response relationships for cancer incidence varied with mouse strain, gender and tissue/organ. Risk of cancer in Macaca mulatta was not raised at 0.25-2.8 Gy. From the atomic bomb survivor study, risk is accepted as increasing linearly to 2 Sv for establishing exposure standards. In irradiated patients, risk of cancer increased significantly from 1 to 45 Gy (a low to a high dose level) for stomach and pancreas, but not for bladder and rectum (1-60 Gy) or kidney (1-15 Gy). Risk for several organs/tissues increased substantially at doses far above 2 Gy. There is great heterogeneity in risk of radiation-associated cancer between species, strains of a species, and organs within a species. At present, the heterogeneity between and within patient populations of virtually every parameter considered in risk estimation results in substantial uncertainty in quantification of a general risk factor. An implication of this review is that reduced risks of secondary cancer should be achieved by any technique that achieved a dose reduction down to approximately [corrected] 0.1 Gy, i.e. dose to tissues distant from the target. The proportionate gain should be greatest for dose decrement to less than 2 Gy.

Animals↗
PubMed2006

Proton beam irradiation for neovascular age-related macular degeneration.

OBJECTIVE: To evaluate safety and visual outcomes after proton therapy for subfoveal neovascular age-related macular degeneration (AMD). DESIGN: Randomized dose-ranging clinical trial. PARTICIPANTS: One hundred sixty-six patients with angiographic evidence of classic choroidal neovascularization resulting from AMD and best-corrected visual acuity of 20/320 or better. METHODS: Patients were assigned randomly (1:1) to receive 16-cobalt gray equivalent (CGE) or 24-CGE proton radiation in 2 equal fractions. Visual acuity was measured using standardized protocol refraction. Complete ophthalmological examinations, color fundus photography, and fluorescein angiography were performed before and 3, 6, 12, 18, and 24 months after treatment. MAIN OUTCOME MEASURE: Proportion of eyes losing 3 or more lines of vision from baseline. Kaplan-Meier statistics were used to compare cumulative rates of vision loss between the 2 treatment groups. RESULTS: At 12 months after treatment, 36 eyes (42%) and 27 eyes (35%) lost 3 or more lines of vision in the 16-CGE and 24-CGE groups, respectively. Rates increased to 62% in the 16-CGE group and 53% in the 24-CGE group by 24 months after treatment (P = 0.40). Radiation complications developed in 15.7% of patients receiving 16 CGE and 14.8% of patients receiving 24 CGE. CONCLUSIONS: No significant differences in rates of visual loss were found between the 2 dose groups. Proton radiation may be useful as an adjuvant therapy or as an alternative for patients who decline or are not appropriate for approved therapies.

Aged↗
PubMed2005

Swedish protons.

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Humans↗
PubMed2004

Organ and tumor motion: an overview.

An overview is presented of some of the issues that arise when considering how to manage motion of the patient (including setup errors), the tumor within the patient, and normal tissues that are sufficiently close to the tumor as to be likely to be at least partially irradiated. Problems arise in 3 areas: (1) at the tumor periphery where the question of just where the tumor surface is must be decided, (2) within the tumor proper where interplay effects between tumor motion and the radiation application (eg, in intensity-modulated radiation therapy) may result in dose inhomogeneity within the tumor, and (3) just outside the target volume where the extent to which organs at risk are to be irradiated (which needs to be based on an estimate of the consequences to them) must be decided. In the context of these problems, one must decide how to deal with potential motion. This involves 3 issues: (1) how to limit motion-the available techniques ranging from simple and unobtrusive to complicated, quasi-invasive, and quite costly; (2) how to handle the residual motion; and (3) how to calculate and present the consequences of the residual motion. These issues are discussed, and the importance of an explicit estimation of uncertainty is emphasized.

Humans↗
PubMed2003

Intensity modulation in radiotherapy: photons versus protons in the paranasal sinus.

PURPOSE: The purpose of this study is to investigate whether successive tightening of normal tissue constraints on an intensity modulated X-ray therapy plan might be able to improve it to the point of clinical comparability with the corresponding intensity modulated proton therapy plan. MATERIALS AND METHODS: Photon and proton intensity modulated plans were calculated for a paranasal sinus case using nominal dose constraints. Additional photon plans were then calculated in an effort to match the dose-volume histograms of the critical structures to those of the proton plan. RESULTS: On reducing the low dose contribution to both orbits in the photon plan by tightening the constraints on these structures, an increased dose heterogeneity across the target resulted. When all critical structures were more strictly constrained, target dose homogeneity and conformity was further compromised. An increased integral dose to the non-critical normal tissues was observed for the photon plans as dose was progressively removed from the critical structures. CONCLUSIONS: Both modalities were found to provide comparable target volume conformation and sparing of critical structures, when the nominal dose constraints were applied. However, the use of intensity modulated protons provided the only method by which critical structures could be spared at all dose levels, whilst simultaneously providing acceptable dose homogeneity within the target volume.

Algorithms↗
PubMed2002

Effects of intra-fraction motion on IMRT dose delivery: statistical analysis and simulation.

There has been some concern that organ motion, especially intra-fraction organ motion due to breathing, can negate the potential merit of intensity-modulated radiotherapy (IMRT). We wanted to find out whether this concern is justified. Specifically, we wanted to investigate whether IMRT delivery techniques with moving parts, e.g., with a multileaf collimator (MLC), are particularly sensitive to organ motion due to the interplay between organ motion and leaf motion. We also wanted to know if, and by how much, fractionation of the treatment can reduce the effects. We performed a statistical analysis and calculated the expected dose values and dose variances for volume elements of organs that move during the delivery of the IMRT. We looked at the overall influence of organ motion during the course of a fractionated treatment. A linear-quadratic model was used to consider fractionation effects. Furthermore, we developed software to simulate motion effects for IMRT delivery with an MLC, with compensators, and with a scanning beam. For the simulation we assumed a sinusoidal motion in an isocentric plane. We found that the expected dose value is independent of the treatment technique. It is just a weighted average over the path of motion of the dose distribution without motion. If the treatment is delivered in several fractions, the distribution of the dose around the expected value is close to a Gaussian. For a typical treatment with 30 fractions, the standard deviation is generally within 1% of the expected value for MLC delivery if one assumes a typical motion amplitude of 5 mm (1 cm peak to peak). The standard deviation is generally even smaller for the compensator but bigger for scanning beam delivery. For the latter it can be reduced through multiple deliveries ('paintings') of the same field. In conclusion, the main effect of organ motion in IMRT is an averaging of the dose distribution without motion over the path of the motion. This is the same as for treatments with conventional beams. Additional effects that are specific to the IMRT delivery technique appear to be relatively small, except for the scanning beam.

Computer Simulation↗
PubMed2002

Relative biological effectiveness (RBE) values for proton beam therapy.

PURPOSE: Clinical proton beam therapy has been based on the use of a generic relative biological effectiveness (RBE) of 1.0 or 1.1, since the available evidence has been interpreted as indicating that the magnitude of RBE variation with treatment parameters is small relative to our abilities to determine RBEs. As substantial clinical experience and additional experimental determinations of RBE have accumulated and the number of proton radiation therapy centers is projected to increase, it is appropriate to reassess the rationale for the continued use of a generic RBE and for that RBE to be 1.0-1.1. METHODS AND MATERIALS: Results of experimental determinations of RBE of in vitro and in vivo systems are examined, and then several of the considerations critical to a decision to move from a generic to tissue-, dose/fraction-, and LET-specific RBE values are assessed. The impact of an error in the value assigned to RBE on normal tissue complication probability (NTCP) is discussed. The incidence of major morbidity in proton-treated patients at Massachusetts General Hospital (MGH) for malignant tumors of the skull base and of the prostate is reviewed. This is followed by an analysis of the magnitude of the experimental effort to exclude an error in RBE of >or=10% using in vivo systems. RESULTS: The published RBE values, using colony formation as the measure of cell survival, from in vitro studies indicate a substantial spread between the diverse cell lines. The average value at mid SOBP (Spread Out Bragg Peak) over all dose levels is approximately 1.2, ranging from 0.9 to 2.1. The average RBE value at mid SOBP in vivo is approximately 1.1, ranging from 0.7 to 1.6. Overall, both in vitro and in vivo data indicate a statistically significant increase in RBE for lower doses per fraction, which is much smaller for in vivo systems. There is agreement that there is a measurable increase in RBE over the terminal few millimeters of the SOBP, which results in an extension of the bioeffective range of the beam in the range of 1-2 mm. There is no published report to indicate that the RBE of 1.1 is low. However, a substantial proportion of patients treated at approximately 2 cobalt Gray equivalent (CGE)/fraction 5 or more years ago were treated by a combination of both proton and photon beams. Were the RBE to be erroneously underestimated by approximately 10%, the increase in complication frequency would be quite serious were the complication incidence for the reference treatment >or=3% and the slope of the dose response curves steep, e.g., a gamma(50) approximately 4. To exclude >or=1.2 as the correct RBE for a specific condition or tissue at the 95% confidence limit would require relatively large and multiple assays. CONCLUSIONS: At present, there is too much uncertainty in the RBE value for any human tissue to propose RBE values specific for tissue, dose/fraction, proton energy, etc. The experimental in vivo and clinical data indicate that continued employment of a generic RBE value and for that value to be 1.1 is reasonable. However, there is a local "hot region" over the terminal few millimeters of the SOBP and an extension of the biologically effective range. This needs to be considered in treatment planning, particularly for single field plans or for an end of range in or close to a critical structure. There is a clear need for prospective assessments of normal tissue reactions in proton irradiated patients and determinations of RBE values for several late responding tissues in laboratory animal systems, especially as a function of dose/fraction in the range of 1-4 Gy.

Animals↗
PubMed2002

Evidence-based estimates of outcome in patients irradiated for intraocular melanoma.

BACKGROUND: Melanoma of the eye is the only potentially fatal ocular malignancy in adults. Until radiation therapy gained wide acceptance in the 1980s, enucleation was the standard treatment for the tumor. Long-term results after proton beam irradiation are now available. METHODS: We developed risk score equations to estimate probabilities of the 4 principal treatment outcomes-local tumor recurrence, death from metastasis, retention of the treated eye, and vision loss-based on an analysis of 2069 patients treated with proton beam radiation for intraocular melanoma between July 10, 1975, and December 31, 1997. Median follow-up in surviving patients was 9.4 years. RESULTS: Tumor regrowth occurred in 60 patients, and 95% of tumors (95% confidence interval, 93%-96%) were controlled locally at 15 years. Risk scores were developed for the other 3 outcomes studied. Overall, the treated eye was retained by 84% of patients (95% confidence interval, 80%-87%) at 15 years. The probabilities for vision loss (visual acuity worse than 20/200) ranged from 100% to 20% at 10 years and for death from tumor metastases from 95% to 35% at 15 years, depending on the risk group. CONCLUSIONS: High-dose radiation treatment was highly effective in achieving local control of intraocular melanomas. In most cases, the eye was salvaged, and functional vision was retained in many patients. The mortality rate was high in an identifiable subset of patients who may benefit from adjuvant therapies directed at microscopic liver metastases.

Adolescent↗