PURPOSE: To investigate whether current fractionation and brachytherapy protraction schemes for the treatment of prostatic cancer with radiation are optimal, or could be improved. METHODS AND MATERIALS: We analyzed two mature data sets on radiotherapeutic tumor control for prostate cancer, one using EBRT and the other permanent seed implants, to extract the sensitivity to changes in fractionation of prostatic tumors. The standard linear-quadratic model was used for the analysis. RESULTS: Prostatic cancers appear significantly more sensitive to changes in fractionation than most other cancers. The estimated alpha/beta value is 1.5 Gy [0.8, 2.2]. This result is not too surprising as there is a documented relationship between cellular proliferative status and sensitivity to changes in fractionation, and prostatic tumors contain exceptionally low proportions of proliferating cells. CONCLUSIONS: High dose rate (HDR) brachytherapy would be a highly appropriate modality for treating prostate cancer. Appropriately designed HDR brachytherapy regimens would be expected to be as efficacious as low dose rate, but with added advantages of logistic convenience and more reliable dose distributions. Similarly, external beam treatments for prostate cancer can be designed using larger doses per fraction; appropriately designed hypofractionation schemes would be expected to maintain current levels of tumor control and late sequelae, but with reduced acute morbidity, together with the logistic and financial advantages of fewer numbers of fractions.
Curr Oncol. 2012 Jun ;19 (3):e201-10 22670110
Quality-of-life outcomes in high-risk prostate cancer patients treated with helical tomotherapy in a hypofractionated radiation schedule with long-term androgen suppression.
N Pervez, A V Krauze, D Yee, M Parliament, A Mihai, S Ghosh, K Joseph, A Murtha, J Amanie, M Kamal, R Pearcey
Radiation Oncology, Cross Cancer Institute, Edmonton, AB. Nadeem.Pervez@albertahealthservices.ca
PURPOSE We examined the impact of hypofractionated radiation therapy and androgen suppression therapy (AST) on quality of life (QOL) in high-risk prostate cancer patients. METHODS Between March 2005 and March 2007, 60 patients with high-risk prostate cancer were enrolled in a prospective phase ii study. All patients received 68 Gy (2.72 Gy per fraction) to the prostate gland and 45 Gy (1.8 Gy per fraction) to the pelvic lymph nodes in 25 fractions over 5 weeks. Of the 60 patients, 58 received ast. The University of California-Los Angeles Prostate Cancer Index questionnaire was used to prospectively measure QOL at baseline (month 0) and at 1, 6, 12, 18, 24, 30, and 36 months after radiation treatment. The generalized estimating equation approach was used to compare the QOL scores at 1, 6, 12, 18, 24, 30, and 36 months with those at baseline. RESULTS We observed a significant decrease in QOL items related to bowel and sexual function. Several QOL items related to bowel function were significantly adversely affected at both 1 and 6 months, with improvement toward 6 months. Although decreased QOL scores persisted beyond the 6-month mark, they began to re-approach baseline at the 18- to 24-month mark. Most sexual function items were significantly adversely affected at both 1 and 6 months, but the effects were not considered to be a problem by most patients. A complete return to baseline was not observed for either bowel or sexual function. Urinary function items remained largely unaffected, with overall urinary function being the only item adversely affected at 6 months, but not at 1 month. Urinary function returned to baseline and remained unimpaired from 18 months onwards. CONCLUSIONS In our study population, who received hypofractionated radiation delivered using dynamic intensity-modulated radiotherapy with inclusion of the pelvic lymph nodes, and 2-3 years of ast prescription, QOL with respect to bowel and sexual function was significantly affected; QOL with respect to urinary function was largely unaffected. Our results are comparable to those in other published studies.
J Med Phys. 2012 Apr ;37 (2):90-6 22557798
Equivalent normalized total dose estimates in cyberknife radiotherapy dose delivery in prostate cancer hypofractionation regimens.
Department of Radiotherapy, Apollo Speciality Hospital, Chennai, India.
As the α/β value of prostate is very small and lower than the surrounding critical organs, hypofractionated radiotherapy became a vital mode of treatment of prostate cancer. Cyberknife (Accuray Inc., Sunnyvale, CA, USA) treatment for localized prostate cancer is performed in hypofractionated dose regimen alone. Effective dose escalation in the hypofractionated regimen can be estimated if the corresponding conventional 2 Gy per fraction equivalent normalized total dose (NTD) distribution is known. The present study aims to analyze the hypofractionated dose distribution of localized prostate cancer in terms of equivalent NTD. Randomly selected 12 localized prostate cases treated in cyberknife with a dose regimen of 36.25 Gy in 5 fractions were considered. The 2 Gy per fraction equivalent NTDs were calculated using the formula derived from the linear quadratic (LQ) model. Dose distributions were analyzed with the corresponding NTDs. The conformity index for the prescribed target dose of 36.25 Gy equivalent to the NTD dose of 90.63 Gy (α/β = 1.5) or 74.31 Gy (α/β = 3) was ranging between 1.15 and 1.73 with a mean value of 1.32 ± 0.15. The D5% of the target was 111.41 ± 8.66 Gy for α/β = 1.5 and 90.15 ± 6.57 Gy for α/β = 3. Similarly, the D95% was 91.98 ± 3.77 Gy for α/β = 1.5 and 75.35 ± 2.88 Gy for α/β = 3. The mean values of bladder and rectal volume receiving the prescribed dose of 36.25 Gy were 0.83 cm3 and 0.086 cm3, respectively. NTD dose analysis shows an escalated dose distribution within the target for low α/β (1.5 Gy) with reasonable sparing of organs at risk. However, the higher α/β of prostate (3 Gy) is not encouraging the fact of dose escalation in cyberknife hypofractionated dose regimen of localized prostate cancer.
Radiat Oncol. 2011 ;6 :150 22053922
Impact of pathological tumor stage for salvage radiotherapy after radical prostatectomy in patients with prostate-specific antigen < 1.0 ng/ml.
Rei Umezawa, Hisanori Ariga, Yoshihiro Ogawa, Keiichi Jingu, Haruo Matsushita, Ken Takeda, Keisuke Fujimoto, Toru Sakayauchi, Toshiyuki Sugawara, Masaki Kubozono, Kakutaro Narazaki, Eiji Shimizu, Yoshihiro Takai, Shogo Yamada
Department of Radiation Oncology, Tohoku University School of Medicine, Seiryou-machi 1-1, Aobaku, Sendai, Japan. firstname.lastname@example.org
BACKGROUND To evaluate prognostic factors in salvage radiotherapy (RT) for patients with pre-RT prostate-specific antigen (PSA)< 1.0 ng/ml. METHODS Between January 2000 and December 2009, 102 patients underwent salvage RT for biochemical failure after radical prostatectomy (RP). Re-failure of PSA after salvage RT was defined as a serum PSA value of 0.2 ng/ml or more above the postradiotherapy nadir followed by another higher value, a continued rise in serum PSA despite salvage RT, or initiation of systemic therapy after completion of salvage RT. Biochemical relapse-free survival (bRFS) was estimated using the Kaplan-Meier method. Multivariate analysis was performed using the Cox proportional hazards regression model. RESULTS The median follow-up period was 44 months (range, 11-103 months). Forty-three patients experienced PSA re-failure after salvage RT. The 4-year bRFS was 50.9%(95% confidence interval [95% CI]: 39.4-62.5%). In the log-rank test, pT3-4 (p < 0.001) and preoperative PSA (p = 0.037) were selected as significant factors. In multivariate analysis, only pT3-4 was a prognostic factor (hazard ratio: 3.512 [95% CI: 1.535-8.037], p = 0.001). The 4-year bRFS rates for pT1-2 and pT3-4 were 79.2%(95% CI: 66.0-92.3%) and 31.7%(95% CI: 17.0-46.4%), respectively. CONCLUSIONS In patients who have received salvage RT after RP with PSA < 1.0 ng/ml, pT stage and preoperative PSA were prognostic factors of bRFS. In particular, pT3-4 had a high risk for biochemical recurrence after salvage RT.
Long-term biochemical control of prostate cancer after standard or hyper-fractionation: evidence for different outcomes between low-intermediate and high risk patients.
Riccardo Valdagni, Alan E Nahum, Tiziana Magnani, Corrado Italia, Angelo Lanceni, Paolo Montanaro, Tiziana Rancati, Barbara Avuzzi, Claudio Fiorino
Prostate Program, Scientific Director's Office, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
BACKGROUND AND PURPOSE To report the long-term biochemical control of a non-randomized trial comparing standard (STD) and hyper-fractionated (HFX) radiation schedules for prostate cancer treatment. MATERIALS AND METHODS Between 1993 and 2003, 370 patients entered the study; 330/370 (STD: 179; HFX: 151) were evaluable for current analysis. Median doses were 79.2 Gy and 74 Gy for HFX (1.2 Gy/fr, two daily fractions) and STD (2 Gy/fr), respectively; median follow-up was 7.5 yr. The two regimens were compared in terms of biochemical relapse-free survival (according to ASTRO definition, bRFS) by univariate (log-rank test) and multivariate analyses (Cox regression hazard model). Based on published relationships between EQD2 and 5-yr biochemical control, α/β values for each subgroup could be estimated. RESULTS 7.5 yr bRFS were 53.4%(± 4.4%, 95% CI) and 65.4%(± 4.0%) for HFX and STD, respectively (p=0.13); HFX was associated with a poorer outcome in NCCN low+intermediate patients (7.5 yr bRFS: 56.6% vs 73.5%, p=0.048) while no differences were seen for high-risk patients (7.5 yr bRFS: 44.1% vs 45.3%). Multivariate analysis revealed that NCCN risk grouping (high vs low+intermediate; OR: 0.59, p=0.009) and age (< vs ≥ 70 yr; OR: 0.67, p=0.03) were the main predictors of worse bRFS. In the subgroups of low+intermediate-risk patients < 70 yr, the poorer outcome of HFX was more evident (7.5 yr bRFS: 47.1% vs 70.9%, p=0.078) while no difference was seen for older patients (7.5 yr bRFS: 69.4% vs 72.0%, p=0.76). Our α/β estimates differ between low+intermediate-risk and high-risk patients. CONCLUSIONS The bRFS long-term results of this non-randomized trial are consistent with different sensitivities to fractionation depending on NCCN risk grouping. The impact of age on the outcome of HFX for younger low+intermediate patients is consistent with an incomplete repair effect in older patients.
The impact of prostate edema on cell survival and tumor control after permanent interstitial brachytherapy for early stage prostate cancers.
Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT, USA. email@example.com
Previous studies have shown that procedure-induced prostate edema during permanent interstitial brachytherapy (PIB) can cause significant variations in the dose delivered to the prostate gland. Because the clinical impact of edema-induced dose variations strongly depends on the magnitude of the edema, the temporal pattern of its resolution and its interplay with the decay of radioactivity and the underlying biological processes of tumor cells (such as tumor potential doubling time), we investigated the impact of edema-induced dose variations on the tumor cell survival and tumor control probability after PIB with the (131)Cs,(125)I and (103)Pd sources used in current clinical practice. The exponential edema resolution model reported by Waterman et al (1998 Int. J. Radiat. Oncol. Biol. Phys. 41 1069-77) was used to characterize the edema evolutions previously observed during clinical PIB for prostate cancer. The concept of biologically effective dose, taking into account tumor cell proliferation and sublethal damage repair during dose delivery, was used to characterize the effects of prostate edema on cell survival and tumor control probability. Our calculation indicated that prostate edema, if not appropriately taken into account, can increase the cell survival and decrease the probability of local control of PIB. The magnitude of an edema-induced increase in cell survival increased with increasing edema severity, decreasing half-life of radioactive decay and decreasing photon energy emitted by the source. At the doses currently prescribed for PIB and for prostate cancer cells characterized by nominal radiobiology parameters recommended by AAPM TG-137, PIB using (125)I sources was less affected by edema than PIB using (131)Cs or (103)Pd sources due to the long radioactive decay half-life of (125)I. The effect of edema on PIB using (131)Cs or (103)Pd was similar. The effect of edema on (103)Pd PIB was slightly greater, even though the decay half-life of (103)Pd (17 days) is longer than that of (131)Cs (9.7 days), because the advantage of the longer (103)Pd decay half-life was negated by the lower effective energy of the photons it emits (∼21 keV compared to ∼30.4 keV for (131)Cs). In addition, the impact of edema could be reduced or enhanced by differences in the tumor characteristics (e.g. potential tumor doubling time or the α/β ratio), and the effect of these factors varied for the different radioactive sources. There is a clear need to consider the effects of prostate edema during the planning and evaluation of permanent interstitial brachytherapy treatments for prostate cancer.
J Med Phys. 2011 Apr ;36 (2):100-6 21731226
Isoeffect calculations with the linear quadratic and its extensions: An examination of model-dependent estimates at doses relevant to hypofractionation.
Department of Radiation Oncology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
The linear quadratic is the standard model for calculating isoeffects in the range of conventional dose per fraction. However, the use of hypofractionation and stereotactic body radiation therapy can call for isoeffect calculations for large doses per fraction. The purpose of this work is to investigate the linear quadratic at large doses per fraction. The linear quadratic is compared to models that incorporate effects such as dose protraction, whose purpose is to extend the useful range of the linear quadratic to larger doses. The linear quadratic and extended linear quadratic models are fit to 4 data sets. The model-predicted isoeffects for these data sets are calculated. It is found that the linear quadratic and extended linear quadratic predict different isoeffect curves for certain data sets. However, for these data sets, by appropriate selection of a α/β ratio, the linear quadratic can well approximate the extended linear quadratic models. In particular, it is found that a α/β ratio of 0.5 well approximates the extended linear quadratic isoeffect curve for 2 prostate cell lines for conventional and moderate doses per fraction.
Internal radiotherapy techniques using radiolanthanide praseodymium-142: a review of production routes, brachytherapy, unsealed source therapy.
Department of Medical Radiation Engineering, Science and Research Branch, Islamic Azad University, Tehran, Iran. firstname.lastname@example.org
Radionuclides of rare earth elements are gaining importance as emerging therapeutic agents in nuclear medicine. β(-)-particle emitter 142Pr [T (1/2)= 19.12 h, E(-)β = 2.162 MeV (96.3%), Eγ = 1575 keV (3.7%)] is one of the praseodymium-141 (100% abundant) radioisotopes. Production routes and therapy aspects of 142Pr will be reviewed in this paper. However, 142Pr produces via 141Pr(n, γ) 142Pr reaction by irradiation in a low-fluence reactor; 142Pr cyclotron produced, could be achievable. 142Pr due to its high β(-)-emission and low specific gamma γ-emission could not only be a therapeutic radionuclide, but also a suitable radionuclide in order for biodistribution studies. Internal radiotherapy using 142Pr can be classified into two sub-categories:(1) unsealed source therapy (UST),(2) brachytherapy. UST via 142Pr-HA and 142Pr-DTPA in order for radiosynovectomy have been proposed. In addition, 142Pr Glass seeds and 142Pr microspheres have been utilized for interstitial brachytherapy of prostate cancer and intraarterial brachytherapy of arteriovenous malformation, respectively.
Tim J Kruser, David F Jarrard, Andrew K Graf, Sean P Hedican, David R Paolone, John D Wegenke, Glenn Liu, Heather M Geye, Mark A Ritter
Department of Human Oncology, University of Wisconsin Carbone Cancer Center, Madison, WI 53792, USA.
BACKGROUND Postprostatectomy adjuvant or salvage radiotherapy, when using standard fractionation, requires 6.5 to 8 weeks of treatment. The authors report on the safety and efficacy of an expedited radiotherapy course for salvage prostate radiotherapy. METHODS A total of 108 consecutive patients were treated with salvage radiation therapy to 65 grays (Gy) in 26 fractions of 2.5 Gy. Median follow-up was 32.4 months. Median presalvage prostate-specific antigen (PSA) was 0.44 (range, 0.05-9.50). Eighteen (17%) patients received androgen deprivation after surgery or concurrently with radiation. RESULTS The actuarial freedom from biochemical failure for the entire group at 4 years was 67% ± 5.3%. An identical 67% control rate was seen at 5 years for the first 50 enrolled patients, whose median follow-up was longer at 43 months. One acute grade 3 genitourinary toxicity occurred, with no acute grade 3 gastrointestinal and no late grade 3 toxicities observed. On univariate analysis, higher Gleason score (P =.006), PSA doubling time ≤12 months (P =.03), perineural invasion (P =.06), and negative margins (P =.06) showed association with unsuccessful salvage. On multivariate analysis, higher Gleason score (P =.057) and negative margins (P =.088) retained an association with biochemical failure. CONCLUSIONS Hypofractionated radiotherapy (65 Gy in 2.5 Gy fractions in about 5 weeks) reduces the length of treatment by from 1-½ to 3 weeks relative to other treatment schedules commonly used, produces low rates of toxicity, and demonstrates encouraging efficacy at 4 to 5 years. Hypofractionation may provide a convenient, resource-efficient, and well-tolerated salvage approach for the estimated 20,000 to 35,000 US men per year experiencing biochemical recurrence after prostatectomy.
Department of Radiation Oncology, University of California School of Medicine, Los Angeles, Calif., USA.
The hypofractionation of stereotactic body radiotherapy (SBRT) for prostate cancer has become a broad topic, and there are many aspects to consider before accepting this treatment into our clinics. Among the considerations are the data from the Stanford phase II trial, a seminal investigation into this area, which will be presented and reviewed here. A single-arm, prospective phase II trial was initiated at Stanford in December of 2003. This trial uses SBRT as monotherapy for 'low-risk' prostate cancer patients, and 69 patients have been entered to date. We have analyzed the patient data for the first 5 years of this study. For study entry, patients were required to have clinical stage T1c or T2a disease, prostate-specific antigen (PSA) ≤ 10 and a Gleason score of 3 + 3 (or 3 + 4 if the higher grade portion was of small volume, usually <25% of the cores involved). No prior treatment was permitted, including the use of transurethral resections or androgen deprivation therapies. A low urinary IPSS score of < 20 was required for study entry as well. The prescription dose was 7.25 Gy for 5 fractions for a total dose of 36.25 Gy. This was normalized to cover ≥ 95% of the planning target volume with 100% of the prescription dose. Patients were treated using CyberKnife technology. To date, excellent PSA responses have been observed in patients with lower-risk disease selected for treatment and receiving 36.25 Gy in 5 fractions. To date, sexual quality of life outcomes have also been approximately comparable to other radiotherapy approaches. Rates of late GI and GU toxicity have been relatively low and generally comparable to dose-escalated approaches using conventional fractionation.
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Center for Radiological Research, Columbia University, New York, NY, USA.
Center for Radiological Research, Columbia University Medical Center, New York, NY 10032, USA. email@example.com
In recent years, there has been a rapid increase in the number of CT scans performed, both in the US and the UK, which has fuelled concern about the long-term consequences of these exposures, particularly in terms of cancer induction. Statistics from the US and the UK indicate a 20-fold and 12-fold increase, respectively, in CT usage over the past two decades, with per caput CT usage in the US being about five times that in the UK. In both countries, most of the collective dose from diagnostic radiology comes from high-dose (in the radiological context) procedures such as CT, interventional radiology and barium enemas; for these procedures, the relevant organ doses are in the range for which there is now direct credible epidemiological evidence of an excess risk of cancer, without the need to extrapolate risks from higher doses. Even for high-dose radiological procedures, the risk to the individual patient is small, so that the benefit/risk balance is generally in the patients' favour. Concerns arise when CT examinations are used without a proven clinical rationale, when alternative modalities could be used with equal efficacy, or when CT scans are repeated unnecessarily. It has been estimated, at least in the US, that these scenarios account for up to one-third of all CT scans. A further issue is the increasing use of CT scans as a screening procedure in asymptomatic patients; at this time, the benefit/risk balance for any of the commonly suggested CT screening techniques has yet to be established.
Mice heterozygous for the ATM gene are more sensitive to both X-ray and heavy ion exposure than are wildtypes.
Eye Radiation and Environmental Research Laboratory, Columbia University, New York, NY 10032, USA. firstname.lastname@example.org
Previous studies have shown that the eyes of ATM heterozygous mice exposed to low-LET radiation (X-rays) are significantly more susceptible to the development of cataracts than are those of wildtype mice. The findings, as well as others, run counter to the assumption underpinning current radiation safety guidelines, that individuals are all equally sensitive to the biological effects of radiation. A question, highly relevant to human space activities is whether or not, in similar fashion there may exist a genetic predisposition to high-LET radiation damage. Mice haplodeficient for the ATM gene and wildtypes were exposed to 325 mGy of 1 GeV/amu 56Fe ions at the AGS facility of Brookhaven National Laboratory. The fluence was equivalent to 1 ion per lens epithelial cell nuclear area. Controls consisted of irradiated wildtype as well as unirradiated wildtype and heterozygous mice. Prevalence analyses for stage 0.5-3.0 cataracts indicated that not only cataract onset but also progression were accelerated in the mice haplo-deficient for the ATM gene. The data show that heterozygosity for the ATM gene predisposes the eye to the cataractogenic influence of heavy ions and suggest that ATM heterozygotes in the human population may also be radiosensitive. This may have to be considered in the selection of individuals who will be exposed to both HZE particles and low-LET radiation as they may be predisposed to increased late normal tissue damage.
Columbia University Medical Center, College of Physicians and Surgeons, Center for Radiological Research, New York, NY 10032-3795, USA. email@example.com
In the context of space radiation, it is important to know whether the human population includes genetically predisposed radiosensitive subsets. One possibility is that haploinsufficiency for ATM confers radiosensitivity, and this defect involves 1-3% of the population. Using knock-out mice we chose to study cataractogenesis in the lens and oncogenic transformation in mouse embryo fibroblasts to assay for effects of ATM deficiency. Radiation induced cataracts appeared earlier in the heterozygous versus wild-type animals following exposure to either gamma rays or 1 GeV/nucleon iron ions. In addition, it was found that embryo fibroblasts of Atm heterozygotes showed an increased incidence of oncogenic transformation compared with their normal litter-matched counterparts. From these data we suggest that Ataxia Telangiectasia heterozygotes could indeed represent a societally significant radio sensitive subpopulation. Knock-out mice are now available for other genes including BRCA1 and 2, and Mrad9. An exciting possibility is the creation of double heterozygotes for pairs of mutated genes that function in the same signal transduction pathway, and consequently confer even greater radiosensitivity.
Center for Radiological Research, Columbia University, New York, NY 10032, USA.
PURPOSE To address the relationship between the bystander effect and the adaptive response that can compete to impact on the dose-response curve at low doses. MATERIALS AND METHODS A novel radiation apparatus, where targeted and non-targeted cells were grown in close proximity, was used to investigate these phenomena in C3H 10T(1/2) cells. It was further examined whether a bystander effect or an adaptive response could be induced by a factor(s) present in the supernatants of cells exposed to a high or low dose of X-rays, respectively. RESULTS When non-hit cells were co-cultured for 24 h with cells irradiated with 5 Gy alpha-particles, a significant increase in both cell killing and oncogenic transformation frequency was observed. If these cells were treated with 2 cGy X-rays 5 h before co-culture with irradiated cells, approximately 95% of the bystander effect was cancelled out. A 2.5-fold decrease in the oncogenic transformation frequency was also observed. When cells were cultured in medium donated from cells exposed to 5 Gy X-rays, a significant bystander effect was observed for clonogenic survival. When cells were cultured for 5 h with supernatant from donor cells exposed to 2 cGy and were then irradiated with 4 Gy X-rays, they failed to show an increase in survival compared with cells directly irradiated with 4 Gy. However, a twofold reduction in the oncogenic transformation frequency was seen. CONCLUSIONS An adaptive dose of X-rays cancelled out the majority of the bystander effect produced by alpha-particles. For oncogenic transformation, but not cell survival, radioadaption can occur in unirradiated cells via a transmissible factor(s).
Center for Radiological Research, Columbia University, New York, New York 10032, USA. firstname.lastname@example.org
Although radiation-induced heritable damage in mammalian cells was thought to result from the direct interaction of radiation with DNA, it is now accepted that biological effects may occur in cells that were not themselves traversed by ionizing radiation but are close to those that were. However, little is known about the mechanism underlying such a bystander effect, although cell-to-cell communication is thought to be of importance. Previous work using the Columbia microbeam demonstrated a significant bystander effect for clonogenic survival and oncogenic transformation in C3H 10T(1/2) cells. The present study was undertaken to assess the importance of the degree of cell-to-cell contact at the time of irradiation on the magnitude of this bystander effect by varying the cell density. When 10% of cells were exposed to a range of 2-12 alpha particles, a significantly greater number of cells (P < 0.0001) were inactivated when cells were irradiated at high density (>90% in contact with neighbors) than at low density (<10% in contact). In addition, the oncogenic transformation frequency was significantly higher in high-density cultures (P < 0.0004). These results suggest that when a cell is hit by radiation, the transmission of the bystander signal through cell-to-cell contact is an important mediator of the effect, implicating the involvement of intracellular communication through gap junctions.
Center for Radiological Research, Columbia University, 630 West 168th St., New York, NY 10032, USA.
Microbeams: a potent mix of physics and biology. Summary of the 5th International Workshop on Microbeam Probes of Cellular Radiation Response.
Center for Radiological Research, Columbia University, 630 West 168th Street, New York, NY 10032, USA. email@example.com
Single-cell microbeam irradiators are of increasing interest to the biological community. The 5th International Workshop on Microbeam Probes of Cellular Radiation Response, which took place in Stresa, Italy, in May 2001, was attended by about 120 registrants, roughly evenly divided between physicists and biologists. Many new microbeam devices are now under development, and there has been a significant diversification of the biological questions addressed. Most current uses of microbeams have been to address radiobiological questions, but the advent of sub-micrometre targeting capabilities, and the development of new single-cell assays, point to the potential for microbeams to make an important contribution to biological, and not just radiobiological, studies.
Cardiovasc Radiat Med. ;2 (4):254-5 12160768
Estimates of the cancer risks from pediatric CT radiation are not merely theoretical: comment on "point/counterpoint: in x-ray computed tomography, technique factors should be selected appropriate to patient size. against the proposition".
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Acta Oncol. 2012 Sep 12;: 22966812
Department of Radiation Physics UHL, County Council of Östergötland , Linköping , Sweden.
Purpose. To determine the dose response parameters and the fractionation sensitivity of prostate tumours from clinical results of patients treated with external beam radiotherapy. Material and methods. The study was based on five-year biochemical results from 14 168 patients treated with external beam radiotherapy. Treatment data from 11 330 patients treated with conventional fractionation have been corrected for overall treatment time and fitted with a logit equation. The results have been used to determine the optimum α/β values that minimise differences in predictions from 2838 patients treated with hypofractionated schedules. Results. Conventional fractionation data yielded logit dose response parameters for all risk groups and for all definitions of biochemical failures. The analysis of hypofractionation data led to very low α/β values (1-1.7 Gy) in all mentioned cases. Neglecting the correction for overall treatment time has little impact on the derivation of α/β values for prostate cancers. Conclusions. These results indicate that the high fractionation sensitivity is an intrinsic property of prostate carcinomas and they support the use of hypofractionation to increase the therapeutic gain for these tumours.
Dose-Fractionation Sensitivity of Prostate Cancer Deduced from Radiotherapy Outcomes of 5,969 Patients in Seven International Institutional Datasets: α/β = 1.4 (0.9-2.2) Gy.
University Hospital, Geneva, Switzerland; Institut Oncològic Teknon, Barcelona, Spain.
PURPOSE: There are reports of a high sensitivity of prostate cancer to radiotherapy dose fractionation, and this has prompted several trials of hypofractionation schedules. It remains unclear whether hypofractionation will provide a significant therapeutic benefit in the treatment of prostate cancer, and whether there are different fractionation sensitivities for different stages of disease. In order to address this, multiple primary datasets have been collected for analysis. METHODS AND MATERIALS: Seven datasets were assembled from institutions worldwide. A total of 5969 patients were treated using external beams with or without androgen deprivation (AD). Standard fractionation (1.8-2.0 Gy per fraction) was used for 40% of the patients, and hypofractionation (2.5-6.7 Gy per fraction) for the remainder. The overall treatment time ranged from 1 to 8 weeks. Low-risk patients comprised 23% of the total, intermediate-risk 44%, and high-risk 33%. Direct analysis of the primary data for tumor control at 5 years was undertaken, using the Phoenix criterion of biochemical relapse-free survival, in order to calculate values in the linear-quadratic equation of k (natural log of the effective target cell number), α (dose-response slope using very low doses per fraction), and the ratio α/β that characterizes dose-fractionation sensitivity. RESULTS: There was no significant difference between the α/β value for the three risk groups, and the value of α/β for the pooled data was 1.4 (95% CI = 0.9-2.2) Gy. Androgen deprivation improved the bNED outcome index by about 5% for all risk groups, but did not affect the α/β value. CONCLUSIONS: The overall α/β value was consistently low, unaffected by AD deprivation, and lower than the appropriate values for late normal-tissue morbidity. Hence the fractionation sensitivity differential (tumor/normal tissue) favors the use of hypofractionated radiotherapy schedules for all risk groups, which is also very beneficial logistically in limited-resource settings.
Hypofractionation results in reduced tumor cell kill compared to conventional fractionation for tumors with regions of hypoxia.
Stanford University School of Medicine, Department of Radiation Oncology, Stanford, CA, USA. firstname.lastname@example.org
PURPOSE Tumor hypoxia has been observed in many human cancers and is associated with treatment failure in radiation therapy. The purpose of this study is to quantify the effect of different radiation fractionation schemes on tumor cell killing, assuming a realistic distribution of tumor oxygenation. METHODS AND MATERIALS A probability density function for the partial pressure of oxygen in a tumor cell population is quantified as a function of radial distance from the capillary wall. Corresponding hypoxia reduction factors for cell killing are determined. The surviving fraction of a tumor consisting of maximally resistant cells, cells at intermediate levels of hypoxia, and normoxic cells is calculated as a function of dose per fraction for an equivalent tumor biological effective dose under normoxic conditions. RESULTS Increasing hypoxia as a function of distance from blood vessels results in a decrease in tumor cell killing for a typical radiotherapy fractionation scheme by a factor of 10(5) over a distance of 130 μm. For head-and-neck cancer and prostate cancer, the fraction of tumor clonogens killed over a full treatment course decreases by up to a factor of ∼10(3) as the dose per fraction is increased from 2 to 24 Gy and from 2 to 18 Gy, respectively. CONCLUSIONS Hypofractionation of a radiotherapy regimen can result in a significant decrease in tumor cell killing compared to standard fractionation as a result of tumor hypoxia. There is a potential for large errors when calculating alternate fractionations using formalisms that do not account for tumor hypoxia.
Acta Oncol. 2010 Nov ;49 (8):1269-75 20712432
Department of Radiation Oncology, James Cancer Hospital & Solove Research Institute, The Ohio State University, Columbus, 43210, USA. email@example.com
Med Phys. 2010 Jun ;37 (6):2572-86 20632569
A radiobiological investigation on dose and dose rate for permanent implant brachytherapy of breast using 125I or 103Pd sources.
Department of Medical Physics and Engineering, Strahlenklinik, Klinikum Offenbach GmbH, 63069 Offenbach, Germany. firstname.lastname@example.org
Radiobiological restrictions and tolerance doses of repeated single-fraction hdr-irradiation of intersecting small liver volumes for recurrent hepatic metastases.
Ricarda Rühl, Lutz Lüdemann, Anna Czarnecka, Florian Streitparth, Max Seidensticker, Konrad Mohnike, Maciej Pech, Peter Wust, Jens Ricke
Universitätsklinikum Magdeburg, Klinik für Radiologie und Nuklearmedizin, Otto-von-Guericke-Universität Magdeburg, Germany. email@example.com
Jose Luis Guinot, Miguel Santos, Maria Isabel Tortajada, Maria Carrascosa, Enrique Estellés, Juan Bosco Vendrell, Rodrigo Muelas, Maria Luisa Chust, Jose Luis Mengual, Leoncio Arribas
Department of Radiation Oncology, Fundación Instituto Valenciano de Oncología (IVO), Valencia, Spain.
PURPOSE: To evaluate the results of high-dose-rate (HDR)-interstitial brachytherapy (ISBT) in oral tongue carcinomas. METHODS AND MATERIALS: Between September 1999 and August 2007, 50 patients were treated for oral tongue carcinoma with HDR-ISBT. The patient's mean age was 58 years. Forty-two patients were in T1-2 stage and 8 patients were in T3 stage; 16 patients were in N+ stage and 34 patients in N0 stage. Exclusive ISBT was given to 17 patients (34%) in T1-2 N0 stage and complementary to external beam radiotherapy (EBRT) to 33 patients (66%). A perioperative technique was performed on 14 patients. The median total dose was 44Gy when HDR was used alone (4Gy per fraction) and 18Gy when complementary to 50Gy EBRT (3Gy per fraction). RESULTS: The median followup was 44 months. Actuarial disease-free survival rates at 3 and 5 years were 81% and 74%, respectively. Local failure developed in 7 patients. Actuarial local control (LC) rates were 87% and 79% at 3 and 5 years in T1-2 stage 94.5% and 91% and T3 stage 43% and 43%(with salvage surgery). Exclusive HDR cases showed LC in 100% of the cases, and the combined group (EBRT+HDR) showed LC in 80% and 69% of the cases at 3 and 5 years (p=0.044). Soft-tissue necrosis developed in 16% and bone necrosis in 4% of the cases. CONCLUSIONS: HDR brachytherapy is an effective method for the treatment of oral tongue carcinoma in low-risk cases. Doses per fraction between 3 and 4Gy yield LC and complication rates similar to low-dose rate. The perioperative technique promises encouraging results.
Genitourinary toxicity after high-dose-rate (HDR) brachytherapy combined with Hypofractionated External beam radiotherapy for localized prostate cancer: an analysis to determine the correlation between dose-volume histogram parameters in HDR brachytherapy and severity of toxicity.
Hiromichi Ishiyama, Masashi Kitano, Takefumi Satoh, Shouko Kotani, Mineko Uemae, Kazumasa Matsumoto, Hiroshi Okusa, Ken-ichi Tabata, Shiro Baba, Kazushige Hayakawa
Department of Radiology, Kitasato University School of Medicine, Kitasato, Sagamihara, Kanagawa, Japan. firstname.lastname@example.org
PURPOSE To evaluate the severity of genitourinary (GU) toxicity in high-dose-rate (HDR) brachytherapy combined with hypofractionated external beam radiotherapy (EBRT) for prostate cancer and to explore factors that might affect the severity of GU toxicity. METHODS AND MATERIALS A total of 100 Japanese men with prostate cancer underwent (192)Ir HDR brachytherapy combined with hypofractionated EBRT. Mean (SD) dose to 90% of the planning target volume was 6.3 (0.7) Gy per fraction of HDR. After 5 fractions of HDR treatment, EBRT with 10 fractions of 3 Gy was administrated. The urethral volume receiving 1-15 Gy per fraction in HDR brachytherapy (V1-V15) and the dose to at least 5-100% of urethral volume in HDR brachytherapy (D5-D100) were compared between patients with Grade 3 toxicity and those with Grade 0-2 toxicity. Prostate volume, patient age, and International Prostate Symptom Score were also compared between the two groups. RESULTS Of the 100 patients, 6 displayed Grade 3 acute GU toxicity, and 12 displayed Grade 3 late GU toxicity. Regarding acute GU toxicity, values of V1, V2, V3, and V4 were significantly higher in patients with Grade 3 toxicity than in those with Grade 0-2 toxicity. Regarding late GU toxicity, values of D70, D80, V12, and V13 were significantly higher in patients with Grade 3 toxicity than in those with Grade 0-2 toxicity. CONCLUSIONS The severity of GU toxicity in HDR brachytherapy combined with hypofractionated EBRT for prostate cancer was relatively high. The volume of prostatic urethra was associated with grade of acute GU toxicity, and urethral dose was associated with grade of late GU toxicity.
Division of Radiation Oncology, Peter MacCallum Cancer Centre and University of Melbourne, Australia.
PURPOSE To evaluate the incidence, timing, nature and outcome of urethral strictures following high dose rate brachytherapy (HDRB) for prostate carcinoma. METHODS AND MATERIALS Data from 474 patients with clinically localised prostate cancer treated with HDRB were analysed. Ninety percent received HDRB as a boost to external beam radiotherapy (HDRBB) and the remainder as monotherapy (HDRBM). Urethral strictures were graded according to the Common Terminology Criteria for Adverse Events v3.0. RESULTS At a median follow-up of 41 months, 38 patients (8%) were diagnosed with a urethral stricture (6-year actuarial risk 12%). Stricture location was bulbo-membranous (BM) urethra in 92.1%. The overall actuarial rate of grade 2 or more BM urethral stricture was estimated at 10.8%(95% CI 7.0-14.9%), with a median time to diagnosis of 22 months (range 10-68 months). All strictures were initially managed with either dilatation (n=15) or optical urethrotomy (n=20). Second line therapy was required in 17 cases (49%), third line in three cases (9%) and 1 patient open urethroplasty (grade 3 toxicity). Predictive factors on multivariate analysis were prior trans-urethral resection of prostate (hazard ratio (HR) 2.81, 95% CI 1.15-6.85, p=0.023); hypertension (HR 2.83, 95% CI 1.37-5.85, p=0.005); and dose per fraction used in HDR (HR for 1 Gy increase per fraction 1.33, 95% CI 1.08-1.64, p=0.008). CONCLUSIONS BM urethral strictures are the most common late grade 2 or more urinary toxicity following HDR brachytherapy for prostate cancer. Most are manageable with minimally invasive procedures. Both clinical and dosimetric factors appear to influence the risk of stricture formation.
Department of Radiation Oncology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA. email@example.com
The purpose of this work was to determine alternative radiotherapy (RT) regimens that are biologically equivalent to clinically proven treatments using different RT modalities or different fractionation schemes. The concept of equivalent uniform dose (EUD) is used with the linear quadratic model to determine equivalent treatment regimens using two representative sets of parameters derived from clinical data:(i) alpha/beta = 3.1 Gy and alpha = 0.15 Gy(-1), and (ii) alpha/beta = 1.5 Gy and alpha = 0.04 Gy(-1). The EUD values for the critical structure (rectum) are also calculated. Representative dose volume histograms were used to account for dose inhomogeneities for different RT modalities. A series of alternative and equivalent fractionation regimens that can be used with different radiotherapy modalities for localized prostate cancer were determined. For example, the alternative regimens, calculated with the alpha/beta ratio of 3.1 Gy, that would be biologically equivalent to external beam RT (EBRT) of 76 Gy (38x2.0 Gy) include: EBRT hypofractionation of 21x3.0 Gy; I-125 implant of 156 Gy; Pd-103 implant of 128 Gy; high dose rate (HDR) brachytherapy of 4x10.5 Gy; I-125 implant of 65 Gy combined with EBRT of 23x2.0 Gy; and HDR brachytherapy of 3x5.9 Gy combined with EBRT of 23x2.0 Gy. Similar data for other parameters are also presented. With caution, the data presented may be useful in designing clinical trials to explore new RT strategies, such as image-guided intensity-modulated RT.