Animal models of radiation retinopathy - From teletherapy to brachytherapy.

Radiation retinopathy is a serious vision-impairing complication of radiation therapy used to treat ocular tumors. Characterized by retinal vasculopathy and subsequent retinal damage, the first sign of radiation retinopathy is the preferential loss of vascular endothelial cells. Ensuing ischemia leads to retinal degradation and late stage neovascularization. Despite the established disease progression, the pathophysiology and cellular mechanisms contributing to radiation retinopathy remain unclear. Clinical experience and basic research for other retinal vasculopathies, such as diabetic retinopathy and retinopathy of prematurity, can inform our understanding of radiation retinopathy; however, the literature investigating the fundamental mechanisms in radiation retinopathy is limited. Treatment trials have shown modest success but, ultimately, fail to address the cellular events that initiate radiation retinopathy. Animal models of radiation retinopathy could provide means to identify effective therapies. Here, we review the literature for all animal models of radiation retinopathy, summarize anatomical highlights pertaining to animal models, identify additional physiological factors to consider when investigating radiation retinopathy, and explore the use of clinically relevant tests for studying in vivo models of radiation retinopathy. We encourage further investigation into the mechanistic characterization of radiation retinopathy in the hope of discovering novel treatments.

Assessment of national dosimetry quality audits results for teletherapy machines from 1989 to 2015.

The purpose of this study was to ensure accuracy in radiation dose delivery, external dosimetry quality audit has an equal importance with routine dosimetry performed at clinics. To do so, dosimetry quality audit was organized by the Secondary Standard Dosimetry Laboratory (SSDL) of Pakistan Institute of Nuclear Science and Technology (PINSTECH) at the national level to investigate and minimize uncertainties involved in the measurement of absorbed dose, and to improve the accuracy of dose measurement at different radiotherapy hospitals. A total of 181 dosimetry quality audits (i.e., 102 of Co-60 and 79 of linear accelerators) for teletherapy units installed at 22 different sites were performed from 1989 to 2015. The percent deviation between users' calculated/stated dose and evaluated dose (in the result of on-site dosimetry visits) were calculated and the results were analyzed with respect to the limits of ± 2.5% (ICRU "optimal model") ± 3.0% (IAEA on-site dosimetry visits limit) and ± 5.0% (ICRU minimal or "lowest acceptable" model). The results showed that out of 181 total on-site dosimetry visits, 20.44%, 16.02%, and 4.42% were out of acceptable limits of ± 2.5% ± 3.0%, and ± 5.0%, respectively. The importance of a proper ongoing quality assurance program, recommendations of the followed protocols, and properly calibrated thermometers, pressure gauges, and humidity meters at radiotherapy hospitals are essential in maintaining consistency and uniformity of absorbed dose measurements for precision in dose delivery.

Secondary radiation dose during high-energy total body irradiation.

AIM: The goal of this work was to assess the additional dose from secondary neutrons and γ-rays generated during total body irradiation (TBI) using a medical linac X-ray beam. BACKGROUND: Nuclear reactions that occur in the accelerator construction during emission of high-energy beams in teleradiotherapy are the source of secondary radiation. Induced activity is dependent on the half-lives of the generated radionuclides, whereas neutron flux accompanies the treatment process only. MATERIALS AND METHODS: The TBI procedure using a 18 MV beam (Clinac 2100) was considered. Lateral and anterior-posterior/posterior-anterior fractions were investigated during delivery of 2 Gy of therapeutic dose. Neutron and photon flux densities were measured using neutron activation analysis (NAA) and semiconductor spectrometry. The secondary dose was estimated applying the fluence-to-dose conversion coefficients. RESULTS: The main contribution to the secondary dose is associated with fast neutrons. The main sources of γ-radiation are the following: (56)Mn in the stainless steel and (187)W of the collimation system as well as positron emitters, activated via (n,γ) and (γ,n) processes, respectively. In addition to 12 Gy of therapeutic dose, the patient could receive 57.43 mSv in the studied conditions, including 4.63 µSv from activated radionuclides. CONCLUSION: Neutron dose is mainly influenced by the time of beam emission. However, it is moderated by long source-surface distances (SSD) and application of plexiglass plates covering the patient body during treatment. Secondary radiation gives the whole body a dose, which should be taken into consideration especially when one fraction of irradiation does not cover the whole body at once.

Using fiducial markers in the prostate bed in postprostatectomy external beam radiation therapy improves accuracy over surgical clips.

BACKGROUND AND PURPOSE: The purpose of this work was to assess the stability of fiducial markers in the prostate bed and compared their use to surgical clips. PATIENTS AND METHODS: In this study, 3-4 gold fiducial markers were transrectally implanted in the prostate bed of 14 patients. The stability of the fiducial markers position (fiducial markers fixity) over an EBRT course was assessed. Furthermore, the advantages of the fiducial markers compared to the surgical clips were assessed and the interobserver variation between the two technologies was compared. RESULTS: The mean fiducial marker migration during a course of EBRT was small with 1.2 mm (SD ± 0.8 mm). Compared to fiducial markers, the matches with surgical clips were mismatched ≥ 2 mm in 68% of treatments. This discrepancy of > 2 mm was on average 3.7 ± 1.3 mm. There was less interobserver variability for matching of fiducial markers (0.8 ± 0.7 mm) than for surgical clips (2.0 ± 1.6 mm). CONCLUSION: Fiducial markers showed less interobserver variability in matching and less variation in position than surgical clips. Fiducial markers could ultimately help in reducing treatment margins.

Dose measurement of cobalt-60 radiotherapy beams in treatment fields.

BACKGROUND: Radiation-therapy is a complex process with multiple steps, each of which has an impact on the quality of treatment. Accurate dosimetry is a critical step during the radiotherapy of cancer patients.The aim of the present study was to measure and evaluate the doses of two cobalt- 60 (60Co) teletherapy units GWXJ80 of NPIC China and Theratron 780 of AECL Canada at various points within fields for different field sizes. METHODS: This cross-sectional descriptive study was done to measure the 60Co doses in the treatment fields.The dose measurements were done in air and 30x30x30 cm3 Phantom at 80 cm SSD by using calibrated NE 2570 Farmer Electrometer & NE 2571 Farmer Ionization Chamber and percentage of doses were calculated. RESULTS: The results showed that 60% central area of all fields ranging from 100-98.79% and 100-96.12% for GWXJ80 in the air and phantom, whereas for Theratron 780, they were ranging from 100-98.50% and 100-96.45% in air and phantom respectively. The percentages of doses at the edges for GWXJ80 and Theratron 780 in the air were 75.39-38.66% & 85.65-46.47% respectively and they were 82.22-40.39% & 49.05-24.55% respectively in phantom. CONCLUSIONS: The doses within 60% central area of fields in air were higher than phantom for both teletherapy units. The doses at field edges in air were lower in GWXJ80 than Theratron 780 whereas in phantom they were vice versa. But all were in the acceptable range as recommended by International Commission on Radiation Units and Measurements.

Fast Monte Carlo simulation for total body irradiation using a (60)Co teletherapy unit.

Our institution delivers TBI using a modified Theratron 780 60Co unit. Due to limitations of our treatment planning system in calculating dose for this treatment, we have developed a fast Monte Carlo code to calculate dose distributions within the patient. The algorithm is written in C and uses voxel density information from CT images to calculate dose in heterogeneous media. To test the algorithm, film-based dose measurements were made separately in a simple water phantom with a high-density insert and a RANDO phantom and then compared to doses calculated by the Monte Carlo algorithm. In addition, a separate simulation in GEANT4 was run for the RANDO phantom and compared to both film and the in-house simulation. All results were analyzed using RIT113 film analysis software. Simulations in the water phantom accurately predict the depth of maximum dose in the phantom at 0.5 cm. The measured PDD along the central axis of the beam closely matches the PDD generated from the Monte Carlo code, deviating on average by only 3% along the depth of the water phantom. Dose measured at planes inside the high-density insert had a mean difference of 4.9% on cross-profile measurement. In the RANDO phantom, gamma pass rates vary between 91% and 99% at 3 mm, 3%, and were >99% at 5 mm, 5% for the four film planes measured. Profiles taken across the film and both simulations resulted in mean relative differences of < 2% for all profiles in each slice measured. The Monte Carlo algorithm presented here is potentially a viable method for calculating dose distributions delivered in TBI treatments at our center. While not yet refined enough to be the primary method of treatment planning, the algorithm at its current resolution determines the dose distribution for one patient within a few hours, and provides clinically useful information in planning TBI. With appropriate optimization, the Monte Carlo method presented here could potentially be implemented as a first-line treatment planning option for 60Co TBI.

[The importance of pathology in the German prostate cancer study PREFERE]. / Die Bedeutung der Pathologie in der deutschen Prostatakrebsstudie PREFERE.

Prostate cancer is the most common carcinoma of elderly males and holds the third place in the ranking of cancer-specific mortality. However, total mortality rate of 3 % is low and half of the patients die from other diseases, which is for the most part due to significantly improved diagnostic methods and the increasing use of prostate-specific antigen (PSA) screening. This has led to a stage migration towards early tumor stages that are prognostically heterogeneous and require differentiated treatment. The German and European guidelines recommend four therapy options (i.e. radical prostatectomy, percutaneous irradiation, permanent seed implantation and active surveillance) for localized prostate cancer and from contemporary study data it is unclear which therapy is most beneficial. This will be the subject of the PREFERE trial, a prospective randomized multicentre trial which plans to recruit 7,600 patients and to observe them over a period of up to 17 years. The histopathological diagnosis of the primary biopsy plays a crucial role in the inclusion criteria, as this article outlines in detail.

[Radiation protection in radiation oncology. Yesterday, today, and tomorrow]. / Strahlenschutz in der Radioonkologie. Gestern, heute und morgen.

Publications about radiation protection issues are not very frequent in the 100-year-old history of Strahlentherapie und Onkologie. While at the beginning of the last century the problems of radiation protection were determined by the technical development of radiation therapy, the importance of radiation protection measures and knowledge about radiation protection by the persons involved has clearly increased. A new challenge is treating patients according to radiation safety issues to avoid the risk of stochastic late effects, such as radiation-induced secondary tumors.

Adaptive off-line protocol for prostate external radiotherapy with cone beam computer tomography.

PURPOSE: The goal of this work was to prepare and to evaluate an off-line adaptive protocol for prostate teleradiotherapy with kilovoltage cone beam computer tomography (CBCT). PATIENTS AND METHODS: Ten patients with localized prostate carcinoma treated with external beams underwent image-guided radiotherapy. In total, 162 CBCT images were collected. Position of prostate and pubis symphysis (PS) with respect to the isocenter were measured off-line. Using the CBCT scans obtained in the first three fractions the average position of prostate in relation (AvPosPr) to PB was calculated. On each CBCT scan, the position of prostate with respect to AvPosPr was calculated and cumulative histogram of prostate displacement with respect to AvPosPr was prepared. Using this data, the adaptive protocol was prepared in which (1) based on the CBCT made in the first three fractions the AvPosPr to PS is obtained, (2) in all other fractions two orthogonal images are acquired and if for any direction set-up error exceeds 0.2 cm the patient's position is corrected, and (3) additionally, the patient's position is corrected if the AvPosPr exceeds 0.2 cm in any direction. To evaluate the adaptive protocol for 30 consecutive patients, the CBCT was also made in 10th and 21st fraction. RESULTS: For the first 10 patients, the results revealed that the prostate was displaced in relation to AvPosPr >0.7 cm in the vertical and longitudinal directions only on 4 and 5 images of 162 CBCT images, respectively. For the lateral direction, this displacement was >0.3 cm in one case. For the group of 30 patients, displacement was never >0.7, and 0.3 cm for the vertical and lateral directions. In two cases, displacements were >0.7 cm for the longitudinal direction. CONCLUSION: Implementation of the proposed adaptive procedure based on the on-line set-up error elimination followed by a reduction of systematic internal error enables reducing the CTV-PTV margin to 0.7, 0.7, and 0.4 cm for the vertical, longitudinal, and lateral directions, respectively.

Circulating CXCL9 and CXCL10 as markers of activity of Graves' orbitopathy during treatment with corticosteroids and teleradiotherapy.

The aim of the study was to assess the usefulness of circulating chemokines CXCL9 and CXCL10 measurements as surrogate markers of GO activity and as a guideline in therapeutic decision-making. Forty-two individuals were divided into 4 groups: 1. 15 euthyroid patients with clinical symptoms of orbitopathy (GO) who underwent corticosteroid therapy consisting of intravenous infusions of methylprednisolone (MP) and teleradiotherapy (TR); 2. 10 patients with hyperthyroid GD (Gtx); 3. 10 patients with GD in euthyreosis (Geu); and 4. 7 healthy volunteers age and sex-matched to groups 1-3. The serum samples were collected 24 h before MP, 24 h after first dose of MP, before TR and at the end of therapy. Serum CXCL9 and CXCL10 were determined by ELISA and TSH-Rab by RIA. There were significant reductions in CXCL9 and CXCL10 serum concentrations during CS and TR treatment as compared both to control group and to basal values in GO patients. Moreover, CXCL9 concentration was significantly diminished in comparison to controls in GO patients who were identified later as corticosteroid-respondent (p<0.001). In this latter group of patients, CXCL9 was also found to be significantly reduced 24 h after first dose of MP as compared to non-respondents (p<0.02). The high-degree positive correlation between CXCL9 and CXCL10 was found (R=0.8; p<0.001). Our results suggest that the increased concentrations of CXCL9 (and CXCL10), at least in part, reflect the activity of orbital inflammation and therefore these chemokines could serve as a guideline in therapeutic decision-making in patients with Graves' orbitopathy.

Aperture superposition dose model versus pencil beam superposition dose model for a finite size Cobalt-60 source for tomotherapy deliveries.

PURPOSE: The finite size pencil beam (FSPB) superposition method is a commonly used dose calculation method in intensity modulated radiation therapy (IMRT). The FSPB model assumes that dose for a broad intensity modulated beam can be calculated by superposition of dose from small, pencil-like beams. However, this model is limited to point-like radiation sources and is not valid for finite size sources, such as a Cobalt-60 (Co-60) source of 2 cm diameter. In this paper, the authors present results that show the limitation of this model and propose an alternative model, namely the aperture superposition (AS) model, to calculate photon dose for intensity modulated beams arising from finite size radiation sources. METHODS: The AS model is based on adding beam apertures rather than pencil beams. Each aperture is defined as a series of adjacently opened leaves of a multileaf collimator with no closed leaves in between them. The apertures are calculated using the EGSnrc Monte Carlo program. The accuracy of the AS model was tested for dose calculations of fan beams, as encountered in tomotherapy treatment plans. The results were compared with the FSPB model and GafChromic film measurements. The measurements and simulations were performed for a clinical Theratronics T780C Co-60 unit with MIMiC binary multileaf collimator mounted on it. RESULTS: The comparisons between the AS model and film measurements show agreement better than 1.5% in the high dose regions and 3.7% in the low dose regions. On the contrary, film measurement comparisons to the FSPB model show that the FSPB model underestimates the dose by up to 7% for small field sizes such as 2 × 2 cm(2) and 20% for larger field sizes such as 20 × 2 cm(2). CONCLUSIONS: The results presented in this paper indicate that the AS model provides better accuracy than the FSPB model when calculating dose for fan beams from large radiation sources. The implementation of this model to the current treatment planning systems has the scope of advancing Co-60 based IMRT and tomotherapy.

Pattern of oncologic emergencies seen in adult cancer patients attending the Radiotherapy and Oncology Centre, Ahmadu Bello University Teaching Hospital, Zaria - Nigeria.

AIMS AND OBJECTIVES: To evaluate the Pattern of Oncologic Emergencies seen in Adult cancer patients and the treatment modalities used. MATERIALS AND METHODS: Between January 2004 and December 2008, a total of 1824 (M:F = 1:1.8) new patients were seen. 196 (M:F = 1:1.4) consecutive patients with histologically confirmed malignancies presenting with or having oncologic emergencies were treated and have been reviewed. Patients' folders were reviewed retrospectively with a structured pro forma. Results were analysed using Epi Info soft ware Version 3.4.1; 2007 Edition. RESULTS: The median age was 49 years and mean age of 42 years (range, 15 - 82 years). M: F = 1:1.4. 162 patients had oncologic emergencies at presentation while 21 during treatments and 13 during follow up. At the time of diagnosis of oncologic emergency, 126 were not on any treatment, 42 patients on hormonal therapy and 28 patients were on diverse chemotherapy. All the patients presented late with 108 patients presenting with metastatic disease and 88 patients with locally advanced disease. Only 35 patients were treated within 1 week of onset of emergency. 59 patients had cervical cancer, 31 patients with breast cancer and 28 patients with prostate cancer. Tumour haemorrhage wass the commonest oncologic emergency seen in 107 patients followed by bone pain with imminent cord compression from bone metastases in 59 patients. Of 107 patients with tumour haemorrhage, 54 patients had cardiovascular collapse with 7 having acute renal failure. Similarly, of the 107 with tumour haemorrhage, 56 patients bled from cervical cancer, 12 patients from breast cancer and 8 patients from urinary bladder. 129 patients were treated with teletherapy, 31 patients had chemotherapy, 27 patients had emergency surgery and 5 patients had chemoradiation. Oncologic emergencies were corrected in 126 patients. CONCLUSION: Tumour haemorrhage is the commonest oncologic emergency in this environment and teletherapy is the commonest therapy used. More radiotherapy centres are needed for prompt treatment and their usefulness in managing emergencies should be made known. Oncologic emergencies are commonly seen in metastatic and locally advanced disease.

Radiotherapy of splenomegaly : a palliative treatment option for a benign phenomenon in malignant diseases.

PURPOSE: Since the 20(th) century, radiotherapy (RT) has been used for treatment of symptomatic splenomegaly (SM). SM occurs in association with hematologic disorders. The purpose of this analysis was to determine the indication, treatment concepts, and efficiency of RT. MATERIAL AND METHODS: Clinical features, treatment concepts, and outcome data during the past 20 years were analyzed. Endpoints were pain relief, symptomatic and hematological response, and treatment-related side effects. RESULTS: From 1989-2009, a total of 122 patients received 246 RT courses because of symptomatic SM. Overall 31 patients had chronic myelogenous leukemia (CML), 37 had chronic lymphocytic leukemia (CLL), 23 had osteomyelofibrosis (OMF), 17 had polycythemia vera (PV), 5 had acute myelogenous leukemia, 4 had idiopathic thrombocytopenic purpura (ITP), 3 had non-Hodgkin lymphoma (NHL), and 2 had multiple myeloma (MM). Patients were treated with (60)Co gamma rays or 5-15MV photons. The fraction size ranged from 10-200 cGy and the total dose per treatment course from 30-1600 cGy. Significant pain relief was achieved for 74.8% of the RT courses given for splenic pain. At least 50% regression was attained for 77% of the RT courses given for SM. 36 patients died within 2 months due to the terminal nature of their disease. Of the RT courses applied for cytopenia, 73.6% achieved a significant improvement of hematological parameters and reduction of transfusion need. Notable hematologic toxicities were reported < EORTC/RTOG II°. CONCLUSION: The present analysis documents the efficacy of RT. In addition, RT as a palliative treatment option for symptomatic SM should not be forgotten.

Treatment results and prognostic factors of patients undergoing postoperative radiotherapy for laryngeal squamous cell carcinoma.

Postoperative radiotherapy (PRT) is widely advocated for patients with squamous cell carcinomas of the head and neck that are considered to be at high risk of recurrence after surgical resection. The aims of this study were to evaluate the treatment outcomes of PRT for patients with laryngeal carcinoma and to identify the value of several prognostic factors. We reviewed the records of 256 patients treated for laryngeal squamous cell carcinoma between January 1993 and December 2005. Disease-free survival (DFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Log-rank test was employed to identify significant prognostic factors for DFS and OS. The Cox proportional hazards model was applied to identify covariates significantly associated with the aforementioned endpoints. Our results showed the 3-, 5-, and 10-year DFS for all patients were 69.9%, 59.5%, and 34.9%, respectively. The 3-, 5-, and 10-year OS rates were 80.8%, 68.6%, and 38.8%, respectively. Significant prognostic factors for both DFS and OS on univariate analysis were grade, primary site, T stage, N stage, overall stage, lymph node metastasis, overall treatment times of radiation, the interval between surgery and radiotherapy, and radiotherapy equipment. Favorable prognostic factors for both DFS and OS on multivariate analysis were lower overall stage, no cervical lymph node metastasis, and using 60Co as radiotherapy equipment. In conclusion, our data suggest that lower overall stage, no cervical lymph node metastasis, and using 60Co as radiotherapy equipment are favorable prognostic factors for DFS and OS and that reducing the overall treatment times of radiation to 6 weeks or less and the interval between surgery and radiotherapy to less than 3 weeks are simple measures to remarkably improve treatment outcome.

Dosimetric evaluation of high-dose-rate interstitial brachytherapy boost treatments for localized prostate cancer.

PURPOSE: To quantitatively evaluate the dose distributions of high-dose-rate (HDR) prostate implants regarding target coverage, dose homogeneity, and dose to organs at risk. MATERIAL AND METHODS: Treatment plans of 174 implants were evaluated using cumulative dose-volume histograms (DVHs). The planning was based on transrectal ultrasound (US) imaging, and the prescribed dose (100%) was 10 Gy. The tolerance doses to rectum and urethra were 80% and 120%, respectively. Dose-volume parameters for target (V90, V100, V150, V200, D90, D(min)) and quality indices (DNR [dose nonuniformity ratio], DHI [dose homogeneity index], CI [coverage index], COIN [conformal index]) were calculated. Maximum dose in reference points of rectum (D(r)) and urethra (D(u)), dose to volume of 2 cm(3) of the rectum (D(2ccm)), and 0.1 cm(3) and 1% of the urethra (D(0.1ccm) and D1) were determined. Nonparametric correlation analysis was performed between these parameters. RESULTS: The median number of needles was 16, the mean prostate volume (V(p)) was 27.1 cm(3). The mean V90, V100, V150, and V200 were 99%, 97%, 39%, and 13%, respectively. The mean D90 was 109%, and the D(min) was 87%. The mean doses in rectum and urethra reference points were 75% and 119%, respectively. The mean volumetric doses were D(2ccm) = 49% for the rectum, D(0.1ccm) = 126%, and D1 = 140% for the urethra. The mean DNR was 0.37, while the DHI was 0.60. The mean COIN was 0.66. The Spearman rank order correlation coefficients for volume doses to rectum and urethra were R(D(r),D(2ccm)) = 0.69, R(D(u),D0.(1ccm)) = 0.64, R(D(u),D1) = 0.23. CONCLUSION: US-based treatment plans for HDR prostate implants based on the real positions of catheters provided acceptable dose distributions. In the majority of the cases, the doses to urethra and rectum were kept below the defined tolerance levels. For rectum, the dose in reference points correlated well with dose-volume parameters. For urethra dose characterization, the use of D1 volumetric parameter is recommended.

Retrospective study of neoadjuvant versus adjuvant radiochemotherapy in locally advanced noninflammatory breast cancer : survival advantage in cT2 category by neoadjuvant radiochemotherapy.

PURPOSE: This retrospective study compares patients treated between 1991 and 1998 with neoadjuvant radiotherapy +/- chemotherapy (RCT) or adjuvant RCT for locally advanced noninflammatory breast cancers (LABC) in terms of pathologic complete response (pCR), 10-year relapse-free (RFS), and overall survival (OS). PATIENTS AND METHODS: Preoperative RCT in 315 and adjuvant RCT in 329 cases consisted in 50 Gy (5 x 2 Gy/week) to the breast and the supra-/infraclavicular lymph nodes. 101 neoadjuvant patients received - in case of breast conservation - a 10-Gy interstitial boost with (192)Ir afterloading before and 214 neoadjuvant patients a preoperative electron boost after external-beam radiotherapy. In the neoadjuvant RCT group, chemotherapy was applied prior to radiotherapy in 192 patients, and simultaneously in 113; ten had no chemotherapy. In the adjuvant RCT group, chemotherapy was applied to 44 patients before surgery and to 166 after surgery; 119 had no chemotherapy. RESULTS: Breast conservation became possible in 50.8% after neoadjuvant RCT for LABC with a pCR rate at surgery of 29.2%. A complete nodal remission (pN0) after RCT was observed in 56% (89/159) of the cN+ (clinically node-positive) neoadjuvant patients. There were trends in favor of preoperative RCT for RFS and OS (hazard ratio [HR] = 0.85; p = 0.09 for RFS; HR = 0.8130; p = 0.1037 for OS). For patients with cT2 tumors the RFS and OS were statistically significantly better (HR = 0.5090; p = 0.0130 for RFS; HR = 0.4390; p = 0.0026 for OS) after neoadjuvant compared to adjuvant RCT. CONCLUSION: Neoadjuvant RCT achieved a pCR rate of 29.2% and a statistically significantly better RFS and OS in patients with cT2-category breast cancer.

Clinical results of iridium-192 high dose rate brachytherapy with external beam radiotherapy.

OBJECTIVE: Here, we report the clinical results of iridium-192 high dose rate brachytherapy at Kanazawa University Hospital. METHODS: The study population consisted of 166 patients diagnosed with T1c-T3bN0M0 prostate cancer treated with high dose rate brachytherapy and external beam radiotherapy and followed up for 6 months or longer. Treatment consisted of external beam radiotherapy to the prostate at 44 Gy/22 fractions and high dose rate brachytherapy at 18 Gy/3 fractions. RESULTS: Median follow-up interval was 31.5 months (range 6.2-88.7). The overall 5-year biological recurrence-free survival rate was 93.0%. The 5-year biological recurrence-free survival rates for the patients in low-, intermediate- and high-risk groups according to the D'Amico risk classification criteria were 96.1%, 89.0% and 91.6%, respectively. When limited to the group that did not receive adjuvant hormonal therapy, the 5-year biological recurrence-free survival rates for the patients in low-, intermediate- and high-risk groups were 96.0%, 96.3% and 82.9%, respectively. Grade 3 or greater adverse effects were rare. Urethral stricture was observed in only 1.0% of the patients. Eighty percent of patients retained erectile function after high dose rate brachytherapy and reported satisfaction with sexual function. CONCLUSIONS: High dose rate brachytherapy is considered a good form of treatment for localized prostate cancer, although longer follow-up is necessary.

[Influence of level-Ib lymphadenopathy on the prognosis of nasopharyngeal carcinoma].

BACKGROUND AND OBJECTIVE: The level-Ib lymph node metastasis is rare in nasopharyngeal carcinoma (NPC). When and how this level should be irradiated with precise radiotherapy remains controversial. This study evaluated the prevalence and prognostic significance of level-Ib lymphadenopathy on the prognosis of NPC patients. METHODS: From January 1990 and December 1999, 933 newly diagnosed patients with NPC treated at Sun Yat-sen University Cancer Center were randomly selected, examined with computed tomography (CT) imagining for evidence of level-Ib lymphadenopathy before treatment. All patients received radical radiotherapy with or without chemotherapy. The relationship between level-Ib lymphadenopathy and post-treatment outcomes including overall survival (OS), locoregional recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were analyzed using Kaplan-Meier methods. The Cox proportional hazards regression model was used to adjust for other prognostic factors. RESULTS: Of the 933 patients, 55 (5.9%) were found to have level-Ib lymphadenopathy, which was associated with carotid sheath involvement, oropharynx involvement and levels, and lateral cervical lymph node involvement. In the subgroup with carotid sheath involvement, with multivariate analysis accounting for all previously known prognostic factors, level-Ib lymphadenopathy was still associated with a risk of decreased OS (RR, 2.124; P<0.001), DMFS (RR, 2.168; P<0.001), and LRFS (RR, 1.989; P=0.001). CONCLUSION: Level-Ib lymphadenopathy in the patients with carotid sheath involvement is an independent prognostic factor.

The Impact of Radiation Energy on Dose Homogeneity and Organ Dose in the Göttingen Minipig Total-Body Irradiation Model.

Animal models of total-body irradiation (TBI) are used to elucidate normal tissue damage and evaluate the efficacy of medical countermeasures (MCM). The accuracy of these TBI models depends on the reproducibility of the radiation dose-response relationship for lethality, which in turn is highly dependent on robust radiation physics and dosimetry. However, the precise levels of radiation each organ absorbs can change dramatically when different photon beam qualities are used, due to the interplay between their penetration and the natural variation of animal sizes and geometries. In this study, we evaluate the effect of varying the radiation energy, namely cobalt-60 (Co-60); of similar penetration to a 4-MV polyenergetic beam), 6 MV and 15 MV, in the absorbed dose delivered by TBI to individual organs of eight Göttingen minipigs of varying weights (10.3-24.1 kg) and dimensions (17.5-25 cm width). The main organs, i.e. heart, lungs, esophagus, stomach, bowels, liver, kidneys and bladder, were contoured by an experienced radiation oncologist, and the volumetric radiation dose distribution was calculated using a commercial treatment planning system commissioned and validated for Co-60, 6-MV and 15-MV teletherapy units. The dose is normalized to the intended prescription at midline in the abdomen. For each animal and each energy, the body and organ dose volume histograms (DVHs) were computed. The results show that more penetrating photon energies produce dose distributions that are systematically and consistently more homogeneous and more uniform, both within individual organs and between different organs, across all animals. Thoracic organs (lungs, heart) received higher dose than prescribed while pelvic organs (bowel, bladder) received less dose than prescribed, due to smaller and wider separations, respectively. While these trends were slightly more pronounced in the smallest animals (10.3 kg, 19 cm abdominal width) and largest animals (>20 kg, ∼25 cm abdominal width), they were observed in all animals, including those in the 9-15 kg range typically used in MCM models. Some organs received an average absorbed dose representing <80% of prescribed dose when Co-60 was used, whereas all organs received average doses of >87% and >93% when 6 and 15 MV were used, respectively. Similarly, average dose to the thoracic organs reached as high as 125% of the intended dose with Co-60, compared to 115% for 15 MV. These results indicate that Co-60 consistently produces less uniform dose distributions in the Göttingen minipig compared to 6 and 15 MV. Moreover, heterogeneity of dose distributions for Co-60 is accentuated by anatomical and geometrical variations across various animals, leading to different absorbed dose delivered to organs for different animals. This difference in absorbed radiation organ doses, likely caused by the lower penetration of Co-60 and 6 MV compared to 15 MV, could potentially lead to different biological outcomes. While the link between the dose distribution and variation of biological outcome in the Göttingen minipig has never been explicitly studied, more pronounced dose heterogeneity within and between organs treated with Co-60 teletherapy units represents an additional confounding factor which can be easily mitigated by using a more penetrating energy.

Clinic based transfer of the N(D,W)(60Co) calibration coefficient using a linear accelerator.

Ionization chambers used for reference dosimetry require a local secondary standard ionization chamber with a 60Co absorbed dose to water calibration coefficient N(D,W)(60Co) traceable to a national primary standards dosimetry laboratory or an accredited secondary dosimetry calibration laboratory. Clinic based (in-house) transfer of this coefficient to tertiary reference ionization chambers has traditionally been accomplished with chamber cross calibration in water using a 60Co beam; however, access to 60Co teletherapy machines has become increasingly limited for clinic based physicists. In this work, the accuracy of alternative methods of transferring the N(D,W)(60Co) calibration coefficient using 6 and 18 MV photon beams from a linear accelerator in lieu of 60Co has been investigated for five different setups and four commonly used chamber types.