Interstitial pneumonitis following autologous bone-marrow transplantation conditioned with cyclophosphamide and total-body irradiation

PURPOSE: To assess the influence of different total-body irradiation (TBI) regimens on interstitial pneumonitis (IP), we retrospectively analyzed our clinical data concerning an homogeneous group of patients conditioned with cyclophosphamide (CY) alone and single-dose or fractionated TBI before autologous bone-marrow transplantation (ABMT). METHODS AND MATERIALS: One hundred eighty-six patients with acute nonlymphoblastic leukemia (n = 101), acute lymphoblastic leukemia (n = 62), chronic myeloid leukemia (n = 11), non-Hodgkin's lymphoma (n = 10), and multiple myeloma (n = 2) referred to our department between May 13, 1981 and September 16, 1992, underwent TBI before ABMT. The male-to-female ratio was 123:63 (1.95), and mean and median age was 33 +/- 12 (6-63 years) and 35 years, respectively. Cyclophosphamide alone (60 mg/kg/day on each of 2 successive days) was used as conditioning chemotherapy in all patients. Patients were irradiated according to two techniques: either with single-dose (STBI) (n = 124; 10 Gy administered to the midplane at the level of L4, and 8 Gy to the lungs) or with fractionated (FTBI) (n = 62; 12 Gy in 6 fractions over 3 consecutive days to the midplane at the level of L4, and 9 Gy to the lungs) TBI. The mean instantaneous dose rate was 0.057 +/- 0.0246 Gy/min (0.0264-0.1692 Gy/min). It was < or = 0.048 Gy/min in 48 patients (LOW group), > 0.048 and < or = 0.09 Gy/min in 129 patients (MEDIUM group), and > 0.09 Gy/min in 9 patients (HIGH group). The median follow-up period was 5 years (24-120 months). RESULTS: In January 1994, the 5-year overall (including all causes of death) and disease-free survival (DFS) rates were 50 and 48%, respectively. The 5-year DFS was 47.9% in the STBI group, and 47.8% in the FTBI group (p = 0.77). It was 44% in the HIGH group, 53% in the MEDIUM group, and 34% in the LOW group (LOW vs. MEDIUM, p = 0.009). The 5-year IP incidence was 17% in all patients, 16% in the STBI group and 18% in the FTBI group (p = 0.37), but it was significantly higher in patients receiving high instantaneous dose rate TBI (56% in the HIGH, 13% in the MEDIUM, 20% in the LOW groups; HIGH vs. MEDIUM, p = 0.002). However, sex (p = 0.37), age (18% for > 20 vs. 10% for < or = 20 years, p = 0.37), and body weight (> 60 kg vs. < or = 60 kg, p = 0.09) did not influence the IP incidence in univariate analyses. Multivariate analysis (Cox model) revealed that the instantaneous dose rate (p = 0.05), and the age (p = 0.04) were the two independent factors influencing the incidence of IP. CONCLUSION: This retrospective study including only the patients transplanted with ABMT conditioned with CY alone and STBI or FTBI concluded that instantaneous dose rate and age significantly influenced the incidence of IP, whereas sex, body weight, and fractionation did not.     

Immediate toxicity during fractionated total body irradiation as conditioning for bone marrow transplantation.

BACKGROUND: Total body irradiation followed by bone marrow transplantation is well established as a part of the conditioning regimen in high dose therapy. The immediate tolerance of fractionated total body irradiation (FTBI) was investigated prospectively. METHODS: From January 1995 to December 1998 162 patients received a FTBI, 6x2 Gy on 3 consecutive days, lung dose 10 Gy, for allogeneic (n=112) or autologous (n=50) bone marrow transplantation. High dose chemotherapy (mostly Cyclophosphamide) was administered after the FTBI. A standardized supportive therapy was administered. The immediate toxicity of FTBI was evaluated prospectively prior to each radiation fraction using a defined questionnaire. RESULTS: Main symptoms distressing the patient during irradiation period were gastrointestinal symptoms like nausea and emesis. The prevalence of nausea per fraction increased to 26.1% after the 4th fraction, with a significant higher prevalence in children younger than 10 years at 1st and 2nd fractions. 42.6 and 22. 8%, respectively, of all patients complained of nausea and episodes of emesis, during FTBI. Mild xerostomia and parotiditis were observed in 29.9 and 7.1% of all patients. Further gastrointestinal side effects during FTBI were loss of appetite in 16.0%, indisposition in 25.3%, mild oesophagitis in 3.7% and diarrhoea in 3. 7% of the patients. During FTBI 41.4% of the patients developed a temporary skin irritation (mild erythema). Pruritus was registered in 3.7% of the patients. Headache was observed in 14.8% and Fatigue syndrome in 49.2% of women and 28.3% of men (P<0.005). CONCLUSION: FTBI is a well tolerated therapeutic regimen in high dose therapy. The 162 patients investigated revealed no severe immediate side effects.     

Lethal pulmonary complications significantly correlate with individually assessed mean lung dose in patients with hematologic malignancies treated with total body irradiation

PURPOSE: To assess the impact of lung dose on lethal pulmonary complications (LPCs) in a single-center group of patients with hematologic malignancies treated with total body irradiation (TBI) in the conditioning regimen for bone marrow transplantation (BMT). METHODS: The mean lung dose of 101 TBI-conditioned patients was assessed by a thorough (1 SD around 2%) in vivo transit dosimetry technique. Fractionated TBI (10 Gy, 3.33 Gy/fraction, 1 fraction/d, 0.055 Gy/min) was delivered using a lateral-opposed beam technique with shielding of the lung by the arms. The median lung dose was 9.4 Gy (1 SD 0.8 Gy, range 7.8--11.4). The LPCs included idiopathic interstitial pneumonia (IIP) and non-idiopathic IP (non-IIP). RESULTS: Nine LPCs were observed. LPCs were observed in 2 (3.8%) of 52 patients in the group with a lung dose < or = 9.4 Gy and in 7 (14.3%) of 49 patients in the >9.4 Gy group. The 6-month LPC risk was 3.8% and 19.2% (p = 0.05), respectively. A multivariate analysis adjusted by the following variables: type of malignancy (acute leukemia, chronic leukemia, lymphoma, myeloma), type of BMT (allogeneic, autologous), cytomegalovirus infection, graft vs. host disease, and previously administered drugs (bleomycin, cytarabine, cyclophosphamide, nitrosoureas), revealed a significant and independent association between lung dose and LPC risk (p = 0.02; relative risk = 6.7). Of the variables analyzed, BMT type (p = 0.04; relative risk = 6.6) had a risk predictive role. CONCLUSION: The mean lung dose is an independent predictor of LPC risk in patients treated with the 3 x 3.33-Gy low-dose-rate TBI technique. Allogeneic BMT is associated with a higher risk of LPCs.     

In-vivo Comparison of Planned and Measured Rectal Doses during Cobalt-60 HDR CT-based Intracavitary Brachytherapy Applications of Cervical Cancer Using the PTW 9112 Semiconductor Probe

Background: A semiconductor rectal probe was used to compare planned and measured rectal doses during Co-60 high dose rate (HDR) CT-based intracavitary brachytherapy applications (ICBT) of cervical cancer. Materials and Methods: A total of 22 HDR brachytherapy applications were included from 11 patients who were first treated with EBRT to the whole pelvis with a total prescribed dose of 50 Gy in 25 fractions. During each application, a PTW 9112 probe rectal probe having a series of five semiconductor diodes (R1 to R5) was inserted into the patient’s rectum and a CT-based HDR ICBT application with a prescribed dose per fraction of 7 or 7.5 Gy to HRCTV was performed. Measurements were carried in water phantom using PTW rectal and universal adaptor plugs. Doses measured in phantom and with patients were compared to those calculated by the treatment planning system. Results: The mean percentage dose difference ΔD (%) between calculated and measured values from phantom study were -5.29%, 1.89%, -2.72%, -4.76, and 0.72% for R1, R2, R3, R4, and R3 diodes, respectively and the overall mean ΔD (%) value with standard deviation (SD) was -2.03%±9.6%. From the patient study, a ΔD (%) that ranged from -19.5% to 24.0%, which corresponded to dose disparities between -0.77 Gy and 0.66 Gy. The median ΔD (%) ranged from 0.4% to 1.3%, or -0.03 to 0.05 Gy, respectively. ΔD (%) values exceeded 10% in approximately 26.4% of measurements (29 out of 110 in 22 applications). The location of Rmax in computed and measured values differs in 5 of 22 applications might be due to possible displacement of rectal probe between simulation and treatment. Conclusion: Despite the likely geometrical shift of measuring detectors between insertion and treatment, in-vivo dosimetry is feasible and can be used to estimate the dose to the rectum during HDR ICBT.     

Biological dosimetry after total body irradiation (TBI) for hematologic malignancy patients

PURPOSE: Biological dosimetry based on scoring chromosomal aberrations in peripheral lymphocytes was compared to physical dosimetry done for total body irradiation (TBI) before bone marrow transplantation (BMT) in patients with hematologic malignancies. PATIENTS AND METHODS: Fifteen patients undergoing TBI were included in the study. A total dose of 12 Gy in 2.5 days was fractionated into 2 or 3 daily doses of 1.8 Gy delivered by a 18 MV linear accelerator (dose rate: 15.8 cGy x min(-1)). Blood samples were obtained from patients before irradiation and after the first fraction of 1.8 Gy. A standard dose-effect curve was established by in vitro irradiation of healthy volunteer lymphocytes. Chromosomal aberrations were scored by the conventional cytogenetics (CCG) method for unstable anomalies and by fluorescent in situ hybridization (FISH) for stable anomalies. RESULTS: Healthy donor lymphocytes before irradiation yielded 0.1% dicentrics and 0.3% translocations of chromosome 4 (Chr. 4), that is 2.5% for the whole genome. Patients before irradiation had 2% of dicentrics and 1.1% of chromosome 4 translocations. The biologically estimated dose of the 15 patients after exposure to 1.8 Gy was 1.93 Gy (95% CI: 1.85-2.05) according to CCG, and 2.06 Gy (95% CI: 1.75-2.15) by FISH. CONCLUSION: The dose estimated by biological dosimetry, in this case of homogeneously distributed radiation of TBI agrees well with the absorbed radiation dose calculated by physical dosimetry.     

Anorectal irradiation in pelvic radiotherapy: an assessment using in-vivo dosimetry

The objectives of this study were to measure by in-vivo techniques the radiation doses received by the anorectum during pelvic radiotherapy and compare these with doses predicted by a GE TARGET treatment planning system. Nine patients with cancers of the prostate, bladder, cervix or uterus were planned with computed tomography (CT) using the TARGET system. A Scanditronix rectal probe containing five n-type photon-detecting diodes was placed in the anorectum during the planning CT scans. The probe position was standardized with the five diodes at 2 cm intervals from the anal verge. The probe diodes were calibrated for 10 MV photons. Doses were measured for each diode for two consecutive fractions in the first four patients and for five consecutive fractions in the remaining five. Thermoluminescent dosimeters were used initially to verify diode doses. The TARGET and diode measured doses were compared. In all patients diodes situated in the target volume were within 7% of predicted doses. This improved to 2.5% after measurement on five fractions. At the edges of the target volume, wide variability existed between measured and predicted doses (measured dose range -68% to +68% of predicted dose). Outside the target volume, considerable doses (up to 0.3 Gy per fraction) were measured in the anal canal, which were not predicted by TARGET. We conclude that TARGET planned doses are accurate within the confines of the target volume. The greatest variability was seen at the edges of the target volume, where dose can vary by 50% across a 1 cm distance in the anterior-posterior plane. TARGET does not account for scattered dose beyond the field edges and therefore underestimates the dose received by the anal canal.     

Total body irradiation using helical tomotherapy: Set-up experience and in-vivo dosimetric evaluation

PurposeHelical Tomotherapy (HT) appears as a valuable technique for total body irradiation (TBI) to create highly homogeneous and conformal dose distributions with more precise repositioning than conventional TBI techniques. The aim of this work is to describe the technique implementation, including treatment preparation, planning and dosimetric monitoring of TBI delivered in our institution from October 2016 to March 2019.Material and methodPrior to patient care, irradiation protocol was set up using physical phantoms. Gafchromic films were used to assess dose distribution homogeneity and evaluate imprecise patient positioning impact. Sixteen patients’ irradiations with a prescribed dose of 12 Gy were delivered in 6 fractions of 2 Gy over 3 days. Pre-treatment quality assurance (QA) was performed for the verification of dose distributions at selected positions. In addition, in-vivo dosimetry was carried out using optically stimulated luminescence dosimeters (OSLD).ResultsPlanning evaluation, as well as results of pre-treatment verifications, are presented. In-vivo dosimetry showed the strong consistency of OSLD measured doses. OSLD mean relative dose differences between measurement and calculation were respectively +0,96% and ?2% for armpit and hands locations, suggesting better reliability for armpit OSLD positioning. Repercussion of both longitudinal and transversal positioning inaccuracies on phantoms is depicted up to 2 cm shifts.ConclusionThe full methodology to set up TBI protocol, as well as dosimetric evaluation and pre-treatment QA, were presented. Our investigations reveal strong correspondence between planned and delivered doses shedding light on the dose reliability of OSLD for HT based TBI in-vivo dosimetry.     

Validation of biological dosimetry in patients conditioned with total body irradiation: conventional cytogenetics and in situ hybridization(FISH)]

PURPOSE: Validation of biological dosimetry versus physical dosimetry in malignant haemopathy patients conditioned by total body irradiation (TBI) before bone marrow transplantation (BMT). PATIENTS AND METHODS: The scoring of chromosomal aberrations in peripheral lymphocytes irradiated in vivo was used to perform the biological dosimetry. The data were compared to those obtained with healthy volunteers' total blood exposed to in vitro irradiation with linear accelerator doses (0.2, 0.5, 0.75, 1, 2, 3, 4 and 5 Gy) for dose-response curves. In experimental animal models, can in vivo and in vitro responses be considered as being the same? All the published human data are based on retrospective dose evaluation with very large uncertainties on the dose precisely delivered to the subject. TBI before BMT was taken as a model where the dose calculation results from the physical method, with homogeneous beam and dose delivered precisely along the entire organism. In vivo response allows us to validate biological dosimetry in 15 adult patients (female + male), before (D = 0 Gy) and after the first fraction of 1.8 Gy, delivered by a linear accelerator (18 MV, dose-rate of 15.8 cGy/min-1). Two methods, conventional cytogenetics (CCG) and fluorescent in situ hybridization (FISH painting) of chromosome 4 were respectively used to analyze the unstable chromosome aberrations and stable chromosome aberrations. RESULTS: Healthy volunteer lymphocytes, before irradiation, yielded 0.1% dicentrics and 0.3% translocations of chromosome 4, with 2.5% for the whole genome. Patients before irradiation had 2% dicentrics and 11.48% chromosome 4 translocations for the whole genome. In the 15 patients, for a physical dose of 1.8 Gy, the evaluated biological dose was 1.93 Gy (95% CI: 1.85-2.05 Gy) with conventional cytogenetics and 2.06 Gy (95% CI: 1.75-2.15 Gy) with FISH. CONCLUSION: These results, in which the biologically estimated dose is in complete agreement with the dose calculated by physical dosimetry in the homogeneous irradiation model, suggest the validation of biological dosimetry in TBI conditioning.     

Toxicity and dosimetry of fractionated total body irradiation prior to allogeneic bone marrow transplantation using a straightforward radiotherapy technique

Since 1989, we have used a relatively straightforward technique for giving total body irradiation (TBI), using anterior and posterior parallel opposed fields with the arms and fists acting as compensators. The dosimetry, toxicity and outcome of 48 patients (26 adults, 22 children) treated with TBI using this technique have been audited. A dose of 14.4 Gy in eight fractions over 4 days was prescribed to all patients with an unrelated donor and 12 Gy in six fractions over 3 days to those with a sibling donor. From May 1994, all children received 14.4 Gy because of a recommendation from the United Kingdom Children's Cancer Study Group. The range of lung dosimetry was −6% to +7% when the dose was specified to the lung maximum. The trunk doses were all within ±10% of the prescribed dose. Doses to other regions of the body were less homogeneous but clinically acceptable in that the minimum doses were never less than −10% of the prescribed dose. Mucositis was the most common side effect; its treatment with opioids was more frequent after 14.4 Gy than after 12 Gy (P = 0.0004) and in adults than in children (P = 0.01). No cataracts have yet been seen in these patients. The radiation was not found to be a proven cause of clinical pneumonitis, although there was one death due to interstitial pneumonitis, which was likely to have been caused by cytomegalovirus infection in which radiation pneumonitis could not be excluded. There were no other suspected TBI-related deaths.In conclusion, this straightforward technique achieved acceptable dosimetry and was well tolerated.     

全身照射及半导体实时剂量监测技术在造血干细胞移植中应用

目的 探讨全身照射及半导体实时剂量监测方法 在造血干细胞移植中应用的安全性和临床疗效.方法 采用6 MV X线对57例需造血干细胞移植的患者行半坐立姿或侧卧式两野或四野前后平行对穿野单次或分次照射,并在照射中使用6个半导体探头对患者不同部位进行实时剂量监测,根据监测结果 采用不同厚度的铅皮调整人体中平面受照剂量的均匀性.结果 接受分次照射的41例患者疗后均有轻度和中度恶心、呕吐、腮腺肿胀等症状,但均能耐受,经对症治疗后好转,顺利完成造血干细胞的移植,无一发生间质性肺炎.实时监测也表明,患者全身照射剂量均匀性符合临床治疗要求.结论 采用半导体探测器实时剂量监测与半坐立姿或侧卧式前后平行对穿照射技术是一种安全、有效的全身照射方法 .     

Radiation therapy induced changes in male sex hormone levels in rectal cancer patients.

BACKGROUND AND PURPOSE: To determine the effect of curative radiation therapy (46-50 Gy) on the sex hormone levels in male rectal cancer patients. MATERIALS AND METHODS: Twenty-five male rectal cancer patients (mean age 65 years), receiving pelvic radiation therapy (2 Gyx23-25 fractions in 5 weeks) were included. Serum testosterone, FSH and LH were determined before start of treatment, at the 10th and 25th fractions, and 4-6 weeks after completed radiotherapy. The testicular dose was determined by thermoluminescent dosimetry. RESULTS: Five weeks of radiation therapy (46-50 Gy) resulted in a 100% increase in serum FSH, a 70% increase in LH, and a 25% reduction in testosterone levels. After treatment, 35% of the patients had serum testosterone levels below lower limit of reference. The mean radiation dose to the testicles was 8.4 Gy. A reduction in testosterone values was observed already after a mean dose of 3.3 Gy (10th fraction). CONCLUSION: Radiation therapy (46-50 Gy) for rectal cancer resulted in a significant increase in serum FSH and LH and a significant decrease in testosterone levels, indicating that sex hormone production is sensitive to radiation exposure in patients with a mean age of 65 years.     

In-vivo dosimetry for gynaecological brachytherapy: physical and clinical considerations.

INTRODUCTION: The study aimed to estimate the dosimetric uncertainty using diodes (PTW/Germany) for a high-dose rate Iridum-192 source under clinical conditions. Finally, the role of in-vivo dosimetry for cervix cancer patients was evaluated. MATERIAL AND METHODS: First, diode calibration and factors influencing diode response were investigated and phantom studies compared doses measured and computed by the treatment planning system. Based on that, the uncertainty for diode measurements was estimated to be 7% (1 sigma). Secondly, 55 applications of patients with cervix carcinoma were evaluated. Doses in rectum and bladder were measured and compared to the computed doses and differences were calculated. If the differences exceeded 10% the corresponding shift in probe position was evaluated. Additionally, the in-vivo dosimetry data were compared to doses at the ICRU 38 [ICRU Report No. 38, dose and volume specification for reporting intracavitary therapy in gynaecology. In: Chassagne D, Dutreix A, Almond P, Burgers J, Busch M, Joslin C editors. International commissioning on radiation units and measurements. Bethesda: 1985.] reference points for rectum and bladder. RESULTS: In patients, in-vivo dosimetry resulted in differences between calculated and measured doses ranging from -31 to+90% (mean 11%) for the rectum and from -27 to+26% (mean 4%) for the bladder. Shifts in probe position of 2.5mm for the rectal probe and 3.5mm for the bladder probe caused dose differences exceeding 10%. The dose at the ICRU rectum reference point was underestimated by the calculated doses at probe position ranging from -61 to 156% (mean 29%). The dose to the ICRU bladder reference point was underestimated by the calculated dose ranging from 12 to 162% (mean 58%). CONCLUSION: The study shows that diode accuracy and reproducibility is sufficient for clinical applications. For accurate in-vivo dosimetry geometric conditions are of utmost importance. It is recommended that in-vivo dosimetry should be performed in addition to computation.     

容积调强弧形治疗技术全身照射的初次临床应用及剂量学验证

目的 介绍香港大学深圳医院初次使用容积调强弧形治疗技术(VMAT)行全身照射(TBI)患者的计划设计及剂量学验证方法。方法 在头、脚位两套定位图像上共同确定全身计划靶体积,处方剂量12Gy分6次,设计含5个中心15个全弧的TBI计划。优化时先在脚位图像中进行,并以此为剂量基础进行头位计划优化,最后两段综合剂量累加并评估。多种剂量学验证方式:Delta 4模体验证单等中心VMAT计划剂量;EBT 3胶片验证两相邻中心射野衔接处剂量分布;PinPoint电离室测量两段图像衔接区点剂量;MOSFET剂量仪实时监测患者体表剂量。另对计划结果参数、治疗时间等进行分析。结果 患者两段靶区的平均剂量分别为12.45Gy和12.37Gy,肺平均剂量为10.8Gy。每次治疗总机器跳数2883 MU,出束时间平均约24.3min,床旁平均总时间约121min。与计划计算相比:单中心VMAT计划绝对剂量3%/3mmγ通过率平均为(99.74±0.42)%;射野衔接区域绝对剂量5%/5mmγ通过率平均为(90.11±2.72)%;头、脚位图像衔接区域点剂量平均偏差(3.6±0.4)%;实时监测患者体表8个点,各部位每次剂量在1.57~2.04Gy范围内。结论 基于多中心VMAT技术的TBI计划及剂量学验证结果显示能可靠实施于临床,但还需不断改进、改善剂量分布和测量结果,提高治疗效率。     

Repair capacity of mouse lung after total body irradiation alone or combined with cyclophosphamide

Purpose. Cyclophosphamide (CTX) combined with fractionated total body irradiation (TBI) is frequently used in the conditioning of patients prior to bone marrow transplantation (BMT). This study was performed to investigate the effect of CTX on the repair capacity of lung tissue after TBI in a mouse model for BMT. Materials and methods. TBI was given as a single fraction, 3 fractions in 3 days (Fx 3) or 9 fractions in 3 days (Fx 9) either alone or 24 h after a single dose of CTX. The single fraction TBI was given at either high dose rate (HDR) of 0.71 Gy/min or low dose rate (LDR) of 0.08 Gy/min. All mice were transplanted 4–6 h after the last TBI fraction. Lung damage was assessed using ventilation rate (VR) and lethality between 28 and 180 days. The repair capacity of lung tissue was estimated using the direct analysis method with the probability of reaching the end point described by a logistic formulation of the linear quadratic model. Results. The VR data confirmed the high repair capacity of lung tissue with an /β ratio of 4.4 Gy though with a wide 95% confidence interval (CI = 0.03–10.5). Giving CTX before fractionated TBI markedly reduced the doses needed to cause response in 50% of the animals. The sparing effect of using fractionated TBI was still evident in the combined CTX-TBI schedules. The estimated /β ratio was 1.6 Gy (CI = 0.01–4.7) which is within the range of values reported after thoracic radiation only. On the other hand, the sparing effect seen in going from single fraction HDR to LDR was completely abolished when CTX was given 24 h before TBI. The same pattern was repeated when lethality between 28–180 days was used. Yet, the use of lethality to estimate lung damage in a TBI model, markedly underestimated the repair capacity. Conclusions. These results confirm the high repair capacity of lung tissue after TBI and emphasize the value of using a specific end point in testing lung damage after TBI. It also shows that there can be a negative effect of CTX on the repair capacity of lung damage which is more pronounced when CTX is followed (24 h later) by single fraction TBI at LDR than by a fractionated TBI course over a few days.     

Cataracts after total body irradiation and bone marrow transplantation in patients with acute leukemia in complete remission: a study of the european group for blood and marrow transplantation

Purpose: Advances in bone marrow transplantation (BMT) have consistently improved long-term survival. Therefore, evaluation of late complications such as cataracts is of paramount importance.Methods and Materials: We analyzed data of 2149 patients from the EBMT registry. A cohort of 1063 patients were evaluable for survival and ophthalmologic status after transplant for acute leukemia (AL) in first or second complete remission. Conditioning therapy included either single-dose total body irradiation (STBI) or fractionated TBI (FTBI) grouped in different dose rates (low: LDR ≤ 0.04 Gy/min; high: HDR > 0.04 Gy/min).Results: The overall 10-year estimated cataract incidence (ECI) was 50%. It was 60% in the STBI group, 43% in the FTBI group ≤ 6 fractions, and 7% in the FTBI group > 6 fractions (p < 10⁻⁴). It was significantly lower (30%) in the LDR than in the HDR groups (59%; p < 10⁻⁴). Patients receiving heparin for veno-occlusive disease prophylaxis had fewer cataracts than those who did not (10-year ECI: 33% vs. 53%, respectively; p = 0.04). The 10-year ECI was 65% in the allogeneic vs. 46% in the autologous BMT patients (p = 0.0018).Factors independently associated with an increased risk of cataract were an older age (> 23 years), higher dose rate (> 0.04 Gy/min), allogeneic BMT, and steroid administration (> 100 days). The use of FTBI was associated with a decreased risk of cataract. Heparin administration was a protective factor in patients receiving STBI. In terms of cataract surgery, the unfavorable factors for requiring surgery were: age > 23 yr, STBI, dose rate > 0.04 Gy/min, chronic graft-vs.-host disease (cGvHD), and absence of heparin administration. Among the patients who required cataract surgery (111 out of 257), secondary posterior capsular opacification was observed in 15.7%.Conclusion: High dose rate and STBI are the main risk factors for cataract development and the need for surgery, and the administration of heparin has a protective role in cataractogenesis.     

Prospective evaluation of pulmonary function in cancer patients treated with total body irradiation, high-dose melphalan, and autologous hematopoietic stem cell transplantation

Pulmonary function tests (standard vital capacity, SVC; total lung capacity, TLC; forced expiratory volume in 1 second-forced vital capacity ratio, FEV1/FVC; carbon monoxide transfer factor, DLCO) were prospectively evaluated in patients (median age 25 years, 13-52 years; median follow-up 20 months, 6-51 months) with Hodgkin's disease (15 patients), non-Hodgkin's lymphoma (9 patients), and inflammatory breast cancer (3 patients) treated with sequential high-dose therapy comprising the following phases over approximately 2 months: a) cyclophosphamide (7 g/m2); b) vincristine (1.4 mg/m2), methotrexate (8 g/m2), and cisplatinum (120 mg/m2) or etoposide (2 g/m2); c) total body irradiation (TBI; 12.5 gy, 5 fractions over 48 hours), intravenous melphalan (120-180 mg/m2), and transplantation of autologous peripheral blood and/or bone marrow hematopoietic stem cells. Within 2 months after transplantation, 12 patients also received 25 Gy radiotherapy boost to mediastinum and clavicular regions. In vivo dosimetry evaluations of fractionated TBI treatments showed that mean radiation dose absorbed by lungs was 12.18 Gy (97.4% of TBI dose). Despite such a high radiation dose, we observed only transient and subclinical decrease of SVC, TLC, and DLCO. The decrease of SVC, TLC, and DLCO was more evident and prolonged in patients receiving radiotherapy boost. All parameters progressively recovered to normal values within 2 years after transplantation. In contrast, FEV1/FVC remained within normal limits in all patients, thus demonstrating the absence of obstructive ventilatory changes. In addition, no interstitial pneumonia was observed.     

不同肺体积确定方法和剂量分割方法对肺剂量体积参数的影响

目的 分析不同肺体积确定方法和不同剂量分割方法对肺剂量体积参数的影响.方法 随机搜集20例肺癌患者,根据病情以瓦里安Eclipse TPS进行三维适形治疗计划设计.以不同CT值范围确定患者肺体积、靶体积(GTV、CTV、PTV)是否从肺体积中减除及不同分割剂量为影响因素,计算肺剂量体积参数受影响的程度.结果 当CT值在-300～ -980至-500～ -980范围变化时,全肺体积减少的中位数为-9.10%,明显高于V30、V20、V10和MLD的中位变化(为-3.18%、-1.13%、0.82%和-0.79%).CT值-400～ -980确定的全肺体积随减除靶体积的增加V30、V20、V10和MLD的变化也加大,其中V30变化最大,V10变化最小.5例PTV体积＜140 cm3(中位PTV体积为78 cm3)患者设置总物理剂量60 Gy,分割剂量由2 Gy增加至10 Gy时,由物理剂量转换为生物等效剂量的V30、V20、V10和MLD逐渐增加(呈正相关),且三者变化相同(增加幅度约为40%).在＞6Gy分割剂量后,MLD变化更大(36%).结论 不同CT值范围勾画并确定肺体积时,对全肺体积影响最大,V30变化有统计学意义(尚不足以左右放疗计划的取舍),V20、V10和MLD的变化无统计学意义.全肺体积减去与之相重叠的靶体积(GTV、CTV、PTV)后,V30的变化最大,而影响最小的是V10.增加分割剂量也明显增加剂量体积参数,而剂量分割方式在3个因素中似乎影响最大(＞10%).     

Dosimetry and radiobiologic model comparison of IMRT and 3D conformal radiotherapy in treatment of carcinoma of the prostate

INTRODUCTION: Intensity-modulated radiotherapy (IMRT) has introduced novel dosimetry that often features increased dose heterogeneity to target and normal structures. This raises questions of the biologic effects of IMRT compared to conventional treatment. We compared dosimetry and radiobiologic model predictions of tumor control probability (TCP) and normal tissue complication probability (NTCP) for prostate cancer patients planned for IMRT as opposed to standardized three-dimensional conformal radiotherapy (3DCRT). METHODS AND MATERIALS: Segmented multileaf collimator IMRT treatment plans for 32 prostate cancer patients were compared to 3DCRT plans for the same patients. Twenty-two received local-field irradiation (LFI), and 10 received extended-field irradiation (EFI) that included pelvic lymph nodes. For LFI, IMRT was planned for delivery of 2 Gy minimum dose to the prostate (> or =99% volume coverage) for 35 fractions. The 3DCRT plans, characterized by more homogenous dose to the target, were designed according to a different protocol to deliver 2 Gy to the center of the prostate for 37 fractions. Mean total dose from 35 fractions of IMRT was equal to mean total dose from 37 fractions of 3DCRT. For EFI, both IMRT and 3DCRT were planned for 2 Gy per fraction to a total dose of 50 Gy to prostate and pelvic lymph nodes, followed by 2 Gy per fraction to 20 Gy to the prostate alone. Treatment dose for EFI-IMRT was defined as minimum dose to the target, whereas for EFI-3DCRT, it was defined as dose to the center of the prostate. TCP was calculated for the prostate in the linear-quadratic model for two choices of alpha/beta. NTCP was calculated with the Lyman model for organs at risk, using Kutcher-Burman dose-volume histogram reduction with Emami parameters. RESULTS AND CONCLUSIONS: Dose to the prostate, expressed as mean +/- standard deviation, was 74.7 +/- 1.1 Gy for IMRT vs. 74.6 +/- 0.3 Gy for 3D for the LFI plans, and 74.8 +/- 0.6 Gy for IMRT vs. 71.5 +/- 0.6 Gy for 3D for the EFI plans. For the studied protocols, TCP was greater for IMRT than for 3D across the full range of target sensitivity, for both localized- and extended-field irradiation. For LFI, this was due to the smaller number of fractions (35 vs. 37) used for IMRT, and for EFI, this was due to the greater mean dose for IMRT, compared to 3D. For all organs, mean NTCP tended to be lower for IMRT than for 3D, although NTCP values were very small for both 3D and IMRT. Differences were statistically significant for rectum (LFI and EFI), bladder (EFI), and bowel (EFI). For both LFI and EFI, the calculated NTCPs qualitatively agreed with early published clinical data comparing genitourinary and gastrointestinal complications of IMRT and 3D. Present calculations support the hypothesis that accurately delivered IMRT for prostate cancer can limit dose to normal tissue by reducing treatment margins relative to conventional 3D planning, to allow a reduction in complication rate spanning several sensitive structures while maintaining or increasing tumor control probability.     

Single dose versus hyperfractionated total body irradiation before allogeneic bone marrow transplantation: a non-randomized comparative study of 54 patients at the Institut Gustave-Roussy

At the Institut Gustave-Roussy (IGR), from January 1982 to December 1986, 54 patients received total body irradiation (TBI) as a part of the conditioning regimen before allogeneic bone marrow transplantation. The patients were non-randomly assigned to either single dose TBI (STBI) (31 patients receiving 10 Gy at a 4.5 cGy/min dose rate, 8 Gy to the lungs) or to a hyperfractionated scheme (HTBI) (23 patients receiving 13.2 Gy in 11 fractions, 3 fractions per day, 9 Gy to the lungs). Relapse rate and overall survival were not significantly different in the two STBI and HTBI groups, in spite of a larger number of 2nd and 3rd remission patients in the HTBI subset. The incidence of interstitial pneumonitis (IP) was significantly reduced in the HTBI group (13%, versus 45% after STBI, p = 0.02). Lethality by IP was also lower after HTBI (4%, versus 26% after STBI, p = 0.08). There was no case of veno-occlusive disease of the liver in the HTBI group, whereas three cases were observed after STBI. Based on these results, the IGR activated, in January 1987, a randomized trial comparing the single dose 10 Gy TBI (8 Gy to the lung) to a new hyperfractionated schedule (11 fractions of 1.35 Gy, 3 fractions per day, 9 Gy to the lungs).