The predictive role of bioeffect dose models in radiation-induced late effects in glottic cancers.

Late radiation-induced laryngeal oedema for different doses per fraction was analyzed in 208 cases with squamous cell carcinoma of the vocal cord. The series comprised 156 cases with T1N0M0 and 52 cases with T2N0M0 lesions. Radical radiotherapy was given with three different regimens delivering 3.33 Gy, 2.5 Gy, and 2.25 Gy per fraction. There were 52 cases of late radiation-induced laryngeal oedema. A strong correlation (p less than 0.015) between the dose per fraction and the risk of the late complication in the vocal cord has been demonstrated. The analysis suggests that the empirical models like Nominal Standard Dose (NSD) or Time-Dose Factors (TDF) do not predict correctly the late normal tissue reactions for different dose fractionations. The analysis with extrapolated response dose (ERD) values of the linear-quadratic (L-Q) model also fail to correlate with the late complications (p greater than 0.5). Care should be exercised when using these bioeffect dose models to calculate regimens iso-effective for late damage, even when modest changes in fraction size from 2 to 3 Gy are contemplated.     

High-dose-rate intracavitary brachytherapy: results of analyses of late rectal complications

: To examine the incidence of radiation-induced late rectal complications by analyzing the data of measured rectal doses in patients with cancer of the uterine cervix treated with high-dose-rate intracavitary brachytherapy.

: We measured doses to the rectum in 105 patients with cancer of the cervix during high-dose-rate intracavitary brachytherapy with a semiconductor dosimeter that can measure five points in the rectum simultaneously. On the basis of these measurements, equivalent doses, to which the biologically equivalent doses were converted as if given as fractionated irradiation at 2 Gy/fraction, were calculated as components of the cumulative dose at five rectal points in intracavitary brachytherapy combined with the external whole pelvic dose.

: The calculated values of equivalent doses for late effects at the rectum ranged from 15 to 100 Gy (median 60 Gy for patients who did not develop complications and 76 Gy for patients who subsequently developed Grade II or III complications). When converted to a graph of absolute rectal complication probability, the data could be fitted to a sigmoid curve. The data showed a very definite dose-response relationship, with a threshold for complications at approximately 50 Gy and the curve starting to rise more steeply at approximately 60 Gy. The steepest part of the curve had a slope equivalent to approximately 4% incidence/1 Gy increase in equivalent doses.

: The radiation tolerance dose, 5% and 50% complication probability, was about 64 and 79 Gy, respectively. Our data almost agree with the prescribed dose for the rectum for the radiation tolerance doses on the basis of the recorded human and animal data. The probability of rectal complications increased drastically after the maximal rectal dose was >60 Gy.     

常规与后加速超分割及常规加腔内照射治疗食管癌的远期疗效

目的　观察和比较常规分割、后程加速超分割及常规分割加腔内照射三种方式治疗局部中晚期食管癌的疗效及放射反应。方法　对 111例局部中晚期食管癌首治病例进行前瞻性随机分组研究。常规分割照射组 (常规组 ) 4 0例 :2 .0Gy/次 ,1次 /d ,5d/周 ,共 6 0Gy,30分次 ,6周完成。后程加速超分割组 (后超组 ) 4 1例 :前 3周常规分割 ,30Gy ,15分次 ,3周完成 ;后 2周加速超分割照射 ,1.5Gy/次 ,2次 /d ,5d/周 ,共 30Gy ,2 0分次 ,2周完成。常规外照射加腔内照射组 (腔内组 ) 30例 :常规外照射达 34～ 36Gy时与腔内照射同期进行 (腔内照射当天停外照射 1次 ) ,腔内照射 5 .0Gy/次 ,1次 /周 ,共 2次 ,外照射总量为 5 0Gy。结果　常规组和后超组及腔内组的 1、3、5年生存率分别为 5 7.5 %、2 2 .5 %、14 .1%和 5 7.5 %、2 9.3%、2 4 .4 %及 5 3.3%、2 6 .7%、2 3.3% ,急性放射性食管炎的发生率分别为 2 2 .5 %和 4 1.5 %及 5 0 .0 % ,出血、穿孔的发生率分别为 7.7%和 7.3%及 16 .7%。结论　虽然后程加速超分割放射治疗有提高生存率的趋势 ,但与常规分割照射组及常规外照射加腔内放射治疗组的生存率差异无显著性意义 ,但其是否在治疗中晚期食管癌方面占有绝对优势尚有待大样本前瞻性随机临床研究和长期观察     

Are doses to ICRU reference points valuable for predicting late rectal and bladder morbidity after definitive radiotherapy in uterine cervix cancer?

AIMS AND BACKGROUND: To evaluate whether doses or dose rates at International Commission on Radiation Units (ICRU) reference points are of value for predicting risks of late rectal and bladder morbidity in patients with uterine cervical cancer who have undergone external beam radiotherapy and intracavitary irradiation. METHODS: Late rectal complications and late bladder complications were evaluated in 54 patients who were treated by external beam radiotherapy followed by intracavitary irradiation between January 1996 and December 1999. External beam radiotherapy was delivered in 1.8 Gy daily fractions to a whole pelvis dose of 50.4 Gy followed by intracavitary irradiation at total point A doses ranging from 75 Gy to 85 Gy. Intracavitary irradiation was performed with dose rates of 0.5-0.7 Gy/h to point A in most patients, but 8 patients were treated at a higher dose rate (0.83-1.15 Gy/h) to shorten the hospitalization period. Biologically effective doses for the reference points were calculated using a linear quadratic model. RESULTS: Grade 3 rectal and bladder morbidity by Radiation Therapy Oncology Group (RTOG) criteria developed in 4 patients (7.4%) and 1 (1.9%), respectively. An age of >60 years (P = 0.01) and a total dose to the rectal reference point of > or =80 Gy (P = 0.03) were found to be correlated with a higher rate of rectal morbidity. Total dose (> or =80 Gy), dose rate (> or = 0.75 Gy/h), and biologically effective doses (> or =135 Gy3) at the bladder reference point were found to be significant factors for the development of late bladder morbidity. By multivariate analysis, age was identified as the only significant factor of late rectal complications, and biologically effective doses at the bladder reference point was the only significant factor of late bladder complications. CONCLUSIONS: RTOG grade 3 late rectal and bladder morbidity developed in respectively 7.4% and 1.9% of the patients. The significant risk factors for late rectal and bladder morbidity were old age and biologically effective doses at the bladder reference point, respectively.     

The dose time relationship in the radiotherapy of carcinoma of the cervix--application of CRE formalism.

A retrospective analysis of 291 patients with cancer of the uterine cervix treated with a combination of external and intracavitary radiotherapy was carried out. Patients were either treated with 45 Gy in 20 fractions by five fractions per week or with 42 Gy in 14 fractions by three fractions per week or with 42 Gy in 14 fractions by three fraction per week schedule by external radiotherapy. For brachytherapy the total dose was 24 to 32 Gy at a dose rate of 1.4 to 2.2 Gy per hour. Complication were correlated with total CRE values for point A (CRE TA) and for rectum CRE TR. Correlations of CRE TA with overall complication rate (p value < 0.05) and rectal complication rate (p value < 0.01) were excellent. Lack of correlation was observed between CRETR and overall complication rate (p value > 0.1) as well as rectal complication rate (p value > 0.1). In order to limit Grade II and III rectal and bladder complications to acceptable level, in combined external and intracavitary treatments, CRETA value of less than 2500 reu is suggested.     

Optimum fractionation for high-dose-rate endoesophageal brachytherapy following external irradiation of early stage esophageal cancer

PURPOSE: To establish the optimum fractionation for high-dose-rate (HDR) endoesophageal brachytherapy (EBT) for early stage esophageal cancer from retrospective data of patients treated with different HDR schedules following external beam irradiation (EBI). METHODS AND MATERIALS: The study population consisted of 35 consecutive early stage esophageal cancer patients who received EBI to the mediastinum, plus EBT, between May 1992 and November 1995 at the Hiroshima University Medical Center and Hiroshima City Hospital. All patients were treated with EBI, with doses ranging from 50 to 61 Gy. The spinal cord was spared after 44-45 Gy. HDR EBT was performed using a double-balloon applicator in conjunction with an Ir-192 remote afterloading system. One group of 10 patients was given a weekly endoesophageal boost of 4 or 5 Gy at a distance of 5 mm from the applicator surface over a period of 1-2 weeks. Another group of 25 patients was treated with 4 or 5 endoesophageal boosts with a fraction dose of either 2.5 or 2 Gy for 1 week. The linear quadratic (LQ) formula was used to calculate the biologically effective dose (BED) for tumor (Gy10) and esophageal mucosa (Gy3); Gy10 means alpha/beta equals 10 Gy, and Gy3 means alpha/beta equals 3 Gy.The Kaplan-Meier method was used to calculate the local control and late complication rates, while the Cox-Mantel test was used to evaluate statistical significance (p < 0.01). RESULTS: Nine (26%) of the 35 patients recurred locally and 7 (20%) had late complications (esophageal ulcer grade by RTOG/EORTC criteria > 1). The 5-year overall survival, local control, and late complication rates were 38%, 57%, and 26%, respectively. The probability of local recurrence was not affected by the treatment parameters. Results from the LQ formula significantly correlate with data on late complications. A BED > 134 Gy3 and a fraction number = < 3 were associated with late complications (grade > 1). BED analysis showed that the fractionation dose should be decreased to 2.5 or 2.0 Gy at a distance of 5 mm from the applicator surface, and the number of doses increased to 4 or 5, respectively, to yield a satisfactory BED (< 134 Gy3). CONCLUSION: A significant reduction in endoesophageal brachytherapy dose per fraction is necessary to reduce late complications. Our current treatment protocol for early-stage esophageal cancer consists of EBI of 60 Gy followed by 4 EBT doses at a fraction dose of 2.5 Gy applied over 1 week.     

局部晚期宫颈癌CT图像引导下适形调强后程推量的临床研究

目的：观察利用三维适形调强技术（Intensity modulated radiotherapy,IMRT）、采用5Gy×5f分割模式对于局部晚期宫颈癌患者盆腔外照射后残留病灶局部推量的治疗效果及并发症发生。方法：33例局部晚期宫颈癌患者在完成盆腔外照射及同期DDP化疗后,行CT模拟定位扫描,定位前及每次治疗前均进行膀胱灌注以控制膀胱的充盈程度,勾画子宫颈、宫旁及阴道侵犯区域以及2cm阴道组织、子宫体下段2/3为CTV-boost,CTV-boost加5、15mm为PTV-boost,设计并执行7野三维适形调强计划,处方剂量为5Gy/f×5f,2f/w。结果：1年总生存率、无病生存率、盆腔控制率分别为82%、76%、79%,其中15mm PTV边界组的1年盆腔控制率为90%。结论：对于不能进行腔内后装治疗的部分局部晚期宫颈癌患者,采用5Gy×5f分割模式的三维适形调强技术进行后程推量可达到根治效果,1年内未见严重直肠、膀胱并发症出现,远期疗效及并发症正在进一步观察中。     

The optimized dosage specific for different organs with regard to late effect

Clinical and experimental evidence indicates that the optimized dosage may be different from organ to organ. In an effort to find an optimized dosage for laryngeal cancer treated in our department, the NSD-TDF concept and linear-quadratic (LQ) model were employed. The dose-fractionations using 2.5 Gy per fraction gave better results in terms of local control and complications than those using bigger fraction size and shorter treatment period. It is generally agreed that the maxillary cancer is best managed by combined radiation and surgery with or without chemotherapy. When irradiation is given in 16 fractions over 4 weeks, the local control and survival were decreased with increasing total dose, suggesting the presence of the supra-lethal dose phenomenon which was first mentioned by the Manchester group. The optimized dosage for carcinoma of the uterine cervix is more complicated, because both the external irradiation and intracavitary irradiation are combined for this disease. Our clinical data indicated that the optimal fractionation is: 50 Gy of total pelvic irradiation with the last 10-15 Gy given using a central shielding followed by RALS treatment delivering 30 Gy in 6 fractions at point A.     

Linear-quadratic model underestimates sparing effect of small doses per fraction in rat spinal cord.

The application of the linear-quadratic (LQ) model to describe iso-effective fractionation schedules for dose fraction sizes less than 2 Gy has been controversial. This paper describes experiments in which the effect of daily fractionated irradiation given with a wide range of fraction sizes was assessed in rat cervical spinal cord. The first group of rats were given doses in 1, 2, 4, 8 and 40 daily fractions. The second group of animals received three initial "top-up" doses of 9 Gy given once daily, representing three-quarters of tolerance, followed by doses in 1, 2, 10, 20, 30 and 40 daily fractions. The fractionated portion of the irradiation schedule therefore constituted only the final quarter of the tolerance dose. The endpoint of the experiments was paralysis of the forelimbs secondary to white matter necrosis. Direct analysis of data from experiments with full course fractionation up to 40 daily fractions (25.0-1.98 Gy per fraction) indicated consistency with the LQ model yielding an alpha/beta value of 2.41 Gy. Analysis of data from experiments in which the three "top-up" doses were followed by up to 10 fractions (10.0-1.64 Gy per fraction) gave an alpha/beta value of 3.41 Gy. However, data from "top-up" experiments with 20, 30 and 40 fraction (1.60-0.55 Gy per fraction) were inconsistent with the LQ model and gave a very small alpha/beta value of 0.48 Gy. It is concluded that the LQ model based on data from large doses per fraction underestimates the sparing effect of small doses per fraction provided sufficient time is allowed between each fraction for repair of sublethal damage.     

The prediction of late rectal complications in patients treated with high dose-rate brachytherapy for carcinoma of the cervix

: The aim of this work is to invetigate an unusually high rate of late rectal complications in a group of 43 patients treated with concomitant irradiation and chemotherapy for carcinoma of the cervix between December 1988 and April 1991, with a view to identifying predictive factors.

: The biologically effective dose received by each patient to the rectal reference point defined by the International Commission of Radiation Units and Measurements, Report 38, were calculated. Radiotherapy consisted of 46 Gy external beam irradiation plus three dose-rate intracavitary treatments of 10 Gy each prescribed to point A. Cisplatin 30 mg/m² was given weekly throughout the duration of the irradiation. The results have been compared to data from 119 patients treated with irradiation alone to assess the cofounding effect of the cisplatin.

: The relationship between the biologically effective dose delivered to the rectal reference point and the development of late complications shows a strong dose-response with a threshold for complications occurring at aproximately the same biologically effective dose threshold as that found for external beam irradiation in the head and neck region. The date from the group of patients treated wihout cisplatin is comparable to the date from the first group of patients in the lower dose ranges; the higher doses were not used and thus are not available for comparison.

: Using the linear quadratic model applied to our clinical results, we have established a threshold for late rectal complications for patients treated with external beam irradiation and high dose-rate brachytherapy for carcinoma of the cervix. This threshold is consistent with similar data for external irradiation in the head and neck region.     

Radiobiological aspects of continuous low dose-rate irradiation and fractionated high dose-rate irradiation

The biological effects of continuous low dose-rate irradiation and fractionated high dose-rate irradiation in interstitial and intracavitary radiotherapy and total body irradiation are discussed in terms of dose-rate fractionation sensitivity for various tissues. A scaling between dose rate and fraction size was established for acute and late normal-tissue effects which can serve as a guideline for local treatment in the range of dose rates between 0.02 and 0.005 Gy/min and fraction sizes between 8.5 and 2.5 Gy. This is valid provided cell-cycle progression and proliferation can be ignored. Assuming that the acute and late tissue responses are characterised by alpha/beta values of about 10 and 3 Gy and a mono-exponential repair half-time of about 3 h, the same total doses given with either of the two methods are approximately equivalent. The equivalence for acute and late non-hemopoietic normal tissue damage is 0.02 Gy/min and 8.5 Gy per fraction; 0.01 Gy/min and 5.5 Gy per fraction; and 0.005 Gy/min and 2.5 Gy per fraction. A very low dose rate, below 0.005 Gy/min, is thus necessary to simulate high dose-rate radiotherapy with fraction sizes of about 2 Gy. The scaling factor is, however, dependent on the repair half-time of the tissue. A review of published data on dose-rate effects for normal-tissue response showed a significantly stronger dose-rate dependence for late than for acute effects below 0.02 Gy/min. There was no significant difference in dose-rate dependence between various acute non-hemopoietic effects or between various late effects. The consistent dose-rate dependence, which justifies the use of a general scaling factor between fraction size and dose rate, contrasts with the wide range of values for repair half-time calculated for various normal-tissue effects. This indicates that the model currently used for repair kinetics is not satisfactory. There are also few experimental data in the clinical dose-rate range, below 0.02 Gy/min. It is therefore necessary to verify further the presented scaling between fraction size and dose rate.     

The role of age and tumor grade in the choice of fractionation regimen in patients with high-grade gliomas

There are currently no conventional guidelines for radiotherapy in gliomas. The treatment program is mainly formed in accordance with tumor morphology and the "golden standard" of irradiation is still the traditional mode of fractionation with a single focal dose of 2 Gy and total focal dose (TFD) of 60 Gy. In this report the treatment results of 396 patients with morphologically verified grade 3-4 malignant brain tumors receiving conventional irradiation regimen and irradiation by medium-sized fractions were analyzed to form institutional guidelines. The standard fractionation mode with a single focal dose of 2 Gy is preferable in patients with grade 3 glioma or elderly patients (over 60 years). TFD increase to 60-62 Gy in grade 4 gliomas and 54-56 Gy in grade 3 gliomas grants a significant improve in overall survival. An increase of a single irradiation fraction to 3 Gy may be used for patients younger than 60 years. In these cases it is advisable to use the TFD of 45 Gy or more (TFD of equivalent regimen with a dose greater than 54 Gy). The mentioned fractionation regimens could be recommended for the use in clinical practice to improve the results of high-grade gliomas treatment.     

High Dose Rate Brachytherapy in Two 9 Gy Fractions in the Treatment of Locally Advanced Cervical Cancer - a South Indian Institutional Experience

Background: Although 3D image based brachytherapy is currently the standard of treatment in cervicalcancer, most of the centres in developing countries still practice orthogonal intracavitary brachytherapy due tofinancial constraints. The quest for optimum dose and fractionation schedule in high dose rate (HDR) intracavitarybrachytherapy (ICBT) is still ongoing. While the American Brachytherapy Society recommends four to eightfractions of each less than 7.5 Gy, there are some studies demonstrating similar efficacy and comparable toxicitywith higher doses per fraction. Objective: To assess the treatment efficacy and late complications of HDR ICBTwith 9 Gy per fraction in two fractions. Materials and Methods: This is a prospective institutional study inSouthern India carried on from 1st June 2012 to 31st July 2014. In this period, 76 patients of cervical cancersatisfying our inclusion criteria were treated with concurrent chemo-radiation following ICBT with 9 Gy perfraction in two fractions, five to seven days apart. Results: The median follow-up period in the study was 24months (range 10.6 - 31.2 months). The 2 year actuarial local control rate, disease-free survival and overallsurvival were 88.1%, 84.2% and 81.8% respectively. Although 38.2% patients suffered from late toxicity, only 3patients had grade III late toxicity. Conclusions: In our experience, HDR brachytherapy with 9 Gy per fractionin two fractions is an effective dose fractionation for the treatment of cervical cancer with acceptable toxicity.     

The role of functional status and recursive partition analysis (RPA) classes for the choice of fractionation regimen in patients with high-grade gliomas

The treatment results of 396 patients with morphologically verified grade 3-4 malignant brain tumors receiving conventional irradiation regimen and irradiation by medium-sized fractions were analyzed to form institutional guidelines.The standard mode of fractionation with a single dose of 2 Gy and total focal dose (TFD) of 60 Gy is appropriate for patients with initial Karnofsky status of 60-100% and Recursive Partition Analysis (RPA) class I-III. TFD increase to 60-62 Gy in grade 4 gliomas and 54-56 Gy in grade 3 gliomas grants a significant improve in overall survival. An increase of a single irradiation fraction to 3 Gy may be used for patients with initially low functional status (Karnofsky 30-50%) and RPA classes IV-VI. In these cases it is advisable to use the TFD of 45 Gy or more (TFD of equivalent regimen with a dose greater than 54 Gy). The mentioned fractionation regimens could be recommended for the use in clinical practice to improve the results of high-grade gliomas treatment.     

Application of radiation effect models in combined external and intracavitary radiotherapy of carcinoma of the uterine cervix.

A retrospective analysis of 291 patients with cancer of the uterine cervix treated with a combination of external and intracavitary radiotherapy was carried out. Patients were treated with an external radiotherapy dose of 45 Gy in 20 fractions, 5 fractions per week, or 42 Gy in 14 fractions, 3 fractions per week. For brachytherapy the total dose was 24 to 32 Gy at a dose rate of 1.4 to 2.2 Gy per hour. Treatment results in terms of survival, local disease-free survival and complication rates were compared with cumulative radiation effect (CRE) and extrapolated response dose (ERD) values for point A (CRETA and ERDTA respectively) and for rectum (CRETr and ERDTr respectively). CRETA and ERDTA values did not significantly correlate with local disease-free and survival rates. Correlations of CRETA and ERDTA with overall complication rate and with rectal complication rate (p-value less than 0.025) were good. No significant correlation was observed between CRETr or ERDTr and overall complication rate and rectal complication rate. In order to limit grades II and III rectal complications to acceptable level, in combined external and intracavitary treatment, CRETA and ERDTA values of less than 2,500 and 93 respectively are suggested.     

高剂量率192铱后装机腔内加外照射治疗宫颈癌60例临床分析

目的:探讨高剂量率192铱后装腔内加体外照射治疗宫颈癌的疗效及副作用等。方法:2005年3月至2007年1月本院放疗中心共60例宫颈癌患者,采用8MV-X线直线加速器全盆照射,开始体外全盆腔照射,5次/周,2Gy/次,剂量25-40Gy;然后中间挡铅,4个野照射,5次/周,2Gy/次,宫旁剂量20-25Gy:同时腔内治疗,1次/周,6Gy/次,剂量为35-40Gy。腔内治疗采用ZL-HDR18铱高剂量率后装治疗机,全部病例均宫颈阴道同时进行。腔内治疗每周1次,A点剂量36-40GY/6-7F/6-7w,腔内治疗当日停体外照射,治疗时间56-77天。结果:CR+PR 100%,随访超过3年,随访率达95%,3年生存率Ⅱ期88.3%,Ⅲ期82.9%;早期放射性直肠反应发生率为12.4%,膀胱反应发生率5.2%;晚期放射性直肠炎发生率13.8%,膀胱炎3.8%。结论:高剂量率192铱后装机腔内加体外治疗宫颈癌的疗效满意,患者生存率较高,耐受好,并发症少。     

Dose optimization of fractionated external radiation and high-dose-rate intracavitary brachytherapy for FIGO stage IB uterine cervical carcinoma

: To determine the optimal dose combination scheme of external beam radiotherapy (EBRT) and high-dose-rate (HDR) intracavitary radiation (ICR) for maximizing tumor control while conferring an acceptable late complication rate in the treatment of Stage IB uterine cervical cancer.

: We retrospectively analyzed 162 patients with International Federation of Gynecology and Obstetrics (FIGO) Stage IB squamous cell carcinoma of the uterine cervix who received definitive RT between May 1979 and December 1990. Before HDR-ICR, all patients received EBRT to a total dose of 40–46 Gy (median 45), administered during 4–5 weeks to the whole pelvis. HDR-ICR was given 3 times weeks to a total dose of 24–51 Gy (median 39) at point A, using a dose of 3 Gy/fraction. Central shielding from EBRT was begun after the delivery using 20–45 Gy (median 40) of the external dose. The total dose to point A, calculated by adding the EBRT biologically effective dose (BED) and the ICR BED to point A, was 74.1–118.1 Gy (mean 95.2). The rectal point dose was calculated at the anterior rectal wall at the level of the cervical os. The local control rate, survival rate, and late complication rate were analyzed according to the irradiation dose and BED.

: The initial complete response rate was 99.4%. The overall 5-year survival rate and 5-year disease-free survival rate was 91.1% and 90.9%, respectively. The local failure rate was 4.9%, and the distant failure rate was 4.3%. Late complications were mild and occurred in 23.5% of patients, with 18.5% presenting with rectal complications and 4.9% with bladder complications. The mean rectal BED (the sum of the external midline BED and the ICR rectal point BED) was lower in the patients without rectal complications than in those with rectal complications (125.6 Gy vs. 142.7 Gy, p = 0.3210). The late rectal complication rate increased when the sum of the external midline BED and the rectal BED by ICR was ≥131 Gy (p = 0.1962). However, 5-year survival rates did not increase with the external midline BED (p = 0.4093). The late rectal complication rate also increased, without a change in the survival rate, when the sum of the external midline BED and the ICR point A BED was >90 Gy.

: In treating Stage IB carcinoma of the uterine cervix with HDR-ICR, using fractions of 3 Gy, it is crucial to keep the point A BED at ≤90 Gy to minimize late rectal complications without compromising the survival rate. To achieve this goal, appropriate central shielding from EBRT is needed.     

Early and late effects in mouse lung and rectum

No higher RBE's were found for late than for early damage in mouse rectum up to 70 weeks or mouse lungs up to 48 weeks after irradiation with 3.0 MeV neutrons (4 MeV deuterons on Be). The smallest neutron doses per fraction were 1.5 and 0.6 Gy for rectal and lung irradiation, respectively. There was a suggestion of higher late RBE's for small doses per fraction in the lung. Slow repair after 2 neutron doses split by 31 days was unequivocally demonstrated in the lung, of magnitude about 1 Gy, possibly decreasing after about 40 weeks.