Histological Changes After Fractionated Whole or Partial Irradiation of the Rabbit Urinary Bladder

Effects of x-irradiation on the urinary bladder of male New Zealand rabbits were studied by means of light microscopy 100 weeks after exposure. The absorbed dose was 33, 36 or 39 Gy given in 5 daily fractions administered to the whole, the cranial or the caudal part of the bladder. The changes in the epithelium and in the muscular tissue were dose-dependent while the changes in the submucosa and in the extramuscular layer were not. The transitional epithelium was generally either atrophic or hyperplastic. If dysplastic or neoplastic changes were seen, the involved areas were mostly surrounded by an apparently normally differentiated epithelium and the highly specialized superficial cells lining the bladder cavity were always present. The submucosal and muscular tissues showed fibrosis and changes in blood vessels and, sometimes also in lymph vessels.     

Acute and late radiation damage in mouse bladder: a comparison of urination frequency and cystometry

Functional damage in the mouse bladder was measured sequentially from 1 to 53 weeks after irradiation with a range of X ray doses (10 to 30 Gy). Damage was assessed from the independent assays of urination frequency and cystometric measurement of bladder volume at a constant intravesical pressure. There was an early, transient wave of damage from 1 to 3 weeks after bladder irradiation. During this period the urination frequency was increased to greater than or equal to 2 times control levels in 20 to 70% of the mice (depending on dose) after 15 to 30 Gy. Bladder volume was reduced to less than or equal to 50% of control values in 20 to 40% of the mice after doses of 20 to 30 Gy. This early damage usually lasted for less than 1 week and occurred at times ranging from 5 to 21 days, independent of dose. There was no significant correlation between response as measured by the two assays on an individual animal basis during the early period. The incidence of reduced bladder volume, measured cystometrically in anesthetized mice, tended to be less than the incidence of increased urination frequency, measured in non-anesthetized animals. Late bladder damage developed from 16 to 40 weeks after doses of greater than or equal to 20 Gy, and the time of onset was inversely related to dose. Less than 20% of mice treated with 10 to 15 Gy developed late bladder damage as assessed by increased urination frequency or reduced bladder volume. Late bladder damage was irreversible and there was a good correlation between response of individual animals as measured by the two assays. We conclude that changes in both urination frequency and bladder volume can be used as quantitative measures of early and late functional damage after bladder irradiation. The early, transient damage was not associated with changes in the urothelium or muscle layers of the bladder, whereas the late, persistent damage was accompanied by epithelial denudation and focal hyperplasia, with fibrosis and ulceration after higher doses.     

Hypofractionated radiotherapy for patients with carcinoma of the bladder

In order to develop a low toxicity regimen of bladder radiotherapy for the palliation of patients with poor performance status we carried out a Phase II study of weekly 6 Gy fractions to a maximum dose of 30-36 Gy in 65 patients with T(2)-T(4) bladder cancer (median age 81 years). A complete response was obtained in 23/37 (62%) assessable patients at cystoscopy. Local control was achieved in 16/65 (25%) patients. The median survival of all 65 patients was 35 weeks, and the 2-year actuarial survival 21%. The main acute toxicity was urinary frequency as often as hourly at the peak of the reaction (Radiation Therapy Oncology Group (RTOG) grade 3) in seven patients, and urinary obstruction (RTOG grade 4) in one. The reactions may have been compounded by the effects of locally advanced tumour. Late bladder toxicity amongst the 16 patients who were evaluable after 1 year included four patients with persisting frequency, one with severe haematuria (RTOG grade), and one with a bladder capacity <100 ml (RTOG grade 4). One patient experienced RTOG grade 4 late bowel and bladder morbidity. Weekly 6 Gy fractions to a total dose of 30-36 Gy is a satisfactory palliative regimen for patients with advanced bladder cancer who cannot tolerate standard radical radiotherapy, but it may produce significant late bladder morbidity.     

Long-term recovery and reirradiation tolerance of mouse bladder

The aim of this study was to investigate the influence of overall treatment time on the development and repair of radiation injury in the bladder. The bladders of mice were irradiated with 2 equal doses of X rays separated by 1 day, 3 months or 9 months. Additional groups of mice were given 8 or 16 Gy (approximately 20% and 60%, respectively, of a full tolerance dose) and subsequently reirradiated with a range of test doses after 3 or 9 months. Functional bladder damage was assessed from measurements of urination frequency and bladder compliance (measured cystometrically). There was a very early onset of functional damage (within 2 weeks) when mice were reirradiated 9 months after a dose of 16 Gy. Lower initial doses of 8 Gy did not alter the time of expression of damage after reirradiation. The early damage was probably due to stimulated cellular proliferation, which occurred after 16 Gy but not after 8 Gy, causing rapid expression of retreatment injury. Reirradiation tolerance for late bladder damage was inversely related to the dose given in the first treatment but was independent of the interval between treatments. There was no evidence for increased tolerance as the interval between treatments increased from 1 day to 9 months, which suggests that protracting the overall treatment time will not lead to sparing of late radiation damage in the bladder.     

Radiotherapy for muscle-invasive carcinoma of the bladder: results of a randomized trial comparing conventional whole bladder with dose-escalated partial bladder radiotherapy

PURPOSE: To investigate whether delivering an increased radiation dose to the tumor-bearing region of the bladder alone would improve local disease control without increasing treatment toxicity. METHODS AND MATERIALS: A total of 149 patients with unifocal T2-T3N0M0 bladder carcinoma were randomized between whole bladder conformal radiotherapy (WBRT, 52.5 Gy in 20 fractions, n = 60) and partial bladder conformal RT (PBRT) to tumor alone with 1.5-cm margins within either 4 weeks (PBRT4, 57.5 Gy in 20 fractions, n = 44) or 3 weeks (PBRT3, 55 Gy in 16 fractions, n = 45). The response was assessed cystoscopically after 4 months. RESULTS: The 5-year overall and CFS rate was 58% and 47%, respectively, for the whole population. The CR rate was 75% for WBRT, 80% for PBRT4, and 71% for PBRT3 (p = 0.6), with a 5-year local control rate of 58%, 59%, and 34%, respectively (p = 0.18). Solitary new tumors arose within the bladder, outside the irradiated volume, in 6 (7%) of 89 patients who underwent PBRT. The 5-year overall survival and cystectomy-free survival rate was 61% and 49% for WBRT, 60% and 50% for PBRT4, and 51% and 41% for PBRT3 (p = 0.81 and p = 0.59). The treatment toxicity was mild and equivalent across the three trial arms. CONCLUSION: The reduction in treatment volume allowed delivery of an increased radiation dose without a reduction in local tumor control or the development of excess toxicity. However, this dose-escalated partial bladder approach did not result in significantly improved overall survival.     

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.     

Dose de tolérance à l’irradiation des tissus sains : la vessie

The bladder is a hollow visco-elastic organ involved in urinary continence. In relation to its anatomical location, bladder is exposed in whole or in part to ionizing radiation in external radiotherapy or in brachytherapy of the pelvic region. The acute and late functional changes after external beam radiation consist in urinary frequency, compliance defaults and hematuria. Incidence of urinary side-effects, as well as related modalities of radiotherapy, is poorly described in the literature. Medline^® literature searches were performed via PubMed using the keywords “bladder – radiotherapy – toxicity – radiation cystitis – tolerability – organ at risk” to describe urinary side-effects due to radiation. Some recommendations exist on the dose constraints applied to bladder. These were mainly established from prostate radiation therapy studies but without definitive consensus. In clinical practice, dose constraints take into account clinical settings: bladder cancer which requires total bladder irradiation or others pelvic tumours (prostate, uterus…) in which the bladder is considered as an organ at risk. Risks of radiation cystitis increase with total dose (above 60 Gy), bladder irradiated volume and concomitant chemoradiation. Modern techniques using conformal radiotherapy with modulated intensity will probably have beneficial impact on bladder toxicity.     

Invasive bladder carcinoma: a pilot study of conservative treatment with accelerated radiotherapy and concomitant cisplatin.

From November 1992 to December 1997, 25 patients (inoperable or refusing cystectomy) were included in a prospective study to assess the feasibility, tolerance, and curative potential of accelerated radiotherapy (RT) and concomitant cisplatin. Median age was 74 years (range 49-86). Stage distribution was as follows: 1 T1, 10 T2, 8 T3, and 6 T4. Two patients had clinically positive pelvic nodes. The goal was to deliver a total dose of 40 Gy to the whole pelvis and bladder in 4 weeks using a concomitant boost of 20 Gy to the tumor or to the whole bladder during the third and fourth weeks (total dose 60 Gy), with daily cisplatin (6 mg/m(2)) before RT for patients with creatinine clearance > 50 ml/min. All but one patient completed the RT protocol. Daily cisplatin was successfully delivered in 18 patients. One patient presented with grade III ototoxicity. Diarrhea was scored grade III in two and grade IV in two patients. Acute urinary toxicity was scored grade III in one patient. Posttreatment late effects included bladder grade II and grade III in two patients and one patient, respectively; large bowel grade III in one; urethral grade III in one; and femoral head radionecrosis in one. Four-year overall and disease-specific survival rates were 23% and 35%, respectively. The latter was 60% for patients with T2 tumors. The 4-year actuarial locoregional control rate for all patients was 61%. In summary, accelerated RT and concomitant cisplatin is feasible with acceptable tolerance even in relatively old patients. Although outcome was better for patients with low-stage tumors, local control and survival rates appeared similar to those of standard RT schedules for a similar patient population.     

两种不同腔内后装施源器治疗宫颈癌的临床观察

目的：探讨高剂量率^192Ir腔内后装时不同施源器治疗宫颈癌的疗效及膀胱、肠道晚反应并发症的发生情况。方法：127例宫颈癌患者予全盆外照DT45～50Gy配合腔内后装治疗，依照后装治疗时不同施源器分为固定Ⅲ管组62例，单宫腔管组65例。固定Ⅲ管组开始于全盆外照DT33Gy／18次，A点DT5～7Gy／次，1次／周，总量24～25Gy，6—8周内完成治疗。单官腔管组开始于外照全盆DT38Gy／20次，A点DT6～7Gy／次，1次／周，总量21—25Gy，7～8周内完成治疗。结果：放疗结束后固定Ⅲ管组与单宫腔管组完全缓解病例分别为57例（91．94％）和58例（89．23％），5年生存率分别为66．13％（41／62）和61．50％（40／65），固定Ⅲ管组膀胱、肠道晚反应发生率分别为4．83％（3／62）和9．67％（6／62），明显低于单宫腔管组的10．76％（7／65）和21．53％（14／65）。结论：使用剂量曲线分布合理的固定Ⅲ管施源器行腔内放疗可以有效地治疗宫颈癌，并可明显减少膀胱、肠道晚反应并发症。     

Evaluating the effect of reducing the high-dose volume on the toxicity of radiotherapy in the treatment of bladder cancer

AimsThe radiation dose used to treat bladder cancer is limited by the risk of inducing severe late bladder toxicity. Retrospective data suggest that radiation tolerance is greater for partial rather than whole bladder irradiation. Limiting the high-dose region to a section of the bladder may reduce toxicity, opening the way for dose escalation. The aims of this study were to establish the efficacy and compare the late toxicity between (1) a two-phase technique limiting the high-dose area and (2) a conventional single-phase radiotherapy to the whole bladder.Materials and methodsA cohort study was undertaken of 229 patients with invasive bladder cancer treated with computed tomography-planned radical radiotherapy at the Royal Marsden Hospital from 1984 to 1998. In total, 154 patients received a single-phase treatment to the whole bladder with a 2 cm margin. Seventy-five patients with solitary, well-localised tumours were selected for treatment using a two-phase technique. The first phase (12 Gy) aimed to treat the tumour with a 2 cm margin. A second phase treated the whole bladder with 52 Gy. One hundred and forty-one patients were planned to receive a dose of 60–64 Gy/30–32 fractions over 6–6.5 weeks, whereas 88 patients received an accelerated regime. Data on late bladder and bowel toxicity (using Radiation Therapy Oncology Group criteria) were collected prospectively at the annual review.ResultsAt the 5-year follow-up there was no difference in overall survival (hazard ratio = 0.91, 95% confidence interval 0.64–1.3) or failure-free survival (hazard ratio = 1.02, 95% confidence interval 0.73–1.43) between the two techniques. The two-phase reduced volume treatment was less toxic, with a 19% absolute reduction in overall grade 3–4 late toxicity (P = 0.02). These differences were more marked for bladder toxicity compared with bowel toxicity.ConclusionsThe two-phase reduced volume technique was associated with less bladder and bowel toxicity than conventional whole bladder radiotherapy without evidence of impaired survival.     

Intraoperative and external beam radiotherapy in invasive bladder cancer: pathological findings following cystectomy

The pathological findings observed following intraoperative radiotherapy (IORT) boost (15Gy) to the whole bladder, external beam fractionated irradiation (46Gy in 5 weeks), and planned radical cystectomy in patients with deep invasive bladder carcinoma are analyzed. Clinical pretreatment stage of disease was T3 (16 cases) and T4 (two cases). No evidence of residual tumor (pT0) was demonstrated in 11 cystectomy specimens (61%) and residual tumor (pT+) was observed in seven (39%). Toxicity and complications related to the treatment approaches were minor and reversible. It is concluded that IORT is a feasible boosting modality in the management of invasive bladder cancer, able to induce high rates of pT0 cystectomy specimens, and might be considered as a valuable technique for organ preservation treatment programs.     

Fractionation sensitivity and latency of late radiation injury to the mouse urinary bladder.

Transurethral bladder filling is a functional, non-invasive, in vivo assay of early and late radiation injury to the mouse bladder. Fractionated irradiations using single doses or 2, 3, 5, or 10 dose fractions in an overall time of 4 or 4.5 days, with a range of total doses, were given to the bladder of 12-14 week-old C3D2F1/Bom mice. In 372 mice, bladder volume at an intravesical pressure of 20 mmHg was measured before irradiation and at regular intervals thereafter. The endpoint for late bladder injury was a volume of less than 50% of the median pretreatment volume in all animals, occurring more than 30 days after irradiation. This endpoint was reached after a latent period ranging between 35 and 401 days. Fractionation and latency parameters were estimated using a mixture model. There was a highly statistically significant dose-dependency of the latent period (p < 10(-8)). The alpha/beta ratio was estimated at 5.8 Gy [95% confidence limits (3.6; 8.8) Gy] for 250 kVp X-rays. Thus late radiation injury in the mouse urinary bladder is one of the least sensitive late endpoints with respect to change in dose per fraction. Introducing early bladder injury as a variable in the model improved the fit significantly (p = 0.03), but the alpha/beta ratio remained unchanged. Thus the hypothesis that late bladder injury may be, at least in part, consequent upon early injury did not explain the relatively high alpha/beta ratio for this late endpoint.     

Leydig cell function in the pubertal rat following local testicular irradiation

Dose- and time-response relationships were measured after irradiation of the pubertal rat testis with between 1 and 20 Gy of 300 kVp X-rays. The threshold dose for Leydig cell dysfunction was about 5 Gy. Dysfunction after higher doses was observed by 2 weeks post-irradiation as a dose-dependent decrease in serum testosterone (T) concentrations, and the levels were undetectable after 15 or 20 Gy. Despite the recovery of serum T by 24 and 36 weeks, dysfunction of the Leydig cell population was still observed as an increase in luteinizing hormone (LH) secretion (1.5 to 2-fold increase after 15 or 20 Gy at 24 weeks; 2 to 3-fold increase after 10 or 20 Gy at 36 weeks). The endocrine changes were probably due to the observed loss of Leydig cells following irradiation. These results indicate that the Leydig cells of pubertal rats are more radioresponsive than those of the adult.     

Adaptive radiotherapy in muscle invasive urinary bladder cancer - An effective method to reduce the irradiated bowel volume

Background and purpose

To evaluate the benefits of adaptive radiotherapy for bladder cancer in decreasing irradiation of small bowel.

Material and methods

Five patients with muscle invasive bladder cancer received adaptive radiotherapy to a total dose of 55.8-65 Gy with daily cone-beam computed tomography scanning. The whole bladder was treated to 45-50.4 Gy, followed by a partial bladder boost. The plan of the day was chosen from 3 to 4 pre-planned treatment plans according to the visible extent of bladder wall in cone-beam computed tomography images. Dose volume histograms for intestinal cavity volumes were constructed and compared with corresponding histograms calculated for conventional non-adaptive radiotherapy with single treatment plan of 2 cm CTV-PTV margins. CTV dose coverage in adaptive treatment technique was compared with CTV dose coverage in conventional radiotherapy.

Results

The average volume of intestinal cavity receiving ?45 Gy was reduced from 335 ± 106 cm³ to 180 ± 113 cm³ (1SD). The maximum volume of intestinal cavity spared at 45 Gy on a single patient was 240 cm³, while the minimum volume was 65 cm³. The corresponding reduction in average intestinal cavity volume receiving ?45 Gy calculated for the whole bladder treatment only was 66 ± 36 cm³. CTV dose coverage was improved on two out of five patients and decreased on three patients.

Conclusions

Adaptive radiotherapy considerably reduces dose to the small bowel, while maintaining the dose coverage of CTV at similar level when compared to the conventional treatment technique.     

Influence of bladder and rectal volume on spatial variability of a bladder tumor during radical radiotherapy

PURPOSE: To assess the spatial variability of a bladder tumor relative to the planning target volume boundaries during radical radiotherapy, and furthermore to develop strategies to reduce spatial variability. METHODS AND MATERIALS: Seventeen patients with solitary T2-T4N0M0 bladder cancer were treated with a technique delivering 40 Gy/2 Gy in 20 fractions to the whole bladder with a concomitant boost to the bladder tumor of 20 Gy in 1 Gy fractions in an overall time of 4 weeks. CT scans were made weekly, immediately after treatment, and matched with the planning CT scan. Spatial variability of the tumor, as well as bladder volume and rectal diameter, were scored for each patient each week. RESULTS: In 65% of patients, a part of the tumor appeared outside the planning target volume boundaries at least one time during the course of radiotherapy. No consistent relation of this variability with time was found. Bladder volumes and rectal diameters showed marked variability during the course of treatment. A large initial bladder volume and rectal diameter predicted a large volume variation and a large tumor spatial variability. CONCLUSION: In this study, a margin of 1.5 to 2 cm seemed to be inadequate in 65% of the patients with respect to spatial variability. Bladder volume and rectal diameter were found to be predictive for spatial variability of a bladder tumor during concomitant boost radiotherapy.     

宫颈癌调强放疗膀胱受照剂量的评价

目的:研究宫颈癌调强放疗计划设计中膀胱壁与膀胱受照剂量的差别,从而在计划设计中正确设置和评价膀胱的限制剂量。方法:随机选取19例宫颈癌病例,为其设计调强计划。为了便于比较,分别给19例患者设计第一程全盆照射计划,处方剂量50 Gy/25次,利用DVH图分别评价膀胱和膀胱壁的受量。结果:调强计划中膀胱、膀胱壁的最小剂量、最大剂量差异均无统计学意义。膀胱平均剂量、D70、D50、D40和D30分别为38.45、30.07、38.68、43.90和47.54 Gy,膀胱壁平均剂量、D70、D50、D40和D30分别为40.97、32.80、45.83、49.16和50.24 Gy。用膀胱所受剂量评价膀胱壁剂量,膀胱壁平均剂量、D70、D50、D40和D30分别被低估6.55%、9.08%、18.49%、11.98%和5.68%。结论:在宫颈癌调强计划设计中,简单的用整个膀胱受量评价膀胱壁受量,将会低估膀胱壁的真正受量,从而加大膀胱并发症的概率,对膀胱造成不必要的损伤。     

Comparison of methods for calculating rectal dose after (125)I prostate brachytherapy implants

PURPOSE: To compare several different methods of calculating the rectal dose and examine how accurately they represent rectal dose surface area measurements and, also, their practicality for routine use. METHODS AND MATERIALS: This study comprised 55 patients, randomly selected from 295 prostate brachytherapy patients implanted at the Vancouver Cancer Center between 1998 and 2000. All implants used a nonuniform loading of 0.33 mCi (NIST-99) 125I seeds and a prescribed dose of 144 Gy. Pelvic CT scans were obtained for each patient approximately 30 days after implantation. For the purposes of calculating the rectal dose, several structures were contoured on the CT images: (1) a 1-mm-thick anterior rectal wall, (2) the anterior half rectum, and (3) the whole rectum. Point doses were also obtained along the anterior rectal surface. The thin wall contour provided a surrogate for a dose-surface histogram (DSH) and was our reference standard rectal dose measurement. Alternate rectal dose measurements (volume, surface area, and length of rectum receiving a dose of interest [DOI] of > or =144 Gy and 216 Gy, as well as point dose measures) were calculated using several methods (VariSeed software) and compared with the surrogate DSH measure (SA(DOI)).RESULTS: The best correlation with SA(144 Gy) was the dose volumes (whole or anterior half rectum) (R = 0.949). The length of rectum receiving > or =144 Gy also correlated well with SA(144 Gy) (R > or =0.898). Point dose measures, such as the average and maximal anterior dose, correlated poorly with SA(144 Gy) (R < or =0.649). The 216-Gy measurements supported these results. In addition, dose-volume measurements were the most practical (approximately 6 min/patient), with our surrogate DSH the least practical (approximately 20 min/patient). CONCLUSION: Dose-volume measurements for the whole or anterior half rectum, because they were the most practical measures and best represented the DSH measurements, should be considered a standard method of reporting the rectal dose when calculating the DSH is not practical. Average or maximal anterior rectal doses are not reliable indicators of surface area dosimetry.     

Adaptive Radiotherapy for Carcinoma of the Urinary Bladder: Long-term Outcomes With Dose Escalation

AimsTo report long-term outcomes with dose-escalated, image-guided adaptive radiotherapy (ART) for bladder preservation in muscle-invasive bladder cancer (MIBC).Materials and methodsAll MIBC patients receiving bladder-preserving ART at our institute from 2009 to 2018 were analysed. For ART, three anisotropic planning target volumes (PTV) were concentrically grown around the simulation bladder volume. A library of intensity-modulated radiotherapy plans was created for each patient. A total dose of 64 Gy in 32 fractions to the entire bladder and 55 Gy to pelvic nodes was planned, with 68 Gy to the tumour bed (2 Gy equivalent dose = 68.7 Gy, α/β = 10) as simultaneous integrated boost for solitary tumours. The most appropriate PTV encompassing the bladder (‘plan-of-the-day’) was chosen daily using on-board megavoltage imaging. Neoadjuvant and concurrent chemotherapy was prescribed for medically fit patients.ResultsOf a total of 106 patients, most had T2 (68%) or T3 (19%) disease. Ninety-two patients (87%) completed 64 Gy to the whole bladder. Sixty-three patients (59%) received 68 Gy as tumour bed boost. Seventy-six per cent received concurrent weekly chemotherapy. At a median follow-up of 26 months, 3-year locoregional control, disease-free survival and overall survival were 74.3, 62.9 and 67.7%, respectively. Eighty-two per cent of patients retained disease-free bladder. Radiation Therapy Oncology Group grade III/IV acute genitourinary and gastrointestinal toxicities were 7.5% and 0%, respectively, and late genitourinary/gastrointestinal toxicities were 6.5% and 3.8%, respectively. Overall survival, disease-free survival, locoregional control and grade III/IV genitourinary/gastrointestinal toxicities did not differ significantly with dose escalation.ConclusionPlan-of-the-day ART is clinically safe and effective for bladder preservation and can be implemented in routine clinical practice. A high bladder preservation rate is achievable without compromising on survival or toxicities. Dose escalation does not seem to affect outcomes.     

Radiobiological prediction of normal tissue toxicities and tumour response in the radiotherapy of advanced non-small-cell lung cancer.

A number of randomized studies have been carried out in the UK and USA to determine the optimal radiotherapy dose schedule for advanced non-small-cell lung cancer (NSCLC). We have examined eight radiotherapy regimens from data taken from four randomized phase III studies carried out in the UK (1264 patients): 10 Gy single fraction; 17 Gy in two fractions over 8 days; 30 Gy in ten fractions over 14 days; 22.5 Gy in five fractions in 5 days; 27 Gy in six fractions over 11 days; 30 Gy in six fractions over 11 days; 36 Gy in 12 fractions over 16 days; and 39 Gy in 13 fractions over 17 days. We compared the clinical results in palliation, toxicity and survival with four regimens taken from one randomized study from the USA (365 patients): 40 Gy in 20 fractions over 4 weeks; 40 Gy ''split course'' in ten fractions in 4 weeks; 50 Gy in 25 fractions over 5 weeks; and 60 Gy in 30 fractions over 6 weeks. Using the linear-quadratic (LQ) radiobiological model, we have calculated the radiobiological equivalent dose (BED) for acute-reacting tissues (BED10), late-reacting tissues (BED1.7) and tumour (BED25), and related the predicted response to the observed response in each tissue. There was a good correlation between the predicted response and the reported response in the case of late-reacting tissue toxicity and tumour response. The model confirmed that, in good performance status patients, a higher value for BED25 correlated with a higher degree of local control and survival and that radiotherapy regimens with a higher value for BED1.7 were associated with five cases of cord myelopathy, if the spinal cord was not shielded. In poor performance status patients the model suggested that the optimal regimen was a single fraction of 10 Gy because this resulted in an equivalent degree of symptom control as other regimens, needed only one hospital visit and was less likely to result in cord damage, thus, allowing for the possibility of retreatment at a later date.