Urology mythbusters: Radiation and radiophobia.

In this episode of Mythbusters we critically examine the premise that there is strong biological and epidemiologic evidence that radiation exposure at levels associated with modern genitourinary diagnostic imaging increases the risk of subsequent malignancy, especially in children.

Incidence of sarcoma in patients treated with fast neutrons.

PURPOSE: The aim of this study is to report the incidence of soft tissue sarcoma in a large group of patients treated with fast neutrons. METHODS: A systematic review was conducted of long-term follow-up after trials of fast neutron therapy for cancers at various sites. The study took place at Edinburgh Cancer Centre, Western General Hospital, Edinburgh, Scotland, United Kingdom. From 1977 to 1984, 620 patients were treated using fast neutrons in the MRC cyclotron unit in Edinburgh. Most of these were treated within randomized controlled trials. Follow-up was maintained in all except 2 patients, who left the area to return abroad. The main outcome measure was the incidence of new soft-tissue sarcomas during long-term follow-up. RESULTS: Three cases of sarcoma, developing within the treatment volume, were observed in a small group of patients treated some years earlier using fast neutrons. This incidence was 111 times what would have been expected in the normal population and 15 times the incidence in a comparable photon-treated group of patients. CONCLUSION: The long-term incidence of sarcomas in patients previously treated with fast neutrons is significant.

Is routine chest radiography a useful test in the follow up of all adult patients with soft tissue sarcoma?

Following treatment for localized soft tissue sarcoma the risk of relapse is either locally or in the lungs. In Edinburgh patients are reviewed every 6 months with a chest X-ray (CXR). The radiation exposure over a 10 year follow up remains small, but it is unclear if all patients, irrespective of the initial grade of their primary tumour, require this. To determine the pick up rate of lung metastases by routine CXR over a 10 year period and to review the primary histology. Adult patients on routine follow up between 1994 and 2004 were identified and the notes of those with lung metastases reviewed. Data was collected on their initial histology, and date and method of diagnosis of lung metastases. 179 patients were under follow up. 24 (13%) developed lung metastases. For 2, notes were not found. 6 (27%) had metastases diagnosed by routine CXR, 9 (41%) had metastases diagnosed by non routine CXR and 7 (32%) had metastases diagnosed by CT. On review of histology none were grade 1, 4 (18%) were grade 2 and 18 (82%) were grade 3. 155 patients received. 6 monthly CXR for 10 years with no detection of lung metastases. Lung metastases occurred in a minority of patients (13%) and most (82%) occurred in patients with grade 3 tumours. No patients with grade 1 tumours developed lung metastases. Thus routine CXR may be appropriate on grade 3 tumours, but not on lower grade tumours where other risk factors are absent.

Symptom control and quality of life in people with lung cancer: a randomised trial of two palliative radiotherapy fractionation schedules.

AIMS: To determine whether palliation of chest symptoms from a 10 Gy single fraction (regimen 1) was equivalent to that from 30 Gy in 10 fractions (regimen 2). MATERIALS AND METHODS: Patients with cytologically proven, symptomatic lung cancer not amenable to curative therapy, with performance status 0-3, were randomised to receive either 30 Gy in 10 fractions or a 10 Gy single fraction. Local symptoms were scored on a physician-assessed, five-point categorical scale and summed to produce a total symptom score (TSS). This, performance status, Hospital Anxiety and Depression (HAD) score and Spitzer's quality-of-life index were noted before treatment, at 1 month after treatment and every 2 months thereafter. Palliation was defined as an improvement of one point or more in the categorical scale. Equivalence was defined as less than 20% difference in the number achieving an improvement in the TSS. RESULTS: We randomised 149 patients and analysed 74 in each arm. According to the design criteria, palliation was equivalent between the two arms. TSS improved in 49 patients (77%) on regimen 1, and in 57 (92%) patients on regimen 2, a difference of 15% (95% confidence interval [CI] 3-28) in the proportion improving between the two regimens. A complete resolution of all symptoms was achieved in three (5%) on regimen 1, and in 14 (23%) patients on regimen 2 (P < 0.001), a difference in the proportion between the two regimens of 21% (95% CI 10-33). A significantly higher proportion of patients experienced palliation and complete resolution of chest pain and dyspnoea with regimen 2. No differences were observed in toxicity. The median survival was 22.7 weeks for regimen 1 and 28.3 weeks for regimen 2 (P = 0.197). CONCLUSIONS: Although this trial met the pre-determined criteria for equivalence between the two palliative regimens, significantly more patients achieved complete resolution of symptoms and palliation of chest pain and dyspnoea with the fractionated regimen.

A patient with Rothmund-Thomson syndrome and tongue cancer--experience of radiation toxicity.

We describe a male patient with Rothmund-Thomson syndrome (RTS) given postoperative radiotherapy for squamous carcinoma of the tongue. This was well tolerated. This is only the second reported case of oral cancer and radiotherapy in RTS.

New onset of venous thromboembolism among hospitalized patients at Brigham and Women's Hospital is caused more often by prophylaxis failure than by withholding treatment.

CONTEXT: Guidelines to prevent venous thromboembolism (VTE) have been widely distributed and generally have been assumed to be effective. Therefore, among hospitalized patients, the development of VTE is thought to occur in the context of omitted prophylaxis. OBJECTIVES: To describe hospitalized patients who develop VTE and to determine whether they received antecedent prophylaxis. DESIGN: Case series. SETTING: Brigham and Women's Hospital. PATIENTS: Three hundred eighty-four patients who developed in-hospital deep venous thrombosis or pulmonary embolism or who developed VTE within 30 days of prior hospital discharge. MAIN OUTCOME MEASURES: The relationship of developing new-onset VTE to the use or omission of antecedent in-hospital prophylaxis. RESULTS: Of the 384 identified patients, 272 had deep venous thrombosis alone, 62 had pulmonary embolism alone, and 50 had deep venous thrombosis and pulmonary embolism. Most were medical service patients; fewer than one fourth were general or orthopedic surgery patients. Overall, 52% had received antecedent VTE prophylaxis. Thirteen deaths (3.4%) were ascribed to pulmonary embolism, and prophylaxis was omitted in only 1 of those 13 patients. CONCLUSIONS: Most deaths from pulmonary embolism among patients hospitalized for other conditions occurred in the setting of failed prophylaxis rather than omitted prophylaxis. High-risk patients, especially medical service patients, warrant intensive VTE prophylaxis and close follow-up to ensure successful outcomes.

a controlled trial of intratumoral ONYX-015, a selectively-replicating adenovirus, in combination with cisplatin and 5-fluorouracil in patients with recurrent head and neck cancer.

ONYX-015 is an adenovirus with the E1B 55-kDa gene deleted, engineered to selectively replicate in and lyse p53-deficient cancer cells while sparing normal cells. Although ONYX-015 and chemotherapy have demonstrated anti-tumoral activity in patients with recurrent head and neck cancer, disease recurs rapidly with either therapy alone. We undertook a phase II trial of a combination of intratumoral ONYX-015 injection with cisplatin and 5-fluorouracil in patients with recurrent squamous cell cancer of the head and neck. There were substantial objective responses, including a high proportion of complete responses. By 6 months, none of the responding tumors had progressed, whereas all non-injected tumors treated with chemotherapy alone had progressed. The toxic effects that occurred were acceptable. Tumor biopsies obtained after treatment showed tumor-selective viral replication and necrosis induction.

Anoxic performance of the american eel (Anguilla rostrata L.) heart requires extracellular glucose.

The importance of extracellular glucose in the maintenance of performance of the heart of the American eel (Anguilla rostrata Le Sueur (L.) Under anoxia was assessed under a variety of experimental conditions. Ventricular strips, electrically paced at 36 bpm, in N(2)-gassed medium maintained the imposed pace rate and generated approximately 25% of the initial twitch force of contraction for at least 60 min when glucose was present in the medium. But ventricular strips challenged without glucose in the medium failed to maintain the pacing rate within 5-10 min. Isolated and intact, perfused hearts maintained pressure and followed an imposed pace rate of 24 bpm for at least 2 hr, under anoxic conditions, if glucose was present in the medium. But without glucose in the medium isolated hearts failed within 30 min. Endogenous glycogen stores were utilized in hearts perfused with medium containing NaCN to impair oxidative phosphorylation. The presence of glucose in the medium did not protect against glycogen mobilization. The data indicate that exogenous glucose is necessary to maintain performance under anoxia at high workloads and physiological Ca(2+) levels. Finally, ventricular strips treated with NaCN and forced to contract at 24 bpm lost 70% of initial twitch force. Increasing extracellular Ca(2+) concentration stepwise from 1.5 to 9.5 mM restored twitch force to approximately 50% of the initial level and this response was not dependent on exogenous glucose. However, glucose was required to maintain resting tension even under normoxic conditions in the face of a Ca(2+) challenge.

Effect of gap length and position on results of treatment of cancer of the larynx in Scotland by radiotherapy: a linear quadratic analysis.

PURPOSE: This paper reports on the analysis of the effect of the length and position of unplanned gaps in radiotherapy treatment schedules. MATERIALS AND METHODS: Data from an audit of the treatment of carcinoma of the larynx are used. They represent all newly diagnosed cases of glottic node-negative carcinoma of the larynx between 1986 and 1990, inclusive, in Scotland that were referred to one of the five Scottish Oncology Centres for primary radical radiotherapy treatment. The end-points are local control of cancer of the larynx in 5 years and the length of the disease-free period. The local control rates at > or =5 years, Pc were analyzed by log linear models and Cox proportional hazard models were used to model the disease-free period. RESULTS: Unplanned gaps in treatment are associated with poorer local control rates and an increased hazard of a local recurrence through their effect on extending the treatment time. A gap of 1 day is potentially damaging but the greatest effect is at treatment extensions of 3 or more days, where the hazard of a failure of local control is increased by a factor of 1.75 (95% confidence interval 1.20-2.55) compared to no gap. The time factor for the actual time was imprecisely estimated at 2.7 Gy/day with a standard error of 13.2 Gy/day. Among those cases who had exactly one gap resulting in a treatment extension of 1 day, there is no evidence that gap position influences local control (P = 0.17). The treatment extension as a result of the gap is more important than the position of the gap in the schedule. CONCLUSIONS: Gaps in the treatment schedule have a detrimental effect on the disease-free period. A gap has a slightly greater effect than an increase in the prescribed treatment time. Any gap in treatment is potentially damaging. The position of the gap in the schedule was shown to be not important.

Similar decreases in local tumor control are calculated for treatment protraction and for interruptions in the radiotherapy of carcinoma of the larynx in four centers.

PURPOSE: Data on patients with cancer of the larynx are analyzed using statistical models to estimate the effect of gaps in the treatment time on the local control of the tumor. METHODS AND MATERIALS: Patients from four centers, Edinburgh, Glasgow, Manchester, and Toronto, with carcinoma of the larynx and treated by radiotherapy were followed up and the disease-free period recorded. In all centers the end point was control of the primary tumor after irradiation alone. The local control rates at > or = 2 years, Pc, were analyzed by log linear models, and Cox proportional hazard models were used to model the disease-free period. RESULTS: T stage, nodal involvement, and site of the tumor were important determinants of the disease-free interval, as was the radiation schedule used. Elongation of the treatment time by 1 day, or a gap of 1 day, was associated with a decrease in Pc of 0.68% per day for Pc = 0.80, with a 95% confidence interval of (0.28, 1.08)%. An increase of 5 days was associated with a 3.5% reduction in Pc from 0.80 to 0.77. At Pc = 0.60 an increase of 5 days was associated with an 7.9% decrease in Pc. The time factor in the Linear Quadratic model, gamma/alpha, was estimated as 0.89 Gy/day, 95% confidence interval (0.35, 1.43) Gy/day. CONCLUSIONS: Any gaps (public holidays are the majority) in the treatment schedule have the same deleterious effect on the disease free period as an increase in the prescribed treatment time. For a schedule, where dose and fraction number are specified, any gap in treatment is potentially damaging.

Adverse effect of treatment gaps in the outcome of radiotherapy for laryngeal cancer.

BACKGROUND AND PURPOSE: A correlation has been demonstrated between unplanned prolongation of radiotherapy and increased local relapse. This review was performed to assess the importance of overall time on the outcome of curative radiotherapy of larynx cancer. MATERIALS AND METHODS: Retrospective analysis was performed of 383 patients with laryngeal cancer managed by elective radiotherapy between 1976-1988 in the Department of Clinical Oncology, University of Edinburgh, Western General Hospital, Edinburgh All cancers were confirmed histologically to be squamous cell carcinomas. All subjects received radiotherapy in 20 daily fractions (except Saturdays and Sundays), employing individual beam direction techniques and computer dose distribution calculations. Main outcome measures were complete resolution of the cancer in the irradiated volume; local relapse; survival and cause-specific survival rates. RESULTS: Radiotherapy was completed without any unplanned interruption (28 +/- 2 days) in 230/383 (60%) of patients. A statistically significant two-fold increase in local relapse rates was observed when treatment was given in 31 days or more. There also was a statistically significant four-fold increase in laryngeal cancer deaths when the treatment time exceeded 30 days. CONCLUSIONS: In patients with laryngeal cancer, accelerated repopulation of cancer cells probably occurs after the start of radiotherapy. When the overall treatment time is 4 weeks or less, gaps at weekends are not detrimental. However, long holiday periods or gaps in treatment longer than 4 days increase the risk of laryngeal cancer relapse and cancer-related mortality. Significant gaps in treatment should be avoided. If treatment has to be prolonged, additional radiation dose should be prescribed to compensate for increased tumour cell proliferation.

Bolus recombinant urokinase versus heparin in deep venous thrombosis: a randomized controlled trial.

Bolus urokinase (Abbokinase ) is effective for initial treatment of deep venous thrombosis but is associated with a high rate of rigors. This randomized controlled trial was undertaken among patients with deep venous thrombosis to evaluate the efficacy and safety of a novel thrombolytic agent, recombinant urokinase (rUK), administered as three bolus infusions of 1 million U over a 24-hour period versus heparin alone. Of 361 patients with DVT screened, 17 (5%) were enrolled. Recent surgery was the most common reason for exclusion (n = 113, 31%). Images of the patients were obtained at baseline, 24 to 48 hours after randomization, and before hospital discharge. Two patients in each treatment group had minor clot progression. One patient in the heparin group had no change; all other patients showed mild (< 50%; n = 5 in each group) or moderate (> 50%; n = 1 in each group) improvement. No bleeding complications or rigors developed in patients randomized to rUK. Mean bleeding times among patients given rUK were not significantly different from mean values of patients given heparin at any of the measured time points available for comparison (331 vs 387 seconds at baseline and 381 vs 416 seconds at 24 hours). However, mean fibrinogen levels declined with successive urokinase boluses and were significantly lower than levels in patients treated with heparin at 24 (233 mg/dl vs 466 mg/dl, p = 0.01) and 48 hours (270 mg/dl vs 474 mg/dl, p = 0.02). Although bolus rUK had a favorable safety profile, rUK was no more effective than heparin in achieving clot lysis at the doses used in this trial.

Intermittent pneumatic compression in chronic venous insufficiency favorably affects fibrinolytic potential and platelet activation.

Nineteen patients with symptoms of chronic venous insufficiency (CVI) were treated with 13-week cycles of intermittent pneumatic compression (IPC) during 2 h sessions twice weekly, with most treatments at home. At study completion, quantitative subjective scores for total symptomatology were improved in 16/19 patients (84%). Enhancement of fibrinolytic potential in vivo was detected in 86% of observations on specimens from CVI patients over 2 h of IPC, with accelerated euglobulin clot lysis times (ELT) noted within 15 min of initiating compression. The enhanced fibrinolytic potential was attributed to increased urokinase plasminogen activator (u-PA), probably released from perturbed endothelial cells by IPC. Significant decreases in total t-PA antigen (mass concentration) but not t-PA activity, were produced by IPC in CVI patients only (P = 0.0001), with greater effects noted in the non-anticoagulated versus the anticoagulated cohort. Plasminogen activator inhibitor type 1 (PAI-1) levels rose rapidly after IPC only in the controls and non-anticoagulated CVI patients. PAI-1 decreased in those receiving anticoagulation. No platelet perturbation was detected during IPC by measuring levels of beta-thromboglobulin or the thromboxane A2 metabolite, 11-dehydrothromboxane B2; however, significant (P < 0.003) decreases in plasma prostacyclin (PGI2) levels (measured as the stable 6-ketoprostaglandin F-1-alpha-metabolite) were observed after 15 min of IPC in non-anticoagulated CVI patients only. There was no evidence of increased thrombin generation by IPC, determined by urinary excretion of fibrinopeptide A and prothrombin fragment 1. Concurrent anticoagulation appears to mediate more favorable biochemical alterations in CVI, although subjective improvement did not correlate with anticoagulation. The mechanism(s) by which these physiologic changes compliment the mechanical effects of IPC remain to be elucidated and will require adequately controlled and powered studies.

Prevention of venous thrombosis after coronary artery bypass surgery (a randomized trial comparing two mechanical prophylaxis strategies).

Although venous thrombosis may occur often after coronary artery bypass grafting, prophylaxis with low-dose heparin is rarely used due to the risk of bleeding. Therefore, we compared the efficacy of 2 mechanical regimens of prophylaxis against deep vein thrombosis (DVT). Consecutive patients undergoing coronary artery bypass without concomitant valve surgery or coronary endarterectomy were randomized to either a more intensive regimen of intermittent pneumatic compression (IPC) plus graduated compression stockings (GCS) versus standard compression stockings alone. Of 611 patients screened, 184 were excluded due to peripheral vascular disease, postoperative intraaortic balloon support, or immediate postoperative anticoagulation. An additional 83 patients refused consent, leaving 172 in each prophylaxis group. The primary study end point was DVT diagnosed by a predischarge leg ultrasound examination performed on postoperative days 4 to 6. Of 344 patients enrolled, 330 (96%) underwent predischarge ultrasonography. DVT was detected in 19% of patients assigned to IPC plus stockings versus 22% assigned to GCS alone (95% confidence interval for the difference, -11% to 6%, p = 0.62). The addition of IPC did not add significant incremental benefit to GCS alone for DVT prophylaxis among patients undergoing coronary artery bypass surgery.

Salvage laryngectomy after radical radiotherapy for laryngeal carcinoma.

Of 376 patients who were treated by radical radiotherapy for squamous carcinoma of the larynx, 56 subsequently underwent total laryngectomy. Residual or recurrent tumour was identified in 43 of the resection specimens, and necrosis alone in 13 cases, although a positive biopsy had been obtained in 3 of these prior to salvage laryngectomy. No disease related factors such as site or stage of the original tumour, or treatment related factors such as radiation type or dose, were found to be predictive of whether or not tumour was present. The clinical opinion of an experienced surgeon was found to have a positive predictive value of 0.86 for the presence of tumour. The fistula rate of salvage laryngectomy, 15 out of 56, was similar to that of other series. The actuarial cause specific 5-year survival for patients with tumour was 0.589, and for patients with necrosis only was 0.923. Intercurrent, smoking related disease was the cause of death in 16 of the 33 patients who have died.

The effect of laryngeal irradiation on pharyngoesophageal motility.

The upper esophageal sphincter (UES) receives the full radiation dose during external beam radiotherapy to the adjacent larynx. The aim of the study was to assess the effects, if any, of radical laryngeal radiotherapy on motility patterns in the pharyngoesophageal segment. A strain gauge assembly and a digital manometric recorder were used to assess 19 patients 13 to 71 months after irradiation of T1 to T3 glottic cancer to a central dose of 52.5 to 55.7 Gy in 20 daily fractions. Results were compared with those of 23 healthy controls. Tonic lower esophageal sphincter (LES) pressure, distal peristaltic contraction, tonic UES pressure, and eight parameters of pharyngoesophageal dynamics during water and bread swallows were studied. No difference was found between the two groups in tonic LES pressure, peristaltic amplitude, or tonic UES pressure. Water swallow pharyngoesophageal wave velocity was significantly lower in patients than in controls, and the irradiated group also showed a trend toward increased duration of the distal esophageal peristaltic wave. The reduction in upper esophageal wave velocity was associated with the interval following irradiation. The post-treatment interval was also inversely related to the amplitude of UES after-contraction, and associated with an increase in wave duration throughout the pharyngoesophageal segment. A study of 23 laryngectomy specimens, 5 of which had been removed following radiotherapy, failed to identify pathological features in nerves or muscle which characterised previous laryngopharyngeal irradiation. We conclude that laryngeal irradiation has no effect on upper or lower esophageal sphincter tone but causes an increase in wave duration and a reduction in wave velocity in the pharyngoesophageal segment. These changes are independent of age and sex and are not associated with pathological features like the neural degeneration described in the myenteric plexus of irradiated rectum.

Fast neutron treatment for squamous cell carcinoma of the head and neck: final report of Edinburgh randomised trial.

OBJECTIVE: To compare neutron treatment and megavoltage (photon) radiotherapy in locally advanced squamous cell carcinoma of the head and neck. DESIGN: Randomised trial of patients stratified by site of primary tumour and presence or absence of lymph node metastases. Follow up of patients after treatment. SETTING: Department of clinical oncology, Western General Hospital, Edinburgh. PATIENTS: 165 Patients with untreated, histologically proved squamous cell carcinoma of the oral cavity, oropharynx, larynx, or hypopharynx. All patients completed treatment, and no patient was lost to follow up. INTERVENTION: Treatment with either neutrons or photons. MAIN OUTCOME MEASURES: Disease state and morbidity (scored with the system of the European Organisation for Research on Treatment of Cancer) at each visit during follow up. RESULTS: Of the 165 patients, 85 were randomised to receive neutron treatment and 80 to receive photon treatment. Minimum follow up was five years. Local control of cancer remained similar in the two groups, being achieved in 37 (44%) patients after neutron treatment and 36 (45%) after photon treatment. Five year and actuarial 10 year survival rates were 24% (20/85) and 14% respectively in the group treated with neutrons and 34% (27/80) and 30% respectively in the group treated with photons. Five year survival rates without local disease were 19% (16/85) and 30% (24/80) respectively. Necrosis was more common after neutron treatment than after photon treatment. Seven patients in the neutron group who developed necrosis died whereas no deaths were associated with photon treatment. CONCLUSION: Rates of long term local control were similar in the two groups. Necrosis related to radiation was more common in patients treated with neutrons, and the mortality related to treatment was significantly higher in these patients.

An analysis of the radiation related morbidity observed in a randomized trial of neutron therapy for bladder cancer.

This report is an analysis of the morbidity in the bladder and bowel observed in a randomized trial of d(15)+Be neutrons versus megavoltage photons in the treatment of bladder cancer. Acute reactions in the bladder and bowel were significantly worse after photon therapy. Of the patients treated with photons 45.7% had severe reactions in the bladder compared with 10.6% after neutron therapy (p less than 0.001). Severe acute bowel reactions were observed in 8.5% of the patients after photon therapy compared with 3.8% after neutron therapy (p less than 0.05). Late reactions were significantly worse after neutrons. Severe late reactions in the bladder were seen in 58.5% of patients after neutron therapy and in 40.5% after photon therapy (p less than 0.05). In the bowel they were observed in 53.3% of patients after neutron therapy compared with 8% after photon therapy (p less than 0.0001). The disparity in the degree of early and late complications makes assessment of RBE values difficult. It is estimated that for bladder morbidity the RBE value, for photon dose fractions of 2.75 Gy, is less than 3.3 for early reactions and equal to 3.4 for late effects. The respective RBE values for early and late effects in the bowel are less than 3.4 and 3.8.

A report of a randomized trial of d(15)+Be neutrons compared with megavoltage X ray therapy of bladder cancer.

The results of a randomized trial of d(15)+Be neutrons compared with 4 or 6 MV photons for the treatment of transitional cell carcinoma of the bladder. Between December 1978 and December 1981, 113 patients were accrued, 53 allocated to be treated by neutrons and 60 by photons. Complete local tumor regression was observed in 64% of patients treated by neutrons and 62% treated by photons. Recurrent cancer was subsequently confirmed in 31% of patients, similar in both treatment groups. There was no significant difference in the control rates by T stage between the two treatment groups. Late morbidity was significantly worse in patients treated by neutrons. Following neutron therapy, 78% of patients had serious late morbidity in at least one tissue compared with 38% in the group treated by photons. Survival was significantly better in the photon treated group 45.3% (+/- 11%) at 5 years compared with 12% (+/- 6%) after neutron therapy.