The association of frailty and outcomes of geriatric assessment with acute radiation-induced toxicity in patients with head and neck cancer.

BACKGROUND AND PURPOSE: Geriatric impairments and frailty are highly prevalent in patients with head and neck cancer (HNC). This study investigated the association of frailty and outcomes of geriatric assessment (GA) with radiation-induced toxicity (RIT) in patients undergoing (chemo)radiotherapy ((C)RT) for HNC. MATERIALS AND METHODS: Between October 2014 and April 2016, patients with HNC were prospectively included in OncoLifeS, an institutional data-biobank. Before treatment initiation, patients underwent GA and frailty screening (Groningen Frailty Indicator and Geriatric 8). The main outcome of this study was RIT (weight loss, mucositis, salivary gland inflammation, oral pain, sore throat, hoarseness, dry mouth, dysgeusia, dysphagia and general pain) according to the common terminology criteria of adverse events (CTCAE) version 4.0. Linear mixed models were performed, to analyse factors associated with increasing mean RIT over time during the treatment period. RESULTS: 160 patients were included. 114 (71.3%) were male and the mean age was 66.1 years. Age ≥ 65 (ß = 0.03(95 %CI = 0.01;0.05), p = 0.01), regional RT (ß = 0.05(95 %CI = 0.02;0.09), p = 0.004), and concurrent chemotherapy (ß = 0.04(95 %CI = 0.02;0.07), p = 0.001), were independent factors associated with increasing toxicity during the 7-week treatment period, adjusted for relevant covariates. None of the single items of GA, as well as the frailty screening instruments, were associated with increasing RIT. CONCLUSION: In this study, frailty and GA were not associated with additional RIT during treatment. These results suggest that (C)RT is equally tolerated in frail and non-frail patients, with respect to acute RIT. RT could be a suitable alternative to surgery in selected frail patients.

Assessment of the confidence interval in the multivariable normal tissue complication probability model for predicting radiation-induced liver disease in primary liver cancer.

We developed a confidence interval-(CI) assessing model in multivariable normal tissue complication probability (NTCP) modeling for predicting radiation-induced liver disease (RILD) in primary liver cancer patients using clinical and dosimetric data. Both the mean NTCP and difference in the mean NTCP (ΔNTCP) between two treatment plans of different radiotherapy modalities were further evaluated and their CIs were assessed. Clinical data were retrospectively reviewed in 322 patients with hepatocellular carcinoma (n = 215) and intrahepatic cholangiocarcinoma (n = 107) treated with photon therapy. Dose-volume histograms of normal liver were reduced to mean liver dose (MLD) based on the fraction size-adjusted equivalent uniform dose. The most predictive variables were used to build the model based on multivariable logistic regression analysis with bootstrapping. Internal validation was performed using the cross-validation leave-one-out method. Both the mean NTCP and the mean ΔNTCP with 95% CIs were calculated from computationally generated multivariate random sets of NTCP model parameters using variance-covariance matrix information. RILD occurred in 108/322 patients (33.5%). The NTCP model with three clinical and one dosimetric parameter (tumor type, Child-Pugh class, hepatitis infection status and MLD) was most predictive, with an area under the receiver operative characteristics curve (AUC) of 0.79 (95% CI 0.74-0.84). In eight clinical subgroups based on the three clinical parameters, both the mean NTCP and the mean ΔNTCP with 95% CIs were able to be estimated computationally. The multivariable NTCP model with the assessment of 95% CIs has potential to improve the reliability of the NTCP model-based approach to select the appropriate radiotherapy modality for each patient.

Radiation enteritis: from diagnosis to management.

PURPOSE OF REVIEW: As cancer treatments improve more patients than ever are living for longer with the side effects of these treatments. Radiation enteritis is a heterogenous condition with significant morbidity. The present review aims to provide a broad overview of the condition with particular attention to the diagnosis and management of the condition. RECENT FINDINGS: Radiation enteritis appears to be more prevalent than originally thought because of patient underreporting and a lack of clinician awareness. Patient-related and treatment-related risk factors have now been identified and should be modified where possible. Medical and surgical factors have been explored, but manipulation of the gut microbiota offers one of the most exciting recent developments in disease prevention. Diagnosis and treatment are best approached in a systematic fashion with particular attention to the exclusion of recurrent malignancy and other gastrointestinal conditions. Surgery and endoscopy both offer opportunities for management of the complications of radiation enteritis. Experimental therapies offer hope for future management of radiation enteritis but large-scale human trials are needed. SUMMARY: Radiation enteritis is an important clinical problem, but awareness is lacking amongst patients and physicians. Clinical guidelines would allow standardised management which may improve the burden of the disease for patients.

Long-term neurocognitive and other side effects of radiotherapy, with or without chemotherapy, for glioma.

BACKGROUND: Gliomas are brain tumours arising from glial cells with an annual incidence of 4 to 11 people per 100,000. In this review we focus on gliomas with low aggressive potential in the short term, i.e. low-grade gliomas. Most people with low-grade gliomas are treated with surgery and may receive radiotherapy thereafter. However, there is concern about the possible long-term effects of radiotherapy, especially on neurocognitive functioning. OBJECTIVES: To evaluate the long-term neurocognitive and other side effects of radiotherapy (with or without chemotherapy) compared with no radiotherapy, or different types of radiotherapy, among people with glioma (where 'long-term' is defined as at least two years after diagnosis); and to write a brief economic commentary. SEARCH METHODS: We searched the following databases on 16 February 2018 and updated the search on 14 November 2018: Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 11) in the Cochrane Library; MEDLINE via Ovid; and Embase via Ovid. We also searched clinical trial registries and relevant conference proceedings from 2014 to 2018 to identify ongoing and unpublished studies. SELECTION CRITERIA: Randomised and non-randomised trials, and controlled before-and-after studies (CBAS). Participants were aged 16 years and older with cerebral glioma other than glioblastoma. We included studies where patients in at least one treatment arm received radiotherapy, with or without chemotherapy, and where neurocognitive outcomes were assessed two or more years after treatment. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed risk of bias. We assessed the certainty of findings using the GRADE approach. MAIN RESULTS: The review includes nine studies: seven studies were of low-grade glioma and two were of grade 3 glioma. Altogether 2406 participants were involved but there was high sample attrition and outcome data were available for a minority of people at final study assessments. In seven of the nine studies, participants were recruited to randomised controlled trials (RCTs) in which longer-term follow-up was undertaken in a subset of people that had survived without disease progression. There was moderate to high risk of bias in studies due to lack of blinding and high attrition, and in two observational studies there was high risk of selection bias. Paucity of data and risk of bias meant that evidence was of low to very low certainty. We were unable to combine results in meta-analysis due to diversity in interventions and outcomes.The studies examined the following five comparisons.Radiotherapy versus no adjuvant treatmentTwo observational studies contributed data. At the 12-year follow-up in one study, the risk of cognitive impairment (defined as cognitive disability deficits in at least five of 18 neuropsychological tests) was greater in the radiotherapy group (risk ratio (RR) 1.95, 95% confidence interval (CI) 1.02 to 3.71; n = 65); at five to six years the difference between groups did not reach statistical significance (RR 1.38, 95% CI 0.92 to 2.06; n = 195). In the other study, one subject in the radiotherapy group had cognitive impairment (defined as significant deterioration in eight of 12 neuropsychological tests) at two years compared with none in the control group (very low certainty evidence).With regard to neurocognitive scores, in one study the radiotherapy group was reported to have had significantly worse mean scores on some tests compared with no radiotherapy; however, the raw data were only given for significant findings. In the second study, there were no clear differences in any of the various cognitive outcomes at two years (n = 31) and four years (n = 15) (very low certainty evidence).Radiotherapy versus chemotherapyOne RCT contributed data on cognitive impairment at up to three years with no clear difference between arms (RR 1.43, 95% CI 0.36 to 5.70, n = 117) (low-certainty evidence).High-dose radiotherapy versus low-dose radiotherapyOnly one of two studies reporting this comparison contributed data, and at two and five years there were no clear differences between high- and low-dose radiotherapy arms (very low certainty evidence).Conventional radiotherapy versus stereotactic conformal radiotherapyOne study involving younger people contributed limited data from the subgroup aged 16 to 25 years. The numbers of participants with neurocognitive impairment at five years after treatment were two out of 12 in the conventional arm versus none out of 11 in the stereotactic conformal radiotherapy arm (RR 4.62, 95% CI 0.25 to 86.72; n = 23; low-certainty evidence).Chemoradiotherapy versus radiotherapyTwo RCTs tested for cognitive impairment. One defined cognitive impairment as a decline of more than 3 points in MMSE score compared with baseline and reported data from 2-year (110 participants), 3-year (91 participants), and 5-year (57 participants) follow-up with no clear difference between the two arms at any time point. A second study did not report raw data but measured MMSE scores over five years in 126 participants at two years, 110 at three years, 69 at four years and 53 at five years. Authors concluded that there was no difference in MMSE scores between the two study arms (P = 0.4752) (low-certainty evidence).Two RCTs reported quality of life (QoL) outcomes for this comparison. One reported no differences in Brain-QoL scores between study arms over a 5-year follow-up period (P = 0.2767; no raw data were given and denominators were not stated). The other trial reported that the long-term results of health-related QoL showed no difference between the arms but did not give the raw data for overall HRQoL scores (low-certainty evidence).We found no comparative data on endocrine dysfunction; we planned to develop a brief economic commentary but found no relevant economic studies for inclusion. AUTHORS' CONCLUSIONS: Radiotherapy for gliomas with a good prognosis may increase the risk of neurocognitive side effects in the long term; however the magnitude of the risk is uncertain. Evidence on long-term neurocognitive side effects associated with chemoradiotherapy is also uncertain. Neurocognitive assessment should be an integral part of long-term follow-up in trials involving radiotherapy for lower-grade gliomas to improve the certainty of evidence regarding long-term neurocognitive effects. Such trials should also assess other potential long-term effects, including endocrine dysfunction, and evaluate costs and cost effectiveness.

International validation of the EORTC QLQ-PRT20 module for assessment of quality of life symptoms relating to radiation proctitis: a phase IV study.

BACKGROUND: Although patients experience radiation proctitis post radiotherapy no internationally tested instruments exist to measure these symptoms. This Phase IV study tested the scale structure, reliability and validity and cross-cultural applicability of the EORTC proctitis module (QLQ-PRT23) in patients who were receiving pelvic radiotherapy. METHODS: Patients (n = 358) from six countries completed the EORTC QLQ-C30, QLQ-PRT23 and EORTC Quality of Life Group debriefing questions. Clinicians completed the EORTC Radiation Therapy Oncology Group scale. Questionnaires were completed at four time-points. The module's scale structure was examined and validated using standard psychometric analysis techniques. RESULTS: Three items were dropped from the module (QLQ-PRT23 → QLQ-PRT20). Factor analysis identified five factors in the module: bowel control; bloating and gas; emotional function/lifestyle; pain; and leakage. Inter-item correlations were within r = 0.3-0.7. Test-Retest reliability was high. All multi-item scales discriminated between patients showing symptoms and those without symptomology. The module discriminated symptoms from the clinician completed scoring and for age, gender and comorbidities. CONCLUSION: The EORTC QLQ-PRT20 is designed to be used in addition to the EORTC QLQ-C30 to measure quality of life in patients who receive pelvic radiotherapy. The EORTC QLQ-PRT20 is quick to complete, acceptable to patients, has good content validity and high reliability. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry (ANZCTR) ACTRN12609000972224 .

Assessment of indomethacin oral spray for the treatment of oropharyngeal mucositis-induced pain during anticancer therapy.

PURPOSE: The efficacy and safety of indomethacin (IM) oral spray (OS) as a pain control therapy for oropharyngeal mucositis due to anticancer chemo- and radiotherapy were assessed in patients with head and neck carcinomas and haematological tumours. METHOD: We observed 35 patients (male/female, 20/15; 53 ± 17 years) with oropharyngeal mucositis who were treated with IM-OS preparation for pain relief at University of Tsukuba Hospital, Japan. Analgesic effects were assessed using the six-grade face scale for pain in 28 patients at the start of IM oral spray treatment. Systemic exposure was assessed by determining urinary excretions of IM in seven patients. RESULTS: Pain relief was achieved in 26 (93%) patients at 25 (5-60) min after applying the IM-OS preparation (15.6 ± 3.4 µg/kg) and analgesic effects were maintained for 120 (10-360) min. The pain was significantly decreased after using the spray (3.6 ± 0.7 vs. 2.4 ± 0.9, p < 0.01). Moreover, urinary IM excretion rates after applying the IM spray preparation were 1.8 ± 0.8% of the IM oral spray dose (130.5 ± 77.7 µg/kg/day), which was markedly lower than that following oral administration of IM (60%). No adverse events were observed following application of the spray. CONCLUSIONS: The present IM spray is an effective and safe preparation for pain relief and can be used as an alternative therapeutic option for oropharyngeal mucositis in cancer patients.

Propensity-Weighted Comparison of Long-Term Risk of Urinary Adverse Events in Elderly Women Treated For Cervical Cancer.

PURPOSE: Cervical cancer treatment is associated with a risk of urinary adverse events (UAEs) such as ureteral stricture and vesicovaginal fistula. We sought to measure the long-term UAE risk after surgery and radiation therapy (RT), with confounding controlled through propensity-weighted models. METHODS AND MATERIALS: From the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, we identified women ≥66 years old with nonmetastatic cervical cancer treated with simple surgery (SS), radical hysterectomy (RH), external beam RT plus brachytherapy (EBRT+BT), or RT+surgery. We matched them to noncancer controls 1:3. Differences in demographic and cancer characteristics were balanced by propensity weighting. Grade 3 to 4 UAEs were identified by diagnosis codes plus treatment codes. Cumulative incidence was measured using Kaplan-Meier methods. The hazard associated with different cancer treatments was compared using Cox models. RESULTS: UAEs occurred in 272 of 1808 cases (17%) and 222 of 5424 (4%) controls; most (62%) were ureteral strictures. The raw cumulative incidence of UAEs was highest in advanced cancers. UAEs occurred in 31% of patients after EBRT+BT, 25% of patients after RT+surgery, and 15% of patients after RH; however, after propensity weighting, the incidence was similar. In adjusted Cox models (reference = controls), the UAE risk was highest after RT+surgery (hazard ratio [HR], 5.07; 95% confidence interval [CI], 2.32-11.07), followed by EBRT+BT (HR, 3.33; 95% CI, 1.45-7.65), RH (HR, 3.65; 95% CI, 1.41-9.46) and SS (HR, 0.99; 95% CI, 0.32-3.01). The higher risk after RT+surgery versus EBRT+BT was statistically significant, whereas, EBRT+BT and RH were not significantly different from each other. CONCLUSIONS: UAEs are common after cervical cancer treatment, particularly in patients with advanced cancers. UAEs are more common after RT, but these women tend to have the advanced cancers. After propensity weighting, the risk after RT was similar to that after surgery.

Assessment of the quality-of-life and functional outcomes in patients undergoing cystectomy and urinary diversion for the management of radiation-induced refractory benign disease.

OBJECTIVE: To investigate the impact of cystectomy for the treatment of refractory benign disease secondary to radiation therapy on the health-related quality of life (HRQOL). METHODS: A retrospective review was performed on patients undergoing cystectomy for the management of treatment-refractory disease secondary to radiation therapy. Overall, 29 patients underwent cystectomy for refractory fistulas (n = 12, 41.4%), radiation cystitis (n = 12, 41.4%), pelvic pain (n = 4, 13.8%), or incontinence (n = 1, 3.4%) from 2004 to 2013. Preoperative and postoperative HRQOL were measured using a modified version of the Short Form version 2 (SF-36v2). RESULTS: A total of 19 patients (65.5%) reported a 30-day postoperative complication, of which 80% were Clavien grade I or II. Nineteen (65.5%) of the patients completed the SF-36v2 survey. Low scores were noted in the preoperative setting in the physical and mental health domains of these patients, especially in the role limitations due to health and emotional problems. Clinically meaningful improvements were noted in all the physical and mental health domains after cystectomy. Significant improvements were found in certain domains, namely in the level of pain control, general health, role limitations due to emotional problems, and social functioning (all P <.01). CONCLUSION: Treatment-refractory disease from radiation therapy significantly impairs patients' HRQOL. Although cystectomy with urinary diversion is associated with perioperative complication risks, cystectomies can be safely performed in this high-risk population and significantly improve patients' physical and mental HRQOL. Further studies are needed to characterize the role of cystectomy in treatment-refractory disease from radiation therapy.

Assessing the uncertainty in QUANTEC's dose-response relation of lung and spinal cord with a bootstrap analysis.

PURPOSE: To apply a statistical bootstrap analysis to assess the uncertainty in the dose-response relation for the endpoints pneumonitis and myelopathy reported in the QUANTEC review. METHODS AND MATERIALS: The bootstrap method assesses the uncertainty of the estimated population-based dose-response relation due to sample variability, which reflects the uncertainty due to limited numbers of patients in the studies. A large number of bootstrap replicates of the original incidence data were produced by random sampling with replacement. The analysis requires only the dose, the number of patients, and the number of occurrences of the studied endpoint, for each study. Two dose-response models, a Poisson-based model and the Lyman model, were fitted to each bootstrap replicate using maximum likelihood. RESULTS: The bootstrap analysis generates a family of curves representing the range of plausible dose-response relations, and the 95% bootstrap confidence intervals give an estimated upper and lower toxicity risk. The curve families for the 2 dose-response models overlap for doses included in the studies at hand but diverge beyond that, with the Lyman model suggesting a steeper slope. The resulting distributions of the model parameters indicate correlation and non-Gaussian distribution. For both data sets, the likelihood of the observed data was higher for the Lyman model in >90% of the bootstrap replicates. CONCLUSIONS: The bootstrap method provides a statistical analysis of the uncertainty in the estimated dose-response relation for myelopathy and pneumonitis. It suggests likely values of model parameter values, their confidence intervals, and how they interrelate for each model. Finally, it can be used to evaluate to what extent data supports one model over another. For both data sets considered here, the Lyman model was preferred over the Poisson-based model.

Radiation induced brain injury: assessment of white matter tracts in a pre-clinical animal model using diffusion tensor MR imaging.

We aim to study radiation induced white matter injury in a pre-clinical model using Diffusion tensor MR imaging (DTI). Nineteen 12-week old Sprague-Dawley rats were irradiated to the right hemisphere using a linear accelerator. The dose distribution map was coregistered to the DTI map to generate the actual radiation dose to each white matter tract. Rats underwent longitudinal DTI scans at five time points from 4 to 48 weeks post-radiation with histological evaluations. Fractional anisotropy (FA) of the external capsule, fornix, cerebral peduncle, anterior commissure, optic tract and optic nerve was evaluated. Radiation dose was highest at the ipsilateral external capsule and fornix (29.4 ± 1.3 and 29.8 ± 1.1 Gy, respectively). Optic nerve received 50 % dose to the external capsule and other white matter tracts received 80 % dose. Significantly lower FA was firstly found in the ipsilateral external capsule at 4 weeks post-radiation and in the ipsilateral fornix at 40 weeks post-radiation compared to the contralateral side. Significantly lower FA was found in contralateral optic nerve compared to ipsilateral optic nerve at 48 weeks post-radiation despite ipsilateral optic nerves receiving higher radiation dose than contralateral optic nerve (p = 0.021). No differences were found in other white matter regions until 48 weeks. Histology indicated demyelination, axonal degeneration and coagulative necrosis in all injured white matter. DTI can serve as a promising tool for assessment of radiation induced white matter injury and regional radiosensitivity of white matter tracts.

[Delayed medical consequences of the Chernobyl accident in Armenia. Assessment of life quality and accelerated biological aging of accident liquidators].

In this paper, some final results of 25-year investigations carried out in Scientific Centre for Radiation Medicine and Burns MH RA (SCRMB) on the Armenian cohort of the Chernobyl accident consequences liquidators are shown. These results show that health conditions of the liquidators became worse during the whole observation period. A considerable development of both pathological states atypical of radiation damages and diseases, which may be considered as radiation-induced ones, was determined. Rise of the sickness rate of almost all organism systems, first of all, nervous, cardiovascular, respiratory and digestive ones, was observed. In 70% of liquidators the main disease was primarily detected after working on CNPP. In the intervening years, the average number of diagnoses per 1 liquidator increased from 1.5 in 1987 to 7-8 in the recent time. In addition to the detected diseases, particular functional shifts in neuropsychological and vegetative status of the liquidators were observed. The overwhelming majority of them have increased tonicity of the sympathetic vegetative nervous system, asthenic and depressive syndromes occurring in the form of weakness, somnolence, mood instability, mental capacity decrease, and memory defects. In the paper, the results of investigations aimed at clarification of changes in biological aging processes of the liquidators and assessment of their "life quality" features in terms of physical, psychical and social welfare are considered. Biological aged-related passportization in a definite part of liquidators elucidated an accelerated aging rate. The studies were performed with the help of SF-36 inquirer and indicated that health status aggravation of the liquidators also affected their life satisfaction. The "life quality" indices of the liquidators significantly concede the overall average standards by both physical health and psychical and social welfare scales.

Outcomes after intensity-modulated versus conformal radiotherapy in older men with nonmetastatic prostate cancer.

PURPOSE: There is little evidence comparing complications after intensity-modulated (IMRT) vs. three-dimensional conformal radiotherapy (CRT) for prostate cancer. The study objective was to test the hypothesis that IMRT, compared with CRT, is associated with a reduction in bowel, urinary, and erectile complications in elderly men with nonmetastatic prostate cancer. METHODS AND MATERIALS: We undertook an observational cohort study using registry and administrative claims data from the SEER-Medicare database. We identified men aged 65 years or older diagnosed with nonmetastatic prostate cancer in the United States between 2002 and 2004 who received IMRT (n = 5,845) or CRT (n = 6,753). The primary outcome was a composite measure of bowel complications. Secondary outcomes were composite measures of urinary and erectile complications. We also examined specific subsets of bowel (proctitis/hemorrhage) and urinary (cystitis/hematuria) events within the composite complication measures. RESULTS: IMRT was associated with reductions in composite bowel complications (24-month cumulative incidence 18.8% vs. 22.5%; hazard ratio [HR] 0.86; 95% confidence interval [CI], 0.79-0.93) and proctitis/hemorrhage (HR 0.78; 95% CI, 0.64-0.95). IMRT was not associated with rates of composite urinary complications (HR 0.93; 95% CI, 0.83-1.04) or cystitis/hematuria (HR 0.94; 95% CI, 0.83-1.07). The incidence of erectile complications involving invasive procedures was low and did not differ significantly between groups, although IMRT was associated with an increase in new diagnoses of impotence (HR 1.27, 95% CI, 1.14-1.42). CONCLUSION: IMRT is associated with a small reduction in composite bowel complications and proctitis/hemorrhage compared with CRT in elderly men with nonmetastatic prostate cancer.

Heart irradiation as a risk factor for radiation pneumonitis.

PURPOSE: to investigate the potential role of incidental heart irradiation on the risk of radiation pneumonitis (RP) for patients receiving definitive radiation therapy for non-small-cell lung cancer (NSCLC). MATERIAL AND METHODS: two hundred and nine patient datasets were available for this study. Heart and lung dose-volume parameters were extracted for modeling, based on Monte Carlo-based heterogeneity corrected dose distributions. Clinical variables tested included age, gender, chemotherapy, pre-treatment weight-loss, performance status, and smoking history. The risk of RP was modeled using logistic regression. RESULTS: the most significant univariate variables were heart related, such as heart heart V65 (percent volume receiving at least 65 Gy) (Spearman Rs = 0.245, p < 0.001). The best-performing logistic regression model included heart D10 (minimum dose to the hottest 10% of the heart), lung D35, and maximum lung dose (Spearman Rs = 0.268, p < 0.0001). When classified by predicted risk, the RP incidence ratio between the most and least risky 1/3 of treatments was 4.8. The improvement in risk modeling using lung and heart variables was better than using lung variables alone. CONCLUSIONS: these results suggest a previously unsuspected role of heart irradiation in many cases of RP.

Toxicity assessment of pelvic intensity-modulated radiotherapy with hypofractionated simultaneous integrated boost to prostate for intermediate- and high-risk prostate cancer.

PURPOSE: To evaluate the toxicity of pelvic intensity-modulated radiotherapy (IMRT) with hypofractionated simultaneous integrated boost (SIB) to the prostate for patients with intermediate- to high-risk prostate cancer. METHODS AND MATERIALS: A retrospective toxicity analysis was performed in 30 consecutive patients treated definitively with pelvic SIB-IMRT, all of whom also received androgen suppression. The IMRT plans were designed to deliver 70 Gy in 28 fractions (2.5 Gy/fraction) to the prostate while simultaneously delivering 50.4 Gy in 28 fractions (1.8 Gy/fraction) to the pelvic lymph nodes. The National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0, was used to score toxicity. RESULTS: The most common acute Grade 2 events were cystitis (36.7%) and urinary frequency/urgency (26.7%). At a median follow-up of 24 months, late toxicity exceeding Grade 2 in severity was uncommon, with two Grade 3 events and one Grade 4 event. Grade 2 or greater acute bowel toxicity was associated with signficantly greater bowel volume receiving > or =25 Gy (p = .04); Grade 2 or greater late bowel toxicity was associated with a higher bowel maximal dose (p = .04) and volume receiving > or =50 Gy (p = .02). Acute or late bladder and rectal toxicity did not correlate with any of the dosimetric parameters examined. CONCLUSION: Pelvic IMRT with SIB to the prostate was well tolerated in this series, with low rates of Grade 3 or greater acute and late toxicity. SIB-IMRT combines pelvic radiotherapy and hypofractionation to the primary site and offers an accelerated approach to treating intermediate- to high-risk disease. Additional follow-up is necessary to fully define the long-term toxicity after hypofractionated, whole pelvic treatment combined with androgen suppression.

Assessment of ovarian reserve in adult childhood cancer survivors using anti-Müllerian hormone.

BACKGROUND: The aim was to assess possible treatment-induced gonadal damage in a cohort of adult female childhood cancer survivors (CCS) using anti-Müllerian hormone (AMH), the most sensitive marker of ovarian reserve. METHODS: A total cohort of 185 survivors was compared with 42 control subjects. The median follow-up time was 18.1 years (range 4.1-43.2 year). RESULTS: Median AMH concentrations in the analysed cohort were not different from controls (median 1.7 versus 2.1 microg/l; P = 0.57). However, AMH levels were lower than the 10th percentile of normal values in 27% (49/182) of our survivors. In addition, 43% (79/182) had AMH levels lower than 1.4 microg/l, a previously established cut-off value which predicts ongoing pregnancy after assisted reproduction. There were no differences in AMH levels in subgroups classified according to disease. However, survivors treated with three or more procarbazine containing chemotherapy cycles had significantly lower AMH levels than controls (median 0.5 microg/l; P = 0.004). Also survivors treated with abdominal or total body irradiation had significantly lower AMH levels than controls (median < 0.1 microg/l; P < 0.001). CONCLUSIONS: AMH can be used to identify subgroups of CCS at risk for decreased fertility or premature ovarian failure. In these survivors, options for fertility preservation should be considered prior to starting treatment since they may be at risk for poor chances of pregnancy after assisted reproductive treatment.

Reliability and validity of a bioimpedance measurement device in the assessment of UVR damage to the skin.

Ultraviolet radiation (UVR) is the primary cause of skin cancers. However, it is difficult to evaluate the amount of UVR absorbed into the skin retrospectively. Therefore, objective and non-invasive quantitative method would be valuable for epidemiological UVR exposure assessment. Photodamage reduces the amount of bound water in the skin, and thus, measuring the skin's dielectric constant can provide an opportunity for assessing the cumulative UVR exposure. The purpose of the study was to assess the reliability and validity of the bioimpedance device, Moisture Meter-D. The measurements were performed on 100 subjects at three separate measurement times. A questionnaire was used to obtain information on the host factors and on the past UVR exposure. The biological samples, to determine the elastin proportion of the dermis, were collected. Some long-term as well as seasonal variations in the dielectric constants were detected. Also, a weak relationship between the dielectric constant and the UVR exposure indicators and host factors was observed. The MoistureMeter-D appears not to measure structural alterations in the skin caused by photodamage, and thus it is not a valid instrument for the assessment of photodamage, i.e., past UVR exposure.

[Evaluation of the endoscopic response to argon plasma coagulation in patients with chronic radiation proctopathy]. / Valoración de la respuesta endoscópica al tratamiento con argón plasma en la rectitis actínica crónica.

OBJECTIVES: To evaluate endoscopic improvement after argon plasma coagulation (APC) in symptomatic patients with chronic radiation proctopathy. METHODS AND PATIENTS: A prospective study of 38 patients with radiation proctitis (26 males and 12 females, mean age 70.9 +/- 7.38 yrs), and with rectal bleeding and or anemia. We performed monthly interviews, blood tests, and APC sessions until rectal bleeding had ceased and hemoglobin and ferritin levels were improved, with a follow-up of 24 months. We used blood testing, bleeding scores (Chutckhan's index), and endoscopic scores to evaluate improvement. RESULTS: Mean time between inclusion and follow-up completion was 28.5 +/- 3.9 months. Mean number of sessions per patient was 3.6 +/- 2.7. There was a significant decrease (2.29 +/- 1.8 vs. 0.59 +/- 1.12, p < 0.05) in rectal bleeding (Chutckan score) from baseline after APC. There was a significant increase in hemoglobin levels (11.3 +/- 3.05 vs. 14.014 +/- 1.29, p < 0.001) and ferritin levels (31.15 +/- 66.45 vs. 80.60 +/- 55.6, p < 0.05) from baseline after APC. Also, there was improvement in the endoscopic index at the end of treatment, as well as in friability (p < 0.0001) and involved surface area (p < 0.0001). CONCLUSION: Argon plasma coagulation is an effective technique, and the endoscopic index is a useful tool to evaluate endoscopic improvement.