Using a retrospective pretest instead of a conventional pretest is replacing biases: a qualitative study of cognitive processes underlying responses to thentest items.

BACKGROUND: The thentest design aims to detect and control for recalibration response shift. This design assumes (1) more consistency in the content of the cognitive processes underlying patients' quality of life (QoL) between posttest and thentest assessments than between posttest and pretest assessments; and (2) consistency in the time frame and description of functioning referenced at pretest and thentest. Our objective is to utilize cognitive interviewing to qualitatively examine both assumptions. METHODS: We conducted think-aloud interviews with 24 patients with cancer prior to and after radiotherapy to elicit cognitive processes underlying their assessment of seven EORTC QLQ-C30 items at pretest, posttest and thentest. We used an analytic scheme based on the cognitive process models of Tourangeau et al. and Rapkin and Schwartz that yielded five cognitive processes. We subsequently used this input for quantitative analysis of count data. RESULTS: Contrary to expectation, the number of dissimilar cognitive processes between posttest and thentest was generally larger than between pretest and posttest across patients. Further, patients considered a range of time frames when answering the thentest questions. Moreover, patients' description at the thentest of their pretest functioning was often not similar to that which was noted at pretest. Items referring to trouble taking a short walk, overall health and QoL were most often violating the assumptions. CONCLUSIONS: Both assumptions underlying the thentest design appear not to be supported by the patients' cognitive processes. Replacing the conventional pretest-posttest design with the thentest design may simply be replacing one set of biases with another.

Combining Mitomycin C and Regional 70 MHz Hyperthermia in Patients with Nonmuscle Invasive Bladder Cancer: A Pilot Study.

PURPOSE: Despite intravesical therapy with immunotherapy or chemotherapy intermediate and high risk nonmuscle invasive bladder cancer is associated with a high risk of recurrence and progression to muscle invasive bladder carcinoma. While intravesical hyperthermia combined with mitomycin C has proved effective to treat nonmuscle invasive bladder cancer, there is less experience with invasive regional 70 MHz hyperthermia and mitomycin C. Therefore, we examined the safety and feasibility of this treatment combination for intermediate and high risk nonmuscle invasive bladder cancer. MATERIALS AND METHODS: Between 2009 and 2011, 20 patients with intermediate and high risk nonmuscle invasive bladder cancer were treated with intravesical mitomycin C (40 mg) combined with regional hyperthermia. Treatment consisted of 6 weekly sessions followed by a maintenance period of 1 year with 1 hyperthermia-mitomycin C session every 3 months. Regional hyperthermia was administered using a 70 MHz phased array system with 4 antennas. Toxicity was scored using CTC (Common Toxicity Criteria) 3.0. RESULTS: The records of 18 of 20 patients could be analyzed. Median followup was 46 months. Of the 18 patients 15 (83%) completed the induction period of 6 treatments. Four patients (22%) discontinued treatment because of physical complaints without exceeding grade 2 toxicity. Toxicity scored according to CTC 3.0 was limited to grade 1 in 43% of cases and grade 2 in 14%. Mean T90 and T50 bladder temperatures were 40.6C and 41.6C, respectively. The 24-month recurrence-free survival rate was 78%. CONCLUSIONS: Treatment with regional hyperthermia combined with mitomycin C in patients with intermediate and high risk nonmuscle invasive bladder cancer is feasible with low toxicity and excellent bladder temperatures.

Improved tumour control probability with MRI-based prostate brachytherapy treatment planning.

BACKGROUND: Due to improved visibility on MRI, contouring of the prostate is improved compared to CT. The aim of this study was to quantify the benefits of using MRI for treatment planning as compared to CT-based planning for temporary implant prostate brachytherapy. MATERIAL AND METHODS: CT and MRI image data of 13 patients were used to delineate the prostate and organs at risk (OARs) and to reconstruct the implanted catheters (typically 12). An experienced treatment planner created plans on the CT-based structure sets (CT-plan) and on the MRI-based structure sets (MRI-plan). Then, active dwell-positions and weights of the CT-plans were transferred to the MRI-based structure sets (CT-plan(MRI-contours)) and resulting dosimetric parameters and tumour control probabilities (TCPs) were studied. RESULTS: For the CT-plan(MRI-contours) a statistically significant lower target coverage was detected: mean V100 was 95.1% as opposed to 98.3% for the original plans (p < 0.01). Planning on CT caused cold-spots that influence the TCP. MRI-based planning improved the TCPs by 6-10%, depending on the parameters of the radiobiological model used for TCP calculation. Basing the treatment plan on either CT- or MRI-delineations does not influence plan quality. CONCLUSION: Evaluation of CT-based treatment planning by transferring the plan to MRI reveals underdosage of the prostate, especially at the base side. Planning on MRI can prevent cold-spots in the tumour and improves the TCP.

Reirradiation and hyperthermia for radiation-associated sarcoma.

BACKGROUND: The objective of this study was to evaluate the role of reirradiation and hyperthermia in the treatment of radiation-associated sarcoma (RAS) in the thoracic region, which is an increasing, yet extremely rare condition with a poor prognosis. METHODS: Between 1979 and 2009, 16 patients with RAS in the thoracic region were treated in the Academic Medical Center and the Institute Verbeeten with reirradiation and hyperthermia. In 13 patients, this treatment was given for unresectable disease and 3 times after resection as adjuvant treatment. The median latency period between the original malignancy diagnosis and the RAS diagnosis was 86 months (range 19-212 months). Histology was angiosarcoma in 11 patients (69%). The literature on reirradiation with or without hyperthermia for RAS was reviewed. RESULTS: The median survival was 15.5 months (range, 3-204 months). Four patients were not evaluable for response. The response rate for the remaining 12 patients was 75% (7 complete responses and 2 partial responses). Six patients remained free of local failure until death (5 months and 7 months) or last follow-up (8 months, 11 months, 39 months, and 68 months). CONCLUSIONS: The current study indicates that combined reirradiation and hyperthermia for RAS in the thoracic region is feasible. The high response rate and the possibility of durable local control suggest that this treatment is promising.

Do radiation oncologists tailor information to patients needs? And, if so, does it affect patients?

BACKGROUND: Our study aims to investigate whether information given by radiation oncologists to their patients is tailored to the patient's desired level of information and, if so, what the effect of tailoring is on patient-reported outcomes, i.e. satisfaction, health, anxiety and self-efficacy. MATERIAL AND METHODS: Consecutive radiotherapy patients (n = 150) completed a baseline questionnaire one week before their initial consultation, immediately following this consultation, and again one week prior to their first follow-up visit. The initial consultation was videotaped and 10 radiation oncologists' information giving behavior (content and duration) analyzed. RESULTS: The overall amount of information provided by the radiation oncologists matched with patients' information needs in 50.8% (k = 0.07) of the consultations. No significant associations between tailored information giving and patient-reported outcomes were found, except for tailoring of information on procedures, and patients' anxiety and global health. These associations were no longer significant when correcting for patients' background characteristics. CONCLUSION: This study shows that radiation oncologists poorly tailor their information to the needs of their patients. However, lack of tailoring is not associated with worse patient-reported outcomes. Until more evidence is available, radiation oncologists may explicitly ask patients about their information preferences and tailor the information provided accordingly.

Do patients' information needs decrease over the course of radiotherapy?

PURPOSE: We aimed to investigate if cancer patients' information needs decrease during radiotherapy and if so, which patient, consultation and radiation oncologist characteristics are associated with a decrease in information needs over time. METHODS: In this longitudinal study, patients (n = 104) completed a baseline questionnaire a week before the initial radiotherapy consultation, immediately following this initial consultation, and 1 week prior to the first follow-up visit, which took place on average 3-5 weeks after the initial visit. Besides information needs, measured by the Information Preference for Radiotherapy Patients scale, the questionnaire assessed patient, consultation and radiation oncologist characteristics. RESULTS: Information needs decreased over time, but remained at a high level. Being religious, being male, having low health literacy and higher perceived involvement during the consultation were all statistically significantly associated to a decrease in information needs on specific domains (e.g. procedures or side effects). CONCLUSIONS: Cancer patients' information needs decline between the initial consultation and the first follow-up visit, but remain high. It is therefore advised to investigate the patients' information needs at every radiotherapy visit and not rely on giving information just once. Furthermore, radiation oncologists should check if the information given at first consultation is understood and remembered. By those means, tailored information giving becomes possible.

Assessing measurement invariance of a health-related quality-of-life questionnaire in radiotherapy patients.

OBJECTIVE: If the assumption of measurement invariance is not tested, we cannot be sure whether differences observed are due to true differences in health-related quality-of-life (HRQoL), or are measurement artifacts. We aim to investigate this assumption in a sample of heterogeneous cancer patients, focusing on whether age, sex, previous treatment for cancer, and information regarding treatment preferences result in biased HRQoL scores. METHODS: 155 cancer patients who were about to begin their first session of radiotherapy were included. HRQoL was measured using the EORTC QLQ-C30. Structural equation modeling was applied to assess whether there was a violation of the assumption of invariance. RESULTS: A satisfactory single construct (Functioning HRQoL) measurement model was found and two violations of invariance were identified. Irrespective of patients' Functioning HRQoL, older patients reported worse physical functioning and patients who had received treatment prior to radiotherapy reported worse emotional functioning than we would otherwise expect. CONCLUSIONS: In the present study, accounting for measurement bias lead to a substantial improvement in the overall fit of the model. By ignoring the bias, we would have concluded that the model fit was unsatisfactory. The findings underline the importance of investigating measurement invariance in scales designed for heterogeneous samples.

Pulmonary function impairment measured by pulmonary function tests in long-term survivors of childhood cancer.

BACKGROUND: Childhood cancer survivors (CCSs) have an increased risk of morbidity and mortality. The prevalence and risk factors of pulmonary function impairment were investigated in a large cohort of CCSs treated with potentially pulmotoxic therapy with a minimal follow-up of 5 years after diagnosis. METHODS: The study cohort consisted of all adult 5-year CCSs who were treated with bleomycin, pulmonary radiotherapy and/or pulmonary surgery in the Emma Children's Hospital/Academic Medical Center between 1966 and 1996. Pulmonary function tests were performed to diagnose obstructive and restrictive pulmonary function impairment, and diffusion capacity impairment. RESULTS: The study population consisted of 220 out of 248 eligible CCSs, of whom 193 (87.7%) had performed a pulmonary function test at a median follow-up of 18 years after diagnosis. 85 (44.0%) out of 193 CCSs developed a pulmonary function impairment. Pulmonary function impairments occurred in all treatment groups. Most prevalent were restrictive pulmonary function impairment (17.6%) and a decreased carbon monoxide diffusion capacity (39.9%). Multivariate logistic regression models showed that, compared with bleomycin treatment only, treatment with radiotherapy, radiotherapy combined with bleomycin and radiotherapy combined with surgery were associated with the highest risk of pulmonary function impairment. CONCLUSIONS: The prevalence of pulmonary function impairment in long-term adult CCSs who received potentially pulmotoxic therapy is high. Bleomycin, pulmonary radiotherapy and pulmonary surgery are all associated with pulmonary function impairment. Pulmonary radiotherapy, especially in combination with bleomycin or surgery, is the most important risk factor. This emphasises the need for adequate counselling and follow-up for this patient population.

Measuring cancer patients' reasons for their information preference: construction of the Considerations Concerning Cancer Information (CCCI) questionnaire.

OBJECTIVES: This paper describes the further development and psychometric properties of an instrument to measure cancer patients' reasons to want complete or limited information: the Considerations Concerning Cancer Information questionnaire (CCCI). Understanding cancer patients' reasons to want complete or limited information will provide the physician with information that enables him or her to tailor information giving. METHODS: CCCI's content validity, internal structure, and convergent validity were investigated among 145 cancer patients, new to radiotherapy. RESULTS: Underlying reasons for information preference among cancer patients were derived from existing qualitative studies, narratives, and interviews. This resulted in the CCCI containing two parts: reasons to favor complete information disclosure and reasons to prefer only limited information about disease and treatment. The four identified dimensions to prefer information consist of: sense of control, expectations of others, anxiety, and autonomy. The four dimensions for reasons to give up on acquiring information consist of: avoidance, optimism, comprehension, and not wanting to be a burden. Confirmatory factor analysis indicated that the measurement model provided good fit to the data. Scales had good internal consistency, satisfactory item-total correlations corrected for overlap and satisfactory convergent validity. CONCLUSIONS: These findings confirm evidence of the reliability and validity of the CCCI for use in cancer care. Researchers and health-care providers can use the instrument to assess cancer patients' reasons to want complete or limited information and provide tailored care.

A 'short walk' is longer before radiotherapy than afterwards: a qualitative study questioning the baseline and follow-up design.

BACKGROUND: Numerous studies have indirectly demonstrated changes in the content of respondents' QoL appraisal process over time by revealing response-shift effects. This is the first known study to qualitatively examine the assumption of consistency in the content of the cognitive processes underlying QoL appraisal over time. Specific objectives are to examine whether the content of each distinct cognitive process underlying QoL appraisal is (dis)similar over time and whether patterns of (dis)similarity can be discerned across and within patients and/or items. METHODS: We conducted cognitive think-aloud interviews with 50 cancer patients prior to and following radiotherapy to elicit cognitive processes underlying the assessment of 7 EORTC QLQ-C30 items. Qualitative analysis of patients' responses at baseline and follow-up was independently carried out by 2 researchers by means of an analysis scheme based on the cognitive process models of Tourangeau et al. and Rapkin & Schwartz. RESULTS: The interviews yielded 342 comparisons of baseline and follow-up responses, which were analyzed according to the five cognitive processes underlying QoL appraisal. The content of comprehension/frame of reference changed in 188 comparisons; retrieval/sampling strategy in 246; standards of comparison in 152; judgment/combinatory algorithm in 113; and reporting and response selection in 141 comparisons. Overall, in 322 comparisons of responses (94%) the content of at least one cognitive component changed over time. We could not discern patterns of (dis)similarity since the content of each of the cognitive processes differed across and within patients and/or items. Additionally, differences found in the content of a cognitive process for one item was not found to influence dissimilarity in the content of that same cognitive process for the subsequent item. CONCLUSIONS: The assumption of consistency in the content of the cognitive processes underlying QoL appraisal over time was not found to be in line with the cognitive processes described by the respondents. Additionally, we could not discern patterns of (dis)similarity across and within patients and/or items. In building on cognitive process models and the response shift literature, this study contributes to a better understanding of patient-reported QoL appraisal over time.

Elective re-irradiation and hyperthermia following resection of persistent locoregional recurrent breast cancer: A retrospective study.

PURPOSE: To analyse the therapeutic effect and toxicity of re-irradiation (re-RT) combined with hyperthermia (HT) following resection or clinically complete remission (CR) of persistent locoregional recurrent breast cancer in previously irradiated area. METHODS AND MATERIALS: Between 1988 and 2001, 78 patients with high risk recurrent breast cancer underwent elective re-RT and HT. All patients received extensive previous treatments, including surgery and high-dose irradiation (> or =50Gy). Most had received one or more lines of systemic therapy; 44% had been treated for > or = one previous locoregional recurrences. At start of re-RT + HT there was no macroscopically detectable tumour following surgery (96%) or chemotherapy (CT). Re-RT typically consisted of eight fractions of 4Gy, given twice weekly. Hyperthermia was added once a week. RESULTS: After a median follow up of 64.2 months, three-year survival was 66%. Three- and five-year local control rates were 78% and 65%. Acute grade 3 toxicity occurred in 32% of patients. The risk of late > or = grade 3 toxicity was 40% after three years. Time interval to the current recurrence was found to be most predictive for local control in univariate and multivariate analysis. The extensiveness of current surgery was the most relevant treatment related factor associated with toxicity. CONCLUSIONS: For patients experiencing local recurrence in a previously radiated area, re-irradiation plus hyperthermia following minimisation of tumour burden leads to a high rate of local control, albeit with significant toxicity. The latter might be reduced by a more fractionated re-RT schedule.

Comparison of biologically equivalent dose-volume parameters for the treatment of prostate cancer with concomitant boost IMRT versus IMRT combined with brachytherapy.

BACKGROUND AND PURPOSE: The two main modalities to deliver high dose to the prostate and prevent high doses to neighboring organs are intensity modulated radiotherapy (IMRT) or external beam radiotherapy combined with brachytherapy. Because of the different biological effectiveness the physical dose distributions were converted to 3-dimensional linear quadratic dose at 2 Gy per fraction (EQD(2)). From the latter, cumulative EQD(2)-volume histograms were determined for comparison of the modalities. MATERIAL AND METHODS: An IMRT plan was made on the contoured planning target volume (PTV1) and organs at risk (OAR) of 20 patients (IMRT-only). A dose of 70 Gy was prescribed on the PTV1 with a concomitant boost to a total of 76 Gy on a subvolume (PTV2). Also a 46 Gy IMRT plan was made combined with either a pulsed dose-rate (PDR) or a high dose-rate (HDR) brachytherapy boost. The EQD(2) on the PTV1 of the combined IMRT-PDR and IMRT-HDR plans were made equivalent to the EQD(2) of the 70 Gy IMRT-only plan. The alpha/beta-ratio for prostate was set to 1.5 Gy and 10 Gy. For normal tissues an alpha/beta-ratio of 3.0 Gy was taken. Several EQD(2)-volume histogram parameters were calculated for comparison and analyzed by two-way ANOVA. RESULTS: The mean EQD(2) to 95% of the prostate volume was slightly higher for the IMRT-only plan than for the brachytherapy modalities (P<0.001), in contrast to the mean EQD(2) to 50% of the prostate volume in which the opposite was the case (P<0.001). Rectum and bladder doses for IMRT-only are significantly higher (P<0.001). The urethra dose for IMRT-HDR was much higher than the other modalities only when the alpha/beta-ratio for prostate was 10 Gy. CONCLUSION: Because of the high doses within an implant, the dose in 50% of the prostate volume is much higher with the brachytherapy modalities than IMRT-only which may have clinical consequences. With brachytherapy the doses to the OAR are lower or similar to IMRT-only. Dose escalation for prostate tumors is more easily achieved with brachytherapy than with IMRT alone. Therefore, brachytherapy might be the preferred modality to achieve further dose escalation.

Concurrent Daily Cisplatin and High-Dose Radiation Therapy in Patients With Stage III Non-Small Cell Lung Cancer.

PURPOSE: The purpose of this study was to determine survival, local and distant control, toxicity, and prognostic factors in patients with stage III non-small cell lung cancer (NSCLC) treated with concurrent chemoradiation therapy (CCRT). METHODS AND MATERIALS: Consecutive patients with stage IIIA and IIIB NSCLC (N = 154) staged with 18F-fluorodeoxyglucose positron emission tomography/computed tomography were retrospectively selected (2005-2015). CCRT consisted of daily low-dose cisplatin (6 mg/m2) combined with 24 fractions of 2.75 Gy to a total dose of 66 Gy. RESULTS: During a median follow-up period of 22 months (range, 1-92 months) the median overall survival was 36 months. The 1-, 2-, 3-, and 5-year survival rates were 79% (95% confidence interval [CI], 73%-86%), 61% (95% CI, 54%-70%), 52% (95% CI, 43%-60%), and 40% (95% CI, 31%-51%), respectively. The local relapse-free survival at 5 years was 55% (95% CI, 44%-69%). Metastasis-free survival at 5 years was 53% (95% CI, 44%-65%). The incidence of severe gastrointestinal disorders (grade 3-5) was 11%, among which grade 3 radiation esophagitis was 8.4%. The incidence of severe respiratory, thoracic, and mediastinal disorders (grade 3-5) was 8.4%, among which grade 3 radiation pneumonitis was 1.3%. Predictors of overall survival were lymph node gross tumor volume (GTV) (hazard ratio [HR], 1.007; 95% CI, 1.000-1.012) and sex (HR, 0.500; 95% CI, 0.320-0.870) in favor of women. Although lymph node GTV was a predictor of treatment toxicity (HR, 1.010; 95% CI, 1.000-1.013), tumor GTV was the predictor for distant metastasis during follow-up (HR, 1.002; 95% CI, 1.001-1.003). CONCLUSIONS: CCRT with daily low-dose cisplatin for locally advanced stage III NSCLC resulted in promising overall survival (3-year survival rate of 52% and 5-year survival rate of 40%) with low toxicity. Lymph node GTV, tumor GTV, and sex were predictors of overall survival, treatment toxicity, and distant metastasis.

Randomised trial of sequential versus concurrent chemo-radiotherapy in patients with inoperable non-small cell lung cancer (EORTC 08972-22973).

UNLABELLED: A randomised phase III study was performed comparing sequential (S) and concurrent (C) chemo-radiotherapy (CRT) in non-small cell lung cancer (NSCLC) patients. METHODS: One hundred and fifty-eight patients were randomised to receive two courses of Gemcitabine (1250mg/m(2) days 1, 8) and Cisplatin (75mg/m(2) day 2) prior to, or daily low-dose Cisplatin (6mg/m(2)) concurrent with radiotherapy, consisting of 24 fractions of 2.75Gy in 32 days, with a total dose of 66Gy. RESULTS: Acute haematological toxicity grade 3/4 was more pronounced in the sequential (S) (30% versus 6%), oesophagitis grade 3/4 more frequent in the concurrent (C) arm (5% versus 14%). Late oesophagitis grade 3 was 4% (S and C), pneumonitis grade 3/4 14% (S) and 18% (C). Because of the poor power of the study no significant differences in median survival (MS), overall survival (OS) and progression-free survival (PFS) could be detected. MS was 16.2 (S) and 16.5 (C) months, 2-year OS was 34% (S) and 39% (C), 3-year OS was 22% (S) and 34% (C). CONCLUSION: Radiotherapy 66Gy given concurrently with daily low-dose Cisplatin or after two courses of Gemcitabine/Cisplatin was well tolerated. Due to early closure no conclusions can be reached on the relative merits; both arms showed good OS.

Results of bladder-conserving treatment, consisting of brachytherapy combined with limited surgery and external beam radiotherapy, for patients with solitary T1-T3 bladder tumors less than 5 cm in diameter.

PURPOSE: To evaluate the long-term, local relapse-free, distant metastasis-free, and overall survival rates in patients with a solitary bladder tumor <5 cm in diameter who were treated with external beam radiotherapy, limited surgery, and brachytherapy. METHODS AND MATERIALS: The results of 122 patients after bladder-saving treatment were analyzed. After EBRT, the patients underwent cystotomy, and catheters were implanted. Of the 122 patients, 99 were treated with a continuous low-dose-rate technique and 23 patients with a pulsed-dose-rate technique. The median follow-up period was 5 years. RESULTS: The 5-year local and distant relapse-free survival rate was 76% and 83%, respectively. The 5 and 10-year relapse-free survival rate was 69% and 66%, respectively. For overall survival, the corresponding rates were 73% and 49%. Toxicity was low. No differences were found between the continuous low-dose-rate and pulsed-dose-rate groups. CONCLUSION: The results of our study have shown that external beam radiotherapy followed by brachytherapy as a bladder-saving treatment for a selected group of patients with bladder cancer yields excellent local tumor control and low toxicity.

Medical assessment of adverse health outcomes in long-term survivors of childhood cancer.

CONTEXT: Improved survival of children with cancer has been accompanied by multiple treatment-related complications. However, most studies in survivors of childhood cancer focused on only 1 late effect. OBJECTIVE: To assess the total burden of adverse health outcomes (clinical or subclinical disorders ["adverse events"]) following childhood cancer in a large cohort of childhood cancer survivors with long-term and complete medical follow-up. DESIGN, SETTING, AND POPULATION: Retrospective cohort study of 1362 five-year survivors of childhood cancer treated in a single institution in the Netherlands between 1966 and 1996. All survivors were invited to a late-effects clinic for medical assessment of adverse events. Adverse events occurring before January 2004 were graded for severity in a standardized manner. MAIN OUTCOME MEASURES: Treatment-specific prevalence of adverse events (according to severity) at end of follow-up and relative risk of high or severe burden of disease (> or =2 severe or > or =1 life-threatening or disabling adverse events) associated with various treatments. RESULTS: Medical follow-up was complete for 94.3% of survivors (median follow-up, 17.0 years). The median attained age at end of follow-up was 24.4 years. Almost 75% of survivors had 1 or more adverse events, and 24.6% had 5 or more adverse events. Furthermore, 40% of survivors had at least 1 severe or life-threatening or disabling adverse event. A high or severe burden of adverse events was observed in 55% of survivors who received radiotherapy only and 15% of survivors treated with chemotherapy only, compared with 25% of survivors who had surgery only (adjusted relative risks, 2.18 [95% confidence interval, 1.62-2.95] and 0.65 [95% confidence interval, 0.46-0.90], respectively). A high or severe burden of adverse events was most often observed in survivors of bone tumors (64%) and least often in survivors of leukemia or Wilms tumor (12% each). CONCLUSIONS: In young adulthood, a substantial proportion of childhood cancer survivors already has a high or severe burden of disease, particularly after radiotherapy. This underscores the need for lifelong risk-stratified medical surveillance of childhood cancer survivors.

Risk of Symptomatic Stroke After Radiation Therapy for Childhood Cancer: A Long-Term Follow-Up Cohort Analysis.

PURPOSE: Long-term childhood cancer survivors are at high risk of late adverse effects, including stroke. We aimed to determine the cumulative incidence of clinically validated symptomatic stroke (transient ischemic attack [TIA], cerebral infarction, and intracerebral hemorrhage [ICH]) and to quantify dose-effect relationships for cranial radiation therapy (CRT) and supradiaphragmatic radiation therapy (SDRT). METHODS AND MATERIALS: Our single-center study cohort included 1362 survivors of childhood cancer that were diagnosed between 1966 and 1996. Prescribed CRT and SDRT doses were converted into the equivalent dose in 2-Gy fractions (EQD2). Multivariate Cox regression models were used to analyze the relationship between the EQD2 and stroke. RESULTS: After a median latency time of 24.9 years and at a median age of 31.2 years, 28 survivors had experienced a first stroke: TIA (n=5), infarction (n=13), and ICH (n=10). At an attained age of 45 years, the estimated cumulative incidences, with death as competing risk, among survivors treated with CRT only, SDRT only, both CRT and SDRT, and neither CRT nor SDRT were, respectively, 10.0% (95% confidence interval [CI], 2.5%-17.0%), 5.4% (95% CI, 0%-17.0%), 12.5% (95% CI, 5.5%-18.9%), and 0.1% (95% CI, 0%-0.4%). Radiation at both locations significantly increased the risk of stroke in a dose-dependent manner (hazard ratios: HRCRT 1.02 Gy(-1); 95% CI, 1.01-1.03, and HRSDRT 1.04 Gy(-1); 95% CI, 1.02-1.05). CONCLUSIONS: Childhood cancer survivors treated with CRT, SDRT, or both have a high stroke risk. One in 8 survivors treated at both locations will have experienced a symptomatic stroke at an attained age of 45 years. Further research on the pathophysiologic processes involved in stroke in this specific group of patients is needed to enable the development of tailored secondary prevention strategies.

Comparison of 1 x 8 Gy and 10 x 3 Gy for functional outcome in patients with metastatic spinal cord compression.

PURPOSE: Since life expectancy is markedly reduced in patients with metastatic spinal cord compression (MSCC), a short and effective radiation schedule is desired. This study investigates a reduction of the overall treatment time to only one day by comparing 1 x 8 Gy to the multi-fractionated 10 x 3 Gy for functional outcome. METHODS AND MATERIALS: Data of 204 patients, treated for MSCC with either 1 x 8 Gy (n = 96) or 10 x 3 Gy (n = 108), were analyzed retrospectively. Motor function and ambulatory status were evaluated before and up to 24 weeks after RT. A multivariate analysis (nominal regression) was performed including radiation schedule, performance status, age, irradiated vertebra, and relevant prognostic factors (histology, ambulatory status, time of developing motor deficits). Improvement of motor deficits was selected as basic category and compared with no change and deterioration. RESULTS: Univariate analysis showed no significant difference between the schedules for post-treatment motor function and ambulatory rates. Multivariate analysis demonstrated a significant effect on functional outcome for the prognostic factors, but not for the radiation schedule (p = 0.853 for no change, p = 0.237 for deterioration). CONCLUSIONS: Our data suggest the two fractionation schedules to be comparably effective for functional outcome. Thus, 1 x 8 Gy should be considered for patients with a poor survival prognosis.

Effectiveness and toxicity of single-fraction radiotherapy with 1 x 8 Gy for metastatic spinal cord compression.

Toxicity and functional outcome were evaluated in 199 MSCC-patients irradiated with 1 x 8 Gy. Motor function improved in 54/199 patients (27%). Patients who regained walking ability were 20/78 (26%). Long-term-survivors (> or =12 months) who needed re-irradiation for in-field-recurrence were 19/65 (29%). Acute toxicity was mild, late toxicity not observed. A randomised trial comparing single-fraction RT to multi-fraction RT is mandatory.

Valvular abnormalities detected by echocardiography in 5-year survivors of childhood cancer: a long-term follow-up study.

PURPOSE: To determine the prevalence of valvular abnormalities after radiation therapy involving the heart region and/or treatment with anthracyclines and to identify associated risk factors in a large cohort of 5-year childhood cancer survivors (CCS). METHODS AND MATERIALS: The study cohort consisted of all 626 eligible 5-year CCS diagnosed with childhood cancer in the Emma Children's Hospital/Academic Medical Center between 1966 and 1996 and treated with radiation therapy involving the heart region and/or anthracyclines. We determined the presence of valvular abnormalities according to echocardiograms. Physical radiation dose was converted into the equivalent dose in 2-Gy fractions (EQD2). Using multivariable logistic regression analyses, we examined the associations between cancer treatment and valvular abnormalities. RESULTS: We identified 225 mainly mild echocardiographic valvular abnormalities in 169 of 545 CCS (31%) with a cardiac assessment (median follow-up time, 14.9 years [range, 5.1-36.8 years]; median attained age 22.0 years [range, 7.0-49.7 years]). Twenty-four CCS (4.4%) had 31 moderate or higher-graded abnormalities. Most common abnormalities were tricuspid valve disorders (n=119; 21.8%) and mitral valve disorders (n=73; 13.4%). The risk of valvular abnormalities was associated with increasing radiation dose (using EQD2) involving the heart region (odds ratio 1.33 per 10 Gy) and the presence of congenital heart disease (odds ratio 3.43). We found no statistically significant evidence that anthracyclines increase the risk. CONCLUSIONS: Almost one-third of CCS treated with potentially cardiotoxic therapy had 1 or more asymptomatic, mostly mild valvular abnormalities after a median follow-up of nearly 15 years. The most important risk factors are higher EQD2 to the heart region and congenital heart disease. Studies with longer follow-up are necessary to investigate the clinical course of asymptomatic valvular abnormalities in CCS.