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.

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.

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.

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.

The use of equivalent radiation dose in the evaluation of late effects after childhood cancer treatment.

PURPOSE: In epidemiologic research radiation-associated late effects after childhood cancer are usually analyzed without considering fraction dose. According to radiobiological principles, fraction dose is an important determinant of late effects. We aim to provide the rationale for using equivalent dose in 2-Gy fractions (EQD2(α/ß)) as the measure of choice rather than total physical dose as prescribed according to the clinical protocol. METHODS: Between 1966 and 1996, 597 (43.8%) children in our cohort of 1,362 5-year childhood cancer survivors (CCS) received radiotherapy before the age of 18 years as part of their primary cancer treatment. Detailed information from individual patients' charts was collected and physical doses were converted into the EQD2(α/ß), which includes total dose, fraction dose, and the tissue-specific α/ß ratio. The use of EQD2(α/ß) is illustrated in examples studies describing different analyses using EQD2(α/ß) and physical dose. RESULTS: Radiotherapy information was obtained for 510 (85.4%) CCS. Multivariable analyses rendered different risk estimates for total body irradiation in EQD2(α/ß)-based vs. physical-dose-based models. For other radiotherapy regimens, risk estimates were similar. CONCLUSIONS: Using the total physical dose is not adequate for advanced analyses of radiation-associated late effects in CCS. Therefore, it is advised that for future studies the EQD2(α/ß) is used, because the EQD2(α/ß) incorporates the fraction dose, and the tissue-specific α/ß ratio. Furthermore, it enables comparisons across fractionation regimens and allows for summing doses delivered by various contemporary and future radiation modalities. IMPLICATIONS FOR CANCER SURVIVORS: Risk estimates of radiation-associated side effects expressed in EQD2(α/ß) provide more precise, clinically relevant information for cancer survivor screening guidelines.

Tolerance and benefits of treatment for elderly patients with limited small-cell lung cancer.

OBJECTIVES: Over 20% of all newly diagnosed Dutch patients with small-cell lung cancer (SCLC) are aged ≥75 years. Uncertainties still exist about safety and efficacy of chemotherapy and chemoradiation in elderly patients. We evaluated the association between patient characteristics and (completion of) treatment and also evaluated toxicity, response and survival in elderly patients with SCLC. MATERIALS AND METHODS: Population-based data from patients aged 75 years or older and diagnosed with limited SCLC in 1997-2004 in The Netherlands were used (N = 368). Additional data on co-morbidity, motive for deviating from guidelines, grades 3-5 toxicity, response and survival were gathered from medical records. RESULTS: Although only relatively fit elderly were selected for chemotherapy, almost 70% developed toxicity, leading to early termination of chemotherapy in over half of all patients. Median survival time was 6.7 months, but differed strongly according to type and completion of treatment (13.5 months for chemoradiation, 7.1 months for chemotherapy, 2.9 months for best supportive care, 11.5 months for patients receiving at least 4 cycles of chemotherapy and 3.6 months for less than 4 cycles). CONCLUSION: Although toxicity rate was high and many patients could not complete the full chemotherapy, those who received chemotherapy or chemoradiation had a significantly better survival. We hypothesize that a better selection by proper geriatric assessments is needed to achieve a more favourable balance between benefit and harm.

Glomerular function time trends in long-term survivors of childhood cancer: a longitudinal study.

BACKGROUND: Impaired glomerular function is one of the health problems affecting childhood cancer survivors (CCS). It is unclear whether glomerular function deteriorates or recovers. We investigated time trends and predictors of glomerular function in CCS. METHODS: We evaluated repeated observations of estimated glomerular filtration rate (GFR) and glomerular dysfunction (GFR <90 mL/min/1.73 m(2)) among adult five-year CCS treated in the EKZ/AMC between 1966 and 2003. Ifosfamide, cisplatin, carboplatin, high-dose (HD) methotrexate, HD-cyclophosphamide, radiotherapy to the kidney region, and nephrectomy (i.e., potentially nephrotoxic therapy) were investigated as predictors of glomerular function patterns over time in multivariable longitudinal analyses. RESULTS: At a median follow-up of 21 years after diagnosis, glomerular function was assessed in 1,122 CCS aged ≥18 years. CCS treated with potentially nephrotoxic therapy had a significantly lower GFR and higher glomerular dysfunction probability up to 35 years after cancer diagnosis compared with CCS treated without nephrotoxic therapy (P < 0.001). Especially ifosfamide, cisplatin, and nephrectomy were associated with worse glomerular function that persisted during the entire follow-up period (P < 0.001). Glomerular function deteriorated over time in all CCS (P < 0.001). CCS treated with higher doses of cisplatin seem to have a higher deterioration rate as compared with other CCS (P < 0.005). CONCLUSIONS: The loss in glomerular function starts early, especially for CCS treated with ifosfamide, higher doses of cisplatin, and nephrectomy, and seems to be persistent. We have an indication that CCS treated with higher doses of cisplatin experience faster decline than other CCS. IMPACT: As glomerular function continues to deteriorate, CCS are at risk for premature chronic renal failure.

Toxicity of concurrent radiochemotherapy for locally advanced non--small-cell lung cancer: a systematic review of the literature.

Concurrent radiochemotherapy (RCT) is the treatment of choice for patients with locally advanced non-small-cell lung cancer (NSCLC). Two meta-analyses were inconclusive in an attempt to define the optimal concurrent RCT scheme. Besides efficacy, treatment toxicity will influence the appointed treatment of choice. A systematic review of the literature was performed to record the early and late toxicities, as well as overall survival, of concurrent RCT regimens in patients with NSCLC. The databases of PubMed, Ovid, Medline, and the Cochrane Library were searched for articles on concurrent RCT published between January 1992 and December 2009. Publications of phase II and phase III trials with ≥ 50 patients per treatment arm were selected. Patient characteristics, chemotherapy regimen (mono- or polychemotherapy, high or low dose) and radiotherapy scheme, acute and late toxicity, and overall survival data were compared. Seventeen articles were selected: 12 studies with cisplatin-containing regimens and 5 studies using carboplatin. A total of 13 series with mono- or polychemotherapy schedules--as single dose or double or triple high-dose or daily cisplatin-containing (≤ 30 mg/m(2)/wk) chemotherapy were found. Acute esophagitis ≥ grade 3 was observed in up to 18% of the patients. High-dose cisplatin regimens resulted in more frequent and severe hematologic toxicity, nausea, and vomiting than did other schemes. The toxicity profile was more favorable in low-dose chemotherapy schedules. From phase II and III trials published between 1992 and 2010, it can be concluded that concurrent RCT with monochemotherapy consisting of daily cisplatin results in favorable acute and late toxicity compared with concurrent RCT with single high-dose chemotherapy, doublets, or triplets.

[Bladder-conserving treatment for bladder cancer: potential of and developments in radiotherapy]. / Blaassparende behandelingen bij blaaskanker: mogelijkheden en ontwikkelingen in de radiotherapie.

The standard treatment for muscle-invasive bladder cancer is surgical removal of the bladder and construction of a neobladder. Recently, important improvements have been made in the potential for bladder-conserving treatment using radiotherapy. External beam radiotherapy has undergone technological improvements, as a result of which it is possible to radiate the tumour more precisely while decreasing radiation to healthy tissue. Radiochemotherapy improves local recurrence-free and overall survival compared with radiotherapy alone. The results of this combined treatment are comparable with those of surgery. Additionally, Dutch radiotherapy departments have collected data in a national database of 1040 selected patients with confined bladder cancer. These patients were treated with external beam radiation, limited surgery and brachytherapy. The 5-year local recurrence-free survival was 75%. Bladder conserving treatment options for muscle-invasive bladder cancer should be discussed during the multidisciplinary meeting.

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.

Dose-effect relationships for adverse events after cranial radiation therapy in long-term childhood cancer survivors.

PURPOSE: To evaluate the prevalence and severity of clinical adverse events (AEs) and treatment-related risk factors in childhood cancer survivors treated with cranial radiation therapy (CRT), with the aim of assessing dose-effect relationships. METHODS AND MATERIALS: The retrospective study cohort consisted of 1362 Dutch childhood cancer survivors, of whom 285 were treated with CRT delivered as brain irradiation (BI), as part of craniospinal irradiation (CSI), and as total body irradiation (TBI). Individual CRT doses were converted into the equivalent dose in 2-Gy fractions (EQD(2)). Survivors had received their diagnoses between 1966 and 1996 and survived at least 5 years after diagnosis. A complete inventory of Common Terminology Criteria for Adverse Events grade 3.0 AEs was available from our hospital-based late-effect follow-up program. We used multivariable logistic and Cox regression analyses to examine the EQD(2) in relation to the prevalence and severity of AEs, correcting for sex, age at diagnosis, follow-up time, and the treatment-related risk factors surgery and chemotherapy. RESULTS: There was a high prevalence of AEs in the CRT group; over 80% of survivors had more than 1 AE, and almost half had at least 5 AEs, both representing significant increases in number of AEs compared with survivors not treated with CRT. Additionally, the proportion of severe, life-threatening, or disabling AEs was significantly higher in the CRT group. The most frequent AEs were alopecia and cognitive, endocrine, metabolic, and neurologic events. Using the EQD(2), we found significant dose-effect relationships for these and other AEs. CONCLUSION: Our results confirm that CRT increases the prevalence and severity of AEs in childhood cancer survivors. Furthermore, analyzing dose-effect relationships with the cumulative EQD(2) instead of total physical dose connects the knowledge from radiation therapy and radiobiology with the clinical experience.

Does being informed and feeling informed affect patients' trust in their radiation oncologist?

OBJECTIVE: We investigated whether the content of information provided by radiation oncologists and their information giving performance increase patients' trust in them. METHODS: Questionnaires were used to assess radiotherapy patients (n=111) characteristics before their first consultation, perception of information giving after the first consultation and trust before the follow-up consultation. Videotaped consultations were scored for the content of the information provided and information giving performance. RESULTS: Patients mean trust score was 4.5 (sd=0.77). The more anxious patients were, the less they tended to fully trust their radiation oncologist (p=0.03). Patients' age, gender, educational attainment and anxious disposition together explained 7%; radiation oncologists' information giving (content and performance) explained 3%, and patients' perception of radiation oncologists' information-giving explained an additional 4% of the variance in trust scores. CONCLUSION: It can be questioned whether trust is a sensitive patient reported outcome of quality of communication in highly vulnerable patients. PRACTICE IMPLICATIONS: It is important to note that trust may not be a good patient reported outcome of quality of care. Concerning radiation oncologists' information giving performance, our data suggest that they can particularly improve their assessments of patients' understanding.

Surveillance of hepatic late adverse effects in a large cohort of long-term survivors of childhood cancer: prevalence and risk factors.

BACKGROUND: Childhood cancer survivors (CCS) are a growing group of young individuals with a high risk of morbidity and mortality. We evaluated the prevalence and risk factors of hepatic late adverse effects, defined as elevated liver enzymes, in a large cohort of CCS. METHODS: The cohort consisted of all five-year CCS treated in the EKZ/AMC between 1966 and 2003, without hepatitis virus infection and history of veno-occlusive disease (VOD). Liver enzyme tests included serum levels of alanine aminotransferase (ALT) for hepatocellular injury and gamma-glutamyltransferase (γGT) for biliary tract injury. We performed multivariable linear and logistic regression analyses. RESULTS: The study population consisted of 1404 of 1795 eligible CCS, of whom 1362 performed liver enzyme tests at a median follow-up of 12 years after diagnosis. In total, 118 (8.7%) of 1362 CCS had hepatic late adverse effects defined as ALT or γGT above the upper limit of normal. Abnormal ALT and γGT levels were found in 5.8% and 5.3%, respectively. In multivariable regression analyses treatment with radiotherapy involving the liver, higher body mass index, higher alcohol intake and longer follow-up time were significantly associated with elevated ALT and γGT levels; older age at diagnosis was only significantly associated with elevated γGT levels (all p<0.05). CONCLUSION: One in twelve CCS showed signs of hepatic late adverse effects after a median follow-up of 12 years. Several risk factors have been identified. Future studies should focus on the course of long-term liver related outcomes and on the influence of radiotherapy and chemotherapy dose.

Adaptive margin radiotherapy for patients with prostate carcinoma: what's the benefit?

With daily portal images and repeated CT scans from 20 patients with gold markers (GM) an adaptive margin radiotherapy strategy (AMRT) was simulated and compared to traditional bony anatomy (BA) and standard GM verification protocols. AMRT is comparable with BA. GM protocols are superior.

[Re-irradiation of painful bone metastases]. / Herbestraling van pijnlijke botmetastasen: te weinig kennis over effect.

Little is known about what the best treatment is for patients returning with painful bone metastases after their first radiotherapy. Treatment should be individualized and should depend on the histology of the primary tumour, the general condition of the patient, systemic treatment options and prognosis. The precise effect of re-irradiation of painful bone metastases has scarcely been studied. A recent meta-analysis published in the Dutch Journal of Medicine sheds only some light on this subject; the meta-analysis provided only some indications as to the effects of re-irradiation, but did not provide any evidence. The studies included were, methodologically speaking, not very strong, as much data were derived from very small numbers of patients. In addition, re-irradiation was never the primary object of study. An international, prospective, randomized clinical trial into the effects of re-irradiation of bone metastases has recently achieved its patient-inclusion target. The first results will be available by the end of 2012; these results will hopefully fill the current gaps in our knowledge.

Renal dysfunction and elevated blood pressure in long-term childhood cancer survivors.

BACKGROUND AND OBJECTIVES: Little is known about renal function and blood pressure (BP) in long-term childhood cancer survivors. This cross-sectional study evaluated prevalence of these outcomes and associated risk factors in long-term childhood cancer survivors at their first visit to a specialized outpatient clinic. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Estimated GFR; percentages of patients with albuminuria, hypomagnesemia, and hypophosphatemia; and BP were assessed in 1442 survivors ≥5 years after diagnosis. Multivariable logistic regression analyses were used to estimate effect of chemotherapy, nephrectomy, and radiation therapy on the different outcomes. RESULTS: At a median age of 19.3 years (interquartile range, 15.6-24.5 years), 28.1% of all survivors had at least one renal adverse effect or elevated BP. The median time since cancer diagnosis was 12.1 years (interquartile range, 7.8-17.5 years). High BP and albuminuria were most prevalent, at 14.8% and 14.5%, respectively. Sixty-two survivors (4.5%) had an estimated GFR <90 ml/min per 1.73 m(2). Survivors who had undergone nephrectomy had the highest risk for diminished renal function (odds ratio, 8.6; 95% confidence interval [CI], 3.4-21.4). Combined radiation therapy and nephrectomy increased the odds of having elevated BP (odds ratio, 4.92; 95% CI, 2.63-9.19), as did male sex, higher body mass index, and longer time since cancer treatment. CONCLUSION: Almost 30% of survivors had renal adverse effects or high BP. Therefore, monitoring of renal function in high-risk groups and BP in all survivors may help clinicians detect health problems at an early stage and initiate timely therapy to prevent additional damage.

Dose-guided radiotherapy: potential benefit of online dose recalculation for stereotactic lung irradiation in patients with non-small-cell lung cancer.

PURPOSE: To determine whether dose-guided radiotherapy (i.e., online recalculation and evaluation of the actual dose distribution) can improve decision making for lung cancer patients treated with stereotactic body radiotherapy. METHODS AND MATERIALS: For this study 108 cone-beam computed tomography (CBCT) scans of 10 non-small-cell lung cancer patients treated with stereotactic body radiotherapy were analyzed retrospectively. The treatment plans were recalculated on the CBCT scans. The V(100%) of the internal target volume (ITV) and D(max) of the organs at risk (OARs) were analyzed. Results from the recalculated data were compared with dose estimates for target and OARs by superposition of the originally planned dose distribution on CBCT geometry (i.e., the original dose distribution was assumed to be spatially invariant). RESULTS: Before position correction was applied the V(100%) of the ITV was 100% in 65% of the cases when an ITV-PTV margin of 5 mm was used and 52% of the cases when a margin of 3 mm was used. After position correction, the difference of D(max) in the OARs with respect to the treatment plan was within 5% in the majority of the cases. When the dose was not recalculated but estimated assuming an invariant dose distribution, clinically relevant errors occurred in both the ITV and the OARs. CONCLUSION: Dose-guided radiotherapy can be used to determine the actual dose in OARs when the target has moved with respect to the OARs. When the workflow is optimized for speed, it can be used to prevent unnecessary position corrections. Estimating the dose by assuming an invariant dose instead of recalculation of the dose gives clinically relevant errors.

High risk of symptomatic cardiac events in childhood cancer survivors.

PURPOSE: To evaluate the long-term risk for validated symptomatic cardiac events (CEs) and associated risk factors in childhood cancer survivors (CCSs). PATIENTS AND METHODS: We determined CEs grade 3 or higher: congestive heart failure (CHF), cardiac ischemia, valvular disease, arrhythmia and/or pericarditis (according to Common Terminology Criteria for Adverse Events [CTCAE], version 3.0) in a hospital-based cohort of 1,362 5-year CCSs diagnosed between 1966 and 1996. We calculated both marginal and cause-specific cumulative incidence of CEs and cause-specific cumulative incidence of separate events. We analyzed different risk factors in multivariable Cox regression models. RESULTS: Overall, 50 CEs, including 27 cases of CHF, were observed in 42 survivors (at a median attained age of 27.1 years). The 30-year cause-specific cumulative incidence of CEs was significantly increased after treatment with both anthracyclines and cardiac irradiation (12.6%; 95% CI, 4.3% to 20.3%), after anthracyclines (7.3%; 95% CI, 3.8% to 10.7%), and after cardiac irradiation (4.0%; 95% CI, 0.5% to 7.4%) compared with other treatments. In the proportional hazards analyses, anthracycline (dose), cardiac irradiation (dose), combination of these treatments, and congenital heart disease were significantly associated with developing a CE. We demonstrated an exponential relationship between the cumulative anthracycline dose, cardiac irradiation dose, and risk of CE. CONCLUSION: CCSs have a high risk of developing symptomatic CEs at an early age. The most common CE was CHF. Survivors treated with both anthracyclines and radiotherapy have the highest risk; after 30 years, one in eight will develop severe heart disease. The use of potentially cardiotoxic treatments should be reconsidered for high-risk groups, and frequent follow-up for high-risk survivors is needed.

[Trends in the use of primary radiotherapy for cancer in the Netherlands in patients with breast, prostate, rectal and lung tumours]. / Trends in toepassing van primaire radiotherapie voor kanker in Nederland: Bij patiënten met tumoren van borst, prostaat, endeldarm en long.

OBJECTIVE: To provide insight in the application of radiotherapy as part of primary treatment of patients with cancer in the Netherlands. DESIGN: Retrospective, descriptive population-based study. METHOD: Data concerning patients with breast, prostate, rectal and non-small cell lung cancer were selected from the Netherlands Cancer Registry in 4 regions, covering 50% of the Dutch population. The selection concerned data from 1997-2008 and, except for prostate cancer, only patients without distant metastases were included. RESULTS: Between 1997 and 2008, the use of primary external radiotherapy increased approximately 7% in breast cancer patients and approximately 30% in rectal cancer patients. In the latter group preoperative radiotherapy strongly increased, while postoperative radiotherapy decreased. For prostate cancer there was an increase in brachytherapy (9%). The use of external beam radiotherapy in patients with prostate cancer and non-small cell lung cancer remained the same. Regional differences in the extent of use of radiotherapy for breast and rectal cancer clearly decreased. These differences remained limited for external beam radiotherapy in prostate and non-small cell lung cancer. Older patients less often received radiotherapy. CONCLUSION: The increase in use of radiotherapy for breast cancer is explained by the increase in breast conserving surgery. The trends in use in patients with rectal cancer and breast cancer are presumably related to the implementation of multidisciplinary practice guidelines. The implementation of these guidelines probably also contributed to the decrease in regional differences in the use of radiotherapy.