Hodgkin lymphoma (HL) survivors treated with radiotherapy and/or chemotherapy are known to have increased risks of heart failure (HF), but a radiation dose-response relationship has not previously ...been derived. A case-control study, nested in a cohort of 2617 five-year survivors of HL diagnosed before age 51 years during 1965 to 1995, was conducted. Cases (n = 91) had moderate or severe HF as their first cardiovascular diagnosis. Controls (n = 278) were matched to cases on age, sex, and HL diagnosis date. Treatment and follow-up information were abstracted from medical records. Mean heart doses and mean left ventricular doses (MLVD) were estimated by reconstruction of individual treatments on representative computed tomography datasets. Average MLVD was 16.7 Gy for cases and 13.8 Gy for controls (Pdifference = .003). HF rate increased with MLVD: relative to 0 Gy, HF rates following MVLD of 1-15, 16-20, 21-25, and ≥26 Gy were 1.27, 1.65, 3.84, and 4.39, respectively (Ptrend < .001). Anthracycline-containing chemotherapy increased HF rate by a factor of 2.83 (95% CI: 1.43-5.59), and there was no significant interaction with MLVD (Pinteraction = .09). Twenty-five–year cumulative risks of HF following MLVDs of 0-15 Gy, 16-20 Gy, and ≥21 Gy were 4.4%, 6.2%, and 13.3%, respectively, in patients treated without anthracycline-containing chemotherapy, and 11.2%, 15.9%, and 32.9%, respectively, in patients treated with anthracyclines. We have derived quantitative estimates of HF risk in patients treated for HL following radiotherapy with or without anthracycline-containing chemotherapy. Our results enable estimation of HF risk for patients before treatment, during radiotherapy planning, and during follow-up.
•Risk of HF increases following cardiac radiation doses above 20 Gy.•Anthracyclines increase HF rate by threefold independently of radiation.
Cardiovascular diseases are increasingly recognized as late effects of Hodgkin lymphoma (HL) treatment. The purpose of this study was to identify the risk factors for coronary heart disease (CHD) and ...to quantify the effects of radiation dose to the heart, chemotherapy, and other cardiovascular risk factors.
We conducted a nested case-control study in a cohort of 2,617 5-year HL survivors, treated between 1965 and 1995. Cases were patients diagnosed with CHD as their first cardiovascular event after HL. Detailed treatment information was collected from medical records of 325 cases and 1,204 matched controls. Radiation charts and simulation radiographs were used to estimate in-field heart volume and mean heart dose (MHD). A risk factor questionnaire was sent to patients still alive.
The median interval between HL and CHD was 19.0 years. Risk of CHD increased linearly with increasing MHD (excess relative risk ERR) per Gray, 7.4%; 95% CI, 3.3% to 14.8%). This results in a 2.5-fold increased risk of CHD for patients receiving a MHD of 20 Gy from mediastinal radiotherapy, compared with patients not treated with mediastinal radiotherapy. ERRs seemed to decrease with each tertile of age at treatment (ERR/Gy(<27.5years), 20.0%; ERR/Gy(27.5-36.4years), 8.8%; ERR/Gy(36.5-50.9years), 4.2%; P(interaction) = .149). Having ≥ 1 classic CHD risk factor (diabetes mellitus, hypertension, or hypercholesterolemia) independently increased CHD risk (rate ratio, 1.5; 95% CI, 1.1 to 2.1). A high level of physical activity was associated with decreased CHD risk (rate ratio, 0.5; 95% CI, 0.3 to 0.8).
The linear radiation dose-response relationship identified can be used to predict CHD risk for future HL patients and survivors. Appropriate early management of CHD risk factors and stimulation of physical activity may reduce CHD risk in HL survivors.
Objective
Cross‐sectional studies of optical coherence tomography (OCT) show that retinal nerve fiber layer (RNFL) thickness is reduced in multiple sclerosis (MS) and correlates with visual function. ...We determined how longitudinal changes in RNFL thickness relate to visual loss. We also examined patterns of RNFL thinning over time in MS eyes with and without a prior history of acute optic neuritis (ON).
Methods
Patients underwent OCT measurement of RNFL thickness at baseline and at 6‐month intervals during a mean follow‐up of 18 months at 3 centers. Low‐contrast letter acuity (2.5%, 1.25% contrast) and visual acuity (VA) were assessed.
Results
Among 299 patients (593 eyes) with ≥6 months follow‐up, eyes with visual loss showed greater RNFL thinning compared to eyes with stable vision (low‐contrast acuity, 2.5%: p < 0.001; VA: p = 0.005). RNFL thinning increased over time, with average losses of 2.9μm at 2 to 3 years and 6.1μm at 3 to 4.5 years (p < 0.001 vs 0.5–1‐year follow‐up interval). These patterns were observed for eyes with or without prior history of ON. Proportions of eyes with RNFL loss greater than test‐retest variability (≥6.6μm) increased from 11% at 0 to 1 year to 44% at 3 to 4.5 years (p < 0.001).
Interpretation
Progressive RNFL thinning occurs as a function of time in some patients with MS, even in the absence of ON, and is associated with clinically significant visual loss. These findings are consistent with subclinical axonal loss in the anterior visual pathway in MS, and support the use of OCT and low‐contrast acuity as methods to evaluate the effectiveness of putative neuroprotection protocols. ANN NEUROL 2010;67:749–760
The contemporary management of early-stage Hodgkin lymphoma (ES-HL) involves balancing the risk of late adverse effects of radiotherapy against the increased risk of relapse if radiotherapy is ...omitted. This study provides information on the risk of radiation-related cardiovascular disease to help personalize the delivery of radiotherapy in ES-HL.
We predicted 30-year absolute cardiovascular risk from chemotherapy and involved field radiotherapy in patients who were positron emission tomography (PET)-negative following three cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine chemotherapy within a UK randomized trial of PET-directed therapy for ES-HL. Cardiac and carotid radiation doses and chemotherapy exposure were combined with established dose-response relationships and population-based mortality and incidence rates.
Average mean heart dose was 4.0 Gy (range 0.1-24.0 Gy) and average bilateral common carotid artery dose was 21.5 Gy (range 0.6-38.1 Gy), based on individualized cardiovascular dosimetry for 144 PET-negative patients receiving involved field radiotherapy. The average predicted 30-year radiation-related absolute excess overall cardiovascular mortality was 0.56% (range 0.01%-6.79%; < 0.5% in 67% of patients and > 1% in 15%), whereas average predicted 30-year excess incidence was 6.24% (range 0.31%-31.09%; < 5% in 58% of patients and > 10% in 24%). For cardiac disease, the average predicted 30-year radiation-related absolute excess mortality was 0.42% (0.79% with mediastinal involvement and 0.05% without) and for stroke, it was 0.14%.
Predicted excess cardiovascular risk is small for most patients, so radiotherapy may provide net benefit. However, for a minority of patients receiving high doses of radiation to cardiovascular structures, it may be preferable to consider advanced radiotherapy techniques to reduce doses or to omit radiotherapy and accept the increased relapse risk. Individual assessment of cardiovascular and other risks before treatment would allow personalized decision making about radiotherapy in ES-HL.
AbstractObjectivesTo describe long term breast cancer mortality among women with a diagnosis of breast cancer in the past and estimate absolute breast cancer mortality risks for groups of patients ...with a recent diagnosis.DesignPopulation based observational cohort study.SettingRoutinely collected data from the National Cancer Registration and Analysis Service.ParticipantsAll 512 447 women registered with early invasive breast cancer (involving only breast and possibly axillary nodes) in England during January 1993 to December 2015, with follow-up to December 2020.Main outcome measuresAnnual breast cancer mortality rates and cumulative risks by time since diagnosis, calendar period of diagnosis, and nine characteristics of patients and tumours.ResultsFor women with a diagnosis made within each of the calendar periods 1993-99, 2000-04, 2005-09, and 2010-15, the crude annual breast cancer mortality rate was highest during the five years after diagnosis and then declined. For any given time since diagnosis, crude annual breast cancer mortality rates and risks decreased with increasing calendar period. Crude five year breast cancer mortality risk was 14.4% (95% confidence interval 14.2% to 14.6%) for women with a diagnosis made during 1993-99 and 4.9% (4.8% to 5.0%) for women with a diagnosis made during 2010-15. Adjusted annual breast cancer mortality rates also decreased with increasing calendar period in nearly every patient group, by a factor of about three in oestrogen receptor positive disease and about two in oestrogen receptor negative disease. Considering just the women with a diagnosis made during 2010-15, cumulative five year breast cancer mortality risk varied substantially between women with different characteristics: it was <3% for 62.8% (96 085/153 006) of women but ≥20% for 4.6% (6962/153 006) of women.ConclusionsThese five year breast cancer mortality risks for patients with a recent diagnosis may be used to estimate breast cancer mortality risks for patients today. The prognosis for women with early invasive breast cancer has improved substantially since the 1990s. Most can expect to become long term cancer survivors, although for a few the risk remains appreciable.
The optimum dose and fractionation in radiation therapy of curative intent for non-small cell lung cancer remains uncertain. We undertook a published data meta-analysis of randomized trials to ...examine whether radiation therapy regimens with higher time-corrected biologically equivalent doses resulted in longer survival, either when given alone or when given with chemotherapy.
Eligible studies were randomized comparisons of 2 or more radiation therapy regimens, with other treatments identical. Median survival ratios were calculated for each comparison and pooled.
3795 patients in 25 randomized comparisons of radiation therapy dose were studied. The median survival ratio, higher versus lower corrected dose, was 1.13 (95% confidence interval CI 1.04-1.22) when radiation therapy was given alone and 0.83 (95% CI 0.71-0.97) when it was given with concurrent chemotherapy (P for difference=.001). In comparisons of radiation therapy given alone, the survival benefit increased with increasing dose difference between randomized treatment arms (P for trend=.004). The benefit increased with increasing dose in the lower-dose arm (P for trend=.01) without reaching a level beyond which no further survival benefit was achieved. The survival benefit did not differ significantly between randomized comparisons where the higher-dose arm was hyperfractionated and those where it was not. There was heterogeneity in the median survival ratio by geographic region (P<.001), average age at randomization (P<.001), and year trial started (P for trend=.004), but not for proportion of patients with squamous cell carcinoma (P=.2).
In trials with concurrent chemotherapy, higher radiation therapy doses resulted in poorer survival, possibly caused, at least in part, by high levels of toxicity. Where radiation therapy was given without chemotherapy, progressively higher radiation therapy doses resulted in progressively longer survival, and no upper dose level was found above which there was no further benefit. These findings support the consideration of further radiation therapy dose escalation trials, making use of modern treatment methods to reduce toxicity.
A cardiac contouring atlas for radiotherapy Duane, Frances; Aznar, Marianne C; Bartlett, Freddie ...
Radiotherapy and oncology,
03/2017, Letnik:
122, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Abstract Background and purpose The heart is a complex anatomical organ and contouring the cardiac substructures is challenging. This study presents a reproducible method for contouring left ...ventricular and coronary arterial segments on radiotherapy CT-planning scans. Material and methods Segments were defined from cardiology models and agreed by two cardiologists. Reference atlas contours were delineated and written guidelines prepared. Six radiation oncologists tested the atlas. Spatial variation was assessed using the DICE similarity coefficient (DSC) and the directed Hausdorff average distance ( d → H , avg ). The effect of spatial variation on doses was assessed using six different breast cancer regimens. Results The atlas enabled contouring of 15 cardiac segments. Inter-observer contour overlap (mean DSC) was 0.60–0.73 for five left ventricular segments and 0.10–0.53 for ten coronary arterial segments. Inter-observer contour separation (mean d → H , avg ) was 1.5–2.2 mm for left ventricular segments and 1.3–5.1 mm for coronary artery segments. This spatial variation resulted in <1 Gy dose variation for most regimens and segments, but 1.2–21.8 Gy variation for segments close to a field edge. Conclusions This cardiac atlas enables reproducible contouring of segments of the left ventricle and main coronary arteries to facilitate future studies relating cardiac radiation doses to clinical outcomes.
Hodgkin lymphoma (HL) survivors are at increased risk of developing valvular heart disease (VHD). We evaluated the determinants of the risk and the radiation dose-response.
A case-control study was ...nested in a cohort of 1852 five-year HL survivors diagnosed at ages 15 to 41 years and treated between 1965 and 1995. Case patients had VHD of at least moderate severity as their first cardiovascular diagnosis following HL treatment. Control patients were matched to case patients for age, gender, and HL diagnosis date. Treatment and follow-up data were abstracted from medical records. Radiation doses to heart valves were estimated by reconstruction of individual treatments on representative computed tomography datasets. All statistical tests were two-sided.
Eighty-nine case patients with VHD were identified (66 severe or life-threatening) and 200 control patients. Aortic (n = 63) and mitral valves (n = 42) were most frequently affected. Risks increased more than linearly with radiation dose. For doses to the affected valve(s) of less than or equal to 30, 31-35, 36-40, and more than 40 Gy, VHD rates increased by factors of 1.4, 3.1, 5.4, and 11.8, respectively (P trend < .001). Approximate 30-year cumulative risks were 3.0%, 6.4%, 9.3%, and 12.4% for the same dose categories. VHD rate increased with splenectomy by a factor of 2.3 (P = .02).
Radiation dose to the heart valves can increase the risk of clinically significant VHD, especially at doses above 30 Gy. However, for patients with mediastinal involvement treated today with 20 or 30 Gy, the 30-year risk will be increased by only about 1.4%. These findings may be useful for patients and doctors both before treatment and during follow-up.
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