Background: Traditionally, patients with pulmonary embolism (PE) are initially treated in the hospital with low molecular weight heparin (LMWH). The results of a few small non‐randomized studies ...suggest that, in selected patients with proven PE, outpatient treatment is potentially feasible and safe. Objective: To evaluate the efficacy and safety of outpatient treatment according to predefined criteria in patients with acute PE. Patients and Methods: A prospective cohort study of patients with objectively proven acute PE was conducted in 12 hospitals in The Netherlands between 2008 and 2010. Patients with acute PE were triaged with the predefined criteria for eligibility for outpatient treatment, with LMWH (nadroparin) followed by vitamin K antagonists. All patients eligible for outpatient treatment were sent home either immediately or within 24 h after PE was objectively diagnosed. Outpatient treatment was evaluated with respect to recurrent venous thromboembolism (VTE), including PE or deep vein thrombosis (DVT), major hemorrhage and total mortality during 3 months of follow‐up. Results: Of 297 included patients, who all completed the follow‐up, six (2.0%; 95% confidence interval CI 0.8–4.3) had recurrent VTE (five PE 1.7% and one DVT 0.3%). Three patients (1.0%, 95% CI 0.2–2.9) died during the 3 months of follow‐up, none of fatal PE. Two patients had a major bleeding event, one of which was fatal intracranial bleeding (0.7%, 95% CI 0.08–2.4). Conclusion: Patients with PE selected for outpatient treatment with predefined criteria can be treated with anticoagulants on an outpatient basis. (Dutch Trial Register No 1319; http://www.trialregister.nl/trialreg/index.asp).
Abstract
Background
Skin cancer is common after radiotherapy among childhood cancer survivors (CCSs). We studied risks and risk factors for subsequent skin cancers, with emphasis on radiation dose, ...exposed skin surface area, and chemotherapeutic agents.
Methods
The DCOG-LATER cohort study includes 5-year Dutch CCSs diagnosed 1963–2001. Subsequent skin cancers were identified from record linkages with the Netherlands Cancer Registry and Dutch Pathology Registry. Incidence rates were compared with general population rates. Multivariable Cox regression models were used, applying a novel method of case-control sampling enabling use of tumor location in cohort analyses. All statistical tests were two-sided.
Results
Among 5843 CCSs, 259 developed 1061 basal cell carcinomas (BCCs) (standardized incidence ratio SIR = 29.8, 95% confidence interval CI = 26.3 to 33.6; excess absolute risk per 10 000 person-years (EAR) = 24.6), 20 had melanoma (SIR = 2.3, 95% CI = 1.4 to 3.5; EAR = 1.1), and 10 had squamous cell carcinoma (SIR = 7.5, 95% CI = 3.6 to 13.8; EAR = 0.8). Cumulative incidence of BCC 40 years after childhood cancer was 19.1% (95% CI = 16.6 to 21.8%) after radiotherapy vs 0.6% expected based on general population rates. After a first BCC, 46.7% had more BCCs later. BCC risk was associated with any radiotherapy to the skin compartment of interest (hazard ratio HR = 14.32, 95% CI = 10.10 to 20.29) and with estimated percentage in-field skin surface area (26–75%: HR = 1.99, 95% CI = 1.24 to 3.20; 76–100%: HR = 2.16, 95% CI = 1.33 to 3.53, vs 1–25% exposed; Ptrend among exposed = .002), but not with prescribed radiation dose and likelihood of sun-exposed skin-area. Of all chemotherapy groups examined, only vinca alkaloids increased BCC risk (HR = 1.54, 95% CI = 1.04 to 2.27).
Conclusion
CCSs have a strongly, 30-fold increased BCC risk. BCC risk appears to increase with increasing skin surface area exposed. This knowledge underscores the need for awareness by survivors and their health care providers.
Although colorectal adenomas serve as prime target for colorectal cancer (CRC) surveillance in other high-risk groups, data on adenoma risk after childhood cancer are lacking. We evaluated the risk ...of histologically confirmed colorectal adenomas among childhood cancer survivors. A secondary aim was to assess CRC risk.
The DCOG-LATER cohort study includes five-year Dutch childhood cancer survivors and a sibling comparison group (n = 883). Colorectal tumors were identified from the population-based Dutch Pathology Registry (PALGA). We calculated cumulative incidences of adenomas/CRCs for survivors and siblings. For adenomas, multivariable Cox regression models were used to evaluate potential risk factors. All statistical tests were two-sided.
Among 5843 five-year survivors (median follow-up = 24.9 years), 78 individuals developed an adenoma. Cumulative incidence by age 45 years was 3.6% (95% confidence interval CI = 2.2% to 5.6%) after abdominopelvic radiotherapy (AP-RT; 49 cases) vs 2.0% (95% CI = 1.3% to 2.8%) among survivors without AP-RT (28 cases; Pdifference = .07) and vs 1.0% (95% CI = 0.3% to 2.6%) among siblings (6 cases) (Pdifference = .03). Factors associated with adenoma risk were AP-RT (hazard ratio HR = 2.12, 95% CI = 1.24 to 3.60), total body irradiation (TBI; HR = 10.55, 95% CI = 5.20 to 21.42), cisplatin (HR = 2.13; 95% CI = 0.74 to 6.07 for <480 mg/m²; HR = 3.85, 95% CI = 1.45 to 10.26 for ≥480 mg/m²; Ptrend = .62), a hepatoblastoma diagnosis (HR = 27.12, 95% CI = 8.80 to 83.58), and family history of early-onset CRC (HR = 20.46, 95% CI = 8.10 to 51.70). Procarbazine was statistically significantly associated among survivors without AP-RT/TBI (HR = 2.71, 95% CI = 1.28 to 5.74). Thirteen CRCs occurred.
We provide evidence for excess risk of colorectal adenomas and CRCs among childhood cancer survivors. Adenoma risk factors include AP-RT, TBI, cisplatin, and procarbazine. Hepatoblastoma (familial adenomatous polyposis-associated) and family history of early-onset CRC were confirmed as strong risk factors. A full benefit-vs-harm evaluation of CRC screening among high-risk childhood cancer survivors warrants consideration.
In a prospective study, long term upper-limb morbidity, perceived disabilities in activities of daily life (ADL) and quality of life (QOL) were assessed before and 2 years after sentinel lymph node ...biopsy (SLNB) or axillary lymph node dissections (ALND) for breast cancer.
Two hundred and four patients with stage I/II breast cancer, mean age 55.6 years (SD: 11.6) entered the study and 181 patients (89%) could be evaluated after 2 years. Fifty-seven patients underwent SLNB (31%) and 124 patients underwent an ALND (69%). Assessments included pain, shoulder range of motion, muscle strength, arm volume, perceived shoulder disability in ADL and QOL.
Significant (P<0.05) changes between before and 2 years after surgery were found in almost all assessments of shoulder function, ADL and several QOL subscales. Patients in the ALND group showed significant more changes in range of motion (ROM), grip strength, arm volume, ADL and QOL physical- and role functioning, pain and sleeplessness and arm symptoms compared to the SLNB group. Multivariate linear regression analysis showed that ALND could predict decrease of ROM, grip strength, ADL and physical functioning (QOL) and increase of arm volume, pain and arm symptoms score (QOL). Radiation on the axilla predicts an additional decrease in shoulder ROM and increase of arm volume.
Two years after surgery for breast cancer, patients show significantly less treatment related upper limb morbidity, perceived disability in ADL and worsening of QOL after SLNB compared with ALND.
To evaluate prospectively the cardiotoxic effects of epirubicin-containing adjuvant chemotherapy in breast cancer patients.
Patients (median age, 46 years; range, 28 to 55 years) were treated with ...five cycles of fluorouracil, epirubicin (90 mg/m2), and cyclophosphamide (FEC) (group I, n = 21) or with four cycles of FEC followed by high-dose chemotherapy consisting of cyclophosphamide, thiotepa, and carboplatin (group II, n = 19). Locoregional radiotherapy was applied subsequently. Cardiac evaluation was performed before chemotherapy (T0), 1 month after chemotherapy, 1 month after radiotherapy (T2), and 1 year after start of chemotherapy (T3). Left ventricular ejection fraction (LVEF) was determined by radionuclide ventriculography and diastolic function by echocardiography. Autonomic function was assessed by 24-hour ECG registration for heart rate variability (HRV) analysis. Time-corrected QT (QTc) was assessed and N-terminal atrial natriuretic peptide (NT-ANP) and brain natriuretic peptide (BNP) were measured as biochemical markers of cardiac dysfunction.
No patient developed overt congestive heart failure (CHF) and the mean LVEF declined from 0.61 at T0 to 0.54 at T3 (P =.001), resulting in an LVEF below 0.50 (range, 0.42 to 0.49) in 17% of the patients, whereas 28% had a decline of more than 0.10. Plasma NT-ANP levels increased gradually from 237 pmol/L at T0 to 347 pmol/L at T3 (P <.01), whereas plasma BNP levels increased from 2.9 pmol/L to 5.1 pmol/L (P =.04). Mean QTc increased from 406 msec at T0 to 423 msec at T3 (P <.01). No persistent alterations were found in diastolic function and HRV.
Relatively low doses of epirubicin in adjuvant chemotherapy for breast cancer results in mild subclinical myocardial damage demonstrated by a decline in LVEF, an increase in natriuretic peptide levels, and an increase in QTc, which may indicate a long-term risk of CHF.
Incubator child: what's happening to me now? Uithoven-Dolsma, J; Cats, B P; Tanke, M ...
Tijdschrift voor ziekenverpleging,
1983-Apr-26, Letnik:
36, Številka:
9
Journal Article
To evaluate toxicity and cosmetic outcome (CO) in breast cancer survivors treated with three-dimensional conformal radiotherapy with a hypofractionated, simultaneous integrated boost (3D-CRT-SIB) and ...to identify risk factors for toxicity, with special focus on the impact of age.
Included were 940 consecutive disease-free patients treated for breast cancer (Stage 0–III) with 3D-CRT-SIB, after breast-conserving surgery, from 2005 to 2010. Physician-rated toxicity (Common Terminology Criteria for Adverse Events version 3.0) and CO were prospectively assessed during yearly follow-up, up to 5 years after radiotherapy. Multivariate logistic regression analyses using a bootstrapping method were performed.
At 3 years, toxicity scores of 436 patients were available. Grade ≥2 fibrosis in the boost area was observed in 8.5%, non-boost fibrosis in 49.4%, pain to the chest wall in 6.7%, and fair/poor CO in 39.7% of cases. Radiotherapy before chemotherapy was significantly associated with grade ≥2 boost fibrosis at 3 years (odds ratio OR 2.8, 95% confidence interval CI 1.3–6.0). Non-boost fibrosis was associated with re-resection (OR 2.2, 95% CI 1.2–4.0) and larger tumors (OR 1.1, 95% CI 1.0–1.1). At 1 year, chest wall pain was significantly associated with high boost dosage (OR 2.1, 95% CI 1.2–3.7) and younger age (OR 0.4, 95% CI 0.2–0.7). A fair/poor CO was observed more often after re-resection (OR 4.5, 95% CI 2.4–8.5), after regional radiotherapy (OR 2.9, 95% CI 1.2–7.1), and in larger tumors (OR 1.1, 95% CI 1.0–1.1).
Toxicity and CO are not impaired after 3D-CRT-SIB. Fibrosis was not significantly associated with radiotherapy parameters. Independent risk factors for fibrosis were chemotherapy after radiotherapy, re-resection, and larger tumor size. Re-resection was most predictive for worse CO. Age had an impact on chest wall pain occurrence.
To evaluate the presence of vascular damage in long-term childhood cancer survivors (CCS) and sibling controls, and to evaluate the association between vascular damage parameters and cancer treatment ...and influence of cardiovascular risk factors.
Vascular assessment was performed in 277 adult CCSs (median age at diagnosis, 9 years; range, 0 to 20 years; median current age, 28 years; range, 18 to 48 years) treated with potentially cardiovascular toxic anticancer treatment (ie, anthracyclines, platinum, and/or radiotherapy RT). Measurements included carotid- and femoral-wall intima-media thickness (IMT), flow-mediated vasodilatation of the brachial artery by ultrasound, assessment of endothelial and inflammatory marker proteins (including tissue-type plasminogen activator t-PA, plasminogen activator inhibitor type 1 PAI-I), and cardiovascular risk factors. CCS assessments were compared with those of 130 sibling controls (median age, 26 years; range, 18 to 51 years).
At a median of 18 years (range, 5 to 31 years) after treatment, carotid and femoral IMTs in CCSs were not different from those of controls. However, CCSs who received RT as part of their treatment regimen had increased carotid and femoral IMTs and higher t-PA and PAI-I levels, indicating vascular damage and persistent endothelial activation. Patients treated with RT to the neck or chest also had greater femoral IMT. Greater IMT was associated with presence of cardiovascular risk factors (eg, hypertension and overweight).
After potentially cardiovascular toxic anticancer treatment, CCSs who received RT showed signs of endothelial damage and an unfavorable cardiovascular risk profile compared with controls. CCSs treated with localized RT had increased IMT outside the primary irradiation field. These abnormalities are probably involved in the pathogenesis of cardiovascular morbidity in CCSs.
Abstract
Background
Pediatric cranial radiotherapy (CrRT) markedly increases risk of meningiomas. We studied meningioma risk factors with emphasis on independent and joint effects of CrRT dose, ...exposed cranial volume, exposure age, and chemotherapy.
Methods
The Dutch Cancer Oncology Group–Long-Term Effects after Childhood Cancer (DCOG-LATER) cohort includes 5-year childhood cancer survivors (CCSs) whose cancers were diagnosed in 1963–2001. Histologically confirmed benign meningiomas were identified from the population-based Dutch Pathology Registry (PALGA; 1990–2015). We calculated cumulative meningioma incidence and used multivariable Cox regression and linear excess relative risk (ERR) modeling.
Results
Among 5843 CCSs (median follow-up: 23.3 y, range: 5.0–52.2 y), 97 developed a benign meningioma, including 80 after full- and 14 after partial-volume CrRT. Compared with CrRT doses of 1–19 Gy, no CrRT was associated with a low meningioma risk (hazard ratio HR = 0.04, 95% CI: 0.01–0.15), while increased risks were observed for CrRT doses of 20–39 Gy (HR = 1.66, 95% CI: 0.83–3.33) and 40+ Gy (HR = 2.81, 95% CI: 1.30–6.08). CCSs whose cancers were diagnosed before age 5 versus 10–17 years showed significantly increased risks (HR = 2.38, 95% CI: 1.39–4.07). In this dose-adjusted model, volume was not significantly associated with increased risk (HR full vs partial = 1.66, 95% CI: 0.86–3.22). Overall, the ERR/Gy was 0.30 (95% CI: 0.03–unknown). Dose effects did not vary significantly according to exposure age or CrRT volume. Cumulative incidence after any CrRT was 12.4% (95% CI: 9.8%–15.2%) 40 years after primary cancer diagnosis. Among chemotherapy agents (including methotrexate and cisplatin), only carboplatin (HR = 3.55, 95% CI: 1.62–7.78) appeared associated with meningioma risk. However, we saw no carboplatin dose-response and all 9 exposed cases had high-dose CrRT.
Conclusion
After CrRT 1 in 8 survivors developed late meningioma by age 40 years, associated with radiation dose and exposure age, relevant for future treatment protocols and awareness among survivors and physicians.
In this study, we tested the hypothesis whether breast conserving therapy (BCT) compared with mastectomy is associated with a negative outcome in terms of distant metastases or death (DMD) and ...investigated the relation between locoregional recurrence (LRR) and DMD in young breast cancer (BC) patients. This study included a consecutive series of 536 patients ≤40 years of age at diagnosis with pathological T1N0-3M0 BC, treated between 1989 and 2005. A multistate survival model was used to evaluate the influences of local treatment and LRR on DMD, adjusted for potential prognostic factors. Patients were treated with mastectomy (
N
= 213) or BCT (
N
= 323). Median age at diagnosis was 36.3 years, with a median follow-up of 9.0 years. The 10-year actuarial cumulative incidence of DMD was 30.6 % after mastectomy and 26.3 % after BCT (
P
= 0.04). In total, 81 (15 %) LRRs were observed. After BCT, patients had a threefold higher risk of LRR than after mastectomy (HR 2.9; 95 % CI 1.6–5.3). Patients with LRR had a higher risk of DMD compared with patients without LRR (HR 5.5; 95 % CI 2.1–14.5). However, BCT was not negatively associated with DMD-after-LRR (HR 0.47; 95 % CI 0.2–1.1, BCT vs mastectomy). In conclusion, although LRR significantly affected DMD, the increased risk of LRR after BCT compared with mastectomy did not lead to a worse DMD outcome in BC patients ≤40 years of age.
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