Routine chest X-rays have no additional value in the detection of relapse during routine follow-up of patients treated with chemotherapy for disseminated non-seminomatous testicular cancer.

BACKGROUND: The routine follow-up of patients with disseminated non-seminomatous testicular cancer (DNSTC) treated with the combination of orchidectomy, polychemotherapy, and if needed, resection of the residual mass, consists of regular physical examinations, chest X-rays (CXR) and tumor marker assessments. Most guidelines for this routine follow-up originate from multi-center trials. In order to estimate the value of CXR in the detection of tumor relapse after complete remission, we reviewed all patients with disseminated testicular cancer treated with chemotherapy at the University Hospital Groningen. PATIENTS AND METHODS: Three hundred and fifty-three consecutive patients with DNSTC treated between February 1977 and February 1999 at our institution were reviewed. Two hundred and ninety (82.2%) patients, who were in complete remission after cisplatin-containing chemotherapy followed by, if necessary, resection of the residual mass, entered this analysis. The follow-up schedule consisted of regular physical examinations, tumor marker assessment (lactate dehydrogenase, beta-human chorionic gonadotropin and alpha-FP) and CXR. In all patients the first diagnostic sign of tumor relapse was documented. RESULTS: During a median follow-up of 107 months (range 8-261) a tumor relapse was documented in 33 patients (11.4%). Median time to relapse was 17 months (range 6-179) after the start of chemotherapy. In 27 patients, tumor relapse was first detected by a rise in tumor markers. Two patients presented their relapse with neurological complaints. Both were diagnosed with brain metastasis. In four patients the relapse was detected by both increase in tumor markers and abnormalities in the physical examination. In none of the 33 relapsed patients was routine CXR during follow-up involved in the detection of tumor recurrence. All but one of the relapsed patients had elevated tumor markers before the start of chemotherapy. The total number of CXR made during follow-up in all 290 patients was 10 160; none were diagnostic for the detected relapses. CONCLUSIONS: These data suggest that routine CXR has no additional value in the detection of tumor relapses during follow-up after chemotherapy in the subset of patients who present their DNSTC with increased tumor markers and are in complete remission after treatment. In order to save valuable resources, CXR can be omitted from the follow-up schedule after chemotherapy for marker-positive non-seminomatous testicular cancer in complete remission.

Prospective evaluation of early cardiac damage induced by epirubicin-containing adjuvant chemotherapy and locoregional radiotherapy in breast cancer patients.

PURPOSE: To evaluate prospectively the cardiotoxic effects of epirubicin-containing adjuvant chemotherapy in breast cancer patients. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Adsorptive voltametry to determine platinum levels in plasma from testicular cancer patients treated with cisplatin.

Patients cured of metastatic testicular cancer with cisplatin chemotherapy may suffer late adverse effects even after 20 years. The cause of these late adverse effects has not been elucidated yet. One cause might be prolonged tissue retention of platinum in these patients. Therefore, an extremely sensitive method for measuring platinum in plasma was used to investigate whether platinum is still detectable in plasma 10 to 20 years after cisplatin chemotherapy. High-pressure decomposition of plasma is followed by adsorptive voltametric determination of platinum, with a limit of quantification of 6 pg/g plasma. This procedure appeared suitable for the measurement of platinum in 44 former patients with platinum levels ranging from 22 to 140 pg/g plasma. This method is approximately 6000 times more sensitive than the standard flameless atomic absorption spectrophotometry (AAS) method. The platinum levels of these 44 patients were significantly elevated when compared with 20 control patients who were cured of testicular cancer but did not receive cisplatin chemotherapy (p < 0.001). There was a significant correlation between plasma platinum concentrations and follow-up time after cisplatin administration (r = -0.658, p < 0.001). This study shows that patients with testicular cancer who were treated with cisplatin can retain platinum in their body for at least 20 years. More data are needed to investigate whether there is a relation between the prolonged retention of platinum and long-term toxicity.

Cardiovascular morbidity in long-term survivors of metastatic testicular cancer.

PURPOSE: To determine whether long-term survivors of metastatic testicular cancer have an increased risk of cardiovascular morbidity more than 10 years after chemotherapy. PATIENTS AND METHODS: Eighty-seven patients treated with cisplatin-containing chemotherapy before 1987 who were in remission for at least 10 years and whose ages were

Circulating plasma platinum more than 10 years after cisplatin treatment for testicular cancer.

We have shown in patients cured from metastatic testicular cancer that up to 20 years after administration of cisplatin-containing chemotherapy, circulating platinum is still detectable in plasma. This finding may influence the development of long-term, treatment-related side-effects.

Long-term chemotherapy-related cardiovascular morbidity.

As a consequence of the successful use of chemotherapy in the treatment of curable neoplasms such as germ cell tumours and malignant lymphomas, and the increasing application of primary and adjuvant chemotherapy for various tumour types, the number of patients with a prolonged life expectancy after treatment is rising. Attention to long-term side-effects, including cardiovascular toxicity, is therefore of growing importance. In this review we evaluate the literature on long-term cardiovascular toxicity related to chemotherapy in adult patients. Two categories of patient with favourable life expectancy have been reviewed, namely patients cured of metastatic disease by chemotherapy and patients treated with adjuvant chemotherapy. In the first category, the literature on long-term cardiovascular morbidity in survivors of metastatic testicular cancer and lymphomas is discussed, while in the second category this is done for patients treated with adjuvant chemotherapy for breast and colon cancer. As well as the direct toxic effects of chemotherapy on the cardiovascular system, the indirect toxic effects such as chemotherapy-related metabolic changes that may cause cardiovascular morbidity are also discussed.

Detection of anthracycline-induced cardiotoxicity.

The use of anthracyclines, a group of potent anti-cancer agents incorporated into the treatment of a wide variety of solid and haematological tumours, is limited by its cardiotoxicity that can result in congestive heart failure (CHF). The best method to detect cardiotoxicity at an early stage in order to prevent severe deterioration, is still an unsolved problem. Although endomyocardial biopsy is considered to be the most sensitive and specific test for this purpose, its use is limited by its invasiveness. In daily practice, oncologists make use of parameters of systolic function (left ventricular ejection fraction, or fractional shortening) to detect cardiotoxicity, but these methods are not able to identify cardiotoxicity at an early stage. Based on increasing knowledge into the pathophysiology of anthracycline-induced cardiotoxicity and heart failure in general, new methods including the determination of diastolic function parameters, anti-myosin scintigraphy, assessment of heart rate variability, and the determination of biochemical markers have been proposed to identify patients at risk of the development of CHF in an early stage. However, most of these newer methods have not yet been adequately evaluated to allow them to be recommended for use in routine clinical practice.

Early detection of anthracycline induced cardiotoxicity in asymptomatic patients with normal left ventricular systolic function: autonomic versus echocardiographic variables.

OBJECTIVE: To investigate left ventricular dysfunction in patients who had been treated with anthracycline based chemotherapy. METHODS: Autonomic function was compared with left ventricular diastolic function in 20 asymptomatic women with normal systolic function (left ventricular ejection fraction (LVEF) > 0.50) treated for breast cancer with high dose anthracycline based chemotherapy, and 20 age matched healthy controls. Left ventricular diastolic function was assessed echocardiographically by measuring the early peak flow velocity to atrial peak flow velocity ratio, isovolumic relaxation time, and deceleration time. Heart rate variability analysis was assessed for time domain and frequency domain parameters. RESULTS: The mean (SD) age of the patients was 45 (7) years and the mean LVEF was 0.59 (0.06). The time interval after the end of chemotherapy was 29 (27) months. One or more diastolic variables were abnormal in 50% of the patients. Heart rate variability was abnormal in 85% of patients. Mean values of both time domain and frequency domain parameters were decreased (p < 0.05), in particular the parasympathetic indices. CONCLUSIONS: Autonomic impairment occurs in a large proportion of asymptomatic patients with normal systolic left ventricular function after high dose anthracycline based chemotherapy. In particular, heart rate variability analysis may be a sensitive tool to identify the first signs of cardiotoxicity in these patients.