Survival of patients with deficient mismatch repair metastatic colorectal cancer in the pre-immunotherapy era.

BACKGROUND: Metastatic colorectal cancer patients with deficient mismatch repair (dMMR mCRC) benefit from immunotherapy. Interpretation of the single-arm immunotherapy trials is complicated by insignificant survival data during systemic non-immunotherapy. We present survival data on a large, comprehensive cohort of dMMR mCRC patients, treated with or without systemic non-immunotherapy. METHODS: Two hundred and eighty-one dMMR mCRC patients (n = 54 from three prospective Phase 3 CAIRO trials; n = 227 from the Netherlands Cancer Registry). Overall survival was analysed from diagnosis of mCRC (OS), from initiation of first-line (OS1) and second-line (OS2) systemic treatment. Cox regression analysis examined prognostic factors. As comparison for OS 2746 MMR proficient mCRC patients were identified. RESULTS: Of 281 dMMR patients, 62% received first-line and 26% second-line treatment. Median OS was 16.0 months (13.8-19.6) with antitumour therapy and 2.5 months (1.8-3.5) in untreated patients. OS1 was 12.8 months (10.7-15.2) and OS2 6.2 months (5.4-8.9) in treated dMMR patients. Treated dMMR patients had a 7.6-month shorter median OS than pMMR patients. CONCLUSION: Available data from immunotherapy trials lack a control arm with standard systemic treatment. Given the poor outcome compared to the immunotherapy results, our data strongly suggest a survival benefit of immunotherapy in dMMR mCRC patients.

Metastatic breast cancer in older patients: A longitudinal assessment of geriatric outcomes.

INTRODUCTION: Approximately 20% of older patients with breast cancer either present with metastatic disease or develop distant metastases after early breast cancer. The aims of this study were to assess the prevalence of psychosocial problems in older patients with metastatic breast cancer, and to assess longitudinal changes in functional status, psychosocial functioning, and quality of life. METHODS: For this prospective cohort study, patients with metastatic breast cancer aged 70 years and older were recruited in four Dutch hospitals. A baseline geriatric assessment was performed evaluating somatic, functional and psychosocial domains. Self-administered questionnaires were performed at baseline, three and six months: the Groningen Activity Restriction Scale, Geriatric Depression Scale, Loneliness scale, Apathy scale, Distress Thermometer and EORTC-QLQ-C30. Longitudinal changes on these scales were assessed by performing crude and adjusted linear mixed models. RESULTS: Of the 100 patients that were included and underwent a geriatric assessment, 85 patients completed the baseline self-administered questionnaires. Almost half of the patients (46%) had depressive symptoms, and up to 64% experienced distress. Apathy was present in 53%, and 36% experienced loneliness. Three- and six-month questionnaires were completed by 77 and 72 patients, respectively. Although a significant increase in loneliness between baseline and six months was seen, this size of this change was not clinically relevant. No other longitudinal changes were found. CONCLUSION: The prevalence of distress, depressive symptoms, apathy and loneliness in older patients with metastatic breast cancer is high. Timely detection, for which a geriatric assessment is effective, could potentially improve quality of life.

Copeptin, a surrogate marker for vasopressin, is associated with kidney function decline in subjects with autosomal dominant polycystic kidney disease.

BACKGROUND: Experimental studies have suggested that vasopressin plays a detrimental role in autosomal dominant polycystic kidney disease (ADPKD). It is, however, unknown whether endogenous vasopressin concentration is associated with kidney function decline in subjects with ADPKD. METHODS: We measured plasma copeptin (a marker of vasopressin) in 79 ADPKD subjects with renal function assessed during short-term follow-up by inulin clearance measured glomerular filtration rate (mGFR) and during long-term follow-up by Modification of Diet in Renal Disease (MDRD) equation estimated GFR (eGFR). RESULTS: In these subjects (43% male, age 36.8 ± 10.1 years, GFR 96.8 ± 18.2 mL/min/1.73 m(2)), median copeptin concentration at baseline was 2.71 [interquartile ranges (IQR) 1.63-5.46] pmol/L. Baseline copeptin concentration was inversely associated both with change in mGFR during follow-up for 3.3 (3.1-3.5) years, (R = -0.300, P = 0.01), as well as with change in eGFR during follow-up for 11.2 (4.5-14.3) years, (R = -0.302, P < 0.01). These associations were independent of age, gender and baseline GFR. Nine subjects started renal replacement therapy during follow-up of which eight had at baseline a copeptin concentration above the median in this population. CONCLUSION: In ADPKD subjects, a higher copeptin concentration is associated with kidney function decline during follow-up, suggesting that copeptin may be a new marker to predict kidney outcome in ADPKD.

No effect of enalapril on progression in autosomal dominant polycystic kidney disease.

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors are capable of reducing proteinuria and microalbuminuria with preservation of renal function in diabetic and non-diabetic renal disease. We designed a study investigating the effect of enalapril on the protection of renal function in autosomal dominant polycystic kidney disease (ADPKD). METHODS: We studied 61 normotensive and 28 hypertensive ADPKD patients. The normotensive group participated in a randomized double-blind placebo-controlled study, using enalapril. The hypertensive group was randomized for open label treatment with enalapril or the beta-blocker atenolol. The follow-up was 3 years, and renal function was established repetitively by measuring the clearance of inulin. RESULTS: In the normotensive group, renal function at baseline was 112 +/- 3 ml/min and decreased by -8 +/- 2 ml/min (P < 0.001). The loss of renal function in the patients treated with enalapril or placebo was similar (-7 +/- 3 vs -9 +/- 1 ml/min; P = 0.4). Although blood pressure significantly decreased with enalapril treatment, it had no effect on microalbuminuria. In the hypertensive group, renal function at baseline was 89 +/- 2 ml/min. The mean decline in renal function was -12 +/- 2 ml/min (P < 0.001), and was equal in patients treated with enalapril and those treated with atenolol. The patients treated with atenolol required more additional treatment to control blood pressure, but no difference on microalbuminuria was observed between the two treatments. CONCLUSION: This study was unable to detect a beneficial effect of ACE inhibition on loss of renal function in ADPKD patients.