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.

[Prolonged activated partial thromboplastin time (aPTT): not always indicative of increased risk of bleeding]. / Een verlengde geactiveerde partiële tromboplastinetijd (APTT): niet altijd een verhoogde bloedingsneiging.

A 69-year-old man of Jewish descent with a second local relapse of rectal carcinoma was found to have a markedly prolonged activated partial thromboplastin time (aPTT). Further evaluation revealed a homozygous factor XI deficiency. Despite various operations in the past he had never displayed any bleeding problems. Severe factor XI deficiency did not prevent venous thrombosis in this patient. The management of patients with prolonged aPTT is described and insight into the pathophysiology of factor XI deficiency is provided. The differential diagnosis in patients with a prolonged aPTT depends on their bleeding tendency. There is a large variability in bleeding tendency in patients with factor XI deficiency. Patients with factor XI deficiency and an increased bleeding tendency can be treated with antifibrinolytic agents prior to small interventions, such as tooth extraction, or with plasma prior to surgery.