Induction therapy with the MATRix regimen in patients with newly diagnosed primary diffuse large B-cell lymphoma of the central nervous system - an international study of feasibility and efficacy in routine clinical practice.

The MATRix chemoimmunotherapy regimen is highly effective in patients with newly diagnosed primary diffuse large B-cell lymphoma of the central nervous system (PCNSL). However, nothing is known about its feasibility and efficacy in everyday practice, where patients are more often older/frailer than those enrolled in clinical trials. We conducted a retrospective study addressing tolerability/efficacy of MATRix in 156 consecutive patients with newly diagnosed PCNSL treated outside a clinical trial. Median age and ECOG Performance Status of considered patients were 62 years (range 28-78) and 2 (range 0-4). The overall response rate after MATRix was 79%. Nine (6%) treatment-related deaths were recorded. After a median follow-up of 27.4 months (95% confidence interval [CI] 24.4-31.9%), the two-year progression-free and overall survival were 56% (95% CI 48.4-64.9%) and 64.1% (95% CI 56.7-72.5%) respectively. Patients not eligible for the IELSG32 trial were treated with lower dose intensity and had substantially worse outcomes than those fulfilling inclusion criteria. This is the largest series of PCNSL patients treated with MATRix outside a trial and recapitulates the IELSG32 trial outcomes in the non-trial setting for patients who fit the trial criteria. These data underscore the feasibility and efficacy of MATRix as induction treatment for fit patients in routine practice.

Salinomycin: Anti-tumor activity in a pre-clinical colorectal cancer model.

OBJECTIVES: Salinomycin is a polyether antibiotic with selective activity against human cancer stem cells. The impact of salinomycin on patient-derived primary human colorectal cancer cells has not been investigated so far. Thus, here we aimed to investigate the activity of salinomycin against tumor initiating cells isolated from patients with colorectal cancer. METHODS: Primary tumor-initiating cells (TIC) isolated from human patients with colorectal liver metastases or from human primary colon carcinoma were exposed to salinomycin and compared to treatment with 5-FU and oxaliplatin. TICs were injected subcutaneously into NOD/SCID mice to induce a patient-derived mouse xenograft model of colorectal cancer. Animals were treated either with salinomycin, FOLFOX regimen, or salinomycin and FOLFOX. Human colorectal cancer cells were used to delineate an underlying molecular mechanism of salinomycin in this tumor entity. RESULTS: Applying TICs isolated from human patients with colorectal liver metastases or from human primary colon carcinoma, we demonstrated that salinomycin exerts increased antiproliferative activity compared to 5-fluorouracil and oxaliplatin treatment. Consistently, salinomycin alone or in combination with FOLFOX exerts superior antitumor activity compared to FOLFOX therapy in a patient-derived mouse xenograft model of colorectal cancer. Salinomycin induces apoptosis of human colorectal cancer cells, accompanied by accumulation of dysfunctional mitochondria and reactive oxygen species. These effects are associated with expressional down-regulation of superoxide dismutase-1 (SOD1) in response to salinomycin treatment. CONCLUSION: Collectively, the results of this pre-clinical study indicate that salinomycin alone or in combination with 5-fluorouracil and oxaliplatin exerts increased antitumoral activity compared to common chemotherapy.

Sphincter-Preserving Surgery for Low Rectal Cancer: Do We Overshoot the Mark?

PURPOSE: Intersphincteric resection (ISR) is an alternative to abdominoperineal resection (APR) for a selected subset of patients with low rectal cancer, combining equivalent oncological outcome and sphincter preservation. However, functional results are heterogeneous and often imperfect. The aim of the present investigation was to determine the long-term functional results and quality of life after ISR. METHODS: One hundred forty-three consecutive patients who underwent surgery for low rectal cancer were analysed. Sixty patients received ISR and 83 patients APR, respectively. Kaplan-Meier estimate was used to analyse patients' survival. The EORTC QLQ-C30, -C29 and the Wexner score were used to determine functional outcome and quality of life. RESULTS: ISR and APR were both associated with comparable morbidity and no mortality. Patients' disease- and recurrence-free survival after ISR and APR were similar (p = 0.2872 and p = 0.4635). Closure of ileostomy was performed in 73% of all patients after ISR. Long-term outcome showed a rate of incontinence (Wexner score ≥10) in 66% of the patients. Despite this, patients' quality of life was significantly better after ISR compared to APR in terms of abdominal complaints and psycho-emotional functioning. CONCLUSIONS: ISR is technically feasible with acceptable postoperative morbidity rates. Functional results following ISR are compromised by incontinence as the most important complication. However, long-term quality of life is superior to APR, which should be considered when selecting patients for ISR.