Real-world implementation of a geriatric-specific ERAS protocol in patients undergoing colonic cancer surgery.

BACKGROUND: The aim of this single-center observational study was to evaluate the impact of implementing Enhanced Recovery After Surgery (ERAS) protocols, combined with systematic geriatric assessment and support, on surgical and oncological outcomes in patients aged 70 or older undergoing colonic cancer surgery. METHODS: Two groups were formed from an actively maintained database from all patients undergoing laparoscopic colonic surgery for neoplasms during a defined period before (standard group) or after (ERAS group) the introduction of an ERAS program associated with systematic geriatric assessment. The primary outcome was postoperative 90-day morbidity. Secondary outcomes were total length of hospital stay, initiated and completed adjuvant chemotherapy (AC) rate, and 1-year mortality rate. RESULTS: A total of 266 patients (135 standard and 131 ERAS) were included in the study. Overall 90-day morbidity and mean hospital stay were significantly lower in the ERAS group than in the standard group (22.1% vs. 35.6%, p = 0.02; and 6.2 vs. 9.3 days, p < 0.01, respectively). There were no differences in readmission rates and anastomotic complications. AC was recommended in 114 patients. The rate of initiated treatment was comparable between the groups (66.6% vs. 77.7%, p = 0.69). The rate of completed AC was significantly higher in the ERAS group (50% vs. 20%, p < 0.01) with a lower toxicity rate (57.1% vs. 87.5%, p = 0.002). The 1-year mortality rate was higher in the standard group (7.4% vs. 0.8%, p < 0.01). CONCLUSIONS: The combination of ERAS protocols and geriatric assessment and support reduces the overall morbidity rate and improves 12-month oncologic outcomes.

A chemogenomic approach to identify personalized therapy for patients with relapse or refractory acute myeloid leukemia: results of a prospective feasibility study.

Targeted next-generation sequencing (tNGS) and ex vivo drug sensitivity/resistance profiling (DSRP) have laid foundations defining the functional genomic landscape of acute myeloid leukemia (AML) and premises of personalized medicine to guide treatment options for patients with aggressive and/or chemorefractory hematological malignancies. Here, we have assessed the feasibility of a tailored treatment strategy (TTS) guided by systematic parallel ex vivo DSRP and tNGS for patients with relapsed/refractory AML (number NCT02619071). A TTS issued by an institutional personalized committee could be achieved for 47/55 included patients (85%), 5 based on tNGS only, 6 on DSRP only, while 36 could be proposed on the basis of both, yielding more options and a better rationale. The TSS was available in <21 days for 28 patients (58.3%). On average, 3 to 4 potentially active drugs were selected per patient with only five patient samples being resistant to the entire drug panel. Seventeen patients received a TTS-guided treatment, resulting in four complete remissions, one partial remission, and five decreased peripheral blast counts. Our results show that chemogenomic combining tNGS with DSRP to determine a TTS is a promising approach to propose patient-specific treatment options within 21 days.

Post-remission therapy of adults aged 60 and older with acute myeloid leukemia in first complete remission: role of treatment intensity on the outcome.

Although complete remission (CR) is achieved in 50 to 70% of older fit patients with acute myeloid leukemia (AML), consolidation therapy in this age group remains challenging. In this retrospective study, we aimed to compare outcome in elderly patients treated with different post-remission modalities, including allogenic and autologous hematopoietic stem cell transplantation (HSCT), intensive chemotherapy, and standard-dose chemotherapy (repeated 1 + 5 regimen). We collected data of 441 patients ≥ 60 years in first CR from a single institution. Median age was 67 years. Sixty-one (14%) patients received allo-HSCT, 51 (12%) auto-HSCT, 70 (16%) intensive chemotherapy with intermediate- or high-dose cytarabine (I/HDAC), and 190 (43%) 1 + 5 regimen. Median follow-up was 6.5 years. In multivariate analysis, allo-HSCT, cytogenetics, and PS had a significant impact on OS and LFS. In spite of a more favorable-risk profile, the patients who received I/HDAC had no significantly better LFS as compared with patients treated with 1 + 5 (median LFS 8.8 months vs 10.6 months, p = 0.96). In transplanted patients, median LFS was 13.3 months for auto-HSCT and 25.8 months for allo-HSCT. Pre-transplant chemotherapy with I/HDAC had no effect on the outcome. Toxicity was significantly increased for both transplanted and non-transplanted patients treated with I/HDAC, with more units of blood and platelet transfusion and more time spent in hospitalization, but no higher non-relapse mortality. This study shows that post-remission chemotherapy intensification is not associated with significantly better outcome as compared with standard-dose chemotherapy in elderly patients for whom, overall results remain disappointing.

Variability induced by the MR imager in dynamic contrast-enhanced imaging of the prostate.

PURPOSE: To evaluate the variability induced by the imager in discriminating high-grade (Gleason≥7) prostate cancers (HGC) using dynamic contrast-enhanced MRI. MATERIAL AND METHODS: We retrospectively selected 3T MRIs with temporal resolution<10 seconds and comprising T1 mapping from a prospective radiologic-pathologic database of patients treated by prostatectomy. Ktrans, Kep, Ve and Vp were calculated for each lesion seen on MRI using the Weinmann arterial input function (AIF) and three patient-specific AIFs measured in the right and left iliac arteries in pixels in the center of the lumen (psAIF-ST) or manually selected by two independent readers (psAIF-R1 and psAIF-R2). RESULTS: A total of 43 patients (mean age, 63.6±4.9 [SD]; range: 48-72 years) with 100 lesions on MRI (55 HGC) were selected. MRIs were performed on imager A (22 patients, 49 lesions) or B (21 patients, 51 lesions) from two different manufacturers. Using the Weinmann AIF, Kep (P=0.005), Ve (P=0.04) and Vp (P=0.01) significantly discriminated HCG. After adjusting on tissue classes, the imager significantly influenced the values of Kep (P=0.049) and Ve (P=0.007). Using patient-specific AIFs, Vp with psAIF-ST (P=0.008) and psAIF-R2 (P=0.04), and Kep with psAIF-R1 (P=0.03) significantly discriminated HGC. After adjusting on tissue classes, types of patient-specific AIF and side of measurement, the imager significantly influenced the values of Ktrans (P=0.0002), Ve (P=0.0072) and Vp (P=0.0003). For all AIFs, the diagnostic value of pharmacokinetic parameters remained unchanged after adjustment on the imager, with stable odds ratios. CONCLUSION: The imager induced variability in the absolute values of pharmacokinetic parameters but did not change their diagnostic performance.

Early prognostic factors in septic shock cancer patients: a prospective study with a proteomic approach.

BACKGROUND: Organ failures are the main prognostic factors in septic shock. The aim was to assess classical clinico-biological parameters evaluating organ dysfunctions at intensive care unit admission, combined with proteomics, on day-30 mortality in critically ill onco-hematology patients admitted to the intensive care unit for septic shock. METHODS: This was a prospective monocenter cohort study. Clinico-biological parameters were collected at admission. Plasma proteomics analyses were performed, including protein profiling using isobaric Tag for Relative and Absolute Quantification (iTRAQ) and subsequent validation by ELISA. RESULTS: Sixty consecutive patients were included. Day-30 mortality was 47%. All required vasopressors, 32% mechanical ventilation, 33% non-invasive ventilation and 13% renal-replacement therapy. iTRAQ-based proteomics identified von Willebrand factor as a protein of interest. Multivariate analysis identified four factors independently associated with day-30 mortality: positive fluid balance in the first 24 h (odds ratio = 1.06, 95% CI = 1.01-1.12, P = 0.02), severe acute respiratory failure (odds ratio = 6.14, 95% CI = 1.04-36.15, P = 0.04), von Willebrand factor plasma level > 439 ng/ml (odds ratio = 9.7, 95% CI = 1.52-61.98, P = 0.02), and bacteremia (odds ratio = 6.98, 95% CI = 1.17-41.6, P = 0.03). CONCLUSION: Endothelial dysfunction, revealed by proteomics, appears as an independent prognostic factor on day-30 mortality, as well as hydric balance, acute respiratory failure and bacteremia, in critically ill cancer patients admitted to the intensive care unit. Endothelial failure is underestimated in clinical practice and represents an innovative therapeutic target.

Adjuvant chemotherapy in pT1ab node-negative triple-negative breast carcinomas: Results of a national multi-institutional retrospective study.

BACKGROUND: Triple-negative breast cancers (TNBCs) are considered as associated with poor outcome, but prognosis of subcentimetric, node-negative disease remains controversial and evidence that adjuvant chemotherapy (CT) is effective in these small tumours remains limited. PATIENTS AND METHODS: Our objective was to investigate the impact of CT on survival in pT1abN0M0 TNBC. Patients were retrospectively identified from a cohort of 22,475 patients who underwent primary surgery in 15 French centres between 1987 and 2013. As rare pathological types may display very particular prognoses in these tumours, we retained only the invasive ductal carcinomas of no special type according to the last World Health Organisation (WHO) classification which is the most common TNBC histological type. End-points were disease-free survival (DFS) and metastasis-free survival (MFS). A propensity score for receiving CT was estimated using a logistic regression including age, tumour size, Scarff Bloom and Richardson (SBR) grade and lymphovascular invasion. RESULTS: Of a total of 284 patients with pT1abN0M0 ductal TNBC, 144 (51%) received CT and 140 (49%) did not. Patients receiving CT had more adverse prognostic features, such as tumour size, high grade, young age, and lymphovascular invasion. CT was not associated with a significant benefit for DFS (Hazard ratio, HR = 0.77 [0.40-1.46]; p = 0.419, log-rank test) or MFS (HR = 1.00 [0.46-2.19]; p = 0.997), with 5-year DFS and MFS in the group with CT versus without of 90% [81-94%] versus 84% [74-90%], and 90% [81-95%] versus 90% [83%-95%], respectively. Results were consistent in all supportive analyses including multivariate Cox model and the use of the propensity score for adjustment and as a matching factor for case-control analyses. CONCLUSIONS: This study did not identify a significant DFS or MFS advantage for CT in subcentimetric, node-negative ductal TNBC. Although current consensus guidelines recommend consideration of CT in all TNBC larger than 5 mm, clinicians should carefully discuss benefit/risk ratio with patients, given the unproven benefits.

Motor-evoked potential gain is a helpful test for the detection of corticospinal tract dysfunction in amyotrophic lateral sclerosis.

OBJECTIVE: The detection of upper motor neuron (UMN) dysfunction is necessary for the diagnosis of amyotrophic lateral sclerosis (ALS). However, signs of UMN dysfunction may be difficult to establish. This study aimed to determine whether motor-evoked potential (MEP) gain (MEP area/background electromyographic activity) represents an efficient alternative to assess UMN dysfunction. METHODS: MEP area, MEP/compound muscle action potential (CMAP) area ratio, and MEP gain were tested at different force levels in healthy control subjects and ALS patients. Receiver operating characteristic (ROC) curve analyses was used to determine the diagnostic utility of MEP gain and compare it to alternative techniques, namely, diffusion tensor imaging (DTI) and the triple stimulation technique (TST). RESULTS: MEP gain revealed a significant difference between the patients and healthy control subjects in contrast to MEP area and MEP/CMAP area ratio. The diagnostic utility of MEP gain was comparable with that of TST and superior to that of DTI. CONCLUSION: MEP gain can distinguish ALS patients from control subjects and may be helpful for the diagnosis of ALS. SIGNIFICANCE: MEP gain appears to be a useful adjunct test and noninvasive method for the assessment of corticospinal dysfunction.