Observational study of chemotherapy-induced Clostridium difficile infection in patients with lung cancer

Abstract

Background

Diarrhea post-antibiotic use is primarily attributed to Clostridium difficile infection (CDI)-induced mucosal lesions, and evidence of CDI in patients undergoing chemotherapy without prior antibiotic treatment is also increasing. However, few studies have investigated the relationship between chemotherapy use and diarrhea. This study aimed to determine whether the incidence of CDI increased in patients with lung cancer undergoing chemotherapy even without prior antibiotic treatment.

Methods

We conducted a retrospective study and investigated the presence of Clostridium difficile (C. difficile) and its toxins in patients who experience diarrhea during chemotherapy. If grade 2 or higher diarrhea was noted, a stool culture was performed to detect anaerobic organisms and C. difficile toxins A and B.

Results

A total of 345 consecutive patients (492 in terms of chemotherapy regimens) were enrolled in the study. Grade 2 or higher diarrhea was observed in patients using 36 (7.3%) of these regimens, among which CDI without prior antibiotic exposure was confirmed in patients using 8 regimens (22.2%).

Conclusions

CDI may remain undetected in patients undergoing chemotherapy even in those who had not received antibiotic treatment previously, unless due attention is paid to its possibility. Testing for C. difficile toxins is highly recommended to expedite timely treatment for diarrhea in such patients. Further studies are needed to clarify the relationship between chemotherapy drug use and CDI to facilitate prevention.

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miR-1268a regulates ABCC1 expression to mediate temozolomide resistance in glioblastoma

Abstract

Introduction

Temozolomide (TMZ) is the preferred chemotherapeutic drug approved for the Glioblastoma multiforme (GBM) treatment. However, resistance to TMZ is the most intractable challenge for treatment of GBM. Screening of miRNAs is becoming a novel strategy to reveal underlying mechanism of drug-resistance of human tumors.

Materials and methods

We conducted RNA sequencing (RNA-seq) for GBM cells treated continuously with TMZ 1 or 2 week or not. Bioinformatic analysis was used to predict targets of these altered miRNAs. Subsequently, we studied the potential role of miR-1268a in TMZ-resistance of GBM cells.

Results

Expression levels of 55 miRNAs were identified altering both after 1 and 2 weeks TMZ treatment. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted to illuminate the biological implication and related pathways of predicted target genes. We showed that miR-1268a was downregulated after TMZ treatment and targeted ABCC1/MRP1, a membrane transporter contributing to drug resistance, using dual-luciferase assay. Furthermore, we confirmed overexpression of miR-1268a inhibited protein translation of ABCC1 and restored upregulated expression of ABCC1 due to TMZ. Inversely, knockdown of miR-1268a increased ABCC1 at protein level and enhanced upregulation of ABCC1 with TMZ treatment. In addition, our data indicated that miR-1268a enhanced TMZ sensitivity in GBM cells.

Conclusion

Through RNA-seq analysis, we discovered miR-1268a and elucidated its role in modulating TMZ-resistance of GBM cells by targeting ABCC1.

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Control of metabolism by p53 – Cancer and beyond

Publication date: Available online 5 June 2018
Source:Biochimica et Biophysica Acta (BBA) - Reviews on Cancer
Author(s): Christiaan F. Labuschagne, Fabio Zani, Karen H. Vousden
p53 is an important tumour suppressor gene, with loss of p53 contributing to the development of most human cancers. However, the activation of p53 in response to stress signals underpins a role for p53 in diverse aspects of health and disease. Activities of p53 that regulate metabolism can play a role in maintaining homeostasis and protecting cells from damage – so preventing disease development. By contrast, either loss or over-activation of p53 can contribute to numerous metabolic pathologies, including aging, obesity and diabetes.



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Inter-observer variation of hippocampus delineation in hippocampal avoidance prophylactic cranial irradiation

Abstract

Background

Hippocampal avoidance prophylactic cranial irradiation (HA-PCI) techniques have been developed to reduce radiation damage to the hippocampus. An inter-observer hippocampus delineation analysis was performed and the influence of the delineation variability on dose to the hippocampus was studied.

Materials and methods

For five patients, seven observers delineated both hippocampi on brain MRI. The intra-class correlation (ICC) with absolute agreement and the generalized conformity index (CI_gen) were computed. Median surfaces over all observers' delineations were created for each patient and regional outlining differences were analysed. HA-PCI dose plans were made from the median surfaces and we investigated whether dose constraints in the hippocampus could be met for all delineations.

Results

The ICC for the left and right hippocampus was 0.56 and 0.69, respectively, while the CI_gen ranged from 0.55 to 0.70. The posterior and anterior-medial hippocampal regions had most variation with SDs ranging from approximately 1 to 2.5 mm. The mean dose (D_mean) constraint was met for all delineations, but for the dose received by 1% of the hippocampal volume (D_1%) violations were observed.

Conclusion

The relatively low ICC and CI_gen indicate that delineation variability among observers for both left and right hippocampus was large. The posterior and anterior-medial border have the largest delineation inaccuracy. The hippocampus D_mean constraint was not violated.

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New wind for the Spanish Federation of Scientific Oncological Societies (FESEO)

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nab-Paclitaxel Plus Carboplatin or Gemcitabine vs Gemcitabine Plus Carboplatin as First-Line Treatment for Patients With Triple-Negative Metastatic Breast Cancer: Results From the tnAcity Trial

Abstract

Background

Metastatic triple-negative breast cancer (mTNBC) has a poor prognosis and aggressive clinical course. tnAcity evaluated the efficacy and/safety of first-line nab-paclitaxel plus carboplatin (nab-P/C), nab-paclitaxel plus gemcitabine (nab-P/G), and gemcitabine plus carboplatin (G/C) in patients with mTNBC.

Patients and methods

Patients with pathologically confirmed mTNBC and no prior chemotherapy for metastatic BC received (1:1:1) nab-P 125 mg/m² plus C AUC 2, nab-P 125 mg/m² plus G 1000 mg/m², or G 1000 mg/m² plus C AUC 2, all on days 1, 8 q3w. Phase II primary endpoint: investigator-assessed progression-free survival (PFS); secondary endpoints included overall response rate (ORR), overall survival (OS), percentage of patients initiating cycle 6 with doublet therapy, and safety.

Results

In total, 191 patients were enrolled (nab-P/C, n = 64; nab-P/G, n = 61; G/C, n = 66). PFS was significantly longer with nab-P/C vs nab-P/G (median, 8.3 vs 5.5 months; HR, 0.59 [95% CI, 0.38-0.92]; P = .02) or G/C (median, 8.3 vs 6.0 months; HR, 0.58 [95% CI, 0.37-0.90]; P = .02). OS was numerically longer with nab-P/C vs nab-P/G (median, 16.8 vs 12.1 months; HR, 0.73 [95% CI, 0.47-1.13]; P = .16) or G/C (median, 16.8 vs 12.6 months; HR, 0.80 [95% CI, 0.52-1.22]; P = .29). ORR was 73%, 39%, and 44% respectively. In the nab-P/C, nab-P/G, and G/C groups, 64%, 56%, and 50% of patients initiated cycle 6 with a doublet. Grade ≥3 adverse events were mainly hematologic.

Conclusions

First-line nab-P/C was active in mTNBC and resulted in a significantly longer PFS and improved risk/benefit profile vs nab-P/G or G/C.

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Platinum-based neoadjuvant chemotherapy in triple-negative breast cancer: a systematic review and meta-analysis

Abstract

Background

The role of platinum-based neoadjuvant chemotherapy in triple-negative breast cancer (TNBC) patients is highly controversial and it is not endorsed by current guidelines. Our meta-analysis aimed to better elucidate its activity, efficacy and safety.

Material and methods

A systematic search of Medline, Web of Science and conferences proceedings up to 30 October 2017 was carried out to identify randomized controlled trials (RCTs) investigating platinum-based versus platinum-free neoadjuvant chemotherapy in TNBC patients. Using the fixed and random effects models, pooled odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CI) were calculated for pathological complete response (pCR, defined as ypT0/is pN0), event-free survival (EFS), overall survival (OS) and grade 3 and 4 adverse events (AEs: neutropenia, anemia, thrombocytopenia and neuropathy).

Results

Nine RCTs (N = 2109) were included. Overall, platinum-based neoadjuvant chemotherapy significantly increased pCR rate from 37.0% to 52.1% (OR 1.96, 95% CI 1.46–2.62, P < 0.001). Platinum-based neoadjuvant chemotherapy remained significantly associated with increased pCR rate also after restricting the analysis to the three RCTs (N = 611) that used the same standard regimen in both groups of weekly paclitaxel (with or without carboplatin) followed by anthracycline and cyclophosphamide (OR 2.53, 95% CI 1.37–4.66, P = 0.003). Conversely, among the 96 BRCA-mutated patients included in two RCTs, the addition of carboplatin was not associated with significantly increased pCR rate (OR 1.17, 95% CI 0.51–2.67, P = 0.711). Two RCTs (N = 748) reported survival outcomes: no significant difference in EFS (HR 0.72, 95% CI 0.49–1.06, P = 0.094) and OS (HR 0.86, 95% CI 0.46–1.63, P = 0.651) was observed.A significant higher risk of grade 3 and 4 hematological AEs, with no increased risk of grade 3 and 4 neuropathy was observed with platinum-based neoadjuvant chemotherapy.

Conclusion

In TNBC patients, platinum-based neoadjuvant chemotherapy is associated with significantly increased pCR rates at the cost of worse hematological toxicities. Platinum-based neoadjuvant chemotherapy may be considered an option in TNBC patients.

PROSPERO registration number

CRD42018080042.

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