Importance of response to neoadjuvant chemotherapy in potentially curable colorectal cancer liver metastases

<p>Abstract</p> <p>Background</p> <p>Surgical resection of liver metastases arising from colorectal cancer is considered the only curative treatment option. However, many patients subsequently experience disease recurrence. We prospectively investigated whether neoadjuvant chemotherapy reduces the risk of recurrence following potentially curative liver resection. Special emphasis was directed to the importance of response.</p> <p>Methods</p> <p>50 patients with resectable liver metastases received neoadjuvant XELOX or FOLFOX4 for six cycles (3 months). Complete resection of liver metastases was intended thereafter. Assessments included response rate, postoperative morbidity and recurrence-free survival.</p> <p>Results</p> <p>An objective response was observed in 72% of all patients, including two complete responses. Chemotherapy was well tolerated and the majority of adverse events were mild to moderate (grade 1/2). Potentially curative R0 resection was performed in all patients and postoperative complications were observed in only 12%. The median recurrence-free survival was significantly influenced by tumor response with 24.7 months (95% CI: 4.50 to 44.97) in responding patients, 8.2 months (95% CI: 3.09 to 13.31) in patients with stable disease and 3.0 months (95% CI: 0 to 8.91) in patients with progressive disease.</p> <p>Conclusion</p> <p>These data suggest that neoadjuvant Oxaliplatin based chemotherapy provides high response rates without increased risk of perioperative morbidity. Response to chemotherapy can lead to long-term recurrence-free survival. Neoadjuvant chemotherapy may identify best candidates for a potentially curative treatment approach.</p

Recent advances in the biology and treatment of brain metastases of non-small cell lung cancer: summary of a multidisciplinary roundtable discussion

This article is the result of a round table discussion held at the European Lung Cancer Conference (ELCC) in Geneva in May 2017. Its purpose is to explore and discuss the advances in the knowledge about the biology and treatment of brain metastases originating from non-small cell lung cancer. The authors propose a series of recommendations for research and treatment within the discussed context

Establishment of a virtual transborder tumor board for cancer patients in Central and Southeastern Europe : an initiative of the Central European Cooperative Oncology Group (CECOG)

o establish a transborder virtual tumor board (VTB) fostering state-of-the-art management of cancer patients by exchanging knowledge and expertise among oncologists in Central and Southeastern Europe (CEE). Methods: We established and implemented a VTB based on the WebEx platform. This allowed for password-protected and secure upload of patient cases to be presented and discussed among colleagues from various oncology centers scattered throughout CEE in order to arrive at a recommendation for further diagnoses and/or treatment. Results: A total of 73 cases from 16 oncology centers located in 11 CEE countries were uploaded by 22 physicians71 were discussed over the course of 17 virtual meetings between June 2018 and May 2019 and 12 different kinds of malignant diseases were discussed with lung cancer (46.6%), melanoma (19.2%) and bladder cancer (13.6%) being the most commonly presented tumor entities. Of the discussed patients, 93.3% had stage IV disease at the time of presentation, 62.6% received chemotherapy or targeted treatment and 67.1% were treated with immune checkpoint inhibitors (ICPIs). The most common causes for presentation and discussion of patient cases were related to the use of ICPIs (80%). Conclusion: When the need for expertise exceeds locally available resources, web-based VTBs provide a feasible way to discuss patient cases and arrive at conclusions regarding diagnoses and/or treatment across large geographic distances. Moreover, VTBs provide an innovative way for proper, state-of-the-art management of patients with malignant diseases in times of social distancing and the resulting need for restricted interaction during the current SARS-CoV‑2 (severe acute respiratory syndrome coronavirus type 2) pandemic

Comparison of atmospheric aerosol optical depths measured with different sun photometers in three regions of Spitsbergen Archipelago

Results of multiyear (2011-2017) aerosol monitoring were used to compare the spectral aerosol optical depths (AOD) of the atmosphere, measured with different sun photometers at three Arctic stations on Spitsbergen Archipelago: Hornsund, Barentsburg, Ny-Ålesund. In addition to agreement of data in three regions, we also found that AOD in Barentsburg slightly (comparable to error) exceeds those from other stations located 110-120 km away. The AOD discrepancy is more pronounced in the shortwave part of the spectrum, indicating more abundant fine-mode aerosol in Barentsburg

Gliotoxin Targets Nuclear NOTCH2 in Human Solid Tumor Derived Cell Lines In Vitro and Inhibits Melanoma Growth in Xenograft Mouse Model

Deregulation of NOTCH2 signaling is implicated in a wide variety of human neoplasias. The current concept of targeting NOTCH is based on using gamma secretase inhibitors (GSI) to regulate the release of the active NOTCH intracellular domain. However, the clinical outcome of GSI remains unsatisfactory. Therefore we analyzed human solid tumor derived cell lines for their nuclear NOTCH activity and evaluated the therapeutic potential of the NOTCH2 transactivation inhibitor gliotoxin in comparison to the representative GSI DAPT. Electrophoretic mobility shift assays (EMSA) were used as a surrogate method for the detection of NOTCH/CSL transcription factor complexes. The effect of gliotoxin on cell viability and its clinical relevance was evaluated in vitro and in a melanoma xenograft mouse model. Cell lines derived from melanoma (518A2), hepatocellular carcinoma (SNU398, HCC-3, Hep3B), and pancreas carcinoma (PANC1) express high amounts of nuclear NOTCH2. Gliotoxin efficiently induced apoptosis in these cell lines whereas the GSI DAPT was ineffective. The specificity of gliotoxin was demonstrated in the well differentiated nuclear NOTCH negative cell line Huh7, which was resistant to gliotoxin treatment in vitro. In xenotransplanted 518A2 melanomas, a single day dosing schedule of gliotoxin was well tolerated without any study limiting side effects. Gliotoxin significantly reduced the tumor volume in early (83 mm3 vs. 115 mm3, p = 0.008) as well as in late stage (218 mm3 vs. 576 mm3, p = 0.005) tumor models. In conclusion, NOTCH2 appears to be a key target of gliotoxin in human neoplasias and gliotoxin deserves further evaluation as a potential therapeutic agent in cancer management

DNA methylation transcriptionally regulates the putative tumor cell growth suppressor ZNF677 in non-small cell lung cancers

In our study, we investigated the role of ZNF677 in non-small cell lung cancers (NSCLC). By comparing ZNF677 expression in primary tumor (TU) and in the majority of cases also of corresponding non-malignant lung tissue (NL) samples from > 1,000 NSCLC patients, we found tumor-specific downregulation of ZNF677 expression (adjusted p-values < 0.001). We identified methylation as main mechanism for ZNF677 downregulation in NSCLC cells and we observed tumor-specific ZNF677 methylation in NSCLC patients (p < 0.0001). In the majority of TUs, ZNF677 methylation was associated with loss of ZNF677 expression. Moreover, ZNF677 overexpression in NSCLC cells was associated with reduced cell proliferation and cell migration. ZNF677 was identified to regulate expression of many genes mainly involved in growth hormone regulation and interferon signalling. Finally, patients with ZNF677 methylated TUs had a shorter overall survival compared to patients with ZNF677 not methylated TUs (p = 0.013). Overall, our results demonstrate that ZNF677 is trancriptionally regulated by methylation in NSCLCs, suggest that ZNF677 has tumor cell growth suppressing properties in NSCLCs and that ZNF677 methylation might serve as prognostic parameter in these patients

Survival prediction using temporal muscle thickness measurements on cranial magnetic resonance images in patients with newly diagnosed brain metastases.

OBJECTIVES: To evaluate the prognostic relevance of temporal muscle thickness (TMT) in brain metastasis patients. METHODS: We retrospectively analysed TMT on magnetic resonance (MR) images at diagnosis of brain metastasis in two independent cohorts of 188 breast cancer (BC) and 247 non-small cell lung cancer (NSCLC) patients (overall: 435 patients). RESULTS: Survival analysis using a Cox regression model showed a reduced risk of death by 19% with every additional millimetre of baseline TMT in the BC cohort and by 24% in the NSCLC cohort. Multivariate analysis included TMT and diagnosis-specific graded prognostic assessment (DS-GPA) as covariates in the BC cohort (TMT: HR 0.791/CI [0.703-0.889]/p < 0.001; DS-GPA: HR 1.433/CI [1.160-1.771]/p = 0.001), and TMT, gender and DS-GPA in the NSCLC cohort (TMT: HR 0.710/CI [0.646-0.780]/p < 0.001; gender: HR 0.516/CI [0.387-0.687]/p < 0.001; DS-GPA: HR 1.205/CI [1.018-1.426]/p = 0.030). CONCLUSION: TMT is easily and reproducibly assessable on routine MR images and is an independent predictor of survival in patients with newly diagnosed brain metastasis from BC and NSCLC. TMT may help to better define frail patient populations and thus facilitate patient selection for therapeutic measures or clinical trials. Further prospective studies are needed to correlate TMT with other clinical frailty parameters of patients. KEY POINTS: • TMT has an independent prognostic relevance in brain metastasis patients. • It is an easily and reproducibly parameter assessable on routine cranial MRI. • This parameter may aid in patient selection and stratification in clinical trials. • TMT may serve as surrogate marker for sarcopenia