Pooled Analysis of Clinical Outcome of Patients with Chemorefractory Metastatic Colorectal Cancer Treated within Phase I/II Clinical Studies Based on Individual Biomarkers of Susceptibility : a Single-Institution Experience

BACKGROUND: Patients with metastatic colorectal cancer (mCRC) refractory to standard therapies have a poor prognosis. In this setting, recruitment into clinical trials is warranted, and studies driven by selection according to individual tumor molecular characteristics are expected to provide added value. OBJECTIVE: We retrospectively analyzed data from patients with mCRC refractory to or following failure of standard therapies who were enrolled into phase I/II clinical studies at the Niguarda Cancer Center based on the presence of a specific molecular profile expected to represent the target of susceptibility to the experimental drug(s). PATIENTS AND METHODS: From June 2011 to May 2016, 2044 patients with mCRC underwent molecular screening. Eighty patients (3.9%) were enrolled in ad hoc studies; the median age was 60 years (range 36-86) and the median number of previous treatment lines was five (range 2-8). Molecular characteristics exploited within these studies were MGMT promoter hypermethylation (48.7%), HER2 amplification (28.8%), BRAF V600E mutation (20%), and novel gene fusions involving ALK or NTRK (2.5%). RESULTS: One patient (1%) had RECIST (Response Evaluation Criteria In Solid Tumors) complete response (CR), 13 patients (16.5%) experienced a partial response (PR), and 28 (35%) stable disease (SD). Median progression-free survival (PFS) was 2.8 months (range 2.63-3.83), with 24% of patients displaying PFS >5 months. Median growth modulation index (GMI) was 0.85 (range 0-15.61) and 32.5% of patients had GMI >1.33. KRAS exon 2 mutations were found in 38.5% of patients, and among the 78 patients with known KRAS status, those with wild-type tumors had longer PFS than those with mutated tumors (3.80 [95% CI 2.80-5.03] vs. 2.13 months [95% CI 1.77-2.87], respectively, p = 0.001). Median overall survival (OS) was 7.83 months (range 7.17-9.33) for all patients, and patients with KRAS wild-type tumors had longer OS than those with mutated tumors (7.83 [95% CI 7.33-10.80] vs. 7.18 months [95% CI 5.63-9.33], respectively, p = 0.06). CONCLUSIONS: This single-institution retrospective study indicates that in a heavily pretreated population approximately 4% of mCRC tumors display a potential actionable molecular context suitable for therapeutic intervention. Application of molecular selection is challenging but improves clinical outcome even in later lines of treatment

High dose chemotherapy and hematopoietic progenitor cell transplantation for breast cancer

Nowhere has there been more controversy in recent years than in the use of high dose chemotherapy (HDC) with autologous hematopoietic stem cell transplantation for breast cancer, both in the adjuvant setting and for advanced disease. Authors review and comment on the data from the studies so far reported and try to indicate what will be next in this field. They also discuss what may be the attitude to take in our everyday clinical practice, taking into account the availability of new chemotherapeutic agents and targeted therapies

Hydrogen embrittlement evaluation of micro alloyed steels by means of J-integral curve

The aim of this work is the evaluation of the hydrogen effect on the J-integral parameter. It is well-known that the micro alloyed steels are affected by Hydrogen Embrittlement phenomena only when they are subjected at the same time to plastic deformation and hydrogen evolution at their surface. Previous works have pointed out the absence of Hydrogen Embrittlement effects on pipeline steels cathodically protected under static load conditions. On the contrary, in slow strain rate tests it is possible to observe the effect of the imposed potential and the strain rate on the hydrogen embrittlement steel behavior only after the necking of the specimens. J vs. Δa curves were measured on different pipeline steels in air and in aerated NaCl 3.5 g/L solution at free corrosion potential or under cathodic polarization at -1.05 and -2 V vs. SCE. The area under the J vs. Δa curves and the maximum crack propagation rate were taken into account. These parameters were compared with the ratio between the reduction of area in environment and in air obtained by slow strain rate test in the same environmental conditions and used to rank the different steels