EGFR inhibitor as second-line therapy in a patient with mutant RAS metastatic colorectal cancer: circulating tumor DNA to personalize treatment

A 47-year-old male patient presented in March 2016 to our unit with a palpable painless left supraclavicular mass. A whole-body contrastenhanced computed tomography (CT) scan revealed a left supraclavicular lymphadenopathy, transverse colon thickening (3 cm), multiple chest and abdominal lymphadenopathies, and peritoneal carcinomatosis. Colonoscopy revealed a bleeding area at 15 cm from the anal verge; biopsy was performed, and the result was negative for a primary cancer

Crossing-over to imatinib 800 mg in a patient with GIST, after progression with standarddosage: a case report

A 69-years-old patient underwent radical surgery to remove a lesion of small bowel with histological diagnosis of malignant primary stromal cancer of the gastro-intestinal wall (GIST). After a disease-free survival of 25 months instrumental evidence of loco-regional recurrence was detected with subsequent resection of the ileum: histology confirmed recurrent high risk GIST. After 34 months, TC scan showed peritoneal and hepatic progression of disease. Treatment with imatinib was started with standard dose of 400 mg/day, obtaining partial response on peritoneum and liver radiological complete response, after 5 months of therapy. Patient continued treatment with the same dose for 20 months. When radiological progression was detected we decided to increase imatinib to 800 mg/day based on the results of two principal phase III studies. Radiological partial response was reached after three months of therapy. Actually patient is still in treatment with imatinib showing stable disease with good tolerance

Clinical outcome and prognostic factors in renal medullary carcinoma: a pooled analysis from 18 years of medical literature

INTRODUCTION: We describe clinical features and prognostic factors of renal medullary carcinoma (RMC) by performing a pooled analysis of all reported cases since 1995. METHODS: A systematic search was performed to identify all articles describing patients with medullary renal cancer until February 2013. Survivals were estimated using Kaplan-Meier method with 95% confidence intervals and compared across the groups using the log-rank test. The following factors were evaluated using the Cox proportional hazards model: association of extension of disease at diagnosis, response to therapy, and surgical treatment of primary tumour with overall. RESULTS: A total 47 articles were selected; these described 165 patients with RMC plus 1 from our centre. The median age was 21 years and 98% of cases had the sickle cell trait. The mean size of the primary tumours was 6.0 cm, with an involvement of loco-regional lymph nodes in 71% of cases. The overall survival at diagnosis was 4.0 months in metastatic patients and 17.0 months in non-metastatic patients. Patients who received platinum-paclitaxel-gemcitabine had longer control of the disease when compared to topoisomerase inhibitors or targeted therapies. The multivariate analysis confirmed that the advanced stage at diagnosis increased the risk of death of about threefold. CONCLUSION: RMC is a tumour with poorer prognosis; based on these results, platinum-based chemotherapy is the preferred systemic treatment. Even if radical nephrectomy as an up-front strategy did not report a survival benefit, it may be considered to palliate local symptoms and to perform a correct diagnosis

BRAFV600E mutation positive metastatic melanoma in a young woman treated with anti-BRAF/anti MEK combination: a case report

The recent Combi-v [1] and Combi-d [2,3], phase III randomized trials, showed, respectively, an OS benefit with Dabrafenib/Trametinib combination versus Vemurafenib and an improvement in PFS and ORR with the same combination versus Dabrafenib alone, in BRAF V600E/K mutation positive metastatic or unresectable cutaneous melanoma. We report the case of a young patient with metastatic melanoma treated with anti- BRAF/antiMEK combination

The promise of liquid biopsy in cancer: a clinical perspective

The clinical utility of liquid biopsy in cancer treatment will increase as circulating tumor cells (CTCs) analysis move from the enumeration to the real-time measurement of tumor characteristics. Intratumor heterogeneity is becoming increasingly recognized as a major drawback to the shift to personalized medicine. Spatial and temporal heterogeneity might be reflected by the serial assessment of CTCs. Indeed, the developing technologies for CTCs analysis now allow digital genomic and next-generation sequencing approaches, able to differentiate molecular subtypes of the disease and to monitor genetic variation over time. The liquid biopsy of cancer might offer a real-time assessment of tumor biology, providing the opportunity to serially evaluate patients most likely to benefit from targeted drugs based on a dynamic characterization of the disease at the molecular level. Although hurdles remain before liquid biopsy is seen in routine clinical practice, the information derived from CTCs may facilitate the real-time identification of actionable mutations in cancer leading the way toward personalized medicine

Relationship and predictive role of the dual expression of FGFR and IL-8 in metastatic renal cell carcinoma treated with targeted agents

Background/Aim: The expression of IL-8 and FGFR has been related to prognosis and pathological features in renal cell carcinoma. We investigated the relationship between IL-8 and FGFR and the outcome in metastatic renal cell carcinoma (mRCC) patients. Materials and Methods: Clinical data and histological samples of patients affected by mRCC and treated with targeted agents were reviewed. The expression of proteins was assessed using immunohistochemistry. Results: FGFR1, FGFR2, and IL-8 were found to be expressed in 16%, 30%, and 50% of cases, respectively. Significant correlations were found between selected proteins. A lack of expression of FGFR2 and IL8 was found to be correlated with increased progression-free survival (PFS). The survival rate at 24 months was 44%, 38%, and 79% of those expressing both, one, or none of the evaluated proteins, respectively (p=0.047). Conclusion: This analysis found a relationship between the expression of IL-8 and FGFR2 in mRCC patients treated with targeted agents

The rationale for liquid biopsy in colorectal cancer: focus on circulating tumor cells

Capturing circulating tumor cells (CTCs) and/or circulating tumor DNA from blood, which represents a precious source of biological material derived from both primary and metastatic tumors, has been named a 'liquid biopsy'. While the circulating tumor DNA might be more representative of the bulk of the metastatic tumor, CTCs are thought to reflect more of the metastases-initiating cells. Consequently, a liquid biopsy made of tumor cells and tumor DNA that is able to track cancer evolution, as a fingerprint of the patient's individual tumor, and is easy to perform at every stage of the disease course, sounds attractive. This article mainly focuses on the applications of CTCs to track tumor dynamics in real time using colorectal cancer as a model system. The analysis of viable CTCs at DNA, RNA and protein levels, as well as their expansion in vitro, may allow deep investigation of the features of metastases-initiating cells

Communicating cancer diagnosis and prognosis: When the target is the elderly patient-a GIOGer study

Background: Effective communication to cancer patients allows better emotional response to diagnosis, coping with health professionals and compliance to treatment. We lack specific studies on patterns of clinical communication in elderly patients, their involvement in decision making and the role of their families. Patients and methods: Structured interviews to collect information on diagnosis and prognosis disclosure, satisfaction with information, compliance to disease experience and willingness toward receiving more information and coping, were administered to patients age 65 years and older and receiving chemotherapy. Results: Six hundred and twenty two patients completed the interviews and were evaluated. Four hundred and twelve (66.2%) were informed, 210 (33.8%) were not informed. Information was associated with age, degree of education, geographical area, ECOG-PS, tumour site and family composition and the patient's perception of being supported in the disease experience. The majority of the patients consider their families as the main source of support in the disease experience (86.5%), wish to have a family member participating in oncology consultation (79.1%) and consider the information received complete and understandable or clear and reassuring (80%). Receiving adequate information facilitates a better patient-health professional relationship for 84.8% of the patients. 63% of the patients dealt positively with cancer and 62.2% showed positive expectations for the future. Informed patients refer better expectation than those not informed. Conclusion: Our study underlines the importance of clinical information for older cancer patients and the need to involve family members in the processes of diagnosis and prognosis disclosure and decision making. Health professionals must consider specific age-related issues including social, cultural and emotional aspects and understand the role that the family members play in the disease experience of elderly patients. Competent caring for elderly cancer patients must provide adequate information and emotional support not only to the patients but also to their family to assure appropriateness of care. © 2008 Elsevier Ltd. All rights reserved

Transient disappearance of RAS mutant clones in plasma: A counterintuitive clinical use of EGFR inhibitors in RAS mutant metastatic colorectal cancer

Genomic studies performed through liquid biopsies widely elucidated the evolutionary trajectory of RAS mutant clones under the selective pressure of EGFR inhibitors in patients with wild type RAS primary colorectal tumors. Similarly, the disappearance of RAS mutant clones in plasma has been more recently reported in some patients with primary RAS mutant cancers, supporting for the first time an unexpected negative selection of RAS mutations during the clonal evolution of mCRC. To date, the extent of conversion to RAS wild type disease at the time of progression has not been clarified yet. As a proof of concept, we prospectively enrolled mCRC patients progressing under anti-VEGF based treatments. Idylla™system was used to screen RAS mutations in plasma and the wild type status of RAS was further confirmed through IT-PGM (Ion Torrent Personal Genome Machine) sequencing. RAS was found mutant in 55% of cases, retaining the same plasma mutation as in the primary tumor at diagnosis, while it was found wild-type in 45%. Four patients testing negative for RAS mutations in plasma at the time of progression of disease (PD) were considered eligible for treatment with EGFR inhibitors and treated accordingly, achieving a clinical benefit. We here propose a hypothetical algorithm that accounts for the transient disappearance of RAS mutant clones over time, which might extend the continuum of care of mutant RAS colorectal cancer patients through the delivery of a further line of therapy

Status of correlation between BMI and response to immunocheck-point inhibitor in advanced non-small-cell lung cancer

Recently, clinical evidence has raised BMI as an emerging prognostic factor for immunotherapy, regardless of cancer types. In this article we rewirw current data about correlation between BMI and response to immunocheck-point inhibitor in advanced non-small-cell lung cance