Maria Cossu Rocca

Hormone-receptor expression and activity of trastuzumab with chemotherapy in HER2-positive advanced breast cancer patients

The relationship between quantitative immunohistochemical hormone receptor expression and response to the combination of trastuzumab with chemotherapy in HER2‐positive advanced breast cancer is currently unknown.

Functional genomics uncover the biology behind the responsiveness of head and neck squamous cell cancer patients to cetuximab

Purpose: To identify the tumor portrait of the minority of head and neck squamous cell carcinoma (HNSCC) patients with recurrent–metastatic (RM) disease who upon treatment with platinum-based chemotherapy plus cetuximab present a long-lasting response. Experimental Design: The gene expression of pretreatment samples from 40 HNSCC-RM patients, divided in two groups [14 long-progression-free survival (PFS) and 26 short-PFS (median = 19 and 3 months, respectively)], was associated with PFS and was challenged against a dataset from metastatic colon cancer patients treated with cetuximab. For biologic analysis, we performed functional and subtype association using gene set enrichment analysis, associated biology across all currently available HNSCC signatures, and inferred drug sensitivity using data from the Cancer Genomic Project. Results: The identified genomic profile exhibited a significant predictive value that was essentially confirmed in the single publicly available dataset of cetuximab-treated patients. The main divergence between long- and short-PFS groups was based on developmental/differentiation status. The long-PFS patients are characterized by basal subtype traits such as strong EGFR signaling phenotype and hypoxic differentiation, further validated by the significantly higher association with the hypoxia metagene. The short-PFS patients presented a strong activation of RAS signaling confirmed in an in vitro model of two isogenic HNSCC cell lines sensitive or resistant to cetuximab. The predicted drug sensitivity for all four EGFR inhibitors was higher in long- versus short-PFS patients (P range: <0.0022–1e−07). Conclusions: Our data uncover the biology behind response to platinum-based chemotherapy plus cetuximab in RM-HNSCC cancer and may have translational implications improving treatment selection. Clin Cancer Res; 22(15); 3961–70. ©2016 AACR. See related commentary by Chau and Hammerman, p. 3710

Gamow states as continuous linear functionals over analytical test functions

The space of analytical test functions ξ, rapidly decreasing on the real axis (i.e., Schwartz test functions of the type S on the real axis), is used to construct the rigged Hilbert space (RHS) (ξ,H,ξ′). Gamow states (GS) can be defined in RHS starting from Dirac’s formula. It is shown that the expectation value of a self‐adjoint operator acting on a GS is real. We have computed exactly the probability of finding a system in a GS and found that it is finite. The validity of recently proposed approximations to calculate the expectation value of self‐adjoint operators in a GS is discussed.

Physical representations of Gamow states in a rigged Hilbert space

Abstract Resonant Gamow States (GS) are constructed in a rigged Hilbert space (RHS) (ξ, H , ξ′) starting from Diracs formula. It is shown that the expectation value of a self-adjoint operator acting on a GS is real. The validity of recently proposed approximations to calculate expectation values on resonant states is discussed.

Role of CT perfusion in monitoring and prediction of response to therapy of head and neck squamous cell carcinoma

This review aims to summarize the technique and clinical applications of CT perfusion (CTp) of head and neck cancer. The most common pathologic type (90%) of head and neck cancer is squamous cell carcinoma (HNSCC): its diagnostic workup relies on CT and MRI, as they provide an accurate staging for the disease by determining tumour volume, assessing its extension, and detecting of lymph node metastases. Compared with conventional CT and MRI, CTp allows for obtaining measures of tumour vascular physiology and functional behaviour, and it has been demonstrated to be a feasible and useful tool in predicting local outcomes in patients undergoing radiation therapy and chemotherapy and may help monitor both treatments.

Prognostic value of circulating tumor cells in primary and metastatic breast cancer

In patients with breast cancer, there is evidence correlating the presence of circulating tumor cells (CTCs) with disease-free survival, progression-free survival and overall survival. The detection of CTCs may be useful in gaining a better understanding of the mechanisms of tumor growth and in the improvement of patient management. This review analyzes the prognostic and predictive relevance of CTCs through the principal published studies, cytometric techniques and nucleic acid-based approaches to detect CTCs, phenotypic expression of specific receptors, molecular pathways and genetic signatures for potential tailored therapies.

Retrospective analysis of factors influencing oncologic outcome in 590 patients with early-intermediate glottic cancer treated by transoral laser microsurgery.

The purpose of this study was to identify the factors influencing oncologic outcomes for patients with early‐intermediate glottic cancer treated by transoral laser microsurgery (TLM).

The incidence and relative risk of cardiovascular toxicity in patients treated with new hormonal agents for castration-resistant prostate cancer

AIM New hormonal agents are available for treating metastatic castration-resistant prostate cancer (mCRPC). We aim to define the incidence and relative risk (RR) of cardiovascular events in mCRPC patients treated with these agents. METHODS Prospective studies were identified by searching the MEDLINE/PubMed, Cochrane Library and ASCO Meeting abstracts. Combined relative risks (RRs) and 95% confidence intervals (CIs) were calculated using fixed- or random-effects methods. RESULTS We included six articles in this meta-analysis covering a total of 6735 patients who were used to evaluate cardiac toxicity. The use of new hormonal agents was associated with an increased risk of all grades of such toxicity (RR=1.32, 95% CI, 1.08-1.60; p=0.006) compared to a placebo, even if the absolute difference in terms of incidence was small at 14.8% versus 11.5%, respectively. No increased risk of grade 3-4 events (RR=1.35, 95% CI, 0.90-2.03; p=0.15) was observed. A total of 7830 patients were used to evaluate hypertension, and it was found that the use of new hormonal agents compared to a placebo was associated with an increased risk of all-grades (RR=1.84, 95% CI, 1.37-2.46; p<0.001) and grade 3-4 events (RR=1.77, 95% CI, 1.13-2.77; p=0.01). The absolute incidence was 12.5% versus 7.5% for all-grades and 3.7% versus 2.4% for grade 3-4. CONCLUSIONS This analysis revealed a significant increase in the incidence and RR of cardiovascular toxicity in mCRPC treated with new hormonal agents as opposed to a placebo, even though the occurrence of all- and grade 3-4 events rose only 14% and 4%, respectively. Follow-ups for the onset of treatment-related cardiovascular events should therefore be considered in these patients.

Algorithm to predict postoperative complications in oropharyngeal and oral cavity carcinoma

Preoperative data in patients with oral cavity/oropharyngeal cancer may predict postoperative complications that may modify therapeutic choices and improve patient care.

Future challenges in head and neck cancer: from the bench to the bedside?

HNC is the 11th most frequent carcinoma with a world-wide yearly incidence exceeding over half a million cases [1], a 10:1 male gender predilection and country specific variability [2]. The principal risk factors are tobacco and alcohol use and, in a growing population without these exposures, HPV infection. While much progress has been made in understanding the molecular basis of cancer, the 5-year mortality of head and neck cancer has remained approximately 50%. To this date we have not been able to translate as much of our basic science knowledge into significant disease altering therapeutic strategies in terms of local, loco-regional, functional and overall survival. Challenges remain in all aspects of head and neck cancer management: prevention, diagnosis, surgical and non-surgical treatment.