On the Identification of the Causal Effects of Audit Activity under Measurement and Selection Biases

We propose a causal analysis based on a linear Structural Equation Model (SEM) of the effect of audits on the compliance level of tax payers. Generally, when the audit rule is not based on randomization and we also have unobserved variables, it is very likely to have confounding and the causal effect estimate can be biased, if not detected by inspection of the graphical model related to the SEM and removed. In addition, both measurement bias and selection bias arise naturally in real situation of observed data, thus increasing the complexity of the problem to be solved. In this case, the classical causal effect identification techniques (backdoor, frontdoor and instrumental variable) cannot be directly applied. To solve the causal effect identification problem in such a context, we extend the effect restoration method for the measurement bias, according to the selection recoverability condition. The proposed method, combining the two techniques, can be used to obtain an estimate of the causal effect closer to the real one, compared to the previous estimation approach adopted in this field. Moreover, the methodology can be applied also in other contexts, on problems sharing the same causal structure, or having an equivalent one

Induction chemotherapy with paclitaxel and cisplatin to concurrent radiotherapy and weekly paclitaxel in the treatment of loco-regionally advanced, stage IV (M0), head and neck squamous cell carcinoma. Mature results of a prospective study

<p>Abstract</p> <p>Background</p> <p>to evaluate activity and toxicity of a sequential treatment in advanced, non metastatic, mostly unresectable, head and neck squamous cell carcinoma.</p> <p>Methods</p> <p>Patients with loco-regionally advanced or unresectable, head and neck cancer, were prospectively treated with 3 courses of induction chemotherapy followed by concurrent chemoradiation. Induction chemotherapy consisted of paclitaxel 175 mg/m2 day 1 and cisplatin 75 mg/m2 day 2, given every 3 weeks, to a total of three courses. Curative radiotherapy started 4 weeks after the last cycle of chemotherapy with the goal of delivering a total dose ≥ 66 Gy. During RT weekly paclitaxel (40 mg/m2) was administered.</p> <p>Results</p> <p>The trial accrued 43 patients from January 1999 to December 2002. All patients received 3 courses of induction chemotherapy and the planned dose of radiotherapy. Thirty-eight patients were able to tolerate weekly paclitaxel during irradiation at least for 4 courses. After induction therapy there were 32 overall responses, 74.4% (23 partial and 9 complete); at completion of concomitant treatment overall responses were 42, 97.7% (20 partial and 22 complete). Median time to treatment failure was 20 months and the disease progression rate at 3 and 5 years was 33% and 23%, respectively. The median overall survival time was 24 months and 3 and 5 years overall survival rates were 37% and 26%, respectively. The major toxicity was mucositis.</p> <p>Conclusions</p> <p>This combined treatment was found to be feasible and active in advanced or unresectable, head and neck squamous cell carcinoma patients. Long-term results observed in this trial encourage to consider this approach in further investigation using newer radiation delivering technique and new molecularly agents.</p

Emerging Targeted Therapies for Castration-Resistant Prostate Cancer

Until recently, few therapeutic options were available for patients with castration-resistant prostate cancer (CRPC). Since 2010, four new molecules with a demonstrated benefit (sipuleucel-T, cabazitaxel, abiraterone, and denosumab) have been approved in this setting, and to-date several other agents are under investigation in clinical trials. The purpose of this review is to present an update of targeted therapies for CRPC. Presented data are obtained from literature and congress reports updated until December 2011. Targeted therapies in advanced phases of clinical development include novel androgen signaling inhibitors, inhibitors of alternative signaling pathways, anti-angiogenic agents, inhibitors that target the bone microenvironment, and immunotherapeutic agents. Radium-223 and MDV3100 demonstrated a survival advantage in phase III trials and the road for their introduction in clinical practice is rapidly ongoing. Results are also awaited for phase III studies currently underway or planned with new drugs given as monotherapy (TAK-700, cabozantinib, tasquinimod, PROSTVAC-VF, ipilimumab) or in combination with docetaxel (custirsen, aflibercept, dasatinib, zibotentan). The optimal timing, combination, and sequencing of emerging therapies remain unknown and require further investigation. Additionally, the identification of novel markers of response and resistance to these therapies may better individualize treatment for patients with CRPC

Bilateral Corneal Perforation in a Patient with Chronic Ocular Graft-Versus-Host Disease: A Case Report and Literature Review

Graft-versus-host disease (GVHD) is a serious complication that may occur in patients receiving allogeneic hematopoietic stem cell transplant (HSCT). GVHD occurs because of the immunological reaction between the donor’s T cells and the recipient’s antigens; GVHD may develop in different tissues, including the eye. Corneal perforation is an uncommon but vision-threatening manifestation of GVHD. We reported the case of a 65-year-old male patient who developed corneal perforation sequentially in both eyes 3 years after receiving HSCT. Conservative treatment with topical steroids and lubricants, bandage contact lens, and lacrimal punctal occlusion surgery resulted in the successful resolution of the corneal perforation with satisfactory visual recovery in the right eye. Therefore, corneal perforation can occur as the presenting manifestation of ocular GVHD. Regular ophthalmological examinations are recommended after HSCT to enable the early diagnosis of ocular GVHD and prompt treatment initiation

Challenges and perspectives in the multidisciplinary management of well-differentiated lung neuroendocrine tumours: a case report

Neuroendocrine tumours of the lung represent a distinct subgroup of primary lung neoplasms, characterized by particular morphologic, ultrastructural, immunohistochemical and molecular peculiarities and different biological behavior. A detailed pathological diagnosis including immunohistochemistry, Ki-67, mitotic rate and necrosis status can be helpful to identify the different subtypes. The optimal management of advanced well-differentiated lung neuroendocrine tumors is still debated and can be very challenging for the clinician. Currently, no established therapeutic algorithm exists for patients with unresectable or metastatic typical carcinoids and atypical carcinoids. To highlight the importance of a multidisciplinary management we report the case of a patient affected by unresectable lung neuroendocrine tumors, who has benefited from integration strategy, resulting in complete surgical excision of the tumour

Challenges with anti-PD1 agents in brain metastases management of NSCLC patients: a case report

Immunotherapy is dramatically changing the therapeutic landscape of advanced Non Small Cell Lung Cancer (NSCLC), with unprecedented results compared with chemotherapy. However, this novel treatment approach poses several novel challenges, including optimal treatment duration, coexistence with other conventional therapies (radiotherapy, targeted therapies, and chemotherapy), and activity in special populations, including patients with brain metastases (BMs). Traditionally, central nervous system (CNS) has been considered an immune-privileged organ, although recent evidences suggest a potential role of the immune system as exploitable target for cancer immunotherapy. Here we present a case of a non-squamous NSCLC patient with a rapid and long-lasting response to the anti-PD1 agent Nivolumab with a remarkable activity in the CNS, without previous brain irradiation

Vincenzo Consolo: punto de unión entre Sicilia y España. Los treinta años de Il sorriso dell'ignoto marinaio

Con ocasión del trigésimo aniversario de la publicación de Il sorriso dell’ignoto marinaio, hemos organizado las Jornadas Internacionales Vincenzo Consolo: punto de unión entre Sicilia y España. Los treinta años de Il sorriso dell’ignoto marinaio, que se celebraron en la Universitat de València los días 23 y 24 de octubre de 2006 y cuyas Actas ofrecemos en el presente volumen monográfico. De esta manera, cerramos el ciclo de dos años dedicado a la obra de Vincenzo Consolo, ciclo que iniciamos el año anterior con unas primeras Jornadas Internacionales, Lunaria vent’anni dopo, que también organizamos en la Universitat de València los días 24 y 25 de octubre de 2005, al cumplirse el vigésimo aniversario de su obra Lunaria

Predictors of long-term response to abiraterone in patients with metastastic castration-resistant prostate cancer: a retrospective cohort study

We aimed to identify clinical predictors of long-term response to abiraterone (defined as &gt;12 months drug exposure) in a retrospective cohort of metastatic castration-resistant prostate cancer patients treated in post-docetaxel setting at 24 Italian centers. The Cox proportional hazards model was used to analyze the association between clinical features and the duration of drug exposure. Results were expressed as hazard ratios (HR) with associated 95% confidence intervals (CI). A total of 143 patients met the inclusion criteria. Their median age was 73 years, median Gleason score 8 and median abiraterone exposure 20 months. At the univariate analysis, a significant correlation with the duration of abiraterone exposure was found for Gleason score (HR 0.82, 95% CI 0.71-0.96; p=0.012), PSA (HR 1.10, 95% CI 1.03-1.18; p=0.08) and lactic dehydrogenase levels (HR 1.22, 95% CI 1.02-1.46; p=0.027), while the association between lower alkaline phosphatase levels and treatment duration was marginally significant (HR 1.07, 95% CI 0.99-1.16; p=0.074). Only PSA and Gleason score were predictive of long-term treatment duration in the multivariate analysis. No other clinical factors resulted to be predictive of sustained response to abiraterone, including metastatic disease at diagnosis and visceral disease, suggesting that all subgroups of patients may derive a substantial clinical benefit from abiraterone treatment. These findings need to be validated in prospective, larger studies

Baseline neutrophilia, derived neutrophil-to-lymphocyte ratio (dNLR), platelet-to-lymphocyte ratio (PLR), and outcome in non small cell lung cancer (NSCLC) treated with Nivolumab or Docetaxel

Nivolumab is a novel therapeutic option in NSCLC, associated with a significant survival gain compared with Docetaxel. However, predictive biomarkers are lacking. The presence of systemic inflammation has been correlated with poor outcome in many cancer types. We aimed to evaluate whether there is a correlation between some indicators of inflammation and response to Nivolumab or Docetaxel in pre-treated NSCLCs. Data of 62 patients receiving Nivolumab or Docetaxel were analyzed. Baseline neutrophilia and thrombocytosis were not associated with response. High dNLR was associated with no response to Nivolumab, but not with Docetaxel, whereas high PLR correlated with low treatment response in both groups. Among refractory patients, a higher incidence of thrombocytosis, neutrophilia, high PLR, and high dNLR levels were observed compared with the overall population. This is one of the first reports in this field and suggests that indicators of inflammation might be included together with other predictive biomarkers in the baseline evaluation of patients candidate for immunotherapy