Sequential chemotherapy in nonsmall-cell lung cancer: cisplatin and gemcitabine followed by docetaxel

Background: Improving results in nonsmall-cell lung cancer (NSCLC) will require the development of new drugs and strategies to combine available agents. On the basis of data indicating the activity of docetaxel as second-line therapy, a Phase II study was conducted to evaluate the efficacy and toxicity of the sequential combination of chemotherapy consisting of cisplatin (P) and gemcitabine (G) followed by docetaxel (DOC) in patients with advanced NSCLC. Methods: Patients with 1997 TNM stage IIIB (pleural effusion)/stage IV NSCLC, performance status (PS) of 0-1, and normal organ function were eligible. Therapy consisted of P at 75 mg/m(2) on Day 1 and G 1200 mg/m(2) on Days 1 and 8 every 3 weeks for 3 cycles followed, in nonprogressive patients, by DOC 30 mg/m(2) every week for 6 consecutive weeks every 8 weeks for 2 cycles. Results: Fifty-two eligible patients were enrolled (M/F, 39/13; stage IIIB/IV, 8/44; PS 0, 73%, PS 1, 27%; median age, 58 years; range, 36-73). The overall response rate was 36.5% (95% confidence interval [CI]: 23-49). The median overall survival was 11 months (95% CI: 9-13); the median progression-free survival was 6 months (95% CI: 5-7); and the 1- and 2-year survivals were 48% and 25%, respectively. One- and 2-year progression-free survivals were 12% and 8%, respectively. Both phases of the treatment protocol were well tolerated. Conclusions: P/G followed by weekly DOC is well tolerated and active as first-line therapy for NSCLC patients and provides a feasible chemotherapeutic option in this clinical setting

Brain metastases from solid tumors: disease outcome according to type of treatment and therapeutic resources of the treating center

<p>Abstract</p> <p>Background</p> <p>To evaluate the therapeutic strategies commonly employed in the clinic for the management of brain metastases (BMs) and to correlate disease outcome with type of treatment and therapeutic resources available at the treating center.</p> <p>Methods</p> <p>Four Cancer centres participated to the survey. Data were collected through a questionnaire filled in by one physician for each centre.</p> <p>Results</p> <p>Clinical data regarding 290 cancer patients with BMs from solid tumors were collected. Median age was 59 and 59% of patients had ≤ 3 brain metastases. A local approach (surgery and stereotactic radiosurgery) was adopted in 31% of patients. The local approach demonstrated to be superior in terms of survival compared to the regional/systemic approach (whole brain radiotherapy and chemotherapy, p = <.0001 for survival at 2 years). In the multivariate analysis local treatment was an independent prognostic factor for survival. When patients were divided into 2 groups whether they were treated in centers where local approaches were available or not (group A vs group B respectively, 58% of patients with ≤ 3 BMs in both cohorts), more patients in group A received local strategies although no difference in time to brain progression at 1 year was observed between the two groups of patients.</p> <p>Conclusions</p> <p>In clinical practice, local strategies should be integrated in the management of brain metastases. Proper selection of patients who are candidate to local treatments is of crucial importance.</p

Quantitative analysis of CT-perfusion parameters in the evaluation of brain gliomas and metastases

<p>Abstract</p> <p>Background</p> <p>The paper reports a quantitative analysis of the perfusion maps of 22 patients, affected by gliomas or by metastasis, with the aim of characterizing the malignant tissue with respect to the normal tissue. The gold standard was obtained by histological exam or nuclear medicine techniques. The perfusion scan provided 11 parametric maps, including Cerebral Blood Volume (CBV), Cerebral Blood Flow (CBF), Average Perfusion (P_mean) and Permeability-surface area product (PS).</p> <p>Methods</p> <p>The perfusion scans were performed after the injection of 40 ml of non-ionic contrast agent, at an injection rate of 8 ml/s, and a 40 s cine scan with 1 s interval was acquired. An expert radiologist outlined the region of interest (ROI) on the unenhanced CT scan, by using a home-made routine. The mean values with their standard deviations inside the outlined ROIs and the contralateral ROIs were calculated on each map. Statistical analyses were used to investigate significant differences between diseased and normal regions. Receiving Operating Characteristic (ROC) curves were also generated.</p> <p>Results</p> <p>Tumors are characterized by higher values of all the perfusion parameters, but after the statistical analysis, only the <it>PS</it>, <it>Pat</it>_{<it>Rsq </it>}(Patlak Rsquare) and <it>T</it>_{<it>peak </it>}(Time to Peak) resulted significant. ROC curves, confirmed both <it>Pat</it>_{<it>Rsq </it>}and <it>PS </it>as equally reliable metrics for discriminating between malignant and normal tissues, with areas under curves (AUCs) of 0.82 and 0.81, respectively.</p> <p>Conclusion</p> <p>CT perfusion is a useful and non invasive technique for evaluating brain neoplasms. Malignant and normal tissues can be accurately differentiated using perfusion map, with the aim of performing tumor diagnosis and grading, and follow-up analysis.</p

Treatment of recurrent malignant gliomas with fotemustine monotherapy: impact of dose and correlation with MGMT promoter methylation

<p>Abstract</p> <p>Background</p> <p>In recurrent malignant gliomas (MGs), a high rate of haematological toxicity is observed with the use of fotemustine at the conventional schedule (100 mg/m²weekly for 3 consecutive weeks followed by triweekly administration after a 5-week rest period). Also, the impact of O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status on fotemustine activity has never been explored in the clinical setting.</p> <p>Methods</p> <p>40 patients with recurrent pretreated MG were identified as being treated with fotemustine at doses ranging from 65 mg/m²to 100 mg/m². Patients were classified into 3 groups according to the dose of fotemustine received, from the lowest dosage received in group A, to the highest in group C. Analysis of MGMT promoter methylation in tumor tissue was successfully performed in 19 patients.</p> <p>Results</p> <p>Overall, 20% of patients responded to treatment, for a disease control rate (DCR, responses plus stabilizations) of 47.5%. Groups A and B experienced a response rate of 40% and 26.5% respectively, while the corresponding value for group C was 10%. Out of 19 patients, MGMT promoter was found methylated in 12 cases among which a DCR of 66.5% was observed. All 7 patients with unmethylated MGMT promoter were progressive to fotemustine.</p> <p>Conclusion</p> <p>Low-dose fotemustine at 65–75 mg/m²(induction phase) followed by 75–85 mg/m²(maintenance phase) has an activity comparable to that of the conventional schedule. By determination of the MGMT promoter methylation status patients might be identified who are more likely to benefit from fotemustine chemotherapy.</p

PSYChosomatic Medicine in ONcologIc and Cardiac Disease (PSYCHONIC) Study&mdash;A Retrospective and Prospective Observational Research Protocol

Psychosocial factors play an important role in non-communicable diseases (NCDs). This observational study is primarily aimed at assessing the relationship of psychological characteristics of patients with the outcomes of different NCDs, and to assess short-term psychotherapy (STP) efficacy in the real world. Methods: One hundred and forty patients with recent acute myocardial infarction, Takotsubo syndrome, or non-metastatic breast cancer and a control group of 140 age and sex-matched healthy subjects, will be enrolled. All subjects will be administered psychometric tests, quality of life tests, a specific body perception questionnaire, a dream questionnaire, and a projective test, the Six Drawing test at baseline and follow-up. All subjects with medical conditions will be asked to freely choose between an ontopsychological STP along with standard medical therapy and, whenever indicated, rehabilitation therapy or medical therapy plus rehabilitation alone. The study endpoints will be to evaluate: the relationship of the psychological characteristics of enrolled subjects with the outcomes of different NCDs, predictors of the choice of psychotherapy, and the efficacy of ontopsychological intervention on psychological and medical outcomes. Conclusion: This study will generate data on distinctive psychological characteristics of patients suffering from different CDs and their relationship with medical outcomes, as well as explore the efficacy of ontopsychological STP in these patients in the real world. (Number of registration: NCT03437642)

IORT with electrons as boost strategy during breast conserving therapy in limited stage breast cancer: long term results of an ISIORT pooled analysis

Linac-based intraoperative radiotherapy with electrons (IOERT) was implemented to prevent local recurrences after breast conserving therapy (BCT) and was delivered as an intraoperative boost to the tumor bed prior to whole breast radiotherapy (WBI). A collaborative analysis has been performed by European ISIORT member institutions for long term evaluation of this strategy

The serine protease HtrA1 is a novel prognostic factor for human mesothelioma

Aims: The objective of our study was to analyze the potential prognostic value of the expression of the serine protease HtrA1 and of EGFR in 70 malignant mesotheliomas. Materials & methods: Immunohistochemistry was used to determine the expression of HtrA1 and EGFR. Univariate and multivariate analyses were used to correlate expression of these molecular factors in combination with available clinicopathologic data to patient survival. Results: A positive, statistically significant relationship has been recorded between HtrA1 expression level and survival (p < 0.0001). By contrast, a negative relationship has been identified between EGFR expression and survival (p = 0.02). Moreover, extension of the tumor (T) and involvement of lymph nodes (N) advanced status (p = 0.001 and 0.002, respectively), as well as the sarcomatoid histotype (p = 0.005), correlated significantly with poor survival. Finally, by a multivariate Cox regression analysis, the only immunohistochemical parameter that resulted to influence overall survival was HtrA1 (p = 0.0001). Interestingly, the prognostic value of HtrA1 expression was completely independent from EGFR expression (p < 0.0001). Conclusion: This is the first study of the relationship between HtrA1 expression and survival of mesothelioma patients. The data obtained strongly indicate the utilization of HtrA1 expression as a prognostic parameter for mesothelioma and suggest this serine protease as a possible molecular target for the treatment of malignant mesotheliomas