Tumori Journal

Among the adjuvant options to be proposed to patients with stage I seminoma after orchiectomy, the administration of a single cycle of carboplatin, at the dosage reaching an area under the curve of 7 mg/mL/min (AUC7), is a relatively recent introduction in clinical practice.

On April 1, 2016, we performed a systematic review of the literature to identify studies on the use of AUC7 carboplatin in the adjuvant setting for stage I seminoma patients. The studies were identified by searching the PubMed electronic database from July 2005 up to April 2016. The aim of this review is to clarify the state of art of this adjuvant option.

Adjuvant AUC7 carboplatin is an effective adjuvant treatment, able to reduce relapse rate in stage I seminoma patients. The heterogeneity of the methods for estimation and measurement of glomerular filtration rate represents an important issue in the administration of the optimal dose of carboplatin.

Even with the lack of validated prognostic factors for relapses, a risk-adapted choice is commonly used to identify the optimal patient to be proposed this treatment.

One cycle of AUC7 carboplatin is an effective, feasible, and safe adjuvant option to be discussed with stage I seminoma patients.

Accurate measurement of outcomes is essential to monitor the effectiveness of public health policies. In Italy, the Ministry of Health has chosen 30-day mortality after major surgical or medical procedures as the main outcome measure, pooling all pulmonary resections for malignancy in a single category. The present audit evaluated all pulmonary resections performed over a 13-year period in a single institution to assess the immediate (30-day mortality) and long-term (5-year survival) outcomes according to type and stage of disease and extent of surgery.

We analyzed the results of 4,234 first pulmonary resections performed from 2003 to 2015 for lung cancer (2,636), lung metastases (1,080), other primary cancers (259) and benign diseases (259). The median follow-up of cancer patients was 4.1 years.

Overall 30-day mortality was 1.1%, being 1.2% for lung cancer, 0.3% for lung metastases, 3.5% for pneumonectomies, 1% for lobectomies, and 0.5% for sublobar resections. Among lung cancer patients, 30-day mortality was 0.7% for simple anatomical resections, 2.8% for complex resections, 0.7% for stage I, and 1.6% for higher stages. Overall 5-year survival was 56% for lung cancer, 49% for lung metastases, and 53% for other primary cancers (p = 0.03). According to the surgical procedure for lung cancer, 5-year survival was 60%, 55% and 36% for lobectomies, segmentectomies and pneumonectomies, respectively (p<0.0001).

For better monitoring of thoracic surgery outcomes in a real-world setting, we suggest evaluating lung cancer separately from other thoracic malignancies, and including 5-year survival rates stratified by resection volume and surgical procedure complexity.

To investigate disease-free survival (DFS) and prognostic factors following the administration of postoperative (chemo)radiotherapy in patients with early-stage cervical cancers.

The medical records of 1,069 patients from 10 participating institutions were reviewed. Statistically and clinically established factors were considered as candidates for constructing the prediction model. This model was validated, using bootstrapping to correct for optimistic bias.

The 5-year DFS rate was 81.1%, with a median follow-up period of 59.6 months. The statistically significant prognostic factors were as follows: pelvic lymph node metastasis, histologic type, parametrial invasion, lymphovascular space invasion, and tumor size. The nomogram for DFS was constructed, and it demonstrated a good discrimination performance, with an internally validated concordance index of 0.72.

Our predictive model exhibited accurate predictions and may be useful in designing clinical trials to study if further chemotherapy can reduce the recurrence of disease in high-risk patients.

To identify clinical factors stratifying the risk of tumor upgrading to increasing patterns of the tumor grading system in low-risk prostate cancer (PCa).

We evaluated the records of 438 patients who underwent radical prostatectomy. Associations between clinical factors and tumor upgrading were assessed by the univariate and multivariate multinomial logistic regression model.

Low-risk PCa included 170 cases (38.8%) and tumor upgrading was detected in 111 patients (65.3%): 72 (42.4%) had pathology Gleason pattern (pGP) 3 + 4, 27 (15.9%) pGP 4 + 3, and 12 (7.1%) pGP 4 + 4. Prostate- specific antigen (PSA) and proportion of positive cores (P+) were independent predictors of upgrading to high-risk disease. These factors also stratified the risk of tumor upgrading to the increasing patterns of the tumor grading system. The model allowed the identification of pGP 4 + 4. The main difference between high-risk PCa and other upgraded tumors related to PSA load (odds ratio 2.4) that associated with high volume disease in the specimen.

Low-risk PCa is a heterogeneous population with significant rates of tumor upgrading. Significant clinical predictors stratifying the risk of tumor upgrading to increasing patterns of the grading system included PSA and P+. These factors allowed the identification of the subset hiding high-grade disease requiring further investigations before delivering active treatments.

Breast is the leading site of cancer onset and death in Italy. Cases diagnosed in stage IV or that progress in metastatic phase represent a specific and challenging task for oncologists. Estimates on the burden of breast cancer (BC) in stage IV in Italy are not available.

We applied mortality-incidence age-specific ratios measured in the United States in 2013 for BC in stage IV at diagnosis (de novo) or following a previous diagnosis in a localized stage (distant recurrence) to the age-specific BC deaths observed in Italy in 2014. The US mortality-prevalence age-specific ratios were used for estimating de novo and distant recurrence prevalent metastatic BC.

In 2014 in Italy, there were 12,330 deaths due to BC. We estimated that in the same year about 3400 BC were newly diagnosed in stage IV (7.1% of all the new cases); moreover, more than 10,000 other BC progressed to stage IV. In addition, in 2014, the overall number of BC in stage IV, whenever diagnosed, was about 37,100 (5.6% of all the estimated prevalent BC).

These estimates quantify, for the first time in Italy, the burden of BC in stage IV, at diagnosis or during the clinical course, providing useful figures for clinicians and policy makers.

To report long-term effects on anorectal function and bowel disorders and late toxicity rate of preoperative chemoradiotherapy in patients with locally advanced rectal cancer.

Between 2000 and 2016, 201 patients treated with different neoadjuvant schedules of chemotherapy and radiotherapy doses were retrospectively analyzed. The Memorial Sloan–Kettering Cancer Center score was used for the evaluation of anal sphincter function.

The median follow-up time was 68 months (interquartile range 35–113 months). Radical resection was performed in 188 (93.5%) patients with a pathologic complete response rate of 26.4%. Overall sphincter function resulted excellent in 105 (52.2%) patients, good in 13 (6.5%), fair in 10 (5.0%), and poor (incontinence) in 40 (19.9%), with a persistent stoma rate of 16.4%. A further evaluation on 194 patients showed an improvement of sphincter function after 2 years in 11.9% of them. Seventy-three patients presenting stoma or poor sphincter function were re-evaluated for quality of life (QoL) indexes. Twenty-one (29%), 19 (26%), and 24 (33%) of them declared some variations concerning well-being, fatigue, and ability to perform daily activities. The 5-year overall survival, disease-free survival, and local recurrence rates were 88.0% ± 2.6%, 86.3% ± 2.5%, and 94.6% ± 1.9%, respectively.

In our study, neoadjuvant chemoradiotherapy was associated with good results in terms of sphincter function, late toxicities, and QoL indexes. A routine use of assessment scales could contribute to a better selection of patients with increased risk of developing functional disorders who could benefit from neoadjuvant therapy.

Radium-223 (²²³Ra) chloride, an alpha emitter, has been shown to improve overall survival (OS) and pain control, and to delay skeletal-related events, in patients with castration-resistant prostate cancer (CRPC) and bone metastases. Our retrospective observational study presents the first Italian experience on the efficacy and safety of ²²³Ra therapy in routine clinical practice.

A total of 83 patients with metastatic CRPC were treated with ²²³Ra at 3 Italian centers between August 2013 and August 2016. ²²³Ra-chloride (55 kBq/kg) was administered every 4 weeks for a total of 6 cycles. Primary endpoints were OS and progression-free survival (PFS). Secondary endpoints included toxicity, pain evaluation using numeric rating scale (NRS), symptomatic skeletal-related events and biomarkers response.

Patients had a median age of 75 (range 53–89) years. The majority of men showed a Gleason score of 7, 8, or 9. Forty-one patients completed 6 treatment cycles; 33 stopped treatment before completing 6 cycles. Nine were still receiving therapy at the time of data collection. At the end of therapy, NRS pain scores significantly improved (p < .000001). OS was a mean of 10.1 months, while median OS had not been attained. According to Kaplan-Meier estimation, OS and PFS were 17.5 and 7.7 months, respectively. There was a significant correlation between OS and PFS with the number of ²²³Ra cycles; patients receiving all 6 cycles experienced the major benefit from the therapy. ²²³Ra was well-tolerated.

²²³Ra alpha therapy is an important therapeutic option for men with CRPC and symptomatic skeletal metastases.

Age-related non-communicable chronic diseases (ArCDs) are the leading cause of mortality. The major metabolic risk factor for their development is the metabolic syndrome (MetS), defined as a clustering of risk factors of metabolic origin such as abdominal obesity, high blood pressure, dyslipidemia and high fasting glycemia. There is increasing observational and experimental evidence that improving diet and the use of metformin (a calorie-restriction mimetic drug) may modify the risk of developing MetS and ArCD. We designed a phase III randomized controlled trial (the Me.Me.Me trial) to evaluate the effect of a comprehensive lifestyle intervention (including moderate physical activity and a Mediterranean-macrobiotic diet) and the effect of treatment with metformin in the prevention of ArCDs in healthy people with MetS. This report describes the scientific protocol of this trial.

The design of the study is 2 × 2 factorial with 2,000 volunteers to be randomized into 4 equal groups of 500 each, which are allocated to the following treatments: metformin (1,700 mg/day) + active lifestyle intervention, placebo + active lifestyle intervention, metformin (1,700 mg/day) alone, and placebo alone. The metformin/placebo component of the study is double blind. The study is planned for a term of 5 years.

The Me.Me.Me. trial is ongoing and recruitment of participants is underway. No patient has completed the 5 years of follow-up.

We believe that the results of the trial will clarify the importance of lifestyle for primary prevention and the role of metformin as a potential chemopreventive agent. The trial is registred on ClinicalTrials.gov with the identification NCT02960711.