Clinical implications of the Drug-Drug Interaction in Cancer Patients treated with innovative oncological treatments.

In the last two-decades, innovative drugs have revolutionized cancer treatments, demonstrating a significant improvement in overall survival. These drugs may present several pharmacokinetics interactions with non-oncological drugs, and vice versa, and, non-oncological drugs can modify oncological treatment outcome both with pharmacokinetic interaction and with an "off-target impact" on the tumor microenvironment or on the peripheral immune response. It's supposed that the presence of a drug-drug interaction (DDI) is associated with an increased risk of reduced anti-tumor effects or severe toxicities. However, clinical evidence that correlate the DDI presence with outcome are few, and results are difficult to compare because of difference in data collection and heterogeneous population. This review reports all the clinical evidence about DDI to provide an easy-to-use guide for DDI management and dose adjustment in solid tumors treated with inhibitors of the cyclin-dependent kinases CDK4-6, Antibody-drug conjugates, Poly ADPribose polymerase inhibitors, androgen-receptor targeted agents, or immunecheckpoints inhibitors.

Early Detection of Disease Progression in Metastatic Cancers: Could CTCs Improve RECIST Criteria?

Early detection of disease progression is a crucial issue in the management of cancer patients, especially in metastatic settings. Currently, treatment selection mostly relies on criteria based on radiologic evaluations (RECIST). The aim of the present retrospective study is to evaluate the potential inclusion of circulating tumor cells (CTCs) in hybrid criteria. CTC counts from a total of 160 patients with different metastatic tumors were analyzed for this purpose. In our cohort, 73 patients were affected by breast cancer, 69 by colorectal cancer and 18 by prostate cancer. PFS and OS were evaluated according to the corresponding prediction of disease progression by CTCs and RECIST criteria. In breast cancer, CTC-I has an important impact on the progression-free survival (PFS) and overall survival (OS) values. When CTC-I predicted earlier than RECIST-I, the disease progression, the PFS and OS were shorter with respect to the opposite case. In particular, PFS was 11 (5-16) vs. 34 (23-45)-with p < 0.001-and OS was 80 (22-138) vs. 116 (43-189), p = 0.33. The results suggest a promising role of CTCs as complementary information which could significantly improve the clinical outcomes, and they encourage consideration of future trials to evaluate new hybrid criteria, particularly for patients with breast cancer.

The value of the multidisciplinary team in metastatic renal cell carcinoma: Paving the way for precision medicine in toxicities management.

The new landscape of treatments for metastatic clear cell renal carcinoma (mRCC) is constantly expanding, but it is associated with the emergence of novel toxicities, adding to up to those observed in the tyrosine-kinase inhibitor (TKI) era. Indeed, the introduction of immune checkpoint inhibitors (ICIs) alone or in combination has been associated with the development of immune-related adverse events (irAEs) involving multiple-organ systems which, even if rarely, had led to fatal outcomes. Moreover, due to the relatively recent addition of ICIs to the previously available treatments, the potential additive adverse effects of these combinations are still unknown. A prompt recognition and management of these toxicities currently represents a fundamental issue in oncology, since it correlates with the outcome of cancer patients. Even if clinical guidelines provide indications for the management of irAEs, no specific protocol to evaluate the individual risk of developing an adverse event during therapy is currently available. A multidisciplinary approach addressing appropriate interventions aimed at reducing the risk of any insidious, severe, and/or dose-limiting toxicity might represent the most efficacious strategy to timely prevent and manage severe irAEs, allowing indirectly to improve both patients' cancer-specific survival and quality of life. In this review, we reported a five-case series of toxicity events that occurred at our center during treatment for mRCC followed by the remarks of physicians from different specialties, pinpointing the relevant role of an integrated and extended multidisciplinary team in a modern model of mRCC patient management.

Multiparametric MRI of the bladder: inter-observer agreement and accuracy with the Vesical Imaging-Reporting and Data System (VI-RADS) at a single reference center.

OBJECTIVES: To evaluate accuracy and inter-observer variability using Vesical Imaging-Reporting and Data System (VI-RADS) for discrimination between non-muscle invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC). METHODS: Between September 2017 and July 2018, 78 patients referred for suspected bladder cancer underwent multiparametric MRI of the bladder (mpMRI) prior to transurethral resection of bladder tumor (TURBT). All mpMRI were reviewed by two radiologists, who scored each lesion according to VI-RADS. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for each VI-RADS cutoff. Receiver operating characteristics curves were used to evaluate the performance of mpMRI. The Ƙ statistics was used to estimate inter-reader agreement. RESULTS: Seventy-five patients were included in the final analysis, 53 with NMIBC and 22 with MIBC. Sensitivity and specificity were 91% and 89% for reader 1 and 82% and 85% for reader 2 respectively when the cutoff VI-RADS > 2 was used to define MIBC. At the same cutoff, PPV and NPV were 77% and 96% for reader 1 and 69% and 92% for reader 2. When the cutoff VI-RADS > 3 was used, sensitivity and specificity were 82% and 94% for reader 1 and 77% and 89% for reader 2. Corresponding PPV and NPV were 86% and 93% for reader 1 and 74% and 91% for reader 2. Area under curve was 0.926 and 0.873 for reader 1 and 2 respectively. Inter-reader agreement was good for the overall score (Ƙ = 0.731). CONCLUSIONS: VI-RADS is accurate in differentiating MIBC from NMIBC. Inter-reader agreement is overall good. KEY POINTS: • Traditionally, the local staging of bladder cancer relies on transurethral resection of bladder tumor. • However, transurethral resection of bladder tumor carries a significant risk of understaging a cancer; therefore, more accurate, faster, and non-invasive staging techniques are needed to improve outcomes. • Multiparametric MRI has proved to be the best imaging modality for local staging; therefore, its use in suitable patients has the potential to expedite radical treatment when necessary and non-invasive diagnosis in patients with poor fitness.