Individualized 3D-printed templates for high-dose-rate interstitial multicathether brachytherapy in patients with breast cancer

Purpose

High-dose-rate, multicatheter interstitial brachytherapy is technically complex and operator-dependent, requiring lengthy training and specialized skills. Furthermore, until the advent of contouring on computerized tomography (CT) images, difficulties existed in locating the target volume precisely. The present article reports the results of a study that aimed at producing and validating a 3D-printed template to aid in target volume localization for multicatheter interstitial brachytherapy in patients with breast cancer.

Early detection by the Tei index of carvedilol-induced improved left ventricular function in patients with heart failure

Twenty-two patients (19 men) with heart failure (16 ischemic, 6 dilated cardiomyopathy; mean age of 67 +/- 6 years) in New York Heart Association classes I (2 patients), II (18 patients), and III (2 patients) under optimal therapy were strictly monitored after carvedilol supplementation. The Tei index decreased significantly from 0.87 +/- 0.17 to 0.53 +/- 0.29 (p <0.03). Conversely, the ejection fraction and transmitral Doppler flow analysis did not show significant improvement, despite a trend toward the amelioration of the ejection fraction, the E-/A-wave ratio, and atrial contribution. The Tei index could represent an earlier marker to evaluate drug-induced left ventricular function improvement in patients with heart failure and could represent a more sensitive tool to monitor left ventricular function during drug interventions.     

Topical Nifedipine With Lidocaine Ointment <Emphasis Type="Italic">vs.</Emphasis> Active Control for Treatment of Chronic Anal Fissure

PURPOSE: Chronic anal fissure may be treated by chemical or surgical sphincterotomy. The aim of this study was to test the efficacy of local application of nifedipine and lidocaine ointment in healing chronic anal fissure. METHODS: The study was performed according to a prospective, randomized, double-blind design. One hundred ten patients who gave informed consent were recruited. They received a clinical examination, a questionnaire to evaluate symptoms and pain, anorectal manometry, and anoscopy. Healing of anal fissure at Day 42 of therapy was defined as the primary efficacy variable of the study. Patients treated with nifedipine (n = 55) used topical 0.3 percent nifedipine and 1.5 percent lidocaine ointment every 12 hours for 6 weeks. The control group (n = 55) received topical 1.5 percent lidocaine and 1 percent hydrocortisone acetate ointment during therapy. Anal pressures were measured by recording resting and maximal voluntary contraction pressures at baseline and at Day 21. Long-term outcomes were determined after a median follow-up of 18 months. RESULTS: Healing of chronic anal fissure was achieved after 6 weeks of therapy in 94.5 percent of the nifedipine-treated patients (P < 0.001) as opposed to 16.4 percent of the controls. Mean anal resting pressure decreased from a mean value +/- standard deviation of 47.2 +/- 14.6 to 42 +/- 12.4 mmHg in the nifedipine group. This represents a mean reduction of 11 percent (P = 0.002). Changes of maximal voluntary contraction in nifedipine-treated patients were not significant. No changes in mean anal resting pressure and maximal voluntary contraction were observed in the control group. We did not observe any systemic side effect in patients treated with nifedipine. After the blinding was removed, recurrence of the fissure was observed in 3 of 52 patients in the nifedipine group within 1 year of treatment, and 2 of these patients healed with an additional course of topical nifedipine and lidocaine ointment. CONCLUSIONS: Our study clearly demonstrates that the therapeutic use of topical nifedipine and lidocaine ointment should be extended to the conservative treatment of chronic anal fissure.     

Ixazomib for the treatment of multiple myeloma

Introduction: Proteasome inhibition is a mainstay in the treatment of multiple myeloma (MM). Bortezomib, the first proteasome inhibitor (PI) approved for MM therapy, has shown efficacy in relapsed/refractory patients and in the front-line setting. Among second-generation PIs, MLN9708 (ixazomib) is the first oral compound to be evaluated in MM treatment and has shown improvement in pharmacokinetic and pharmacodynamic parameters compared with bortezomib with a similar efficacy in the control of myeloma growth and in the prevention of bone loss.

Areas covered: In this review, the authors discuss the rationale for use of PIs. They then summarize the clinical development of ixazomib in MM, from initial Phase I to Phase II studies as a monotherapy and in combination with other chemotherapeutics.

Expert opinion: Preliminary data of Phase I/II trials showed that ixazomib had a good safety profile and exerted anti-myeloma activity as a single agent in relapsed/refractory patients. Furthermore, ixazomib also had efficacy in patients who were refractory to bortezomib. Its use in combination with lenalidomide and dexamethasone was shown to be an effective and well-tolerated regimen in up-front treatment leading to minimal residual disease negativity in a significant number of patients. Results of Phase III trials, evaluating ixazomib in induction or maintenance therapy, are awaited.     

Smoldering multiple myeloma: to treat or not to treat

Introduction: Smoldering multiple myeloma (SMM) is an asymptomatic disorder characterized by the presence of ≥ 30 g/l serum M-protein and/or ≥ 10% bone marrow plasma cell infiltration. The progression risk to active multiple myeloma (MM) is not uniform, and several prognostic parameters are useful for identifying patients at high risk of progression. A watch-and-wait approach has been the standard of care up to now. However, recently, it has been demonstrated that a subset of high-risk cases can benefit from early treatment with new drugs.

Areas covered: In this editorial, we focus on SMM and evaluate the diagnostic work-up and the prognostic factors predicting progression to symptomatic MM. We also review the studies in which the role of early treatment has been evaluated for patients with SMM.

Expert opinion: After the update performed by the International Myeloma Working Group regarding MM diagnosis, it is now time to change the therapeutic paradigm for this disease. While “ultra high-risk” myeloma should now be considered as active MM, for low-risk patients the “watch-and-wait” strategy is still recommended. More caution is needed for the high-risk group: physicians should continue monitoring patients using every tool now available while waiting for results from ongoing trials that will establish if this group will benefit from an early intervention.     

An update on chemotherapy for osteosarcoma

Introduction: In the early seventies chemotherapy significantly improved survival in osteosarcoma. Since then minor innovations have occurred although recent years have offered insights of clinical and scientific relevance.Areas covered: This review focuses on the most recent results of phase 3 and 2 studies. Published data or presentations at International meetings are discussed. A specific section discusses recent insights from studies supporting the hypothesis of a possible personalized chemotherapy approach.Expert opinion: Osteosarcoma is a rare tumor and any effort should be made to improve the level of International collaboration. The MAP (methotrexate, doxorubicin and cisplatin) regimen has become the treatment of choice. Poor pathological response to primary chemotherapy is confirmed as a predictive factor of survival and, presently with the available drugs, it is not recommended to intensify or change post-operative treatment on the basis of pathological response to primary chemotherapy. The genomic complexity and the heterogeneity of osteosarcoma makes active and effective molecularly targeted therapies unlikely to be available in the near future. A relation between pharmacogenetic profile and chemotherapy toxicity and prognosis has been reported. The new frontier for clinical research in osteosarcoma is to optimize the use of the active drugs available by personalizing chemotherapy treatment.