Corrigendum: Cancer survivorship at heart: a multidisciplinary cardio-oncology roadmap for healthcare professionals.

[This corrects the article DOI: 10.3389/fcvm.2023.1223660.].

Cancer survivorship at heart: a multidisciplinary cardio-oncology roadmap for healthcare professionals.

In cancer, a patient is considered a survivor from the time of initial diagnosis until the end of life. With improvements in early diagnosis and treatment, the number of cancer survivors (CS) has grown considerably and includes: (1) Patients cured and free from cancer who may be at risk of late-onset cancer therapy-related cardiovascular toxicity (CTR-CVT); (2) Patients with long-term control of not-curable cancers in whom CTR-CVT may need to be addressed. This paper highlights the importance of the cancer care continuum, of a patient-centered approach and of a prevention-oriented policy. The ultimate goal is a personalized care of CS, achievable only through a multidisciplinary-guided survivorship care plan, one that replaces the fragmented management of current healthcare systems. Collaboration between oncologists and cardiologists is the pillar of a framework in which primary care providers and other specialists must be engaged and in which familial, social and environmental factors are also taken into account.

Low and Ultra-Low HER2 in Human Breast Cancer: An Effort to Define New Neoplastic Subtypes.

HER2-low and ultra-low breast cancer (BC) have been recently proposed as new subcategories of HER2 BC, supporting a re-consideration of immunohistochemical negative scores of 0, 1+ and the 2+/in situ hybridization (ISH) negative phenotype. In the present review, we outline the criteria needed to exactly distinguish HER2-low and ultra-low BC. Recent clinical trials have demonstrated significant clinical benefits of novel HER2 directing antibody-drug conjugates (ADCs) in treating these groups of tumors. In particular, trastuzumab-deruxtecan (T-Dxd), a HER2-directing ADC, has been recently approved by the US Food and Drug Administration as the first targeted therapy to treat HER2-low BC. Furthermore, ongoing trials, such as the DESTINY-Breast06 trial, are currently evaluating ADCs in patients with HER2-ultra low BC. Finally, we hope that new guidelines may help to codify HER2-low and ultra-low BC, increasing our knowledge of tumor biology and improving a targetable new therapeutical treatment.

Consensus statements and treatment algorithm to guide clinicians in the selection of maintenance therapy for patients with newly diagnosed, advanced ovarian carcinoma: Results of a Delphi study.

INTRODUCTION: Standard treatment of newly diagnosed, advanced ovarian carcinoma (OC) consists of cytoreductive surgery followed by platinum-based chemotherapy with or without bevacizumab. Maintenance therapy with PARP inhibitors and olaparib-bevacizumab has recently shown to significantly improve progression-free survival in the first-line setting. Some practical aspects of maintenance therapy, however, are still poorly defined. AIM OF THE STUDY: To provide guidance to clinicians in the selection of maintenance therapy for newly diagnosed, advanced ovarian carcinoma. METHODS: A board of six gynecologic oncologists with expertise in the treatment of OC in Italy convened to address issues related to the new options for maintenance treatment. Based on scientific evidences, the board produced practice-oriented statements. Consensus was reached via a modified Delphi study that involved a panel of 22 experts from across Italy. RESULTS: Twenty-seven evidence- and consensus-based statements are presented, covering the following areas of interest: use of biomarkers (BRCA mutations and presence of homologous recombination deficiency); timing and outcomes of surgery; selection of patients eligible for bevacizumab; definition of response to treatment; toxicity and contraindications; evidence of synergy of bevacizumab plus PARP inhibitor. Two treatment algorithms are also included, for selecting maintenance therapy based on timing and outcomes of surgery, response to platinum-based chemotherapy and biomarker status. A score for the assessment of response to chemotherapy is proposed, but its validation is ongoing. CONCLUSIONS: We provide here consensus statements and treatment algorithms to guide clinicians in the selection of appropriate and personalized maintenance therapy in the first-line setting of advanced OC management.

Therapeutic efficacy of platinum/etoposide regimens in the treatment of advanced poorly differentiated neuroendocrine carcinomas of the lung: A retrospective analysis.

Background: Lung neuroendocrine neoplasms (NENs) are rare malignancies developed from bronchial mucosa. Because of its rarity and complex histopathology, there is limited data on the role of chemotherapy in this subset of tumors. Few studies regarding the treatment of poorly differentiated lung NENs, known as neuroendocrine carcinomas (NECs), are available and many limits are detectable as heterogeneity of tumor samples including different origins and different clinical behaviors, moreover, no evidence of therapeutic advances have been achieved along the last thirty years. Method: We performed a retrospective analysis of 70 patients affected by poorly differentiated lung NECs: half of patients underwent a first line therapy with a combination of cisplatin plus etoposide; the remaining patients receiving carboplatin instead of cisplatin, plus etoposide. Results: In our analysis, the outcomes of patients treated with either cisplatin or carboplatin schedule are similar in terms of ORR (44% versus 33%), DCR (75% versus 70%), PFS (6.0 versus 5.0 months) and OS (13.0 versus 10 months). Median number of chemotherapy cycles was 4 (range 1-8). The 18% of patients required a dose reduction. Main toxicities reported were hematological (70.5%), gastrointestinal (26.5%) and fatigue (18%). Conclusion: Survival rate in our study suggests that high grade lung NENs are characterized by an aggressive behavior and a poor prognosis, despite the treatment with platinum/etoposide according to available data. Clinical results of present study contribute to strengthen available data on the usefulness of platinum/etoposide regimen in the treatment of poorly differentiated lung NENs.

Correction: The prognostic significance of combined androgen receptor, E-Cadherin, Ki67 and CK5/6 expression in patients with triple negative breast cancer.

[This corrects the article DOI: 10.18632/oncotarget.20293.].

Eribulin mesylate use as third-line therapy in patients with metastatic breast cancer (VESPRY): a prospective, multicentre, observational study.

BACKGROUND: In real-world practice, eribulin mesylate provides significant survival benefit, with a manageable safety profile in heavily pretreated patients with metastatic breast cancer (MBC). METHODS: In this prospective, open-label, multicentre, observational study we evaluated the effectiveness and tolerability of eribulin as third-line treatment in a homogeneous population. The primary endpoints were the safety profile and response in metastatic sites; secondary endpoints included the response in different subtypes, overall response rate (ORR), progression-free survival (PFS) and overall survival (OS). RESULTS: From 2013 to 2016, 118 women were treated in 21 Sicilian institutions; the median age was 58 years (range 29-79), with 69% of patients under 65. The median cycles of eribulin were 5.5 (range 1-26). The most common adverse event was neutropenia (9.3%, 3 cases of grade 3, 4 of grade 4); only 1 case of QT prolongation was reported. Eribulin was effective in controlling metastatic disease in all sites, and it achieved the highest ORR in brain (16%) and liver (14.9%). Median OS was 31.8 months (95% CI 27.9-34.4) and median PFS 5.5 months (95% CI 4.2-6.6). PFS was 5.2 months (95% CI 2.8-8.4) in patients with triple-negative subtype. Median PFS was longer in patients over 65 years (6.1 months, 95% CI 4.4-8.3). In patients who had visceral metastases PFS was 5.5 months (95% CI 95% 3.5-6.6) and OS 33.9 months (95% CI 29.8-40.8). CONCLUSIONS: Eribulin as third-line treatment shows an acceptable safety profile and a substantial antitumour activity in the treatment of MBC, even in elderly patients and in those with visceral disease.

Efficacy of T-DM1 for leptomeningeal and brain metastases in a HER2 positive metastatic breast cancer patient: new directions for systemic therapy - a case report and literature review.

BACKGROUND: Herein, we report a complete response after whole brain radiotherapy (WBRT) and concomitant T-DM1 in a patient with HER2-positive metastatic breast cancer (MBC) and extensive brain and leptomeningeal involvement. CASE PRESENTATION: A 46 years old Caucasian woman with HER2-positive MBC and no baseline CNS involvement, started in August 2015 1st line therapy with Pertuzumab-Trastuzumab-Docetaxel, with partial response. However, in April 2016 the patient eventually progressed with emergence of brain and leptomeningeal metastases. Hence, she started in May 2016 2nd line therapy with T-DM1 and concomitant WBRT, with complete response (CR) after 3 courses of therapy, with complete resolution of neurological symptoms and no relevant toxicities. The CR is lasting over 13 months and the patient is out of corticosteroid use. CONCLUSIONS: To the best of our knowledge, this is the first case reporting interesting antitumor activity of T-DM1 and concomitant WBRT in both brain and leptomeningeal metastases, with a favorable safety profile and prolonged extracranial disease control. Further prospective studies should confirm these findings.

The prognostic significance of combined androgen receptor, E-Cadherin, Ki67 and CK5/6 expression in patients with triple negative breast cancer.

Background: Triple Negative Breast Cancer (TNBC) represents a heterogeneous group of tumors with poor prognosis owing to aggressive tumor biology and lack of targeted therapies. No clear prognostic biomarkers have been identified to date for this subgroup. Materials and Methods: In this retrospective study we evaluated the prognostic role of 4 different molecular determinants, including androgen receptor (AR), E-cadherin (CDH1), Ki67 index, and basal cytokeratins (CKs) 5/6, in a cohort of 99 patients with TNBC. All patients received neo/adjuvant chemotherapy (mostly anthracycline/taxane-based). Immunohistochemistry (IHC) was performed in formalin-fixed paraffin-embedded primary tumor samples. CDH1 expression was considered positive as ≥ 30% of the membrane cells staining. AR positivity was defined as > 10% of positive tumor cells. High Ki67 was defined as ≥20% positive tumor cells. CK5/6 expression was judged positive if the score was ≥1. Results: The absence of AR expression was significantly associated with highly undifferentiated tumors. Univariate analyses showed that lack of expression of CDH1, tumor size and nodal status were significantly correlated with worse RFS and OS (p< 0.05). AR expression and low Ki67 showed a trend towards better RFS and OS. Patients with absent CK5/6 expression in univariate and multivariate analyses had poorer RFS (p=0.02 and p=0.002, respectively) and OS (p=0.05 and p=0.02, respectively). Multivariate analysis showed an independent association between CDH1 expression and better RFS and OS (p< 0.05) beyond tumor size, nodal status, and grade. The Kaplan-Meier curves showed that patients with AR and CDH1 negative expression and high Ki-67 levels have a significant correlation with poor outcome. Conclusions: Our study supports the use of IHC expression of AR, CDH1, Ki67, and CK5/6 as prognostic markers in TNBCs and suggests a link between their expression and prognosis and may help to stratify TNBC patients in different prognostic classes.

Emerging role of Radium-223 in the growing therapeutic armamentarium of metastatic castration-resistant prostate cancer.

INTRODUCTION: During the last few years, the therapeutic armamentarium of castration resistant prostate cancer (mCRPC) has been enriched with the introduction of new effective therapies with proved survival benefit and quality of life gain, including cabazitaxel, abiraterone, enzalutamide, and Radium-223. Areas covered: Bone metastases represent a substantial cause of morbidity in mCRPC with a high rate of related skeletal events (SREs). In case of multifocal pain due to diffuse osteoblastic metastases, treatment with bone-targeting radiopharmaceutical agents can provide palliation from pain. Radium-223, a calcium-mimetic, is the first α-particle emitting radiopharmaceutical that prolonged overall survival, delayed symptomatic skeletal events and improved quality of life in mCRPC. Expert opinion: In this therapeutic scenario, no clear evidences support the best way to sequence these available agents and there is an urgent need for prospective studies to define it. 223Ra is a firmly established therapeutic option in CRPC with symptomatic bone metastases and no visceral/bulky nodal involvement, with an undeniable advantage over new hormonal agents, given its peculiar mechanism of action. Current ongoing randomized clinical trials will clarify the optimal use of this effective therapy in the therapeutic armamentarium of CRPC either alone or combined with other new approved agents and whether there is a role in patients with asymptomatic disease.