Antibody-Drug Conjugates in Prostate Cancer: A Systematic Review.

The prognosis in the setting of metastatic castration-resistant prostate cancer patients (mCRPC) remains limited. Therefore, novel treatment strategies remain an unmet need. Antibody-drug conjugates (ADC) emerged as a new drug concept with the potential to deliver a cytotoxic payload with limited off-target toxicity and potentially bystander effect. Following the success of ADCs in breast cancer and urothelial tumours, their activity in prostate cancer is now under investigation. Thus, the aim of this systematic review was to identify published and ongoing prospective clinical trials regarding ADC treatment in prostate cancer. A systematic search of PubMed, MEDLINE, and Web of Science was conducted as per PRISMA guidelines to identify prospective clinical trials of ADCin prostate cancer. Trials are currently ongoing on ClinicalTrials.gov and in the EU. The Clinical Trials Register was also identified. Abstracts, publications in languages other than English, review articles, retrospective analyses, and phase I trials were excluded. A total of six phase I/II prospective clinical trials already published were included. Seven ongoing trials were also identified. All studies were in the refractory/advanced tumour setting, and two included only mCRPC patients. The ADC targets were prostate-specific membrane antigen (PSMA), trophoblast cell surface antigen-2 (TROP-2), six-transmembrane epithelial antigen of prostate-1 (STEAP-1), tissue factor (TF), delta-like protein 3 (DLL-3), B7-H3 family of proteins (B7-H3), and human epidermal growth factor receptor 2 (HER2). Regarding the efficacy of PSMA ADC treatment in the second-line or beyond mCRPC setting, a PSA ≥ 50% decline rate in 14% of all treated patients was reported. One patient achieved a complete response with TROP-2 ADC. Overall, a wide range of safety issues were raised, particularly in connection with neuropathy and hematologic toxicity. Novel therapies have been changing the scope of treatment in mCRPC. ADCs seem to provide efficacy benefits, even with potential toxicity. The results of most prospective ongoing studies are still awaited, and a longer follow-up time is warranted to evaluate the real impact of ADCs in PCa.

Myocardial Work Brings New Insights into Left Ventricular Remodelling in Cardio-Oncology Patients.

Serial transthoracic echocardiographic (TTE) assessment of 2D left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) are the gold standard screening methods for cancer therapeutics-related cardiac dysfunction (CTRCD). Non-invasive left ventricular (LV) pressure-strain loop (PSL) provides a novel method of quantifying myocardial work (MW) with potential advantages to evaluate the impact of cardiotoxic treatments on heart function. We prospectively assessed breast cancer female patients undergoing cancer therapy through serial monitoring by 2D and 3D TTE. Patients were evaluated at T0, T1 and T2 (before, 4-6 and 12-14 months after starting therapy, respectively). Through PSL analysis, MW indices were calculated. A total of 122 patients, with a mean age of 54.7 years, who received treatment with anthracyclines (77.0%) and anti-HER2 (75.4%) were included. During a mean follow-up of 14.9 ± 9.3 months, LVEF and GLS were significantly diminished, and 29.5% developed CTRCD. All MW indices were significantly reduced at T1 compared with baseline and tended to return to baseline values at T2. Global work index and global work efficiency showed a more pronounced variation in patients with CTRCD. The presence of more than one cardiovascular risk factor, obesity and baseline left atrium volume were predictors of changes in MW parameters. In conclusion, breast cancer treatment was associated with LV systolic dysfunction as assessed by MW, with its peak at 4-6 months and a partial recovery afterwards. Assessment of myocardial deformation parameters allows a more detailed characterization of cardiac remodelling and could enhance patient screening and selection for cardioprotective therapeutics.

What Has Changed During the COVID-19 Pandemic? - The Effect on an Academic Breast Department in Portugal.

INTRODUCTION: One year ago, Portugal entered its first lockdown because of the coronavirus disease-2019 (COVID-19) pandemic. The impact of this on delays in cancer diagnosis and treatment is a major concern, which may negatively affect the outcomes of these patients. MATERIALS AND METHODS: This retrospective, single-center analysis compared the clinical and pathological characteristics of breast cancer (BC) patients referred to a medical oncology first appointment between March 2020 and 2021, with the same period in the previous year. RESULTS: Strikingly, there was a 40% reduction in the number of BC patients during lockdown. However, there was a statistically significant increase in the proportion of metastatic BC patients admitted for the first time for systemic therapy (13.6% vs. 28.9%, p = 0.003). Additionally, a statistically significant increase in the number of patients with bilateral early BC at diagnosis after March 2020 was found (7.2% vs. 1.9%, p = 0.043). CONCLUSION: These findings support international recommendations for an accelerated restoration of BC screening, to reduce incidence of advanced breast cancer at diagnosis and mitigate the expected impact of the COVID-19 pandemic on patients with cancer. Further work is needed to examine in detail the impact of measures to manage the COVID-19 pandemic on breast cancer outcomes.

Hyperleukocytosis in Solid tumors: A Rare Paraneoplastic Syndrome Associated with Poor Prognosis.

Hematological paraneoplastic syndromes are fairly uncommon. While mild leukocytosis in solid tumors is well reported, white blood cell (WBC) count over 50,000 u/L, described as paraneoplastic leukemoid reaction (PLR), is not. Indeed, when found, it is usually associated with a higher burden of disease, tumor activity and worse clinical outcomes. We report the case of a challenging and burdensome diagnosis of a presumptive hematological paraneoplastic syndrome in a patient with a locally advanced lung cancer admitted in the Internal Medicine ward. After the end of chemotherapy, clinical and laboratory benefit was observed; however, the aggressive course of the disease became clear, with progression and downhill course that was unresponsive to treatment.

Full recovery of a stage IV cancer patient facing COVID-19 pandemic.

Coronavirus disease 2019 (COVID-19), first recognized in Wuhan, China, was recently declared a global pandemic by the World Health Organization (WHO). Advanced age and comorbid disease, well-known characteristics in the solid tumor population, have been reported as risk factors for severe disease and death. Cancer-related immunosuppression and its treatments also seem to play an active role in the prognosis, response, and clinical outcomes of these patients. The most effective combination therapy for COVID-19 is still under investigation, and the use of corticosteroids is controversial. Although, as a group, metastatic cancer patients are often considered not to be good candidates for ICU treatment, the individual prognosis should always come into consideration, even in a context of high pressure on medical facilities. We report the case of a stage IV prostate cancer patient infected with SARS-CoV-2 who required ICU admission and recovered from COVID-19 infection. Further studies are needed in order to identify accurate clinical prognostic criteria and provide the best treatment for these challenging patients.

Full recovery of a stage IV cancer patient facing COVID-19 pandemic

Coronavirus disease 2019 (COVID-19), first recognized in Wuhan, China, was recently declared a global pandemic by the World Health Organization (WHO). Advanced age and comorbid disease, well-known characteristics in the solid tumor population, have been reported as risk factors for severe disease and death. Cancer-related immunosuppression and its treatments also seem to play an active role in the prognosis, response, and clinical outcomes of these patients. The most effective combination therapy for COVID-19 is still under investigation, and the use of corticosteroids is controversial. Although, as a group, metastatic cancer patients are often considered not to be good candidates for ICU treatment, the individual prognosis should always come into consideration, even in a context of high pressure on medical facilities. We report the case of a stage IV prostate cancer patient infected with SARS-CoV-2 who required ICU admission and recovered from COVID-19 infection. Further studies are needed in order to identify accurate clinical prognostic criteria and provide the best treatment for these challenging patients.