Modern combined treatment of multiple cerebral and visceral metastases of skin melanoma on the example of clinical observation

Introduction. The article discusses modern methods of combined treatment of patients with cerebral and visceral metastases of melanoma, including drug therapy and radiation therapy, the place of neurosurgery, and also discusses a clinical case of long-term relapse-free survival after effective treatment of multiple intracerebral and extracranial metastases of non-pigmented melanoma without a driver mutations. Purpose. Analysis of the results of the application of modern methods of antitumor treatment of melanoma with metastases to the brain and their effect on survival on the example of a clinical case of a patient with metastatic non-pigmented melanoma without an identified primary focus without driver mutations with multiple metastases to the brain, single metastases to the cervical lymph node and left adrenal gland. Materials and methods. Using a clinical example, a possible sequence of an individual approach to the treatment of a patient with multiple intracerebral metastases of non-pigmented melanoma without a primary identified focus without driver mutations and metastasis to the left adrenal gland is considered, the place of modern methods of treatment and examination. Results. The use of a combination of modern methods of anticancer therapy, including immunotherapy, stereotactic radiosurgery and radiation therapy, has increased the overall and relapse-free survival of patients with metastases of melanoma to the brain and visceral organs, and, moreover, reduces the need in neurosurgical interventions. As confirmation of this, the patient is alive for more than 25 months from the moment of progression with a life expectancy of 3-6 months. Conclusions. Modern methods of anticancer therapy can significantly increase the survival rate of patients with metastases of melanoma to the brain and visceral organs, and the accumulation of clinical experience will contribute to the optimization of approaches in the combined and sequential treatment of metastatic melanoma.

Clinical case of the treatment of metastatic luminal breast cancer

Hormone therapy currently open up the prospect of long-term, comfortable and relatively low-toxic treatment for patients with hormone receptor – positive advanced breast cancer. For a long time, the presence of visceral metastases prompted oncologists to abandon hormone therapy in favor of cytostatic agents. Now days, even in the presence of visceral metastases, clinical guidelines allow use of modern hormonal therapy in the absence of a visceral crisis. In particular, the so-called CDK 4/6 inhibitors, presented on the Russian market by drugs: palbociclib, ribociclib and abemacyclib, became the drugs that significantly improved the results of hormone therapy. Each of them has demonstrated its effectiveness in clinical trials; moreover, there are lots of clinical cases demonstrating the benefits of this therapy in real clinical practice. The article presents a clinical case of treatment of advanced hormone receptor-positive breast cancer. The effectiveness of treatment with CDK 4/6 inhibitors has been demonstrated, a comparatively analysed with the data obtained in the course of clinical trials. The analysis of the tactics of treatment of cytomegalovirus infection of the cornea during therapy with ribociclib was carried out.

Highlighting the Place of Metastasis-Directed Therapy in Isolated Liver Metastases in Prostate Cancer: A Case Report

Metastatic prostate cancer remains a challenge for clinicians. Metastases involve mainly the bone compartment and can manifest as oligometastatic disease. In this setting, the role of metastasis-directed therapies (MDT) including surgery and/or stereotactic body radiotherapy is currently evaluated. Visceral metastases are less common and have very poor prognosis in mPC. Whether treating isolated visceral metastases such as liver metastases with MDT could increase the prognosis remains unknown. We report the management of a prostate cancer patient who progressed on androgen deprivation therapy with apparition of two liver metastases. We describe the feasibility of combining MDT with abiraterone acetate and prednisone in a patient with metastatic castration-resistant prostate cancer. MDT allowed the interruption of abiraterone acetate, preventing cumulative toxicity of this agent.

Phase II trail of nab-paclitaxel in metastatic breast cancer patients with visceral metastases

Background Visceral metastases account for 48–67% of metastatic breast cancer (MBC) patients and presage a worse overall survival. Previous study suggested potential effect of nab-paclitaxel on patients with visceral metastases subgroups. This phase II trial was conducted to explore the efficacy and safety of nab-paclitaxel in such a high-risk group of patients. Methods In this prospective, single-center, open-label, phase II study, MBC patients with visceral metastases (N = 80) received nab-paclitaxel (Abraxane, 125 mg/m2, D1, D8, D15 every 28 days). Results The median PFS was 5.1 months (95% CI: 4.2–6.0 months), with an ORR of 33.8% (95% CI 21.3–43.8%) and CBR of 66.2% (95% CI 56.3–75.0%). In univariate analysis, patients with premenopausal status had a trend of better treatment outcome. Multivariate analysis demonstrated non brain metastasis (adjusted HR 0.31, 95% CI 0.12–0.83, P = 0.019) and first line treatment (adjusted HR 0.37, 95% CI 0.17–0.81, P = 0.013) as independent predictors of longer PFS. The overall safety was acceptable with most common treatment-related, grade ≥ 3 toxicities of neutropenia (16.3%) and sensory neuropathy (3.7%). Conclusions This phase II trial documented satisfactory efficacy and safety of nab-paclitaxel in MBC patients with visceral metastases, providing evidence for relative clinical practice. Patients in first line therapy had better treatment outcome. For patients with premenopausal status or brain metastasis, further alternatives (for example, combined chemotherapy or targeting therapy) might be required. This study also demonstrated the efficacy and safety of 125 mg/m2 nab-paclitaxel among Asian patients. Trial registration This research is registered under clinicaltrials.gov (NCT 02687490, February 22, 2016).

10 years of success achieved by eribulin while treating HER2-negative mBC: from randomized studies to routine practice

The article reviews studies evaluating the efficacy and safety of eribulin chemotherapy in patients with HER2-negative advanced breast cancer. It analyzes the results derived from large randomized studies, highlights the main advantages peculiar to eribulin, and describes the key mechanisms of the antitumor activity displayed by the drug. Among those presented, there are significant retrospective studies evaluating the role of eribulin chemotherapy in late and early advanced breast cancer treatment lines, as well as an analysis of surveys aimed to evaluate the efficacy of the drug in various clinical settings (for visceral metastases, brain lesion, and in elderly patients). This article reflects the main results of Russian population analyses evaluating the efficacy and safety of eribulin chemotherapy in routine clinical practice.

Cutaneous Metastasis from Colorectal Cancer: Making Light on an Unusual and Misdiagnosed Event

Cutaneous metastasis from solid tumors is a rare event and usually represents a late occurrence in the natural history of an advanced visceral malignancy. Rarely, cutaneous metastasis has been described in colorectal cancer patients. The most frequent cutaneous site of colorectal metastasis is the surgical scar in the abdomen following the removal of the primary malignancy, followed by the extremities, perineum, head, neck, and penis. Metastases to the thigh and back of the trunk are anecdotical. Dermatological diagnosis of cutaneous metastasis can be quite complex, especially in unusual sites, such as in the facial skin or thorax and in cases of single cutaneous lesions since metastasis from colorectal cancer is not usually the first clinical hypothesis, leading to misdiagnosis. To date, due to the rarity of cutaneous metastasis from colorectal cancer, little evidence, most of which is based on case reports and very small case series, is currently available. Therefore, a better understanding of the clinic-pathological characteristics of this unusual metastatic site represents an unmet clinical need. We present a large series of 29 cutaneous metastases from colorectal cancer with particular concerns regarding anatomic localization and the time of onset with respect to primitive colorectal cancer and visceral metastases.

Burned-Out Testicular Tumors in Adolescents: Clinical Aspects and Outcome

Purpose: Testicular germ cell tumors are the fourth most common neoplasm in adolescents, accounting for 8% of all tumors in the age group 15–19 years. On rare instances, the primary testicular lesion is not clinically or radiologically evident while nodal or visceral metastases represent the clinical manifestations of the disease. This phenomenon is described as “burned-out testicular tumor.” In this paper, the authors report a single-institution experience with burned-out testicular tumors in adolescents and discuss their clinical implications.Patients and Methods: All the patients diagnosed with metastatic testicular germ cell tumors at Bambino Gesù Children Hospital between January 1, 2010, and June 30, 2020, were included in the study. Patients were categorized into two groups: “primary testicular” and “burned out.” All the patients were staged and treated according to the AIEOP–TCGM 2004 protocol.Results: Eleven patients were classified as “primary testicular,” and five patients were classified as “burned out.” “Burned-out” tumors were associated with the presence of systemic symptoms compared to “primary testicular” tumors (80 vs. 0%; p = 0.0027) and higher aFP, hCG, and LDH levels (p < 0.00001). The “burned-out” population had a statistically significant higher incidence of relevant toxicity than the “primary testicular” population (80 vs. 18%; p = 0.0357) and a worse outcome in terms of both mean overall survival (15 vs. 43 months; p = 0.0299) and mean event-free survival (12 vs. 38 months; p = 0.0164).Conclusion: “Burned-out” testicular tumors seem to be a well-distinct clinical entity with a high treatment-related toxicity and poor prognosis. Further studies are needed to clarify the “burned-out phenomenon” and to identify more effective therapeutic strategies for these patients.

Real-World Data on Outcomes in Metastatic Castrate-Resistant Prostate Cancer Patients Treated With Abiraterone or Enzalutamide: A Regional Experience

BackgroundBoth abiraterone and enzalutamide have shown to improve overall survival (OS), progression-free survival (PFS) and prostate-specific antigen (PSA) response in patients with metastatic castration-resistant prostate cancer (mCRPC) regardless of previous treatment with chemotherapy (COU-AA3011, COU-AA3022, AFFIRM3 and PREVAIL4). The data regarding the impact of these treatments in the real world setting is scarce. This study assessed the real world survival and disease outcomes in mCRPC patients in a regional health service in Victoria with the use of abiraterone and enzalutamide.MethodsThis retrospective clinical audit included 75 patients with diagnosis of mCRPC treated with either abiraterone or enzalutamide between January 1, 2014, and December 31, 2019, at Goulburn Valley Health. Patients were stratified according to the drug received, Eastern Cooperative Oncology Group (ECOG) performance status, Gleason score, burden of disease at diagnosis, presence of visceral metastases and use of previous chemotherapy. The primary end point was PSA response (defined as a reduction in the PSA level from baseline by 50% or more). The secondary outcomes were PSA PFS, radiographic PFS, and OS.ResultsThirty-seven patients received enzalutamide, and the other 38 received abiraterone. Only 20% of patients in either group had visceral metastases. 32% of patients receiving enzalutamide had a high burden of disease, compared to 53% receiving abiraterone. 38% of patients in the enzalutamide group and 53% in the abiraterone group had received prior chemotherapy. PSA response rates were higher in the enzalutamide group than abiraterone group (70.3% vs 37.8%). Both PSA and radiographic PFS were longer in the enzalutamide group than abiraterone group; 7 months vs 5 months for both end points. OS was also found to be longer in patients receiving enzalutamide; 30 months compared to only 13 months in patients receiving abiraterone.ConclusionBoth abiraterone and enzalutamide have shown to result in significant PSA response rates, as well as PFS and OS benefit in mCRPC patients in the real world setting. The difference in responses and survival benefit are probably impacted by the unbalanced burden of disease.