The Role of Electrochemotherapy in the Cutaneous and Subcutaneous Metastases From Breast Cancer: Analysis of Predictive Factors to Treatment From an Italian Cohort of Patients

The treatment of cutaneous and subcutaneous localizations from breast cancer (BC) is still a therapeutic challenge. Electrochemotherapy (ECT) is one of the available options, and it is characterized by the association between the administration of a chemotherapic agent (Bleomycin) with the temporary raise of permeability of the cellular membrane induced by the local administration of electrical impulses (electroporation). ECT represents an effective therapy for loco-regional control of this disease. This study aimed to investigate the predictive factors of response in cutaneous and subcutaneous localizations from breast cancer treated with ECT. We decided to evaluate the response to this treatment in 55 patients who underwent ECT between January 2013 and March 2020 at our Institute. We performed a monocentric retrospective cohort study. ECT was administered following the ESOPE (European Standard Operative Procedure of Electrochemotherapy) guidelines, a set of criteria updated in 2018 by a panel of European experts on ECT who defined the indications for selecting the patients who can benefit from the ECT treatment and the ones for technically performing the procedure. The responses were evaluated with the RECIST criteria (Response Evaluation Criteria in Solid Tumor). We found after 12 weeks of treatment a complete response (CR) in 64% of our patients. From the analysis divided for subgroups of covariates is emerged that lower BMI, reduced body surface, and absence of previous radiation treatment could be predictive for a better complete response. This study suggests that the efficacy of the ECT treatment is related to the concurrent systemic therapies while administering ECT. The association between ECT and immunotherapy has offered better results than the association between ECT and chemotherapy (p-value = 0.0463). So, ECT is a valuable tool in the treatment of cutaneous and subcutaneous metastases from breast cancer and its efficacy in local control of these lesions improves when it is well planned in a therapeutic scenario.

Metachronous port site, muscular and subcutaneous metastases from a gastric adenocarcinoma: a case report and review of articles

Background Port site metastasis (PSM) after curative gastrectomy for gastric cancer and muscular metastasis from gastric cancer are rare manifestations. Similarly, subcutaneous metastasis from gastric cancer is rare, and muscular and subcutaneous metastases are associated with poor prognosis. We report a case of long-term survival in a patient who underwent curative resection of gastric cancer and repeated recurrence of port site, muscular and subcutaneous metastases from gastric cancer, treated by resection. Case presentation A 75-year-old man was diagnosed with gastric cancer and referred to our department. Upper endoscopy demonstrated a 5-cm circumferential ulcerated lesion at the cardia. Biopsy findings showed a poorly differentiated tubular adenocarcinoma. He underwent laparoscopic total gastrectomy with lymph node dissection, and pathologic examination revealed a moderately differentiated tubular adenocarcinoma stage T4aN1M0 and IIIA according to the UICC (Union for International Cancer Control) classification. He refused adjuvant chemotherapy and was only carefully observed. Twenty-three months after the primary gastrectomy, computed tomography (CT) revealed an irregular mass near the port site wounds. Then the patient underwent mass resection, and the pathological diagnosis was consistent with metastatic adenocarcinoma, located in the subcutaneous tissue at the port site wounds. Thirteen months after the second surgery, CT revealed an enhanced mass in the abdominal wall. Positron emission tomography (PET) CT showed an elevated uptake in the rectus abdominis muscle and a standardized uptake value (SUV) of 3.1. The patient underwent another mass resection, and the pathological diagnosis was consistent with metastatic adenocarcinoma in the rectus abdominis muscle. Thirty-five months after the third surgery, CT revealed a mass in the left gluteal subcutaneous region. Furthermore, PET-CT revealed a 35-mm mass with an elevated SUV of 9.6. Another mass resection procedure was performed, and the pathological diagnosis was consistent with metastatic adenocarcinoma in the subcutaneous tissue. Since tumor cells were present at the resection margin, additional radiation therapy was performed. The patient has survived 78 months after primary gastrectomy. Conclusion The prognosis of muscular and subcutaneous metastases from gastric cancer is poor. However, if the metastatic tumor is solitary, surgical excision could be a feasible treatment option and might prolong survival.

Melanoma metastasis mimicking gastric cancer: a challenge that starts from diagnosis

The gastrointestinal tract is an uncommon site of metastasis in melanoma. However, when the primary melanoma cannot be found, the diagnosis of gastric melanoma by endoscopic biopsy is problematic mainly because some tumors are amelanotic and do not contain melanin granules detectable by microscopy. A 56-year-old Caucasian man with melanoma was referred to us following an initial histopathological diagnosis via gastroscopy of poorly differentiated primary gastric carcinoma. A computerized tomography (CT) scan showed metastatic disease and on the basis of this information we started palliative chemotherapy. However, the atypical presentation of the disease with subcutaneous metastases prompted us to make a more in-depth evaluation. Immunohistochemical evaluation modified the diagnosis to melanoma. After only one cycle of chemotherapy, treatment was changed to dabrafenib + trametinib, which was better tolerated and initially induced a partial response. The patient is currently in good clinical condition 20 months after diagnosis. Our case report highlights the difficulty in diagnosing melanoma of the gastrointestinal tract and indicates the need for pathologists and clinicians to consider such a possibility when they are faced with a diagnosis of poorly differentiated gastric cancer and unusual sites of metastasis.

Case Report of a Mare Diagnosed with a Metastatic Mammary Carcinoma after the Excision of a Recurrent Intraocular Neuroepithelial Tumor

A 24-year-old Irish Cob mare was presented with a peripheral iris mass, which was surgically resected and diagnosed as an undifferentiated neuroepithelial tumor. A few months later, a relapse occurred with histological features characterized by a more solid appearance and squamous differentiation. Subsequently, the mare was presented with rapidly spreading multiple subcutaneous masses and, at the onset of neurological signs, was humanely euthanized and subjected to a complete post mortem examination. The necropsy confirmed the presence of numerous widespread masses in the subcutaneous tissue, several internal organs, and mammary gland. Histological and immunohistochemical (IHC) examinations were performed on all masses, allowing the diagnosis of mammary carcinoma with several visceral and subcutaneous metastases. Considering the post mortem findings, the second intraocular mass was submitted to histological and IHC re-evaluation to differentiate it from an intraocular metastasis of the mammary carcinoma. The results of the histological and IHC analyses confirmed the diagnosis of neuroepithelial tumor relapse. This is the first case of a metastatic mammary carcinoma concurrent with a recurrent intraocular neuroepithelial tumor in a mare. This case was a challenge for both clinicians and pathologists involved and highlighted the importance of post mortem and IHC evaluations.

Subcutaneous fat metastasis at presentation in cervical cancer: case report and review of the literature

Subcutaneous metastases at presentation in cervical cancer are rare and they are associated with ominous prognosis. In this literature review, we present a case of skin metastasis and systematically review the current literature with the aim to discuss trends, treatment and survival of the reported cases.

Immediate results of electrochemotherapy for malignant tumors of the skin and soft tissues, cutaneous and subcutaneous metastases of melanoma

Relevance: Surgical removal of locally advanced forms of skin cancer and multiple cutaneous and subcutaneous metastases of melanoma does not always provide satisfactory aesthetic, functional, and long-term results. The treatment outcomes depend on the size, shape, location, and some other characteristics of the tumor. The relapse rate after surgical removal of locally advanced skin cancer is 12.5-34%, and the long-term survival of patients with cutaneous and subcutaneous metastases of melanoma does not exceed 30%. Cutaneous and subcutaneous metastases of melanoma and some superficial tumors are usually initially inoperable. Their complications such as bleeding, infection, pain, and pitting cause serious clinical problems and often require local therapy even at the 4th stage of the disease. Electrochemotherapy (ECT) is one of the modern treatment methods for skin cancer, soft tissue sarcoma, and metastatic melanoma. ECT is a treatment of choice in the presence of contraindications to surgical and radiation therapy. ECT combines the physical properties of current-induced electroporation with the chemical properties of chemotherapeutic drugs. In this method, an electric current affecting the tissue causes a temporary increase in cell membrane permeability, thereby providing free access to the cell of large molecules, including cytostatics, which are not initially transferred to the cytosol. This significantly increases the potential toxicity of cytostatics. The purpose of this study was to demonstrate the immediate results of ECT in patients with malignant tumors of the skin, soft tissue, cutaneous, and subcutaneous melanoma metastases. Results: Since 2017, 27 patients were treated by ECT at the Centre for bone and soft tissue tumors and melanomas of Kazakh Institute of Oncology and Radiology (Almaty, Kazakhstan). After two months, 67% of patients had a complete response (CR), 26% – a partial response (PR), and 7% had progression of the tumor. Side effects included local edema (n=13, 40%) which independently disappeared within several days to 2 weeks, local pains (12%) which disappeared within six months after treatment in 3% and within a month in 11% of patients, and hyperthermia in the early postoperative period in 6% of patients which was stopped within 10-15 min after the procedure

Immediate results of electrochemotherapy for malignant tumors of the skin and soft tissues, cutaneous and subcutaneous metastases of melanoma

Relevance: Surgical removal of locally advanced forms of skin cancer and multiple cutaneous and subcutaneous metastases of melanoma does not always provide satisfactory aesthetic, functional, and long-term results. The treatment outcomes depend on the size, shape, location, and some other characteristics of the tumor. The relapse rate after surgical removal of locally advanced skin cancer is 12.5-34%, and the long-term survival of patients with cutaneous and subcutaneous metastases of melanoma does not exceed 30%. Cutaneous and subcutaneous metastases of melanoma and some superficial tumors are usually initially inoperable. Their complications such as bleeding, infection, pain, and pitting cause serious clinical problems and often require local therapy even at the 4th stage of the disease. Electrochemotherapy (ECT) is one of the modern treatment methods for skin cancer, soft tissue sarcoma, and metastatic melanoma. ECT is a treatment of choice in the presence of contraindications to surgical and radiation therapy. ECT combines the physical properties of current-induced electroporation with the chemical properties of chemotherapeutic drugs. In this method, an electric current affecting the tissue causes a temporary increase in cell membrane permeability, thereby providing free access to the cell of large molecules, including cytostatic drugs, which are not initially transferred to the cytosol. This significantly increases the potential toxicity of cytostatic drugs. The purpose of this study was to demonstrate the immediate results of ECT in patients with malignant tumors of the skin, soft tissue, cutaneous, and subcutaneous melanoma metastases. Results: Since 2017, 27 patients were treated by ECT at the Centre for bone and soft tissue tumors and melanomas of Kazakh Institute of Oncology and Radiology (Almaty, Kazakhstan). After two months, 67% of patients had a complete response (CR), 26% – a partial response (PR), and 7% had progression of the tumor. Side effects included local edema (n=13, 40%) which independently disappeared within several days to 2 weeks, local pains (12%) which disappeared within six months in 3% and within a month after treatment in 11%, and hyperthermia in the early postoperative period in 6% of patients which was stopped within 10-15 min after the procedure.

Role of the anatomic site in the association of HLA class I antigen expression level in metastases with clinical response to ipilimumab therapy in patients with melanoma

BackgroundThe clinical response to immune checkpoint inhibitors (ICIs) in only part of the treated patients, in conjunction with the potentially serious side effects associated with this type of therapy, has emphasized the need to identify biomarkers to select patients who may benefit from ICI treatment. The aim of our study was to test human leukocyte antigen (HLA) class I and II expression in melanoma metastases as potential biomarkers of response to ipilimumab and survival in patients with metastatic melanoma, since these molecules play a crucial role in the interactions of malignant cells with host’s immune system.Materials and methodsHLA class I and II antigen expression level in pretreatment surgical tissue samples (50 lymph node and 35 cutaneous or subcutaneous metastases) from 30 patients was analyzed by immunohistochemical staining with monoclonal antibodies. Expression levels were correlated to intratumoral density of lymphocytes expressing cluster of differentiation (CD)8, CD45RO, CD4, forkhead box P3 (FOXP3) and/or programmed cell death protein 1 (PD-1), to clinical response to treatment, and to patients’ survival.ResultsHLA class I antigen expression level in lymph node metastases, but not in cutaneous or subcutaneous metastases was significantly correlated to density of CD8+ and CD45RO+ T cells and of lymphocytes expressing PD-1, as well as to clinical response and to patients’ survival.ConclusionsOur results corroborate the role of HLA class I expression level (alone or in combination with T-cell density values) as a predictive biomarker of response to ipilimumab in patients with melanoma. In addition, our results show that this association is influenced by the anatomic site of the metastasis used to measure the HLA class I antigen expression level.