Checkpoint inhibitors in metastatic gastric and GEJ cancer: a multi-institutional retrospective analysis of real-world data in a Western cohort

Background Safety and efficacy of immune checkpoint inhibitors in advanced gastric or gastroesophageal junction (GEJ) cancer could be demonstrated in predominantly Asian cohorts, whereas data in Western patients outside of clinical trials are vastly missing. Methods In this multi-institutional retrospective analysis conducted at nine oncologic centers in Austria, we tried to assess feasibility of checkpoint inhibitors in advanced gastric/GEJ cancer in a real-world Western cohort. Results In total, data from 50 patients with metastatic gastric/GEJ cancer who received nivolumab or pembrolizumab in a palliative setting between November 2015 and April 2020 have been evaluated. The median number of previous palliative therapy lines was two. The median progression-free survival (PFS) and overall survival (OS) were 2.1 (95% CI: 1.4–2.8) and 6.3 (95% CI: 3.3–9.3) months, respectively. There was no statistically significant difference in median OS according to microsatellite or PD-L1 status. However, a trend towards prolonged PFS and OS for the microsatellite instability high subgroup could be observed. Patients with an ECOG Performance Status (PS) ≥ 2 displayed a significantly worse outcome than those with an ECOG PS ≤ 1 (p = .03). Only one patient discontinued immunotherapy due to treatment-related toxicity. Conclusions Our results support feasibility of nivolumab and pembrolizumab in pre-treated patients with metastatic gastric and GEJ cancer in a Western real-world cohort. Further phase II/III studies are needed to confirm clinical efficacy.

Histopathology of hepatocellular carcinoma - when and what

When do you need to take biopsies of the liver, and what information will you get is the topic of this review on hepatocellular carcinoma (HCC). If, clinically, the differential diagnosis of HCC after imaging is suggested, a biopsy has become obligatory as a diagnostic confirmation of HCC in the non-cirrhotic liver prior to definitive therapeutic interventions, as well as in a palliative therapy concept. In the case of hepatic lesions with an uncharacteristic contrast uptake, a biopsy should be performed immediately to confirm the diagnosis of HCC. After diagnosing HCC, a treatment strategy is evaluated. Further, the biopsy, or in case of surgical treatment, the resected tissue, shows us the different subtypes of HCC, with the steatohepatitic subtype being the most common and the lymphocyte-rich subtype being the least common. Further, the histological grade of HCC is determined according to the grading system of the WHO or the Edmonson and Steiner System. Through biopsies, HCC can be differentiated from intrahepatic cholangiocarcinoma or combined hepatocellular-cholangiocarcinoma or metastases of other malignant tumors, especially metastases of the gastrointestinal tract. In summary, biopsies are fundamental in the diagnosis of HCC.

Efficacy and potential predictors of vagus nerve stimulation therapy in refractory postencephalitic epilepsy

Background: Vagus nerve stimulation (VNS) is a therapeutic approach for patients with refractory postencephalitic epilepsy (PEE), which is characterized by drug resistance and disappointing surgical outcomes. However, the efficacy of VNS has not yet been studied in patients with refractory PEE. The present study aimed to demonstrate the efficacy of VNS and evaluate potential clinical predictors in patients with refractory PEE. Methods: We retrospectively collected the outcomes of VNS with at least a 1-year follow-up in all patients with refractory PEE. Subgroups were classified as responders and non-responders according to the efficacy of VNS (⩾50% or < 50% reduction in seizure frequency). Preoperative data were analyzed to screen for potential predictors of VNS responsiveness. Results: A total of 42 refractory PEE patients who underwent VNS therapy were enrolled, with an average age of 21.13 ± 9.70 years. Seizure frequency was reduced by more than 50% in 64.25% of patients, and 7.14% of patients achieved seizure-free events after VNS therapy. In addition, the response rates increased over time, with 40.5%, 50.0% and 57.1%, respectively at 6 months, 12 months, and 24 months after VNS therapy. Preoperative duration of epilepsy, monthly seizure frequency, and spatial distribution of interictal epileptic discharges (IEDs) were correlated with responders ( p < 0.05) in the univariate analysis. Further multivariate regression analysis demonstrated that refractory PEE patients with high monthly seizure frequency or Focal IEDs (focal or multifocal epileptiform discharges) achieved better efficacy on VNS ( p = 0.010, p = 0.003, respectively). Conclusion: VNS is an effective palliative therapy for patients with refractory PEE. Focal IEDs (focal or multifocal epileptiform discharges) and high seizure frequency were potential preoperative predictors of effectiveness after VNS therapy.

Normalization of the epidermal barrier as a method of pathogenetic therapy of Atopic Dermatitis in children

Background. A key link in the pathogenesis of atopic dermatitis is a violation of the barrier function of the skin. Artificial skin moisturizing with emollients is the basis of palliative therapy for the disease. Aims. The purpose of the study was to assess the effectiveness and tolerability of the cosmetic product Admera. Materials and methods. The article presents the results of an open non-comparative prospective observational study of the efficacy and safety of Admera cream in pediatric patients with mild to moderate atopic dermatitis, conducted at the Pierre Wolkenstein Clinic for Skin Diseases in June-August 2020. Results. The study included 35 patients aged 4 to 17 years. The study included 35 patients aged 4 to 17 years inclusive. The clinical study demonstrated a statistically significant decrease in the Severity scoring of atopic dermatitis (SCORAD) index total score. The average value of this indicator decreased by 33% from the value 36.2 12.3 at the screening visit to 24.2 11.4 at the visit 3 (p 0.001). Assessment of the dynamics of the Eczema area and severity index (EASI) index showed a significant decrease in the total score of the indicator after 14 and 28 days of therapy relative to the baseline (p 0.001). The cosmetic product studied was well tolerated by patients. During the present study, 3 adverse events were reported in 2 patients. According to expert opinion, the recorded undesirable phenomena were not associated with the application of the studied cosmetic product. Reported adverse events were gastrointestinal disorders and included cases of diarrhea, abdominal pain and at the end of the study completely Conclusions. Evaluation of the results of the study showed high efficacy and safety of the study drug as a moisturizing agent: four-week therapy leads to a decrease in the severity of Atopic dermatitis manifestations, a decrease in the intensity of pruritus, an increase in the level of skin hydration in the T-zone and on the patient's body.

Effect of Palliative Radiotherapy in controlling pain of Malignancy

Background: Radiation therapy reported to be an effective in palliating pain. Objective: To describe roles of palliative radiotherapy in controlling pain in metastatic cancerous patients, and evaluation of radio-therapy doses in pain management. Methods: A prospective observational study carried out at the Baghdad Radiotherapy and Nuclear Medicine Center/Baghdad Medical City Complex, Baghdad, Iraq, from 1st of December 2018 to 30th of May 2019. 88 Patients, were included. Patients were assessed before applying radiotherapy, and at the end of treatment. Pain scoring used from 0 to 10. Kaplan Meier survival curve used. Result: The mean±SD of age was 55.44±11.1 years, and the most frequent age group was 41-50years as 37(42.1%). Breast cancer come in 1st rank cases studied in our research as 35(39.8%). 42(47.7%) of patients received radio-therapy on metastatic spine vertebral lesions. Sharp pain, frequent pain, pain at night were the commonest. Before treatment, the most common scoring was (8) in 33(37.5%) patients, while after palliative radio-therapy the scoring shift downward. Radio-therapy dose of 1200 cGy improved overall survival of patients in this study to 21.5 weeks (95%CI= 20.2-22.8). Conclusion: Radiotherapy is effective in palliative therapy. A dose of 1200 cGy improved overall survival of patients in this study to 21.5 weeks.

Feasibility and efficacy of salvage allogeneic stem cell transplantation in AML patients relapsing after autologous stem cell transplantation

Autologous hematopoietic cell transplantation (HCT) is suitable for consolidation of favorable-/intermediate-risk AML patients in CR1. However, ~50% of AML patients relapse after autologous HCT, and efficacy of subsequent salvage strategies including allogeneic HCT remains unclear. We studied 123 consecutive patients with newly diagnosed AML undergoing high-dose chemotherapy (HDCT)/autologous HCT in CR1. In relapsing patients afterwards, we analyzed salvage treatments and outcomes focusing particularly on salvage allogeneic HCT. Of 123 patients, 64 (52%) relapsed after autologous HCT. Subsequently, 13 (21%) received palliative therapy, whereas 51 (79%) proceeded to salvage therapy with a curative intent. Of the 47 patients with a curative intent and who did not proceed directly to allogeneic HCT, 23 (49%) achieved CR2 or had ongoing hematologic CR1 despite molecular relapse. Finally, 30 patients (47%) received allogeneic HCT with estimated 3-year leukemia-free and overall survival rates of 33% and 43%. Hematologic remission at allogeneic HCT and lack of acute GvHD had a positive impact on OS and LFS (p < 0.05). Our study suggests that almost 80% of AML patients can undergo salvage therapy following relapse after front-line HDCT/autologous HCT. Allogeneic HCT can provide cure in one third of patients relapsing after front-line HDCT/autologous HCT.

Abscopal Effects in Metastatic Cancer: Is a Predictive Approach Possible to Improve Individual Outcomes?

Patients with metastatic cancers often require radiotherapy (RT) as a palliative therapy for cancer pain. RT can, however, also induce systemic antitumor effects outside of the irradiated field (abscopal effects) in various cancer entities. The occurrence of the abscopal effect is associated with a specific immunological activation in response to RT-induced cell death, which is mainly seen under concomitant immune checkpoint blockade. Even if the number of reported apscopal effects has increased since the introduction of immune checkpoint inhibition, its occurrence is still considered rare and unpredictable. The cases reported so far may nevertheless allow for identifying first biomarkers and clinical patterns. We here review biomarkers that may be helpful to predict the occurrence of abscopal effects and hence to optimize therapy for patients with metastatic cancers.

Initial Experience of Clinical Use of [99mTc]Tc-PSMA-T4 in Patients with Prostate Cancer. A Pilot Study

Background: Numerous different molecules of prostate-specific membrane antigen (PSMA) ligands are used to detect prostate cancer (PCa); most approaches utilize gallium PET and a few reports describe the role of SPECT/CT. [99mTc]Tc-PSMA-T4 is a new radiopharmaceutical designed for the diagnosis of patients with PCa. Methods: We conducted a single site, prospective, preliminary case series study that included 31 patients with PCa; all had undergone clinical, biochemical or imaging examination and exhibited clear or suspicious active disease or clinical/biochemical recurrence of PCa. Whole-body (WB) SPECT/CT after i.v. administration of [99mTc]Tc-PSMA-T4 was utilized; acquisition images were obtained at three time points. Results: The clinical value of the images was assessed in regard to the evaluation of tumor extent in patients with confirmed PC that qualified for initial therapy and the evaluation of tumor recurrence; both provided encouraging results. The late acquisition of WB-SPECT resulted in better lesions delineation. The results of the analysis of the sensitivity/specificity were: 92%/100% in cases of primary cancer, 83%/100% in terms of pelvic lymph nodes disease, 100%/95% in other lymph nodes and soft tissue involvement, respectively, and bone mets were both 100%. Conclusion: An oncotropic SPECT [99mTc]Tc-PSMA-T4 can help in selecting a rational therapeutic strategy for a patient with an initial diagnosis of PCa by assessing the extent of cancer and also after complex radical or palliative therapy in case of biochemical recurrence for re-staging.

Thirty-day mortality rates after immunotherapy initiation

Background: The aim of this study was to determine the cause of death in patients who died within 30 days after the first dose of immunotherapy. Methods: The data of 1432 patients treated with immunotherapy in six tertiary referral hospitals were retrospectively analyzed. Results: It was determined that 34 (2%) of the patients died within 30 days after the first dose of immunotherapy. Death occurred in all patients who received palliative therapy, and most patients (88%) received immunotherapy as second- or subsequent-line of therapy. The most common cause of death was disease progression and thromboembolic events. Conclusion: Preliminary results of the current study might give some clues to define the patient population in whom the fatal side effects of immunotherapy might be encountered.

Peritoneal Metastasis After Treated With Abemaciclib Plus Fulvestrant for Metastatic Invasive Lobular Breast Cancer: A Case Report and Review of the Literature

Peritoneal metastases from invasive lobular carcinoma (ILC) of breast are uncommon and usually related to poor prognosis due to difficulty of detection in clinical practice and drug resistance. Therefore, recognizing the entities of peritoneal metastases of ILC and the potential mechanism of drug resistance is of great significance for early detection and providing accurate management. We herein report a case of a 60-year-old female who presented with nausea and vomiting as the first manifestation after treated with abemaciclib (a CDK4/6 inhibitor) plus fulvestrant for 23 months due to bone metastasis of ILC. Exploratory laparotomy found multiple nodules in the peritoneum and omentum, and immunohistochemistry confirmed that the peritoneal metastatic lesions were consistent with ILC. Palliative therapy was initiated, but the patient died two months later due to disease progression with malignant ascites. Whole exome sequencing (WES) was used to detect the tumor samples and showed the peritoneal metastatic lesions had acquired ESR1 and PI3KCA mutations, potentially explaining the mechanism of endocrine therapy resistance. We argue that early diagnosis of peritoneal metastasis from breast cancer is crucial for prompt and adequate treatment and WES might be an effective supplementary technique for detection of potential gene mutations and providing accurate treatment for metastatic breast cancer patients.