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Abstract Uveal melanoma (UM) is the most prevalent intraocular malignant tumor in the Western world. The prognosis of survival in the presence of metastatic disease is 2-7 months, depending on the treatment applied. This article presents a case of metastatic UM with successful complex treatment of liver metastases. A 49-year old female, underwent removal of the right eyeball in 1996 due to a histologically confirmed uveal melanoma. After 11 years, CT revealed a mass in the left kidney and multiple metastases in the liver. After left nephrectomy, 6 chemotherapy courses with dacarbazine were performed. The increasing liver metastases were observed. Additional 4 intraarterial (i/a) chemotherapy courses were administered using cisplatin, doxorubicin, fluorouracil, and interferon alfa. After few courses increase in CTC Grade 4 liver transaminases was seen. A partial response was observed, and in December 2008 the patient underwent surgery removing all liver metastases by 7 wedge or atypical resections. All margins were tumor-free. 21 months after liver resections and 14 years since diagnosis, the patient is alive without evidence of disease. Successful treatment of metastatic uveal melanoma was due to a timely application of a combination of several treatment methods and good prognostic factors of the patient.

Clear cell sarcoma harbours recurrent translocation, resulting in EWSR1/ATF1 or less commonly EWSR1/CREB1 fusion. To date, six types of EWSR1/ATF1 fusion have been reported, of which three are in-frame and encode functional proteins. We present a reverse transcription - polymerase chain reaction analysis of a tumour near the hallux of the right foot. The sequencing of obtained fragments revealed the presence of a novel chimerical transcript-the in-frame fusion between EWSR1 exon 7 and ATF1 exon 6 that represents the fourth in-frame type of EWSR1/ATF1 fusion identified in clear cell sarcomas. [ABSTRACT FROM AUTHOR]

Background: Peritoneal metastases (PM) of gastric cancer (GC) are considered a terminal condition, with reported median survival ranging from 2 to 9 months. Standard treatment typically involves systemic chemotherapy alone or combined with targeted therapy or immunotherapy, though efficacy is limited. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) has emerged as a novel technique for treating GC PM, although it remains an experimental treatment under investigation. This study aimed to summarize the outcomes of GC PM treatment with PIPAC from the Lithuanian PIPAC program., Methods: All patients who underwent PIPAC for GC PM at Vilnius University Hospital Santaros Klinikos between 2015 and 2022 were included in this retrospective study. The safety of PIPAC was assessed by postoperative complications according to the Clavien-Dindo classification. Efficacy was evaluated based on the peritoneal carcinomatosis index (PCI), ascites dynamics throughout the treatment, and long-term outcomes., Results: In total, 32 patients underwent 71 PIPAC procedures. Intraoperative and postoperative morbidity related to PIPAC occurred after three (4.2%) procedures. Following PIPAC, there was a tendency towards a decrease in median PCI from 10 (Q1 3; Q3 13) to 7 (Q1 2; Q3 12), p = 0.75, and a decrease in median ascites volume from 1300 mL (Q1 500; Q3 3600) at the first PIPAC to 700 mL (Q1 250; Q3 4750) at the last PIPAC, p = 0.56; however, these differences were not statistically significant. The median overall survival after PM diagnosis was 12.5 months (95% CI 10-17), and the median survival after the first PIPAC procedure was 5 months (95% CI 4-10)., Conclusions: PIPAC is a safe and feasible treatment option for GC PM; however, well-designed prospective studies are needed to fully assess its efficacy.

Arcagen (NCT02834884) is a European prospective study aiming at defining the molecular landscape of rare cancers for treatment guidance. We present data from the cohort of rare thoracic tumors. Patients with advanced pleural mesothelioma (PM) or thymic epithelial tumors (TET) underwent genomic profiling with large targeted assay [>300 genes, tumor mutational burden (TMB), microsatellite instability (MSI) status] on formalin-fixed paraffin-embedded (FFPE) or plasma samples. EORTC molecular tumor board (MTB) advised for biomarker-guided treatments. 102 patients recruited from 8 countries between July 2019 and May 2022 were evaluable: 56 with PM, 46 with TET (23 thymomas, 23 thymic carcinomas). Molecular profiling was performed on 70 FFPE samples (42 PM, 28 TET), and 32 cases on ctDNA (14 PM, 18 TET), within a median turnaround time of 8 days from sample reception. We detected relevant molecular alterations in 66 out of 102 patients (65%; 79% PM, 48% TET), 51 of 70 FFPE samples (73%; 90% PM, 46% TET), and 15 of 32 plasma samples (47%; 43% PM, 50% TET). The most frequently altered genes were CDKN2A/B, BAP1, MTAP in PM and TP53, CDKN2A/B, SETD2 in TET. The TMB was low (mean 3.2 Muts/MB), 2 PM had MSI-high status. MTB advised molecular-guided treatment options in 32 situations, for 17 PM and 15 TET patients (75% clinical trial option, 22% off-label drug or compassionate use, 3% early access program). Molecular testing and MTB discussion were feasible for patients with rare thoracic cancers and allowed the broadening of treatment options for 30% of the cases., (© 2024. The Author(s).)

Purpose: Immunotherapy and chemotherapy combinations have shown activity in endometrial cancer, with greater benefit in mismatch repair (MMR)-deficient (dMMR) than MMR-proficient (pMMR) disease. Adding a poly(ADP-ribose) polymerase inhibitor may improve outcomes, especially in pMMR disease., Methods: This phase III, global, double-blind, placebo-controlled trial randomly assigned eligible patients with newly diagnosed advanced or recurrent endometrial cancer 1:1:1 to: carboplatin/paclitaxel plus durvalumab placebo followed by placebo maintenance (control arm); carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab plus olaparib placebo (durvalumab arm); or carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab plus olaparib (durvalumab + olaparib arm). The primary end points were progression-free survival (PFS) in the durvalumab arm versus control and the durvalumab + olaparib arm versus control., Results: Seven hundred eighteen patients were randomly assigned. In the intention-to-treat population, statistically significant PFS benefit was observed in the durvalumab (hazard ratio [HR], 0.71 [95% CI, 0.57 to 0.89]; P = .003) and durvalumab + olaparib arms (HR, 0.55 [95% CI, 0.43 to 0.69]; P < .0001) versus control. Prespecified, exploratory subgroup analyses showed PFS benefit in dMMR (HR [durvalumab v control], 0.42 [95% CI, 0.22 to 0.80]; HR [durvalumab + olaparib v control], 0.41 [95% CI, 0.21 to 0.75]) and pMMR subgroups (HR [durvalumab v control], 0.77 [95% CI, 0.60 to 0.97]; HR [durvalumab + olaparib v control] 0.57; [95% CI, 0.44 to 0.73]); and in PD-L1-positive subgroups (HR [durvalumab v control], 0.63 [95% CI, 0.48 to 0.83]; HR [durvalumab + olaparib v control], 0.42 [95% CI, 0.31 to 0.57]). Interim overall survival results (maturity approximately 28%) were supportive of the primary outcomes (durvalumab v control: HR, 0.77 [95% CI, 0.56 to 1.07]; P = .120; durvalumab + olaparib v control: HR, 0.59 [95% CI, 0.42 to 0.83]; P = .003). The safety profiles of the experimental arms were generally consistent with individual agents., Conclusion: Carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab with or without olaparib demonstrated a statistically significant and clinically meaningful PFS benefit in patients with advanced or recurrent endometrial cancer.

Background: Gastric cancer (GC) remains among the most common and most lethal cancers worldwide. Peritoneum is the most common site for distant dissemination. Standard treatment for GC peritoneal metastases (PM) is a systemic therapy, but treatment outcomes remain very poor, with median overall survival ranging between 3-9 months. Thus, novel treatment methods are necessary. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is the most novel technique for intraperitoneal chemotherapy. Some preliminary data suggest PIPAC can achieve improved long-term outcomes in patients with GC PM, especially when used in combination with systemic chemotherapy. However, there is a lack of data from well-design prospective studies that would confirm the efficacy of PIPAC and systemic therapy combination for first-line treatment., Methods: This study is an investigator-initiated single-arm, phase II trial to investigate the efficacy of PIPAC combined with systemic FOLFOX (5-fluorouracil, oxaliplatin, leucovorin) as a first-line treatment for GC PM. The study is conducted in 2 specialized GC treatment centers in Lithuania. It enrolls GC patients with histologically confirmed PM without prior treatment. The treatment protocol consists of PIPAC with cisplatin (10.5 mg/m2 body surface in 150 mL NaCl 0.9%) and doxorubicin (2.1 mg/m2 in 50 mL NaCl 0.9%) followed by 2 cycles of FOLFOX every 6-7 weeks. In total 3 PIPACs and 6 cycles of FOLFOX will be utilized. The primary outcome of the study is the objective response rate (ORR) according to RECIST v. 1.1 criteria (Eisenhauer et al., Eur J Cancer 45:228-47) in a CT scan performed 7 days after the 4 th cycle of FOLFOX. Secondary outcomes include ORR after all experimental treatment, PIPAC characteristics, postoperative morbidity, histological and biochemical response, ascites volume, quality of life, overall survival, and toxicity., Discussion: This study aims to assess PIPAC and FOLFOX combination efficacy for previously untreated GC patients with PM., Trial Registration: NCT05644249. Registered on December 9, 2022., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Uveal melanoma (UM) is a rare malignant tumor that differs from cutaneous melanoma in terms of pathogenesis, clinical behavior, and treatment response. Despite treatment for the primary tumor, 50% of UM patients develop metastatic disease, with the liver being the most affected organ. Furthermore, UM responds poorly to chemotherapy and immune checkpoint inhibitors. We present a clinical case of a 58-year-old female patient who was diagnosed with right eye choroidal melanoma cT2aN0M0. For the treatment of the initial tumor, the patient received stereotactic radiotherapy. However, 11 months after the initial diagnosis, the disease had progressed to the liver. The patient underwent radiofrequency ablation of liver metastases, then as the UM progressed - anti-PD-1 immunotherapy with nivolumab and ipilimumab were prescribed for the first-line palliative systemic treatment, later chemotherapy with dacarbazine (5 cycles) as the second-line systemic treatment. Based on the Foundation-One®CDx findings and an overview of clinical trials data, the MEK inhibitor trametinib was prescribed as a third-line palliative treatment. The patient died due to cancerous intoxication, with overall survival (OS) of 28 months (∼2.33 years) and a progression-free survival (PFS) of 11 months (∼0.92 years) since the initial diagnosis. Treatment-related adverse events could have an impact on the general health condition of the patient.

Importance: Pancreatic cancer is the third most common cause of cancer death; however, randomized clinical trials (RCTs) of survival in patients with resectable pancreatic cancer lack mandatory measures for reporting baseline and prognostic factors, which hampers comparisons between outcome measures., Objective: To develop a consensus on baseline and prognostic factors to be used as mandatory measurements in RCTs of resectable and borderline resectable pancreatic cancer., Evidence Review: We performed a systematic literature search of the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, and Embase for RCTs on resectable and borderline resectable pancreatic cancer with overall survival as the primary outcome. We produced a systematic summary of all baseline and prognostic factors identified in the RCTs. A Delphi panel that included 13 experts was surveyed to reach a consensus on mandatory and recommended baseline and prognostic factors., Findings: The 42 RCTs that met inclusion criteria reported a total of 60 baseline and 19 prognostic factors. After 2 Delphi rounds, agreement was reached on 50 mandatory baseline and 20 mandatory prognostic factors for future RCTs, with a distinction between studies of neoadjuvant vs adjuvant treatment., Conclusion and Relevance: This findings of this systematic review and international expert consensus have produced this Consensus Statement on Mandatory Measurements in Pancreatic Cancer Trials for Resectable and Borderline Resectable Disease (COMM-PACT-RB). The baseline and prognostic factors comprising the mandatory measures will facilitate better comparison across RCTs and eventually will enable improved clinical practice among patients with resectable and borderline resectable pancreatic cancer.

New molecular biomarkers that could have an independent prognostic value in endometrial cancer are currently under investigation. Recently, it was suggested that genetic changes in the Notch signaling pathway could be associated with the development of endometrial carcinoma. This study aimed to determine the expression of the Notch signaling pathway components in tumour and adjacent normal uterine tissue and to evaluate their importance for the survival of uterine cancer patients. The present study was performed on uterine body samples collected from 109 patients and paired adjacent noncancerous endometrial tissue samples. Kaplan-Meier curves and Cox regression were used for survival analyses. Expression alterations of NOTCH2 , NOTCH3 , NOTCH4 , JAG2 , and HES1 were evaluated as independent and significant prognostic factors for uterine cancer patients., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Nadezda Lachej et al.)

The pandemic spread of the COVID-19 virus significantly affected daily life, but the highest pressure was piled on the health care system. Our aim was to evaluate an impact of COVID-19 pandemic management measures on cancer services at the National Cancer Institute (NCI) of Lithuania. We assessed the time period from 1 February 2020 to 31 December 2020 and compared it to the same period of 2019. Data for our analysis were extracted from the NCI Hospital Information System (HIS) and the National Health Insurance Fund (NHIF). Contingency table analysis and ANOVA were performed. The COVID-19 pandemic negatively affected the cancer services provided by NCI. Reductions in diagnostic radiology (-16%) and endoscopy (-29%) procedures were accompanied by a decreased number of patients with ongoing medical (-30%), radiation (-6%) or surgical (-10%) treatment. The changes in the number of newly diagnosed cancer patients were dependent on tumor type and disease stage, showing a rise in advanced disease at diagnosis already during the early period of the first lockdown. The extent of out-patient consultations (-14%) and disease follow-up visits (-16%) was also affected by the pandemic, and only referrals to psychological/psychiatric counselling were increased. Additionally, the COVID-19 pandemic had an impact on the structure of cancer services by fostering the application of modified systemic anticancer therapy or hypofractionated radiotherapy. The most dramatic drop occurred in the number of patients participating in cancer prevention programs; the loss was 25% for colon cancer and 62% for breast cancer screening. Marked restriction in access to preventive cancer screening and overall reduction of the whole spectrum of cancer services may negatively affect cancer survival measures in the nearest future.

Background: Historically, melanoma with brain metastases has a poor prognosis. In this retrospective medical record review, we report basic clinicopathological parameters and the outcomes of patients with melanoma and brain metastases treated with different treatment modalities before the era of immunotherapy and modern radiotherapy technique., Methods: Patients with metastatic melanoma were treated with surgery, radiotherapy, and/or systemic therapy from 1998 to 2017. In our study, they were identified and stratified depending on treatment methods. Overall survival was defined as the time from the date of brain metastases to the death or last follow-up (2019 June 1 st ). Survival curves were estimated using the Kaplan-Meier method that was employed to calculate the hazard ratio., Results: Six (12%) of 50 patients are still alive as of the last follow-up. The median overall survival from the onset of brain metastases was 11 months. The longest survival time was observed in patients treated by surgery followed by radiotherapy, surgery followed by radiotherapy and systemic therapy, and also radiotherapy followed by systemic therapy. The shortest survival was observed in the best supportive care group and patients treated by systemic therapy only., Conclusions: Patients with brain metastases achieved better overall survival when treated by combined treatment modalities: surgery followed by radiotherapy (26.6 months overall survival), combining surgery, radiotherapy, and systemic therapy (18.7 months overall survival), and also radiotherapy followed by systemic therapy (13.8 months overall survival)., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 Mantas Janavicius et al.)

Aim: Patients with pre-existing autoimmune disease (AID) are typically excluded from clinical trials of immune checkpoint inhibitors, and there are limited data on outcomes in this population. The single-arm international SAUL study of atezolizumab enrolled a broader 'real-world' patient population. We present outcomes in patients with a history of AID., Methods: Patients with locally advanced/metastatic urinary tract carcinoma received atezolizumab 1200 mg every 3 weeks until loss of clinical benefit or unacceptable toxicity. The primary end-point was safety. Overall survival (OS) was a secondary end-point. Subgroup analyses of AID patients were prespecified., Results: Thirty-five of 997 treated patients had AID at baseline, most commonly psoriasis (n = 15). Compared with non-AID patients, AID patients experienced numerically more adverse events (AEs) of special interest (46% versus 30%; grade ≥3 14% versus 6%) and treatment-related grade 3/4 AEs (26% versus 12%), but without relevant increases in treatment-related deaths (0% versus 1%) or AEs necessitating treatment discontinuation (9% versus 6%). Pre-existing AID worsened in four patients (11%; two flares in two patients); three of the six flares resolved, one was resolving, and two were unresolved. Efficacy was similar in AID and non-AID patients (median OS, 8.2 versus 8.8 months, respectively; median progression-free survival, 4.4 versus 2.2 months; disease control rate, 51% versus 39%)., Conclusions: In 35 atezolizumab-treated patients with pre-existing AID, incidences of special- interest and treatment-related AEs appeared acceptable. AEs were manageable, rarely requiring atezolizumab discontinuation. Treating these patients requires caution, but pre-existing AID does not preclude atezolizumab therapy., Trial Registration: NCT02928406., Competing Interests: Conflict of interest statement Y.L. reports a grant and non-financial support from Roche for the SAUL study and funding of editorial support, a grant from Celsius, grants and personal fees from Sanofi, Janssen and MSD and personal fees from Astellas, AstraZeneca, Roche, BMS, Seattle Genetics and Pfizer. C.N.S. reports consultancy for Pfizer, MSD, Merck, AstraZeneca, Astellas, Sanofi-Genzyme, Roche/Genentech and Incyte. D.C. reports research funding to his institution from Janssen Oncology; adviser/consultancy to Janssen Oncology, Roche/Genentech, Astellas Pharma, AstraZeneca, Pfizer, Novartis, Ipsen, Bristol-Myers Squibb, MSD Oncology, Bayer, Lilly, Sanofi, Pierre Fabre and Boehringer Ingelheim; travel/accommodation/expenses from Pfizer, Roche, Bristol-Myers Squibb and AstraZeneca Spain. S.F.O. reports research grants to institution from Celldex and Novartis. H.D. reports travel/accommodation/expenses from Astellas, Roche, Pfizer, Bayer, AstraZeneca, Novartis, Sanofi, Ipsen, MSD and Janssen-Cilag. R.H. reports grants and personal fees from MSD; grants, personal fees and non-financial support from Roche; personal fees and non-financial support from Nektar and Janssen; personal fees from Bayer, BMS and NICE; partnership in Cancer Centre London. K.V. reports adviser/consultancy to Lilly, Novartis, Bayer and Pfizer; speaker bureau/expert testimony for Roche, AstraZeneca, Lilly and BMS. T.A.G. reports adviser/consultancy to BMS, MSD, Roche, Astellas, Ipsen, Sanofi-Genzyme, Eisai, Bayer; speaker bureau/expert testimony for Pfizer, Ipsen, Janssen and Astellas; research grant/funding to institution from Roche, Ipsen and Pfizer; travel/accommodation/expenses from Pfizer, Sanofi-Genzyme and Ipsen. I.S. reports grants, personal fees and non-financial support from Roche. A.P.F. reports research grants from Roche, personal fees from BMS, Roche, Novartis, Janssen, Astellas, Merck and AstraZeneca and non-financial support from BMS, Roche, Janssen, Astellas, Merck, Ipsen and AstraZeneca. B.B. reports personal fees for adviser/consultant roles from Roche, Novartis, Pfizer, Eli Lilly, Swixx BioPharma and Ipsen, travel/accommodation expenses from AstraZeneca, Janssen, Pfizer, Bausch Health and Ipsen and non-financial support for adviser/consultant roles from GSK. P.M. reports adviser/consultancy to Pfizer, Novartis, Janssen, Roche, Sanofi, Bayer and BMS; research grant/funding to institution from Roche. S.F. works for Roche (under contract via Hayes Schweiz AG). F.Di.N. reports employment with Roche/Genentech; share/stockholder of Roche/Genentech. S.de.D. reports employment with F Hoffmann-La Roche Ltd; shareholder of F Hoffmann-La Roche Ltd. E.C. reports personal fees from Chugai Pharma, Eli Lilly, Janssen, Novartis, Pfizer, Regeneron, Roche, Sanofi, UCB, Gilead, AbbVie, R-Pharm, SynAct Pharma and ObsEva and research grants from Chugai Pharma, Novartis, Pfizer, Roche, Sanofi, UCB, Biogen and Bio-Cancer. F.N. and F.M. declare no conflicts of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)