8p11 myeloproliferative syndrome (EMS) is a rare and aggressive hematological malignancy, characterized by myeloproliferative neoplasms, and associated with eosinophilia and T- or B-cell lineage lymphoblastic lymphoma. The pathogenesis is defined by the presence of chromosomal translocations associated with the fibroblast growth factor-1 (FGFR1) gene, located in the 8p11-12.1 chromosomal locus. At present, only ~100 cases have been reported globally. At least 15 partner genes have been identified, including the most common, the zinc finger MYM-type containing 2 (ZNF198)-FGFR1 fusion gene formed by t(8;13)(p11;q12). Different fusion genes determine the clinical manifestations and prognosis of the disease. Patients with EMS with t(8;13)(p11;q12) commonly present with lymphadenopathy and T-lymphoblastic lymphoma, which usually converts to acute myeloid leukemia (AML) with the progression of the disease. The present study describes the case of an elderly female patient with EMS with t(8;13)(p11;q12), presenting with myeloid/lymphoid syndrome (myeloproliferative neoplasms and T lymphoblastic lymphoma). The patient received the CHOPE regimen combined with tyrosine kinase inhibitor (dasatin) treatment and obtained short-term complete remission. However, 6 months later, the disease progressed from EMS to AML and the patient died due to ineffective induction therapy. The present study also reviews the relevant literature about this unusual entity to enhance the understanding of EMS.

UNASSIGNED: Zanzalintinib (XL092) is a next-generation anti-VEGFR-related multi-targeted TKI that exhibits immunomodulatory effects.
UNASSIGNED: This review explores preclinical and clinical data, along with the future directions associated with zanzalintinib and its combination with immune checkpoint inhibitors (ICIs).
UNASSIGNED: In addition to its anti-VEGFR activity, zanzalintinib demonstrates potential synergistic effects with ICIs through its immunomodulatory impact, attributed to its inhibition of MET and TAM kinases. Recent preclinical studies provide compelling evidence supporting this synergistic potential. Furthermore, a recent phase 1 dose escalation study confirmed the tolerability of the zanzalintinib and anti-PDL1 combination without major safety concerns.Multiple ongoing clinical trials are investigating the combination of zanzalintinib and ICIs across various solid tumor types, including phase 3 studies for renal cell carcinoma, colorectal, and head and neck cancer. These trials aim to elucidate the therapeutic role of this new-generation TKI and ICI combination.However, the identification of reliable predictive biomarkers for the zanzalintinib and ICI combination presents significant challenges. Given the intricate nature of their mechanistic rationale and the difficulties in identifying reliable biomarkers for combined anti-angiogenesis and ICI therapies, addressing this challenge remains a priority for ongoing and future research.

BACKGROUND: While available systemic treatments have modest long term efficacy in advanced angiosarcoma, immunotherapy represents an interesting new therapeutic opportunity. To establish its benefit, it is required to conduct a clinical trial assessing its efficacy and toxicity compared to standard treatments.
METHODS: This is a literature review from PubMed search.
RESULTS: Several systemic treatments (chemotherapy and TKI) are currently used in advanced angiosarcoma with ORR ranging from 12.5 to 68 % and PFS from 2 to 7 months. However, few randomized trials, mainly phase II, has been conducted to compare these treatments. While most centers propose doxorubicin containing regimens or paclitaxel in 1st or 2nd line, a high heterogeneity of regimens administered in this setting is observed even across sarcoma specialized centers with no consensual standard treatment. Encouraging signals of immunotherapy activity have been reported in angiosarcoma from several retrospective and phase II studies assessing anti-PD1 either alone or in combination with anti CTLA4 or TKI. Although cutaneous and head and neck location seems to benefit more from immunotherapy, response may be observed in any angiosarcoma subtype. In sarcoma in general and AS in particular, no biomarker has been clearly established to predict the efficacy of immunotherapy: high tumor mutational burden and presence of tertiary lymphoid structures are under assessment.
CONCLUSIONS: Even essential, developing a randomized clinical trial in AS struggles with the heterogeneity of the disease, the lack of consensual standard regimen, the uncertainty on optimal immunotherapy administration and the absence of established predictive biomarkers.
CONCLUSIONS: International collaboration is essential to run randomized trial in advanced AS and asses the efficacy of immune therapy in this rare and heterogeneous disease.

Interstitial lung disease (ILD) or pneumonitis caused by epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) or immune checkpoint inhibitors (ICI) is a major concern in the treatment of non-small cell lung cancer (NSCLC). Whether the addition of vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) inhibitors can reduce the incidence of drug-induced ILD remains unclear. We conducted a systematic review to assess the incidence of ILD induced by EGFR-TKIs or ICIs in the presence or absence of VEGF/VEGFR inhibitors in relevant randomized trials between January 2009 and October 2023. The primary outcome was the odds ratio for the incidence of ILD in all patients worldwide and Asians. Secondary outcomes were the odds ratios (ORs) of the incidence at grade-3 or higher ILD in all patients worldwide and Asians. We identified 13 randomized studies, one sub-analysis in the EGFR-TKI group, and three randomized studies in the ICI group. In the EGFR-TKI group, the OR of ILD incidence at any grade with VEGF/VEGFR inhibitors was 0.54 (95% CI, 0.32-0.90; p = 0.02), which represented a significantly lower incidence than that without VEGF/VEGFR inhibitors. Contrarily, the OR of ILD incidence at grade ≥ 3 with VEGF/VEGFR inhibitors was 1.00 (95% CI, 0.43-2.36; p = 0.99). In all subjects in the ICI group, the OR of ILD incidence at any grade with VEGF/VEGFR inhibitors was 0.78 (95% CI, 0.51-1.21; p = 0.27). The systematic review demonstrated that the addition of VEGF/VEGFR inhibitors could reduce the incidence of drug-induced ILD at any grade caused by EGFR-TKI in patients with NSCLC but could not reduce that at grade ≥ 3. The ILD induced by ICIs remains undetermined owing to the limited number of randomized trials for which ILD data are available.
UNASSIGNED: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=409534, identifier CRD42023409534.

UNASSIGNED: Endometrial carcinoma is the most widespread gynecological cancer, with increasing morbidity and mortality. Pembrolizumab, a monoclonal antibody that targets PD1 receptor tumors, is approved for patients with microsatellite instability-high (MSI-H) solid tumors. Many clinical trials and observational studies have been conducted to assess the safety and efficacy of Lenvatinib and Pembrolizumab combination therapy in the setting of endometrial cancer. However, results have been inconsistent, and current data is based on a heterogeneous population. The primary objective was to assess the safety and efficacy of Lenvatinib plus Pembrolizumab for endometrial cancer.
UNASSIGNED: The search was conducted from inception from four databases; PubMed, Google Scholar, the Cochrane Library, and ClinicalTrials.gov. The electronic database search was conducted from inception to August 20, 2023.
UNASSIGNED: We considered randomized controlled trials and single-arm observational studies, i.e. cohort, case-control and cross-sectional studies.
UNASSIGNED: We performed a single-arm meta-analysis, involving 7 studies having a total of 495 patients with endometrial cancer were eventually included which had the following outcomes: Complete response, Partial response, Progression-free survival, stable disease, progressive disease, safety outcomes, Adverse events, and the total number of deaths.
UNASSIGNED: Our results showed that 88.6 % of the patients were positive for non-MSI-H/pMMR tumors (95 % CI = 0.825-0.927) whereas 6.5 % (95 % CI = 3.8-9.8 %) of the patients for MSI-H/dMMR tumors. The pooled objective response of endometrial cancer patients treated with Lenvatinib and Pembrolizumab was 36.5 % (95 % CI = 0.258-0.471), the pooled estimate of complete and partial response was 47 % (95 % CI = 0.024-0.070) and 31.3 % (95 % CI = 0.230-0.396). 38.2 % patients had stable disease (95 % CI = 0.329-0.435) and 24.0 % patients had progressive disease (95 % CI = 0.103-0.378). The pooled median progression-free survival was 5.97 (95 % CI 5.43-7.63) months and, whereas the median overall survival was 17.19 months (95 % CI 15.34-19.31). All grade adverse events occurred in 85 % and Grade 3 or worse adverse events occurred in 39 % of patients during the therapy whereas death occurred in 23.8 % during the treatment.
UNASSIGNED: The results of this meta-analysis concludes that although the combined treatment of a Lenvatinib and Pembrolizumab had a PFS and OS that was inferior to the standard therapy used to treat advanced and recurrent endometrial cancer, it is still a novel treatment and shows potential for further research with a greater sample size.

Lifelong immunosuppression, cytotoxic effects of some immunosuppressive drugs, and opportunistic oncogenic viruses increase malignancy risks in solid organ recipients. The risk of myeloid neoplasms including chronic myeloid leukemia (CML) is also increased in this patient population. Tyrosine kinase inhibitors (TKIs), the key element of CML therapy, should be used cautiously in transplantation patients as they may interact with calcineurin inhibitors. With this report, a 63-year-old female kidney transplant recipient who developed CML 9 years after kidney transplantation is presented. CML in this patient was treated with a slightly reduced dose of imatinib (300 mg) due to concerns of adverse events including its interaction with tacrolimus. Deep molecular response (DMR) was achieved at 12 months under imatinib treatment. The patient is still in DMR after 30 months of follow-up, and she did not experience any adverse events or acute rejection episodes. CML and the use of TKIs in kidney transplant patients have been discussed with an extensive literature review. In this patient population, TKIs are generally well tolerated with achievement of treatment responses and good prognosis. Graft functions are also well maintained as long as drug interactions are monitored.

BACKGROUND: The use of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) can potentially result in interstitial lung disease (ILD), which can substantially impact a patient\'s quality of life, subsequently leading to the interruption or discontinuation of EGRF-TKI treatment. Clinicians, therefore, need to thoroughly assess patients to determine if they are at risk for ILD.
METHODS: We searched for observational study in the following databases: MEDLINE via the PubMed, CENTRAL, and IchushiWeb. The primary outcome was risk factors for the development of ILD, while the secondary outcome was risk factors for the severity of ILD. Of the 1602 studies returned, we selected 11 for meta-analysis, performed using a random-effects model.
RESULTS: Risk factors for developing ILD were sex (odds ratio (OR), 1.87; 95% confidence interval (CI), 1.08-3.22; I2 = 0%; P = 0.02), smoking history (OR, 2.13; 95% CI, 1.51-3.00; I2 = 3 4%; P = 0.0001), and history of ILD (OR = 5.95; 95% CI, 3.34-10.59; I2 = 67%; P = 0.0009). Age, previous thoracic surgery or radiotherapy, performance status, histological type of lung cancer, and treatment line were not statistically significant risk factors for ILD. Risk factors identified in one study were serum albumin level, history of nivolumab use, radiographic residual lung volume, and history of pulmonary infection.
CONCLUSIONS: We identified risk factors for developing ILD in patients with non-small cell lung cancer treated with EGFR-TKIs.

BACKGROUND: Interest in hereditary lung cancer is increasing, in particular germline mutations in the Epidermal Growth Factor Receptor (EGFR) gene. We review the current literature on this topic, discuss risk of developing lung cancer, treatment and screening options and describe a family of 3 sisters with lung cancer and their unaffected mother all with a rare EGFR germline mutation (EGFR p.R776H).
METHODS: We searched PubMed, Medline, Embase, the Cochrane Library, Google Scholar and scanned reference lists of articles. Search terms included \"EGFR germline\" and \"familial lung cancer\" or \"EGFR familial lung cancer\". We also describe our experience of managing a family with rare germline EGFR mutant lung cancer.
RESULTS: Although the numbers are small, the described cases in the literature show several similarities. The patients are younger and usually have no or light smoking history. 50% of the patients were treated with a tyrosine kinase inhibitor (TKIs) with OS over six months.
CONCLUSIONS: Although rare, germline p.R776H EGFR lung cancer mutations are over-represented in light or never smoking female patients who often also possess an additional somatic EGFR mutation. Treatment with TKIs appears suitable but further research is needed into the appropriate screening regime for unaffected carriers or light/never smokers.

Treatment and understanding of BCR::ABL1-positive leukaemias is a precision medicine success story. Our appreciation of the BCR::ABL1 gene and resulting BCR::ABL1 oncoprotein in chronic myeloid leukaemia (CML) and Philadelphia chromosome-positive (Ph+) acute leukaemias, has led to treatment advances associated with exceptional improvements in patient outcomes with normal life expectancy for many patients with chronic phase (CP-)CML. However, despite these major therapeutic advances, the management of Ph+ leukaemias remains complex, with development of specific resistance mutations on treatment, as well as the need for lifelong therapy in most patients due to the persistence of CML stem cells despite prolonged tyrosine kinase inhibitors (TKIs) treatment. BCR::ABL1-specific TKIs are associated with chronic toxicities affecting quality-of-life in many patients but can also result in more serious pulmonary and cardiovascular complications. Dose optimisation is increasingly being used to manage side effects and maintain molecular response in CML patients. Here, we review the development of BCR::ABL1-specific TKIs from the discovery of imatinib in 1996 to the more recent second- and third-generation TKIs and emerging specifically targeting the ABL myristoyl pocket (STAMP) inhibitors. We will also evaluate the current evidence for treatment of BCR::ABL1-positive leukaemias, including TKI discontinuation in optimally responding CP-CML patients.

UNASSIGNED: Since the introduction of first tyrosine kinase inhibitor (TKI) imatinib, the treatment of chronic myeloid leukemia (CML) has reached excellent survival expectancies. Long survival rates bring about issues regarding TKI safety.
UNASSIGNED: The aim of this review is to compare the side effects of current TKIs both in the first and later lines and outline a safety andprofile of CML treatment. Seminal studies on TKIs and other newer drugs and extended follow-up of these studies; real-life data of each drug were usedduring the course of this. PubMed was used as a search database and onlyarticles in English were included.
UNASSIGNED: With longer follow-up CML patients, resistant slowgrade adverse events seem to be the major obstacle in the way of treatmentefficacy. If efficacy is the priority, vigorous treatment of side effect and administration of full dose TKI are reasonable. But when treatment goals are reached, dose modifications or alternative treatment regimens may be acceptedpossible. More studies are needed on dose modification protocols and potential benefits and safety of treatment-free remission.