TPS6102
Background: Novel combination therapies are needed to extend survival in patients (pts) with recurrent or metastatic head and neck squamous cell carcinoma (RM-HNSCC). Magrolimab is a ...monoclonal antibody that blocks CD47, a "don't eat me" signal often overexpressed on HNSCC cells. CD47 blockade by magrolimab induces macrophage-mediated phagocytosis of tumor cells and has shown preclinical activity and promising clinical efficacy in hematologic malignancies. Certain chemotherapies, including taxanes, enhance prophagocytic signals on tumor cells, leading to potential synergistic antitumor activity when combined with magrolimab. This study is evaluating the safety, tolerability, and efficacy of magrolimab combination therapy in pts with RM-HNSCC. Methods: This open-label study includes 2 safety run-ins and 2 phase (ph) 2 cohorts. Safety run-in 1 includes pts with RM-HNSCC untreated in the RM setting to receive magrolimab + pembrolizumab (pembro) + platinum (cisplatin or carboplatin) + 5-fluorouracil (FU); safety run-in 2 enrolls pts with locally advanced or RM-HNSCC treated with 1-2 lines of prior systemic therapy in the locally advanced or RM setting who received magrolimab + docetaxel. Magrolimab is given intravenously as a 1-mg/kg priming dose on cycle 1 day 1 (C1 D1) to mitigate on-target anemia and 30 mg/kg on D8 and D15. Magrolimab 30 mg/kg is given on C2 D1, D8, and D15 and 60 mg/kg on D1 of C3+. Once the recommended ph 2 dose is determined, the ph 2 cohorts will follow the same dose schedules. In ph 2 cohort 1, pts receive magrolimab + pembro + platinum + 5-FU (arm A), pembro + platinum + 5-FU (arm B), or magrolimab + zimberelimab (anti-PD-1) + platinum + 5-FU (arm C). Pts enrolled in ph 2 cohort 3 receive magrolimab + docetaxel. An optional safety run-in and ph 2 cohort (cohort 2) of magrolimab + pembro in PD-L1+ RM-HNSCC may be opened at sponsor’s discretion. Pembro, platinum, 5-FU, and docetaxel are given per standard of care. Reasons for treatment discontinuation may include unacceptable toxicity or disease progression. Safety is monitored throughout the study. Primary endpoints of the safety run-ins cohorts were incidence of adverse events and dose-limiting toxicities per CTCAE v5.0. Primary endpoints for the Ph 2 cohorts are progression-free survival (PFS) by independent central review (cohort 1 arm A vs B) and investigator-assessed objective response rate (ORR) by RECIST 1.1 (cohorts 2, 3). Secondary endpoints include magrolimab pharmacokinetics and antidrug antibodies (safety run-in, ph2 all cohorts), ORR assessed by independent central review, investigator-assessed PFS by RECIST 1.1 (all cohorts) and overall survival (all cohorts), duration of response, and pt-reported outcomes. Planned enrollment is ≈230 pts. Clinical trial information: NCT04854499 .
The treatment paradigm of neoplastic diseases has dramatically shifted with the introduction of immune checkpoint inhibitors (ICI). They induce a durable response in a wide variety of solid tumors, ...but this response depends on the infiltration of lymphocytes capable of recognizing and killing tumor cells. The primary predictor of intrinsic immune resistance to ICIs is the absence of lymphocytes in the tumor, the so-called “cold tumors”. Colorectal cancer (CRC) remains one of the most common and challenging cancer, but it is not traditionally considered a highly immunogenic tumor. In fact, immunotherapy showed a remarkable antitumoral activity only on a small subset of CRC patients – the ones with microsatellite instability-high/deficient DNA mismatch repair (MSI-H/dMMR). Most CRCs display a molecular microsatellite stability/proficient DNA mismatch repair (MSS/pMMR) profile, so strategies to improve tumor immunogenicity are crucial. Therefore, ongoing studies investigate new approaches to convert “cold” to “hot” tumors in MSS/pMMR CRCs. In addition, it has been described that gut microbiota influences tumor development and the host immune response. Hence, the microbiota may modulate the immune response, becoming a promising biomarker to identify patients who will benefit from ICIs. Future data will help to better understand microbiota mechanisms and their role in ICI efficacy. Precision medicine in cancer treatment could involve modulation of the microbiota through different strategies to improve tumor immunogenicity. In this review, we aim to present the potential relationship between gut microbiota and the modulation of the immune system and the hypothetical implications in CRC treatment, namely ICIs.
INTRODUÇÃO: O pé diabético é uma complicação frequente da diabetes mellitus com importante repercussão a nível clínico, psicossocial e económico, exigindo dos prestadores de cuidados de saúde uma ...abordagem terapêutica multimodal. Definiu-se como objetivo principal a revisão da literatura sobre o tratamento complementar do pé diabético com oxigenoterapia hiperbárica e as suas perspetivas futuras no tratamento desta complicação.MATERIAL E MÉTODOS: Pesquisa bibliográfica através da PubMed, CINAHL, Cochrane e Google Académicodesde 2014, utilizando os seguintes descritores: pé diabético, úlcera diabética e oxigenoterapia hiperbárica. Foram analisadas trinta e duas publicações, tendo sido selecionados seis artigos de revisão.RESULTADOS: A oxigenoterapia hiperbárica parece eficaz na cicatrização aos seis meses, promissora na cicatrização de lesões com mais de doze meses de evolução e associada a uma baixa incidência de efeitos adversos. A saturação de oxigénio transcutânea foi maior e houve menor incidência de amputação major dos membros inferiores no subgrupo de doentes tratados com esta terapia.DISCUSSÃO: A evidência atual aponta para um benefício clínico da oxigenoterapia hiperbárica enquanto modalidade terapêutica complementar do pé diabético. Ainda não é totalmente conhecido o perfil clínico ideal do doente que beneficiará deste tipo de tratamento pelas heterogeneidades e limitações metodológicas dos estudos considerados. É importante a realização de mais ensaios clínicos prospetivos, aleatorizados e controlados que consubstanciem a sua eficácia.
Primary intracranial myxofibrosarcoma is exceedingly rare, with less than 10 cases published. We present a case of a 23-year-old man with previous history of a primary low grade myxofibrosarcoma of ...the left parietal-occipital convexity resected in March 1999. He subsequently underwent several interventions for multiple local recurrent disease until March 2004. At that time, complete remission was documented. About 8 years later, in February 2012, the patient was admitted to the emergency room with refractory acute pulmonary oedema. On work up, sustained monomorphic ventricular tachycardia and hyperechoic myocardial mass with invasion of the right ventricular cavity were detected. Electrical cardioversion was unsuccessful and irreversible cardiac arrest followed. The autopsy confirmed multiple bilateral lung metastases, malignant pulmonary embolism and myocardial invasion by the primary tumour, with intracavitary cardiac thrombosis and absence of intracranial disease. To the best of our knowledge, this is the first report of extracranial metastases of this neoplasm.
A 66-year-old patient with metastatic renal clear cell carcinoma, developed palpable purpura during systemic treatment with different tyrosine kinase inhibitors (TKI).
A 66-year-old patient with metastatic renal clear cell carcinoma, developed palpable purpura during systemic treatment with different tyrosine kinase inhibitors (TKI).
Breast cancer is a significant global health concern, contributing to substantial morbidity and mortality among women. Hormone receptor-positive (HR+)/HER2-negative (HER2-) breast cancer constitutes ...a considerable proportion of cases, and significant advancements have been made in its management. CDK4/6 inhibitors (CDK4/6is) are a new targeted therapy that has demonstrated efficacy in adjuvant, advanced and metastatic settings. The propensity of lobular breast carcinomas for estrogen-rich sites, such as periocular tissues and orbital fat, may explain their tendency for orbital metastases. Current treatment strategies for these cases are predominantly palliative, and the prognosis remains poor. This article presents a unique case of a 51-year-old female with progressive right periorbital edema, pain, and limited ocular motility. An imaging work-up showed bilateral intra and extraconal orbital infiltration, which was biopsied. The histopathologic analysis disclosed mild chronic inflammatory infiltrate with thickened fibrous tissue and moderately differentiated lobular carcinoma cells, positive for GATA3 and CK7 markers, with 100% of tumor nuclei expressing estrogen receptors (ER+). A systemic evaluation showed a multicentric nodular formation in both breasts. Further diagnostic assessments unveiled an HR+/HER2- bilateral lobular breast carcinoma with synchronous bilateral orbital metastases. Systemic treatment was initiated with abemaciclib 150mg twice daily and letrozole 2.5mg once a day. However, this regimen was interrupted due to toxicity. After two weeks, treatment was resumed with a reduced abemaciclib dose (100mg twice daily) alongside letrozole, with a reasonable tolerance. Nearly two years after the initial diagnosis of inoperable metastatic cancer, the patient remains on the same systemic treatment regimen with no signs of invasive disease. This case report is the first of a patient presenting with bilateral orbital metastases from bilateral lobular breast cancer, showing an impressive and sustained response to a first-line treatment regimen combining abemaciclib and letrozole. A literature review on bilateral orbital metastases from breast cancer is also presented.
Epithelial tumors of the lacrimal gland are rare and usually develop in the orbital lobe. We report the exceedingly rare occurrence of a primary adenoid cystic carcinoma in the palpebral lobe of the ...lacrimal gland. A 26-year-old female was referred for evaluation of a gradually enlarging mass in the lateral upper eyelid, previously diagnosed as a chalazion. Computed tomography revealed a heterogeneous round lesion anterior to the orbital rim. Excisional biopsy was compatible with an adenoid cystic carcinoma. After excluding distant metastasis, and as the patient refused adjuvant radiotherapy, a second surgical procedure, with wide local excision, was indicated. Follow-up showed no recurrence. This case highlights the importance of performing a thorough clinical examination when diagnosing any lateral upper eyelid mass. A high index of suspicion for malignant tumors of the lacrimal gland should always be maintained, and a complete excision with histological analysis should be preferred whenever possible.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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