Case report: Primary CDK4/6 inhibitor and endocrine therapy in locally advanced breast cancer and its effect on gut and intratumoral microbiota.

Locally advanced breast cancer poses significant challenges to the multidisciplinary team, in particular with hormone receptor (HR) positive, HER2-negative tumors that classically yield lower pathological complete responses with chemotherapy. The increasingly significant use of CDK 4/6 inhibitors (CDK4/6i) plus endocrine therapy (ET) in different breast cancer settings has led to clinical trials focusing on this strategy as a primary treatment, with promising results. The impact of the microbiota on cancer, and vice-versa, is an emerging topic in oncology. The authors report a clinical case of a postmenopausal female patient with an invasive breast carcinoma of the right breast, Luminal B-like, staged as cT4cN3M0 (IIIB). Since the lesion was considered primarily inoperable, the patient started letrozole and ribociclib. Following 6 months of systemic therapy, the clinical response was significant, and surgery with curative intent was performed. The final staging was ypT3ypN2aM0, R1, and the patient started adjuvant letrozole and radiotherapy. This case provides important insights on primary CDK4/6i plus ET in locally advanced unresectable HR+/HER2- breast cancer and its potential implications in disease management further ahead. The patient's gut microbiota was analyzed throughout the disease course and therapeutic approach, evidencing a shift in gut microbial dominance from Firmicutes to Bacteroidetes and a loss of microbial diversity following 6 months of systemic therapy. The analysis of the intratumoral microbiota from the surgical specimen revealed high microbial dissimilarity between the residual tumor and respective margins.

Successful management of bilateral orbital metastases from invasive lobular breast cancer with abemaciclib and letrozole: a case report and literature review.

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.

Hyperbaric oxygen therapy as a complementary treatment in neuroblastoma - a narrative review.

Neuroblastoma is the most frequently diagnosed cancer during the first year of life. This neoplasm originates from neural crest cells derived from the sympathetic nervous system, adrenal medulla, or paraspinal ganglia. The clinical presentation can vary from an asymptomatic mass to symptoms resulting from local invasion and/or spread of distant disease spread. The natural history of neuroblastoma is highly variable, ranging from relatively indolent biological behavior to a high-risk clinical phenotype with a dismal prognosis. Age, stage, and biological features are important prognostic risk stratification and treatment assignment prognostic factors. The multimodal therapy approach includes myeloablative chemotherapy, radiotherapy, immunotherapy, and aggressive surgical resection. Hyperbaric oxygen therapy (HBOT) has been proposed as a complementary measure to overcome tumor hypoxia, which is considered one of the hallmarks of this cancer treatment resistance. This article aims to review the relevant literature on the neuroblastoma pathophysiology, clinical presentation, and different biological and genetic profiles, and to discuss its management, focusing on HBOT.

Communication preferences and perceptions of cancer patient during their first medical oncology appointment.

BACKGROUND: The first medical oncology appointment serves as a platform for patients to comprehend their diagnosis and prognostic implications of cancer. This study aimed to determine patients' communication preferences during their first medical oncology appointment and to assess the disparities between patients' preferences and perceptions. METHODS: A total of 169 cancer patients participated by completing the Communication in First Medical Oncology Appointment Questionnaire (C-FAQ), a two-section questionnaire designed to assess patients' preferences and perceptions regarding Content (information provided and its extent), Facilitation (timing and location of information delivery), and Support (emotional support) during their first medical oncology appointment. A comparative analysis was conducted to assess the variations between preferences and perceptions. RESULTS: Content emerged as the most significant dimension compared to Facilitation and Support. The physician's knowledge, honesty, and ability to provide clear information were considered the most important attributes. Patients evaluated most of their preferences as "very important". Patients' perception of the communication dimensions present during their appointment was below preferences for 11 items, indicating significant discrepancies in clinical practice. CONCLUSIONS: Patients highly valued their preferences concerning Content, Facilitation, and Support dimensions of communication. However, patient preferences were more prominently oriented towards the Content dimension. The discrepancies between preferences and perceptions should be viewed as an opportunity for enhancing communication skills through training.

The effectiveness of hyperbaric oxygen therapy for managing radiation-induced proctitis - results of a 10-year retrospective cohort study.

Introduction: Despite modern radiotherapy (RT) techniques, radiation-induced proctitis (RIP) remains a significant complication of RT for pelvic organ malignancies. Over the last decades, an enormous therapeutic armamentarium has been considered in RIP, including hyperbaric oxygen therapy (HBOT). However, the evidence regarding the impact of HBOT on RIP is conflicting. This study aims to evaluate the effectiveness and safety of HBOT in the treatment of RIP. Methods: Ten-year (2013-2023) retrospective analysis of all consecutive patients with RIP treated with HBOT at Centro de Medicina Subaquática e Hiperbárica (CMSH) (Armed Forces Hospital - Lisbon, Portugal). Patients were exposed to 100% oxygen at 2.5 ATA, in a multiplace first-class hyperbaric chamber, for 70-min periods, once daily, five times per week. Fisher's exact test was performed using SPSS (version 23.0); p<0.05 was accepted as statistically significant. Results: Of a total of 151 patients with RIP, 88 were included in the final analysis, of whom 38.6% evidenced other concurrent radiation-induced soft tissue lesions. The most reported primary pelvic tumor treated with RT was prostate cancer (77.3%), followed by cervical cancer (10.2%). Hematochezia was the most observed clinical manifestation (86.4%). After a median of 60 HBOT sessions (interquartile range [IQR]: 40-87.5), 62.5% and 31.8% of patients achieved a clinical complete and partial response, respectively, with a hematochezia resolution rate of 93.7% (complete or partial). While partial and complete responses require fewer than 70 sessions of HBOT in terms of overall RIP symptoms (p=0.069), isolated hematochezia tends to require at least 70 sessions (p=0.075). Individuals with at least two concurrent late radiation tissue injuries were associated with a complete response to HBOT (p=0.029). Only about 5.7% of patients did not respond to the treatment. Eighteen patients (20.5%) developed reversible ear barotrauma. The number of HBOT sessions was a predictor of HBOT side effects (odds ratio: 1.010; 95% confidence interval, 1.000-1.020; p=0.047). Conclusion: The HBOT proved to be an effective and safe treatment for RIP refractory to medical and/or endoscopic treatments. This real-world evidence study adds value to published data on the management of RIP with HBOT.

Mutation Patterns in Portuguese Families with Hereditary Breast and Ovarian Cancer Syndrome.

Germline pathogenic variants in the Breast Cancer Genes 1 (BRCA1) and 2 (BRCA2) are responsible for Hereditary Breast and Ovarian Cancer (HBOC) syndrome. Genetic susceptibility to breast cancer accounts for 5-10% of all cases, phenotypically presenting with characteristics such as an autosomal dominant inheritance pattern, earlier age of onset, bilateral tumours, male breast cancer, and ovarian tumours, among others. BRCA2 pathogenic variant is usually associated with other cancers such as melanoma, prostate, and pancreatic cancers. Many rearrangements of different mutations were found in both genes, with some ethnic groups having higher frequencies of specific mutations due to founder effects. Despite the heterogeneity of germline BRCA1/BRCA2 mutations in Portuguese breast or/and ovarian cancer families, the first described founder mutation in the BRCA2 gene (c.156_157insAlu) and two other variants in the BRCA1 gene (c.3331_3334del and c.2037delinsCC) contribute to about 50% of all pathogenic mutations. Furthermore, the families with the BRCA1 c.3331_3334del or the c.2037delinsCC mutations share a common haplotype, suggesting that these may also be founder mutations in the Portuguese population. Identifying specific and recurrent/founder mutations plays an important role in increasing the efficiency of genetic testing since it allows the use of more specific, cheaper and faster strategies to screen HBOC families. Therefore, this review aims to describe the mutational rearrangements of founder mutations and evaluate their impact on the genetic testing criteria for HBOC families of Portuguese ancestry.

Local Breast Microbiota: A "New" Player on the Block.

The tumour microenvironment (TME) comprises a complex ecosystem of different cell types, including immune cells, cells of the vasculature and lymphatic system, cancer-associated fibroblasts, pericytes, and adipocytes. Cancer proliferation, invasion, metastasis, drug resistance and immune escape are all influenced by the dynamic interaction between cancer cells and TME. Microbes, such as bacteria, fungi, viruses, archaea and protists, found within tumour tissues, constitute the intratumour microbiota, which is tumour type-specific and distinct among patients with different clinical outcomes. Growing evidence reveals a significant relevance of local microbiota in the colon, liver, breast, lung, oral cavity and pancreas carcinogenesis. Moreover, there is a growing interest in the tumour immune microenvironment (TIME) pointed out in several cross-sectional studies on the correlation between microbiota and TME. It is now known that microorganisms have the capacity to change the density and function of anticancer and suppressive immune cells, enabling the promotion of an inflammatory environment. As immunotherapy (such as immune checkpoint inhibitors) is becoming a promising therapy using TIME as a therapeutic target, the analysis and comprehension of local microbiota and its modulating strategies can help improve cancer treatments.

Hyperbaric Oxygen Therapy as a Complementary Treatment in Glioblastoma-A Scoping Review.

Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults. The mainstay of management for GBM is surgical resection, radiation (RT), and chemotherapy (CT). Even with optimized multimodal treatment, GBM has a high recurrence and poor survival rates ranging from 12 to 24 months in most patients. Recently, relevant advances in understanding GBM pathophysiology have opened new avenues for therapies for recurrent and newly diagnosed diseases. GBM's hypoxic microenvironment has been shown to be highly associated with aggressive biology and resistance to RT and CT. Hyperbaric oxygen therapy (HBOT) may increase anticancer therapy sensitivity by increasing oxygen tension within the hypoxic regions of the neoplastic tissue. Previous data have investigated HBOT in combination with cytostatic compounds, with an improvement of neoplastic tissue oxygenation, inhibition of HIF-1α activity, and a significant reduction in the proliferation of GBM cells. The biological effect of ionizing radiation has been reported to be higher when it is delivered under well-oxygenated rather than anoxic conditions. Several hypoxia-targeting strategies reported that HBOT showed the most significant effect that could potentially improve RT outcomes, with higher response rates and survival and no serious adverse events. However, further prospective and randomized studies are necessary to validate HBOT's effectiveness in the 'real world' GBM clinical practice.

Impact of the COVID-19 Pandemic on Breast Cancer Management in Portugal: A Cross-Sectional Survey-Based Study of Medical Oncologists.

INTRODUCTION: Cancer care providers have faced many challenges in delivering safe care for patients during the COVID-19 pandemic. This cross-sectional survey-based study investigated the impact of the pandemic on clinical practices of Portuguese medical oncologists caring for patients with breast cancer. METHODS: An anonymous online survey comprising 42 questions gathered information regarding COVID-19 testing, treatment in (neo)adjuvant and metastatic settings, and other aspects of breast cancer management. Practices before and during the pandemic were compared, and potential differences in outcomes according to respondents' regions, case volumes, and practice type were explored. RESULTS: Of 129 respondents, 108 worked in the public health system, giving a representative national picture of the impact of the COVID-19 pandemic on breast cancer management. Seventy-one percent of respondents reported a reduction in visits for new cases of breast cancer, and there was a shift towards increased use of telemedicine. Clinical decision-making was largely unaffected in the most aggressive indications (i.e., triple-negative, HER2-positive, visceral crisis). The use of neoadjuvant therapy increased when access to surgery was difficult, whereas dose-dense regimens decreased, and cyclin-dependent kinase 4/6 inhibitor treatment decreased for less aggressive disease and increased for more aggressive disease. The use of oral formulations and metronomic chemotherapy regimens increased, and clinical trial participation decreased. Some differences by respondents' region and case volume were noted. CONCLUSION: Medical oncologists in Portugal implemented many changes during the COVID-19 pandemic, most of which were logical and reasonable responses to the current healthcare emergency; however, the true impact on patient outcomes remains unknown.

This study was an online survey of Portuguese medical oncologists to determine how they managed patients with breast cancer during the COVID-19 pandemic. Forty-two questions covered topics such as how COVID testing was done, the types of cancer treatments used, and how this compared to before the pandemic. It also examined whether the geographic region, the number of patients each doctor was responsible for (caseload), and the type of medical institution influenced how patients with breast cancer were managed. One hundred and twenty-nine oncologists completed the survey, of whom 108 worked in the public health system, making this survey representative of breast cancer management during the COVID-19 pandemic across Portugal. Most (71%) said there were fewer visits for new cases of breast cancer during lockdown. The use of telemedicine increased, as did the use of pre-surgery hormone therapy or chemotherapy when access to surgery was difficult, and the use of anticancer medications taken orally or metronomically (low doses given frequently over a long time period). Chemotherapy given very frequently (dose-dense) was used less often, and fewer patients participated in clinical trials. Treatment decisions for patients with aggressive breast cancer types (e.g., triple-negative breast cancer) were largely unchanged, except for greater use of cyclin-dependent kinase 4/6 inhibitors­drugs targeting the cell cycle and cell division control. Geographic region and caseload influenced treatment decisions. All of these changes in breast cancer treatment during the COVID-19 pandemic were logical and reasonable for the circumstances, but their long-term impact is not yet known.

Adenoid cystic carcinoma of the palpebral lobe of the lacrimal gland - case report and literature review.

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.