Antibody-drug conjugates in solid tumors: a new frontier.

PURPOSE OF REVIEW: Antibody-drug conjugates (ADCs) are designed to carry cytotoxic payloads and deliver them to specific molecular targets within tumor cells. Several ADCs are already approved with many more in development across several disease types. In this review, we will provide an overview of the ADCs currently approved and those under investigation in solid tumors. RECENT FINDINGS: Currently there are dozens of ADCs under clinical study evaluation of a variety of solid tumors, and preliminary results are promising. Multiple ADCs have received regulatory approval in disease such as breast cancer, non-small cell lung cancer, and bladder cancer. While some are approved in biomarker selected settings with disease specific indication (e.g. breast cancer), others have been approved irrespective of biomarker expression (urothelial carcinoma) and pan-cancer indications in biomarker selected patients (HER2 3+ expression). SUMMARY: Cytotoxic chemotherapy has been the mainstay of systemic treatment for patients with various solid tumors. ADCs offer the advantage of carrying the cytotoxic payload onto a specific molecular receptor, thereby inducing a more selective response. Optimizing selection of target antigen, payload delivery and investigating biomarkers of response will be crucial for further expanding the therapeutic benefit of ADCs across solid tumors.

Clinical Implications of the Molecular and Genomic Landscape of Upper Tract Urothelial Carcinoma.

PURPOSE OF REVIEW: Upper tract urothelial carcinoma (UTUC) is an aggressive entity with treatment strategies mirroring bladder cancer. Genomic and molecular profiling allows for a better characterization of this disease and allows for patient-tailored approaches. We aim to describe the genomic and molecular implications of this disease. RECENT FINDINGS: Technological advances have the potential for early diagnosis and precise molecular analysis in patients with UTUC. Genomic profile clustering, specific mRNA signatures, and pathway-specific protein abundance tools have oncologic and clinical implications. We describe their utility in the context of this disease. In the era of precision medicine, designing clinical trials that explore the diagnostic and prognostic implications of biomolecular signatures in the context of UTUC is of utmost importance. Promising advances in this arena provide tools for physicians to avoid overtreatment in this patient population.

The gut microbiome and dietary metabolites in the treatment of renal cell carcinoma.

The gut microbiome is interlinked with renal cell carcinoma (RCC) and its response to systemic treatment. Mounting data suggests that certain elements of the gut microbiome may correlate with improved outcomes. New generation sequencing techniques and advanced bioinformatic data curation are accelerating the investigation of specific markers and metabolites that could predict treatment response. A variety of new therapeutic strategies, such as fecal microbiota transplantation, probiotic supplements, and dietary interventions, are currently being developed to modify the gut microbiome and improve anticancer therapies in patients with RCC. This review discusses the preliminary evidence indicating the role of the microbiome in cancer treatment, the techniques and tools necessary for its proper study and some of the current forms with which the microbiome can be modulated to improve patient outcomes.

Risk Factors Associated with Diabetic Retinopathy with and without Macular Edema in Recently Diagnosed Patients with Type 2 Diabetes.

Purpose: To evaluate the risk factors associated with diabetic macular edema (DME) in patients with a recent type 2 diabetes mellitus (T2DM) diagnosis. Patients and Methods: We conducted a case-control study at a third-level hospital in Mexico City. We enrolled patients ≥18 years old, with T2DM less than five years of diagnosis, without disabling complications, and non-smokers. The control group was patients with diabetic retinopathy and without macular edema (DR-DME). Cases were patients with DR+DME. We measured fasting glucose, creatinine, lipid profile, urinary albumin/creatinine ratio (ACR), and HbA1c. An ophthalmological examination consisted of visual acuity measurement, digital three-field fundus photography with an automatic non-mydriatic camera, slit lamp, and Optical coherence tomography (OCT) examination. Results: 183 and 61 patients with DR-DME and DR+DME, respectively, were included in the analysis. The prevalence of mild DR was higher in the DR-DME group, but the frequencies of moderate and severe retinopathy were higher in the DR+DME group. Patients in the DR-DME group had better vision than those in the DR+DME group. Logistic regression analysis revealed that age (OR, 1.07), HbA1c (OR, 1.19), and Albumin-to-Creatinine Ratio (ACR) > 30 mg/g (OR, 3.37) were associated with an increased possibility of DME compared to DR-DME. Conclusion: Our study provides insights into the association between risk factors and DME. We found a statistically strong association between HbA1c levels, age, and ACR. Patients with poor metabolic control should undergo an extensive medical examination to screen for DME, which may be related to the chronicity of DM and renal damage.

Current management of cervical cancer in women living with HIV.

Cervical cancer is a significant global health issue, particularly in low- and middle-income countries. Women living with HIV (WLWH) are not only at higher risk of cervical cancer due to their increased susceptibility to high-risk human papillomavirus (HPV) infection and compromised immune status, but also higher mortality rates have been reported. Therefore, prevention, optimal screening, use of highly active antiretroviral therapy (HAART), and early access to treatment are of utmost importance in this population. While international guidelines for cervical cancer state no treatment differences should be made for WLWH, there is evidence that this population of patients represents a challenge in decision-making for medical oncologists, radiation oncologists, and surgical oncologists. This review summarizes the available evidence on the different treatment strategies for WLWH and invasive cervical cancer and highlights the need for special considerations in screening andprevention of cervical cancer in WLWH.

De-escalating treatment indications for patients who achieve metabolic goals.

INTRODUCTION: Robust evidence exists regarding initiation, intensification or modification of treatments. Recommendations to de-escalate therapy are lacking, specifically in diabetes. A successful treatment de-intensification reduces overtreatment, polypharmacy, and risk of adverse effects. OBJECTIVE: To encompass current recommendations for deprescribing common drugs and create a consensus among health professionals. METHODS: We reviewed four databases for deprescribing approaches published between 2010 and 2022. Articles were divided into different groups of drugs (for uric-acid, hypoglycemic, lipid-lowering, and psychotropic drugs). RESULTS: Hypoglycemic agents: strategies were limited to newer agents and insulin regimens for elderly individuals. Reducing insulin was associated with 1.1% reduction of A1c over time. SGLT2i and GLP-1RAs dose reduction depends on adverse events. Lipid-lowering agents: studies show that patients with very low cholesterol have fewer cardiovascular events without associated increased risk. Antihypertensive agents: Younger patients, lower systolic blood pressure, and few comorbidities are ideal characteristics for discontinuation. Uric acid therapy: we found no recommendation for dose de-escalation. Poor treatment adherence is associated with episodes of gout and deforming arthritis in the long term. CONCLUSION: Deprescribing hypoglycemic, statins, antihypertensives, and urate-lowering agents may be feasible in selected patients, but periodic surveillance is important. More evidence is necessary to support this decision entirely.

Cabozantinib and nivolumab with or without live bacterial supplementation in metastatic renal cell carcinoma: a randomized phase 1 trial.

Supplementation with CBM588, a bifidogenic live bacterial product, has been associated with improved clinical outcomes in persons with metastatic renal cell carcinoma (mRCC) receiving nivolumab and ipilimumab. However, its effect on those receiving tyrosine kinase inhibitor-based combinations is unknown. In this open-label, randomized, investigator-initiated, phase 1 study, 30 participants with locally advanced or mRCC with histological confirmation of clear cell, papillary or sarcomatoid component were randomized in a 2:1 fashion to receive cabozantinib (an inhibitor of vascular endothelial growth factor receptor, MET and AXL) and nivolumab (anti-programmed cell death protein 1) with or without CBM588 as first-line treatment. Metagenomic sequencing was performed on stool samples to characterize their gut microbiome at baseline and 13 weeks into treatment. The primary endpoint was a change in the relative abundance of Bifidobacterium spp.; secondary endpoints included objective response rate (ORR), progression-free survival (PFS) and toxicity profile. The primary endpoint of the study was not met and the addition of CBM588 to cabozantinib and nivolumab did not result in a difference in the relative abundance of Bifidobacterium spp. or alpha diversity (as measured by the Shannon index). However, ORR was significantly higher in participants treated with CBM588 compared to those in the control arm (14 of 19, 74% versus 2 of 10, 20%; P = 0.01). PFS at 6 months was 84% (16 of 19) and 60% (6 of 10) in the experimental and control arms, respectively. No significant difference in toxicity profile was seen between the study arms. Our results provide a preliminary signal of improved clinical activity with CBM588 in treatment-naive participants with mRCC receiving cabozantinib and nivolumab. Further investigation is needed to confirm these findings and better characterize the underlying mechanism driving this effect.ClinicalTrials.gov identifier: NCT05122546.

Overview and characterization of penile cancer content across social media platforms.

Background: Social media platforms (SMP) are an emerging resource that allows physicians, patients, and families to converse on cancer prevention, diagnosis, and treatment. We aimed to characterize penile cancer (PC) content shared on SMP. Methods: We searched PC posts on Twitter, Facebook, and Instagram from July 1st, 2021, through June 30th, 2022. Two independent, blinded reviewers analyzed the hashtags: #PenileCancer, #PenileCancerAwareness, and #PenileNeoplasm. Descriptive statistics were used for posts characterization, Pearson´s correlation coefficient for associations, and Cohen's weighted kappa coefficient for inter-rater agreement rate. Results: A total of 791 posts were analyzed, with Twitter accounting for 52%, Facebook for 12.2%, and Instagram for 35.5%, and. Most posts originated from high-income countries, such as the United Kingdom (48.8%). We found no correlation between the number of posts with PC incidence (p = 0.64) or users on SMP (p = 0.27). Most accounts were classified as "support and awareness communities" (43.6%) and "physicians and clinical researchers" (38.2%). Urology was the most common medical specialty to post (60.9%), followed by oncology (11.3%). Most posts were classified as "prevention and awareness for users" (45.1%). Global inter-reviewer agreement rate was almost perfect (k=0.95; p ≤ 0.01). On Twitter, "physicians and clinical researchers" shared more content on "treatment updates and medical papers published in medical journals," while on Facebook and Instagram, "support and awareness communities" focused on "personal and support comments." Conclusion: Overall, the number of PC posts was low compared to other neoplasms across the SMP evaluated in this study. "Physicians and clinical researchers" shared more content on Twitter, while "support and awareness communities" on Facebook and Instagram. Encouraging the use of a common SMP among the medical community and general users could lead to a more effective communication between physicians, patients, and support groups, and to increased awareness of PC.