Outcomes of Consolidative Nephrectomy following Primary Immunotherapy in Advanced Renal Cell Carcinoma: A Multicenter Analysis.

BACKGROUND: To evaluate effect and outcomes of combination primary immunotherapy (IO) and nephrectomy for advanced renal cell carcinoma (RCC). METHODS: We conducted a multicenter, retrospective analysis of patients with advanced/metastatic RCC who received IO followed by nephrectomy. Primary outcome was Bifecta (negative surgical margins and no 30-day surgical complications). Secondary outcomes included progression-free survival (PFS) following surgery, reduction in tumor/thrombus size, RENAL score, and clinical/pathologic downstaging. Cox regression multivariable analysis was conducted for predictors of Bifecta and PFS. Kaplan-Meier analysis assessed PFS, comparing Bifecta and non-Bifecta groups. RESULTS: A total of 56 patients were analyzed (median age 63 years; median follow-up 22.5 months). A total of 40 (71.4%) patients were intermediate IMDC risk. Patients were treated with immunotherapy for median duration of 8.1 months. Immunotherapy resulted in reductions in tumor size (P < .001), thrombus size (P = .02), and RENAL score (P < .001); 38 (67.9%) patients were clinically downstaged on imaging (P < .001) and 25 (44.6%) patients were pathologically downstaged following surgery (P < .001). Bifecta was achieved in 38 (67.9%) patients. Predictors for bifecta achievement included decreasing tumor size (HR 1.08, P = .043) and pathological downstaging (HR 2.13, P = .047). Bifecta (HR 5.65, P = .009), pathologic downstaging (HR 5.15, P = .02), and increasing reduction in tumor size (HR 1.2, P = .007) were associated with improved PFS. Bifecta patients demonstrated improved 2-year PFS (84% vs. 71%, P = .019). CONCLUSIONS: Primary immunotherapy reduced tumor/thrombus size and complexity. Pathologically downstaged patients were more likely to achieve bifecta, and these patients displayed improved 2-year PFS. Our study supports further inquiry in the use of CRN following primary immunotherapy for advanced renal cancer.

Pathological Outcomes of Patients With Advanced Renal Cell Carcinoma Who Receive Nephrectomy Following Immunotherapy.

BACKGROUND: Even though cytoreductive nephrectomy (CN) was once the standard of care for patients with advanced renal cell carcinoma (RCC), its role in treatment has not been well analyzed or defined in the era of immunotherapy (IO). MATERIALS AND METHODS: This study analyzed pathological outcomes in patients with advanced or metastatic RCC who received IO prior to CN. This was a multi-institutional, retrospective study of patients with advanced or metastatic RCC. Patients were required to receive IO monotherapy or combination therapy prior to radical or partial CN. The primary endpoint assessed surgical pathologic outcomes, including American Joint Committee on Cancer (AJCC) staging and frequency of downstaging, at the time of surgery. Pathologic outcomes were correlated to clinical variables using a Wald-chi squared test from Cox regression in a multi-variable analysis. Secondary outcomes included objective response rate (ORR) defined by response evaluation criteria in solid tumors (RECIST) version 1.1 and progression-free survival (PFS), which were estimated using the Kaplan-Meier method with reported 95% CIs. RESULTS: Fifty-two patients from 9 sites were included. Most patients were male (65%), 81% had clear cell histology, 11% had sarcomatoid differentiation. Overall, 44% of patients experienced pathologic downstaging, and 13% had a complete pathologic response. The ORR immediately prior to nephrectomy was stable disease in 29% of patients, partial response in 63%, progressive disease in 4%, and 4% unknown. Median follow-up for the entire cohort was 25.3 months and median PFS was 3.5 years (95% CI, 2.1-4.9). CONCLUSIONS: IO-based interventions prior to CN in patients with advanced or metastatic RCC demonstrates efficacy, with a small fraction of patients showing a complete response. Additional prospective studies are warranted to investigate the role of CN in the modern IO-era.

Hearing screening and amplifier uptake results in a multidisciplinary head and neck cancer survivorship clinic.

PURPOSE: Hearing loss and tinnitus are prevalent among survivors of head and neck cancer (HNC), but auditory issues are under-addressed in the survivorship literature. The purpose of this study was to describe the hearing loss and management experience of a group of survivors provided with a hearing screening and amplifier assistance if needed during their visit. METHODS: A retrospective chart review of 1176 individuals seen in the HNC Survivorship Clinic between December 2016 and October 2020 who interacted with audiology was performed. RESULTS: Of these survivors, 72% failed the 30-dB HL hearing screening at one or more frequencies. Thirty-three percent of the sample reported tinnitus. Consistent with the general population, this group has a low prevalence of hearing aid use. In this clinic, individuals who fail the hearing screening at all frequencies are offered a simple, non-custom amplifier for use during their visit. Thirty-one percent of individuals offered the amplifier used it during their Survivorship Clinic visit to enhance communication and reduce listening effort. Only 54% of individuals who failed the hearing screening self-reported hearing loss. The poor sensitivity and specificity associated with the self-perception of hearing loss data support the need for hearing screening that consists of responding to tones. Of individuals who received a recommendation for a comprehensive hearing test, 21% received a hearing test with 68% of these individuals receiving the hearing test the same day of their Survivorship Clinic visit. CONCLUSIONS: The data from 1176 survivors of HNC seen by audiology over the past few years as part of the UPMC HNC Survivorship Clinic support the need for hearing management in this population to improve communication during and after the Survivorship Clinic visit. IMPLICATIONS FOR CANCER SURVIVORS: Survivors of HNC have a high prevalence of greater than mild hearing loss and tinnitus (both issues known to negatively impact health-related communication and quality of life). This manuscript describes a hearing screening program within a Survivorship Clinic that identifies individuals in need of non-custom amplification during their appointment to support effective communication. Survivors should be referred to audiologists for evaluation and management of treatment-related issues of hearing.

Overcoming Obstacles in Liquid Biopsy Developments for Prostate Cancer.

Prostate cancer is one of the most common malignancies in men. Over time, it can metastasize and become lethal once it exhausts hormonal therapies and transitions into castration-resistant prostate cancer (CRPC). Several therapies have been recently approved for advanced prostate cancer, but identifying biomarkers for current treatments and searching for more effective treatments are urgently needed. Liquid biopsy is a powerful tool for isolating genetic material, proteins, and whole tumor cells from the blood. In recent decades, this technology has rapidly advanced, allowing for better insights into the pathogenesis and treatment response in different stages of prostate cancer. In this review, we summarize important clinical studies involving liquid biopsies in prostate cancer with a focus on advanced disease, notably regarding circulating tumor DNA, circulating tumor cells, and exosomes. We highlight the progress and the challenges that still exist for these technologies. Finally, we discuss promising avenues that will further expand the importance of liquid biopsy in the care for prostate cancer patients.

Conversations in Cochlear Implantation: The Inner Ear Therapy of Today.

As biomolecular approaches for hearing restoration in profound sensorineural hearing loss evolve, they will be applied in conjunction with or instead of cochlear implants. An understanding of the current state-of-the-art of this technology, including its advantages, disadvantages, and its potential for delivering and interacting with biomolecular hearing restoration approaches, is helpful for designing modern hearing-restoration strategies. Cochlear implants (CI) have evolved over the last four decades to restore hearing more effectively, in more people, with diverse indications. This evolution has been driven by advances in technology, surgery, and healthcare delivery. Here, we offer a practical treatise on the state of cochlear implantation directed towards developing the next generation of inner ear therapeutics. We aim to capture and distill conversations ongoing in CI research, development, and clinical management. In this review, we discuss successes and physiological constraints of hearing with an implant, common surgical approaches and electrode arrays, new indications and outcome measures for implantation, and barriers to CI utilization. Additionally, we compare cochlear implantation with biomolecular and pharmacological approaches, consider strategies to combine these approaches, and identify unmet medical needs with cochlear implants. The strengths and weaknesses of modern implantation highlighted here can mark opportunities for continued progress or improvement in the design and delivery of the next generation of inner ear therapeutics.

Immunotherapies in Genitourinary Oncology: Where Are We Now? Where Are We Going?

For decades, limited options existed to treat metastatic genitourinary cancers, including treatment options that could be classified as immunotherapy. Historically, immunotherapy centered on systemic cytokines for the treatment of metastatic kidney cancer, which had several adverse effects, as well as the Bacillus Calmette-Guérin vaccine for non-metastatic bladder cancer. Within the past decade, advances in immunotherapy have led to several approvals from the United States Food and Drug Administration, particularly in the field of immune checkpoint inhibition. Immune checkpoint inhibitors (ICIs) are now being used extensively to treat multiple solid tumors, including kidney and bladder cancers, and they are also being tested in many other cancers. Despite encouraging data from phase 2/3 clinical trials, less is known about biomarkers that may predict better response to ICIs. The effect of ICIs in genitourinary cancers is heterogeneous, with some tumor types having little clinical data available, or ICIs having limited activity in other tumors. In this review, we briefly discuss approved immunotherapy agents prior to the time of ICIs. Then, given the emergence of this class of agents, we summarize the several important ICIs and the clinical trials that led to their approval. Finally, we mention ongoing and future clinical trials.

Cognitive functioning in Deaf children using Cochlear implants.

BACKGROUND: Cognitive abilities like language, memory, reasoning, visualization, and perceptual functioning shape human action and are considered critical to the successful interaction with the environment. Alternatively, hearing loss can disrupt a child's ability to communicate, and negatively impact cognitive development. Cochlear implants (CI) restore auditory input thereby supporting communication and may enhance cognitive performance. This study compares general cognitive development after cochlear implantation (2017-2019) in two groups of Jordanian children implanted earlier (age:4-6 years, N = 22) and later (7-9 years, N = 16) to the development of randomly selected normal hearing peers (N = 48). DESIGN: Visualization, reasoning, memory, and attention were assessed using the Leiter-R scale at baseline (before implantation), 8 months and 16 months post implantation for children with hearing loss. Same times of testing (baseline, 8 months and 16 months) were used for normal hearing peers. RESULTS: Over the 16-month period, the cognitive improvement of 4-6-year-old deaf children was greater than that of their normal hearing peers on the scales of visualization (5.62 vs. 4.40), reasoning (2.53 vs. 2.38) and memory (17.19 vs. 11.67). while the improvement of 7-9-year-old was less major than that of their normal hearing peers on all scales. CONCLUSIONS: These results suggest that CI not only enhances communication skills but may improve cognitive functioning in deaf children. However, the extent of this improvement was dependent on age at intervention; current results demonstrated that the children received CI at young ages had better cognitive improvements.

Baseline, retest, and post-injury profiles of auditory neural function in collegiate football players.

OBJECTIVES: Recent retrospective studies report differences in auditory neurophysiology between concussed athletes and uninjured controls using the frequency-following response (FFR). Adopting a prospective design in college football players, we compared FFRs before and after a concussion and evaluated test-retest reliability in non-concussed teammates. DESIGN: Testing took place in a locker room. We analysed the FFR to the fundamental frequency (F0) (FFR-F0) of a speech stimulus, previously identified as a potential concussion biomarker. Baseline FFRs were obtained during the football pre-season. In athletes diagnosed with concussions during the season, FFRs were measured days after injury and compared to pre-season baseline. In uninjured controls, comparisons were made between pre- and post-season. STUDY SAMPLE: Participants were Tulane University football athletes (n = 65). RESULTS: In concussed athletes, there was a significant group-level decrease in FFR-F0 from baseline (26% decrease on average). By contrast, the control group's change from baseline was not statistically significant, and comparisons of pre- and post-season had good repeatability (intraclass correlation coefficient = 0.75). CONCLUSIONS: Results converge with previous work to evince suppressed neural function to the FFR-F0 following concussion. This preliminary study paves the way for larger-scale clinical evaluation of the specificity and reliability of the FFR as a concussion diagnostic.HighlightsThis prospective study reveals suppressed neural responses to sound in concussed athletes compared to baseline.Neural responses to sound show good repeatability in uninjured athletes tested in a locker-room setting.Results support the feasibility of recording frequency-following responses in non-laboratory conditions.

Vestibular Toxicity: Causes, Evaluation Protocols, Intervention, and Management.

The loss of vestibular function, typically bilateral, due to chemical solvents and pharmacological agents is not rare and has been investigated and reported for many years. The successful treatment of bacterial infections and sepsis with IV antibiotics and cancer-fighting drugs like cisplatin makes the decision to use these life-saving drugs less of a debate, despite their potential deleterious effect on balance and equilibrium. The purpose of this article is to provide the reader with an overview of the more common substances found in industry and medicine which may decrease or permanently destroy peripheral and/or central vestibular function. A review of bedside and clinical evaluation protocols will be discussed as well as best practice intervention with balance retraining therapy. Finally, the role of the audiologist and opportunities for participation in an interdisciplinary approach to evaluation and management will be presented.