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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., (© 2024. The Author(s).)

We sought to determine racial and ethnic differences in perceptions (quality of communication, expectations, and concerns) of germline or somatic DNA sequencing (genomic profiling). Patients with prostate, urothelial, or kidney cancer were surveyed using a questionnaire that assessed previous experience, beliefs, expectations, and concerns regarding genomic profiling. Descriptive statistics and chi-square tests were used to identify factors associated with patients' perceptions of genomic profiling. A total of 150 consecutive patients were enrolled. The majority were male (74%) with a mean age of 68 years old. Most patients underwent somatic testing (54%), 24% undertook germline testing, and 21% undertook both tests. Significant differences were found across racial and/or ethnicity concerning factors that could have influenced patients' decision to pursue genomic profiling, including ability to guide the type of treatment (White: 54.1% vs. other ethnic groups: 43.9%, p = 0.04) and potential to improve treatment response (White: 10.1% vs. other ethnic groups: 22.0%, p = 0.04). Other ethnic group of patients were more concerned about learning that the cancer was less treatable or aggressive (43.8% vs. 27.7%, p = 0.01) and anxious about what would be learnt from genomic profiling (34.4% vs. 21.3, p = 0.01) as compared to White patients. Our findings reinforce the importance of developing culturally tailored education to help patients participate actively in decisions about genomic profiling., (© 2023 National Society of Genetic Counselors.)

Objectives: To characterise the restrictiveness of eligibility criteria in contemporary renal cell carcinoma (RCC) trials, using recommendations from the American Society of Clinical Oncology (ASCO)-Friends of Cancer Research (FCR) initiative., Methods: vPhase I-III trials assessing systemic therapies in patients with RCC starting between 30 June 2012 and 30 June 2022 were identified. Eligibility criteria regarding brain metastases, prior or concurrent malignancies, hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, and human immunodeficiency virus (HIV) infection were identified and stratified into three groups: exclusion, conditional inclusion, and not reported. Descriptive statistics were used to determine the frequency of eligibility criteria. Fisher's exact test or chi-square test were used to calculate their associations with certain trial characteristics., Results: A total of 423 RCC trials were initially identified of which 112 (26.5%) had sufficient accessible information. Exclusion of patients with HIV infection, HBV/HCV infection, brain metastases, and prior or concurrent malignancies were reported in 74.1%, 53.6%, 33.0%, and 8.0% of trials, respectively. In the context of HIV and HBV/HCV infection, patients were largely excluded from trials evaluating immunotherapy (94.4% and 77.8%, respectively). In addition, brain metastases were excluded in trials assessing targeted therapy (36.4%), combined therapy (33.3%), and immunotherapy (22.2%). Exclusion of patients with prior or concurrent malignancies was less frequently reported, accounting for 9.1%, 8.3%, and 5.6% targeted therapy, combined therapy and immunotherapy trials, respectively., Conclusion: A substantial proportion of RCC trials utilise restrictive eligibility criteria, excluding patients with fairly prevalent comorbidities. Implementing the ASCO-FCR recommendations will ensure resulting data are more inclusive and aligned with patient populations in the real-world., (© 2023 The Authors. BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Hemophagocytic lymphohistiocytosis (HLH) is a rare but often fatal condition characterized by a hyperinflammatory immune response leading to multiorgan failure. It is predominantly observed in the pediatric population and can be classified as familial or acquired HLH. The latter is more common in adults, often associated with malignancy, infection, or autoimmune diseases. Among acquired HLH cases, hematologic neoplasms account for the majority, with only a few isolated reports documenting solid neoplasms as the cause. Herein, we present a case of adult HLH associated with colorectal adenocarcinoma, which, to the best of our knowledge, is only the second reported case of HLH associated with this type of cancer., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: There are limited data regarding the impact of ethnicity among patients receiving immune checkpoint inhibitors. We evaluated real-world outcomes between Latinx and non-Latinx patients with metastatic renal-cell carcinoma (mRCC) treated with first-line nivolumab/ipilimumab within 2 different healthcare settings., Methods: We performed a retrospective analysis of patients with mRCC who received nivolumab/ipilimumab within the Los Angeles County Department of Health Services (LAC-DHS), a safety-net healthcare system, and the City of Hope Comprehensive Cancer Center (COH), a tertiary oncology center, between January 1, 2015 and December 31, 2021. Progression-free survival (PFS) and overall survival (OS) were determined using the Kaplan-Meier method and covariates were adjusted using multivariate Cox proportional hazards regression., Results: Of 94 patients, 40 patients (43%) were Latinx while the remainder were non-Latinx (44 pts [46%] White, 7 pts [7%] Asian, and 3 pts [3%] Other). Fifty (53%) and 44 (47%) patients received their care at COH and LAC-DHS, respectively. Most Latinx patients (95%) were treated at LAC-DHS, and most non-Latinx patients (89%) were treated at COH. Pooled analysis by ethnicity demonstrated significantly shorter PFS in Latinx versus non-Latinx patients (10.1 vs. 25.2 months, hazard ratios [HR] 3.61, 95% CI 1.96-6.66, P ≤ .01). Multivariate analysis revealed a HR of 3.41 (95% CI 1.31-8.84; P = .01). At a median follow-up of 11.0 months, the median OS was not reached in either arm at the time of data cutoff., Conclusion: Latinx patients with mRCC had a shorter PFS treated with frontline nivolumab/ipilimumab compared to their non-Latinx counterparts. No difference was observed in OS although these data were immature. Larger studies are needed to further interrogate the social and economic determinants of ethnicity on clinical outcomes in mRCC., (© The Author(s) 2023. Published by Oxford University Press.)

Purpose: Eligibility criteria illustrate the characteristics of the study population and promote the safety of participants. However, overreliance on restrictive eligibility criteria may limit the generalizability of outcomes. As a result, the American Society of Clinical Oncology (ASCO) and Friends of Cancer Research (Friends) issued statements to curtail these challenges. In this study, we aimed to assess restrictiveness in eligibility criteria across advanced prostate cancer clinical trials., Materials and Methods: We identified all phase I, II, and III advanced prostate cancer clinical trials between June 30, 2012, and June 30, 2022, through Clinicaltrials.gov. We evaluated whether a clinical trial excluded, conditionally included, or did not report 4 common criteria: brain metastases, prior or concurrent malignancies, HIV infection, and hepatitis B virus (HBV)/hepatitis C virus (HCV) infection. Performance status (PS) criteria were recorded based on the Eastern Cooperative Oncology Group (ECOG) scale., Results: Out of 699 clinical trials within our search strategy, 265 (37.9%) trials possessed all the required data and were included in our analysis. The most common excluded condition of our interest was brain metastases (60.8%), followed by HIV positivity (46.4%), HBV/HCV positivity (46.0%), and concurrent malignancies (15.5%). Additionally, 50.9% of clinical trials only included patients with ECOG PS 0 to 1. HIV and HBV/HCV infection were exclusion criteria of 22 (80.8%) and 19 (73.1%) immunotherapy trials, respectively., Conclusion: Patients with brain metastases, prior or concurrent malignancies, HIV infection, HBV/HCV infection, or low-functioning PS were overly restricted from participating in advanced prostate clinical trials. Advocating for broader criteria may ameliorate generalizability., Competing Interests: Disclosure ND reports a consulting role in Vivreon Gastroscience Inc. SL reports consulting roles in Exelixis, Merck, SeaGen, Easai, and EMD Serono. AT reports research funding from Clovis Oncology, Corvus Pharmaceuticals, EMD Serono, Aravive Inc, WindMIL Therapeutics, Bayer; honoraria from Urology times, Cardinal Health, Targeted Oncology; consulting roles Foundation Medicine, Pfizer, Genzyme, EMD Serono, Exelixis, Deka Biosciences, Seattle Genetics, Aadi biosciences, and Seattle Genetics/Astella. TD reports researching funding from Pfizer as well as consulting roles in Bayer, Janssen Oncology, Seattle Genetics, Abbvie, Exelixis, Advanced Accelerator Applications, and Astra Zeneca. SKP reports consulting roles in Genentech, Aveo, Eisai, Roche, Pfizer, Novartis, Exelixis, Ipsen, BMS, Astellas. HE, DC, MF, SP, KL, EC, TP, IS, JP, XL, ZZ, LM, BM, JH, AG, NC, CB, AR, and ACR declare no conflicts of interest, (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: We explored changes in perceptions of cure among patients with genitourinary (GU) cancers starting Immune checkpoint inhibitors (ICIs) therapy., Materials and Methods: This longitudinal study assessed patients before starting therapy and 3-months later with a questionnaire that included patient perceptions of ICIs and the Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety scale. General linear modeling was used to investigate changes in expectation of cure over time, and chi-square tests were used to determine the association between expectation of cure and perceptions of ICIs and anxiety., Results: A total of 45 patients were recruited (73% male, 84% diagnosed with renal cell carcinoma). The proportion of patients who possessed an accurate expectation of cure increased over time (55.6%-66.7%, P = .001). An accurate expectation of cure was associated with lower rates of anxiety over time. Patients with inaccurate expectation of cure reported more severe side effects and worse self-reported ECOG score at the follow-up assessment (P = .04)., Conclusion: We found that patients with GU metastatic cancer treated with ICI therapy have increasingly accurate expectations of cure over time. Accurate expectation of cure is associated with decreased anxiety. Further research is needed to fully explore this dynamic over time and help inform interventions that can help patients develop accurate expectations., Competing Interests: Disclosure All authors declare that they have no potential conflicts of interest for this work., (Copyright © 2023. Published by Elsevier Inc.)

Background: Preclinical evidence demonstrating circadian rhythmicity within the immune system provides a rationale for hypothesis that immune checkpoint inhibitor (ICI) infusion time-of-day may serve as an actionable mechanism to improve outcomes. Herein, we explore the association between ICI time of infusion (TOI) and outcomes in metastatic renal cell carcinoma (mRCC)., Methods: Data from patients with mRCC who received nivolumab or nivolumab/ipilimumab, in first- or second-line were retrospectively collected. Patients who received < 20% of infusions after 16:30 were assigned to the early TOI sub-cohort, while the rest were assigned to the late TOI sub-cohort. Clinical outcomes were compared across the 2 groups., Results: Among 135 patients included, 89 (65.9%) and 46 (34.1%) were assigned to early and late TOI sub-cohorts, respectively. Baseline characteristics were comparable across the 2 sub-cohorts. Objective response rate (ORR) was 36.0% with early TOI versus 29.5% with late TOI (P = .157). Median time to treatment failure (TTF) was 9.5 months in the early TOI sub-cohort versus 4.6 months in the late TOI sub-cohort with a hazard ratio (HR) of 1.405 (95% CI, 0.919-2.149; P = .11) in univariate analysis and 1.694 (95% CI, 1.064-2.698; P = .026) in multivariate analysis. Higher cut offs allocating patients into the late TOI sub-cohort yielded an incremental increase in the HR for TTF and overall survival (OS) that reached statistical significance., Conclusions: In patients with mRCC, early TOI yielded a numerical increase in ORR, TTF and OS, with the TTF difference reaching significance in multivariate analysis. Prospective randomized studies are warranted to examine the impact of chronomodulation on outcomes with ICIs in mRCC., Competing Interests: Disclosure N.D. reports a consulting role for Vivreon Bioscience, Inc. N.A. reports consulting role for Astellas, Astra Zeneca, Aveo, Bayer, Bristol Myers Squibb, Calithera, Clovis, Eisai, Eli Lilly, EMD Serono, Exelixis, Foundation Medicine, Genentech, Gilead, Janssen, Merck, MEI Pharma, Nektar, Novartis, Pfizer, Pharmacyclics, and Seattle Genetics and research funding to their institution from Arnivas, Astellas, Astra Zeneca, Bavarian Nordic, Bayer, Bristol Myers Squibb, Calithera, Celldex, Clovis, Crispr, Eisai, Eli Lilly, EMD Serono, Exelixis, Genentech, Gilead, Glaxo Smith Kline, Immunomedics, Janssen, Lava, Medivation, Merck, Nektar, Neoleukin, New Link Genetics, Novartis, Oric, Pfizer, Prometheus, Rexahn, Roche, Sanofi, Seattle Genetics, Takeda, and Tracon. S.K.P. reports consulting/advisory role for Novartis, Medivation, Astellas Pharma, Pfizer, Aveo, Myriad, Genentech, Exelixis, Bristol-Myers Squibb, and Astellas. All other authors report no conflict of interest., (Copyright © 2023. Published by Elsevier Inc.)

Treatment of metastatic renal cell carcinoma (mRCC) after first-line immune checkpoint inhibitors (ICIs) lacks standardization, with limited evidence from small trials and retrospective data. Vascular endothelial growth factor receptor (VEGFR) inhibition through tyrosine kinase inhibitors (TKIs) is the most widely adopted second-line treatment. Encouraging results have been seen with VEGFR-TKIs in the second-line after exposure to an ICI-based combination, achieving a response rate of 30%, and 75% of patients achieving disease control. Rechallenge with ICI alone seems safe but has limited clinical benefit. Promising regimens with combination therapies and novel drugs are being evaluated in phase 3 trials., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Vaccinations against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have had a transformative impact on morbidity and mortality. However, the long-term impact of vaccination on patients with genitourinary cancers is currently unknown., Materials and Methods: This study aimed to assess seroconversion rates in patients with genitourinary cancers receiving COVID-19 vaccination. Patients with prostate cancer, renal cell carcinoma, or urothelial cancer who had not been vaccinated for COVID-19 were included. Blood samples were obtained at baseline and after 2, 6, and 12 months of one dose of an FDA-approved COVID-19 vaccine. Antibody titer analysis was performed using the SCoV-2 Detect IgG ELISA assay, and the results were reported as immune status ratio (ISR). A paired t-test was used for comparison of ISR values between timepoints. In addition, T-cell receptor (TCR) sequencing was performed to assess for differences in TCR repertoire 2 months after vaccination., Results: Out of 133 patients enrolled, 98 baseline blood samples were collected. At 2-, 6-, and 12-month time points 98, 70, and 50 samples were collected, respectively. Median age was 67 (IQR, 62-75), with the majority of patients diagnosed with prostate (55.1%) or renal cell carcinoma (41.8%). Compared to baseline (0.24 [95% CI, 0.19-0.31]) a significant increase in the geometric mean ISR values was observed at the 2-month timepoint (5.59 [4.76-6.55]) (P < .001). However, at the 6-month timepoint, a significant decrease in the ISR values was observed (4.66 [95% CI, 4.04-5.38]; P < .0001). Notably, at the 12-month timepoint, the addition of a booster dose resulted in an absolute increase in the ISR values compared to those who did not receive a booster dose (P = .04)., Conclusions: Only a minority of patients with genitourinary cancers did not ultimately achieve satisfactory seroconversion after receiving commercial COVID-19 vaccination. Cancer type or treatment rendered did not appear to affect the immune response mounted after vaccination., (© The Author(s) 2023. Published by Oxford University Press.)

Purpose: With increased adoption of next-generation sequencing, tailored therapy on the basis of molecular status is being delivered for patients with early-stage resectable non-small-cell lung cancer (NSCLC). The purpose of this narrative review was to focus on recent developments of targeted therapies in the adjuvant and neoadjuvant/adjuvant setting for early-stage disease., Methods: A systematic search of the MEDLINE/PubMed database was performed, focusing on studies published within the past 10 years. Our search queried "early-stage NSCLC (AND) tyrosine kinase inhibitor (TKI; OR) epidermal growth factor receptor (EGFR; OR) anaplastic lymphoma kinase ( ALK )" and was limited only to prospective and ongoing studies., Results: Most studies examining the benefit of targeted therapies in early-stage resectable NSCLC have been for EGFR-TKIs in the adjuvant setting. Currently, only one study, the ADAURA trial of adjuvant osimertinib, has demonstrated an overall survival benefit with the use of an EGFR-TKI in the adjuvant setting. Future work to build on the success of the ADAURA trial is focused on determining the optimal duration of targeted therapies and using biomarkers, such as circulating tumor DNA, to risk-stratify patients and guide maintenance targeted therapy duration., Conclusion: The results of several ongoing studies are eagerly awaited regarding the use of targeted therapies in the neoadjuvant/adjuvant setting and for more uncommon or rare mutations such as ALK , ROS proto-oncogene 1, rearranged during transfection, mesenchymal-epithelial transition factor, and B-Raf proto-oncogene V600E. The treatment landscape for early-stage NSCLC harboring actionable mutations is likely to shift dramatically in the upcoming decade.

Objective: To characterize and further compare the immune cell populations of the tumor microenvironment (TME) in both clear cell and papillary renal cell carcinoma (RCC) using heavy metal-labeled antibodies in a multiplexed imaging approach (imaging mass cytometry)., Materials and Methods: Formalin-fixed paraffin-embedded (FFPE) baseline tumor tissues from metastatic patients with clear cell renal cell carcinoma (ccRCC) and papillary renal cell carcinoma (pRCC) were retrospectively requisitioned from an institutional biorepository. Pretreated FFPE samples from 33 RCC patients (10 ccRCC, 23 pRCC) were accessioned and stained for imaging mass cytometry (IMC) analysis. Clinical characteristics were curated from an institutional RCC database. FFPE samples were prepared and stained with heavy metal-conjugated antibodies for IMC. An 11-marker panel of tumor stromal and immune markers was used to assess and quantify cellular relationships in TME compartments. To validate our time-of-flight (CyTOF) analysis, we cross-validated findings with The Cancer Genome Atlas Program (TCGA) analysis and utilized the CIBERSORTx tool to examine the abundance of main immune cell types in pRCC and ccRCC patients., Results: Patients with ccRCC had a longer median overall survival than did those with pRCC (67.7 vs 26.8 mo, respectively). Significant differences were identified in the proportion of CD4 + T cells between disease subtypes (ccRCC 14.1%, pRCC 7.0%, p<0.01). Further, the pRCC cohort had significantly more PanCK + tumor cells than did the ccRCC cohort (24.3% vs 9.5%, respectively, p<0.01). There were no significant differences in macrophage composition (CD68 + ) between cohorts. Our results demonstrated a significant correlation between the CyTOF and TCGA analyses, specifically validating that ccRCC patients exhibit higher levels of CD4 + T cells (ccRCC 17.60%, pRCC 15.7%, p<0.01) and CD8 + T cells (ccRCC 17.83%, pRCC 11.15%, p<0.01). The limitation of our CyTOF analysis was the large proportion of cells that were deemed non-characterizable., Conclusions: Our findings emphasize the need to investigate the TME in distinct RCC histological subtypes. We observed a more immune infiltrative phenotype in the TME of the ccRCC cohort than in the pRCC cohort, where a tumor-rich phenotype was noted. As practical predictive biomarkers remain elusive across all subtypes of RCC, further studies are warranted to analyze the biomarker potential of such TME classifications., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Govindarajan, Salgia, Li, Castro, Mirzapoiazova, Armstrong, Zhao, Mercier, Dizman, Chawla, Zengin, Meza, Tripathi, Sayegh, Chehrazi-Raffle, Tripathi and Pal.)

Stereotactic body radiation therapy (SBRT) has been shown to be safe and effective for delaying systemic treatment change among patients with metastatic renal cell carcinoma (mRCC). In this study, we sought to assess the genomic signatures of patients with mRCC who underwent SBRT for oligoprogression. A total of 30 patients with oligoprogressive disease were identified, the majority of whom had clear cell renal cell carcinoma (83.3%) and were receiving first-line treatment (53.3%). Genomic and transcriptomic sequencing were available in 20 and 16 patients, respectively. Duration of systemic treatment (DOT) was categorized as that prior (DOT[P]) and subsequent (DOT[S]) to radiation treatment. The median DOT(P) and DOT(S) were 15.1 and 18.3 mo, respectively, with a median DOT(S)/DOT(P) ratio of 1.4. Patients who had a DOT(S)/DOT(P) ratio of ≥1 had increased expression in pathways related to cell proliferation and development. In contrast, among patients with a ratio of ≤1, the reactive oxygen species pathway was enriched. This study highlights the potential role of genomics and transcriptomics to refine radiation treatment selection in patients with mRCC. PATIENT SUMMARY: In this study, we looked at mutations and genomic expressions among kidney cancer patients who responded better to stereotactic body radiotherapy. We found that enriched expression of certain pathways might play a role in response to radiotherapy., (Copyright © 2022. Published by Elsevier B.V.)

Millions of people are diagnosed with cancer each year in the USA and are living on systemic therapies designed to prolong their life. While these therapies are intended to treat the disease, most exacerbate cancer symptoms such as pain and anxiety. Oncologists and other healthcare providers are now challenged to deliver adjunctive therapies designed to improve quality of life of patients while they undergo cancer treatment, including minimizing already disruptive symptoms such as cancer pain and anxiety. Complementary and alternative medicines such as immersive virtual reality (VR) and neurofeedback (NF) are novel approaches to the management of cancer symptoms. While the evidence for combining VR and NF, specifically for management of cancer pain, while patients undergo systemic therapies, is still emerging; our preliminary findings suggest this treatment modality might offer relief of cancer symptoms. This paper briefly highlights the clinical need for supportive therapies such as VR and NF in the oncological setting and summarizes innovative research in this area., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Integrative oncology is a new and growing field of cancer care. Integrative oncology is a patient-centered, evidence-based field of comprehensive cancer care that utilizes integrative therapies such as mind-body practices, acupuncture, massage, music therapy, nutrition, and exercise in collaboration with conventional cancer treatments. Patient interest and utilization has been growing over the past two decades. Clinical research has shown the benefits of these approaches to improving symptom management and quality of life, and is now being incorporated into national guidelines from the National Comprehensive Cancer Network (NCCN) and American Society for Clinical Oncology (ASCO). The availability of these services at cancer centers is growing, although the structure and implementation of integrative oncology remains highly variable. This article discusses the benefits of integrative oncology and provides an overview of the current state of integrative oncology programs nationwide. Current challenges and opportunities for cancer centers to provide integrative services is reviewed in the areas of programmatic structure, clinical service, education, and research.

The goal of oncology is to provide the longest possible survival outcomes with the therapeutics that are currently available without sacrificing patients' quality of life. In lung cancer, several data points over a patient's diagnostic and treatment course are relevant to optimizing outcomes in the form of precision medicine, and artificial intelligence (AI) provides the opportunity to use available data from molecular information to radiomics, in combination with patient and tumor characteristics, to help clinicians provide individualized care. In doing so, AI can help create models to identify cancer early in diagnosis and deliver tailored therapy on the basis of available information, both at the time of diagnosis and in real time as they are undergoing treatment. The purpose of this review is to summarize the current literature in AI specific to lung cancer and how it applies to the multidisciplinary team taking care of these complex patients., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Recently data suggest that telomerase reverse transcripatase (TERT) promoter mutations portend superior outcomes with immune checkpoint inhibitor (ICI) therapy in mUC. In our retrospective analysis from 2 tertiary cancer centers, we assessed the predictive role of TERT mutations along with other parameters., Methods: Patient registries were queried for patients treated with ICI for mUC with available genomic and clinical data. Select clinical and laboratory parameters, in addition to primary tumor site, histology, treatment modality, and setting were recorded. Tumor mutational burden (TMB), and mutational status of TERT, CDKN2A, CDKN2B, TMB, TP53, RB1, KMT2D, ARID1A, ERBB2, KDM6A, PIK3CA, FGFR3, and ATM were noted. Univariate analysis of significance concerning overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) was conducted., Results: In total, 113 patients were found to meet inclusion criteria. In our study, ORR was 55%, median PFS was 5.1 months (0.2-71.8), and median OS was 13.4 months (0.2-84.8). On univariate analysis, female sex, NLR>5, and ATM mutation were associated with inferior PFS and OS, whereas upper tract primary disease and ECOG score ≥ 2 were associated with worse OS. On multivariate analysis, NLR >5 was associated with worse PFS and OS whereas upper tract primary disease, albumin <3.4 g/dL, hemoglobin <10 g/dL and ATM mutation were significantly associated with worse OS on multivariate analysis. No significant differences were seen in ORR, PFS, or OS regarding TERT promoter mutations., Conclusion: TERT promoter mutations were not significantly associated with any difference in outcome in patients treated with ICI., Competing Interests: Disclosure The authors have stated that they have no conflicts of interest., (Copyright © 2022. Published by Elsevier Inc.)

Histoplasma capsulatum is a geographically specific dimorphic fungus that can cause a spectrum of diseases. While most cases are asymptomatic pulmonary infections, in severe cases, particularly in immunocompromised patients, disseminated disease can occur. Histoplasmosis in California is limited to only a few case reports. In this article, we describe a rare case of disseminated histoplasmosis in a non-endemic region presenting with diagnostically challenging symptomatology, including altered mental status, status epilepticus, septic shock, and bilateral adrenal masses.

Since the approval of the COVID-19 vaccines, their safety and efficacy has been widely demonstrated in patients with cancer. However, there remain patients with reservations regarding vaccination. We aimed to assess genitourinary cancer patients' perceptions of the vaccines as well as barriers and influencers of decision-making through the completion of a questionnaire. While vaccine-associated concerns were observed, most patients with genitourinary cancers were willing to receive the vaccine. Moving forward, differing strategies could be considered to enhance patient education on the utility of vaccination in the setting of cancer and beyond.

This narrative review aims to summarize the currently available evidence for the role of radiation in the treatment of thymus cancers. Thymus cancers are rare, heterogeneous tumors with limited evidence to guide their clinical management. There remains some controversy over the role of radiation in the adjuvant and induction/definitive setting. We performed a systematic search of the MEDLINE/PubMed database, focusing on studies published within the last 30 years. Our search queried "thymoma [OR] thymic carcinoma [AND] radiation" and was limited only to prospective and retrospective studies and metanalyses, omitting books, documents, and reviews. Our search resulted in 174 total references, of which only 31 references were within the scope of interest ranging from 1988 to 2021. For resectable disease, there is prospective evidence to support the avoidance of postoperative radiation (PORT) in completely resected Masaoka stage I thymoma, but there is a lack of prospective evidence guiding the use of PORT in other situations. Several retrospective studies and metanalyses have suggested a benefit with PORT for positive margins and advanced stage disease, although it remains controversial whether PORT is beneficial for all completely resected Masaoka stage II thymoma. For unresectable disease, induction chemotherapy followed by reassessment of resectability is the preferred management. Prospective evidence exists to support the use of induction chemoradiation for patients unable to tolerate anthracycline-based chemotherapy and the use of definitive chemoradiation for those unable to undergo surgery. An effective multidisciplinary approach is the optimal strategy for achieving the best outcomes in patients with thymus cancers., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Competing Interests: The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Over the last decade, the treatment paradigm of metastatic renal cell carcinoma has rapidly evolved, with notable changes in the front-line setting. Combination therapies involving the use of either doublet therapy with immune checkpoint inhibitors or combination VEGFR-directed therapies with immune checkpoint inhibitors have significantly improved clinical outcomes, including prolonged overall survival and durable response to treatment. We aim to highlight the Food and Drug Administration-approved front-line therapy options, the navigation of treatment selection, and the future directions of metastatic renal cell carcinoma therapies.

The combination of immunotherapy and radiotherapy/chemoradiation has demonstrated promising results in some disease sites for cancer patients. However, translation to real-world practice is complicated by limited representation in clinical trials of older adults with comorbidities who comprise a significant percentage of patients treated in the clinic. The purpose of this review is to outline the current evidence for multimodality treatment in the older adult population including extrapolation from single modality therapies and the rationale for combinatorial treatment. Although few in number, ongoing trials specifically targeting older cancer patients are highlighted. Looking toward the future, current gaps in the field are identified with recommendations to consider both in the preclinical setting and when designing clinical trials in order to better inform the use of multimodality therapy in the clinic as this data evolves., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The complexity of head and neck cancers (HNC) mandates a multidisciplinary approach and radiation therapy (RT) plays a critical role in the optimal management of patients with HNC, either as frontline or adjuvant treatment postoperatively. The advent of both definitive and post-operative RT has significantly improved the outcomes of patients with HNC. Herein, we discuss the role of postoperative RT in different subtypes of HNC, its side effects, and the importance of surveillance. The treatment regions discussed in this paper are the oral cavity, nasopharynx, paranasal sinus cavity, oropharynx, larynx and hypopharynx. Multiple studies that demonstrate the importance of definitive and/or postoperative RT, which led to an improved outlook of survival for HNC patients will be discussed.

Background: Extracorporeal membrane oxygenation (ECMO) remains one of the most intensive therapies for newborns in the United States. However, there is limited information on resource utilization for neonates receiving ECMO., Methods: We conducted a retrospective data analysis of the Kids' Inpatient Database from 1997 to 2012. Bivariate and multivariate analysis was completed to identify predictors of LOS, hospital costs and mortality. Cardiac and non-cardiac diagnoses of neonates receiving ECMO were also included in the bivariate and multivariable analysis., Results: Of the 5151 ECMO cases, survival to discharge was 62%. 22% had a principal cardiac diagnosis. After adjusting for covariates, increased mortality was associated with treatment in the midwest compared to the northeast region (aOR=2.0, p<0.01) and decreased among neonates with a non-cardiac diagnosis (aOR=0.4, p<0.01). Living in midwest was associated with longer LOS by 13days and increased hospital costs by 63,000 dollars (p<0.01). When stratified by non-cardiac diagnoses, infants with a diagnosis of congenital diaphragmatic hernia was associated with increased mortality (2.3, p<0.01) and longer LOS (25, p<0.01) and increased costs (11,100, p<0.01)., Conclusion: Neonates who received ECMO in certain regions of the United States were associated with poorer survival outcomes as well as increased LOS and hospital costs., Type of Study: Retrospective study., Level of Evidence: Level III., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Although multiple advances have been made in systemic therapy for renal cell carcinoma (RCC), metastatic RCC remains incurable. In the current review, we focus on the underlying biology of RCC and plausible mechanisms of metastasis. We further outline evolving strategies to combat metastasis through adjuvant therapy. Finally, we discuss clinical patterns of metastasis in RCC and how distinct systemic therapy approaches may be considered based on the anatomic location of metastasis.