The Interplay between Structural Inequality, Allostatic Load, Inflammation, and Cancer in Black Americans: A Narrative Review.

The impact of racial healthcare disparities has been well documented. Adverse social determinants of health, such as poverty, inadequate housing, and limited access to healthcare, are intricately linked to these disparities and negative health outcomes, highlighting the profound impact that social and economic factors have on individuals' overall well-being. Recent evidence underscores the role of residential location on individual health outcomes. Despite the importance of a healthy lifestyle, regular physical activity, balanced nutrition, and stress management for favorable health outcomes, individuals living in socioeconomically disadvantaged areas may face obstacles in achieving these practices. Adverse living conditions, environmental factors, and systemic biases against Black Americans perpetuate allostatic load. This, compounded by decreased physical activity and limited healthy food options, may contribute to increased oxidative stress and inflammation, fundamental drivers of morbidities such as cardiovascular disease and cancer. Herein, we perform a narrative review of associations between healthcare disparities, chronic stress, allostatic load, inflammation, and cancer in Black Americans, and we discuss potential mechanisms and solutions. Additional research is warranted in the very important area of cancer disparities.

Neoadjuvant cabozantinib restores CD8+ T cells in patients with locally advanced non-metastatic clear cell renal cell carcinoma: a phase 2 trial.

Cabozantinib is an oral multikinase inhibitor approved for treatment in metastatic renal cell carcinoma (RCC). We hypothesized that neoadjuvant cabozantinib could downstage localized tumors, facilitating partial nephrectomy, and facilitating surgery in patients with locally advanced tumors that would require significant adjacent organ resection. We, therefore, conducted a phase 2, single-arm trial of cabozantinib treatment for 12 weeks in 17 patients with locally advanced biopsy-proven non-metastatic clear cell RCC before surgical resection. Six patients (35%) experienced a partial response, and 11 patients (65%) had stable disease. We identified that plasma cell-free DNA (cfDNA), VEGF, c-MET, Gas6, and AXL were significantly increased while VEGFR2 decreased during cabozantinib treatments. There was a trend towards CD8+ T cells becoming activated in the blood, expressing the proliferation marker Ki67 and activation markers HLA-DR and CD38. Cabozantinib treatment depleted myeloid populations acutely. Importantly, immune niches made up of the stem-like CD8+ T cells and antigen presenting cells were increased in every patient. These data suggest that cabozantinib treatment was clinically active and safe in the neoadjuvant setting in patients with locally advanced non-metastatic clear cell RCC and activated the anti-tumor CD8+ T cell response. The trial is registered at ClinicalTrials.gov under registration no. NCT04022343.

Long-Term Results of Bladder Preservation With Twice-Daily Radiation Plus 5-Fluorouracil/Cisplatin or Daily Radiation Plus Gemcitabine for Muscle-Invasive Bladder Cancer-Updated Report of NRG/RTOG 0712: A Randomized Phase 2 Trial.

PURPOSE: For bladder-sparing treatment of muscle-invasive bladder cancer, 5-fluorouracil/cisplatin with twice-daily radiation (FCT) or gemcitabine plus daily radiation (GD) are effective chemoradiation (CRT) regimens. This trial evaluated these regimens and demonstrated efficacy with either regimen at 3 years. With further follow-up, longer-term results are reported here. METHODS AND MATERIALS: Patients with cT2 to cT4a muscle-invasive bladder cancer were randomized to FCT or GD. Patients had a transurethral resection and induction CRT to 40 Gy. Patients with a complete response received consolidation CRT to 64 Gy. Others had cystectomy. Adjuvant gemcitabine/cisplatin chemotherapy was administered. The primary endpoint was freedom from distant metastasis (FDM). This updated analysis reports 7-year data. Toxicity and efficacy endpoints, including bladder-intact distant metastasis-free survival (BI-DMFS) were also assessed. RESULTS: From December 2008 to April 2014, 70 patients were enrolled; 66 were eligible for analysis, 33 per arm. Median follow-up was 9.1 years for eligible living patients. At 7 years, FDM was 65% and 73% for FCT and GD, respectively. Bladder-intact distant metastasis-free survival was 58% (95% CI, 41-76) and 68% (95% CI, 51-84), respectively. The post hoc hazard ratio of 0.75 (95% CI, 0.37-1.55) showed no difference between treatments (P = .44). Overall survival at 7 years was 48% and 59%. There were 4 and 5 cystectomies performed for FCT and GD, respectively. In the FCT arm, there were 5 (16%), 1 (3%), and 0 grade 3, 4, and 5 late toxicities reported, respectively. In the GD arm, there were 7 (23%), 0, and 0 grade 3, 4, and 5 late toxicities reported, respectively. CONCLUSIONS: Both regimens maintained high FDM rates at 7 years. Cystectomy rates were low and overall survival rates were high on both arms. Late toxicity rates were low. Either gemcitabine and daily radiation or a cisplatin-based regimen are effective bladder-sparing therapies.

PD-L1 and nectin-4 expression and genomic characterization of bladder cancer with divergent differentiation.

BACKGROUND: Bladder cancer with divergent differentiation (BCDD) comprises a heterogenous group of tumors with a poor prognosis, and differential expression of nectin-4 and programmed death ligand-1 (PD-L1) has been reported in BCDD. Importantly, nectin-4 expression in bladder cancer is associated with response to enfortumab vedotin, and PD-L1 expression is associated with responses to immune checkpoint inhibitors (ICIs). METHODS: The authors conducted a retrospective review identifying 117 patients with advanced or metastatic BCDD who were treated at Winship Cancer Institute from 2011 to 2021. They performed immunohistochemistry staining for nectin-4 and PD-L1 expression by histologic subtype as well as genomic analysis of these patients, including RNA sequencing, whole-exome sequencing, and fusion detection analysis as well as a subgroup genomic analysis of patients with BCDD who received ICIs. RESULTS: The results indicated that nectin-4 expression was highest in the groups who had the squamous and plasmacytoid subtypes, whereas the group that had the sarcomatoid subtype (70.8%) had the highest proportion of PD-L1-positive patients. Genomic analysis yielded several key findings, including a 50% RB1 mutation rate in patients who had small cell BCDD, targetable PIK3CA mutations across multiple subtypes of BCDD, and significantly higher expression of TEC in responders to ICIs. CONCLUSIONS: In this study, the authors identified clinically relevant data on nectin-4 and PD-L1 expression in patients with rare bladder tumors. They also identified several novel findings in the genomic analysis that highlight the role of precision medicine in this population of patients. Larger, prospective studies are needed to validate these hypothesis-generating data.

The role of ischemia-modified albumin, presepsin, delta neutrophil index, and inflammatory markers in diagnosing acute cholecystitis.

BACKGROUND: The purpose of this study is to determine the significance of markers such as C-reactive protein, procalcitonin, complete blood count parameters, delta neutrophil index, ischemia-modified albumin, presepsin, and oxidative stress indicators, which are associated with inflammation, oxidative stress, and ischemia in the pathology and diagnosis of acute cholecystitis in adults. METHODS: Patients diagnosed with acute cholecystitis in the emergency department and healthy individuals in the control group were included in the study. Routine blood count and biochemistry analyses were performed on the participants. Blood serum was used to measure ischemia-modified albumin, presepsin, and oxidative stress indicators. RESULTS: White blood cell count, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, delta neutrophil index, C-reactive protein, procalcitonin, ischemia-modified albumin, ischemia-modified albumin to albumin ratio, presepsin, and oxidative stress indicators were significantly higher in patients with cholecystitis compared to the control group. Measurements of white blood cell count, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and delta neutrophil index can be included as part of the complete blood count. The complete blood count parameters are readily available and do not incur additional costs to the healthcare system. CONCLUSION: The authors believe that the neutrophil-to-lymphocyte ratio, delta neutrophil index, ischemia-modified albumin, ischemia-modified albumin to albumin ratio, and presepsin values can be used as new markers in the diagnosis of acute cholecystitis due to their high sensitivity, specificity, and low negative likelihood ratio.

Comprehensive genomic profiling of penile squamous cell carcinoma and the impact of human papillomavirus status on immune-checkpoint inhibitor-related biomarkers.

BACKGROUND: Advanced penile squamous cell carcinoma (pSCC) is a rare and aggressive malignancy with limited success of immune-checkpoint inhibitors (ICIs). Approximately half of pSCC cases are associated with human papillomavirus (HPV) infection. METHODS: Evaluation was done retrospectively of the landscape of somatic alterations and ICI-related biomarkers in pSCC by using the Caris Life Sciences data set with the aim to establish signatures for HPV-dependent oncogenesis. The pSCC tumors were analyzed by using next-generation sequencing (NGS) of DNA and RNA. Programmed death ligand 1 (PD-L1) expression was evaluated by immunohistochemistry (IHC). Microsatellite instability (MSI) was tested by fragment analysis, IHC (SP142; ≥1%), and NGS. Tumor mutational burden (TMB)-high was defined as ≥10 mutations/Mb. HPV16/18 status was determined by using whole-exome sequencing (WES) when available. Significance was adjusted for multiple comparisons (q value < .05). RESULTS: NGS of the overall cohort (N = 108) revealed TP53 (46%), CDKN2A (26%), and PIK3CA (25%) to be the most common mutations. Overall, 51% of tumors were PD-L1+, 10.7% had high TMB, and 1.1% had mismatch repair-deficient (dMMR)/MSI-high status. Twenty-nine patients had their HPV status made available by WES (HPV16/18+, n = 13; HPV16/18-, n = 16). KMT2C mutations (33% vs. 0%) and FGF3 amplifications (30.8% vs. 0%) were specific to HPV16/18+ tumors, whereas CDKN2A mutations (0% vs. 37.5%) were exclusive to HPV16/18- tumors. TMB-high was exclusively found in the HPV16/18+ group (30.8%). The two groups had comparable PD-L1 and dMMR/MSI-H status. CONCLUSIONS: In a large and comprehensive NGS-based evaluation of somatic alterations in pSCC, HPV16/18+ versus HPV16/18- pSCCs were molecularly distinct tumors. Our finding that TMB-high is exclusive to HPV16/18+ tumors requires confirmation in larger data sets. PLAIN LANGUAGE SUMMARY: Penile squamous cell carcinoma (pSCC) is a rare and aggressive malignancy in the advanced setting, with poor prognosis and little success with immune-checkpoint inhibitors (ICIs) in an unselected patient approach. Human papillomavirus (HPV) infection is a known risk factor for pSCC; its impact on genomic tumor profiling is less defined. Using next-generation sequencing, we explored the genetic landscape and ICI-related biomarkers of pSCC and HPV-driven oncogenic molecular signatures. Our results indicate that HPV-positive and HPV-negative pSCCs are molecularly distinct tumors. Increased tumor mutational burden is associated with HPV-positive tumors, and could serve as a biomarker for predicting therapeutic response to ICI-based therapies. Our results support the growing literature indicating that HPV status in pSCC can be used to guide patient stratification in ICI-based clinical trials.

Nicardipine is a putative EED inhibitor and has high selectivity and potency against chemoresistant prostate cancer in preclinical models.

BACKGROUND: It is imperative to develop novel therapeutics to overcome chemoresistance, a significant obstacle in the clinical management of prostate cancer (PCa) and other cancers. METHODS: A phenotypic screen was performed to identify novel inhibitors of chemoresistant PCa cells. The mechanism of action of potential candidate(s) was investigated using in silico docking, and molecular and cellular assays in chemoresistant PCa cells. The in vivo efficacy was evaluated in mouse xenograft models of chemoresistant PCa. RESULTS: Nicardipine exhibited high selectivity and potency against chemoresistant PCa cells via inducing apoptosis and cell cycle arrest. Computational, molecular, and cellular studies identified nicardipine as a putative inhibitor of embryonic ectoderm development (EED) protein, and the results are consistent with a proposed mechanism of action that nicardipine destabilised enhancer of zeste homologue 2 (EZH2) and inhibited key components of noncanonical EZH2 signalling, including transducer and activator of transcription 3, S-phase kinase-associated protein 2, ATP binding cassette B1, and survivin. As a monotherapy, nicardipine effectively inhibited the skeletal growth of chemoresistant C4-2B-TaxR tumours. As a combination regimen, nicardipine synergistically enhanced the in vivo efficacy of docetaxel against C4-2 xenografts. CONCLUSION: Our findings provided the first preclinical evidence supporting nicardipine as a novel EED inhibitor that has the potential to be promptly tested in PCa patients to overcome chemoresistance and improve clinical outcomes.

Immune-Related Adverse Events and Clinical Outcomes in Advanced Urothelial Cancer Patients Treated With Immune Checkpoint Inhibitors.

BACKGROUND: In advanced urothelial cancers (UC), immune checkpoint inhibitors (ICI) show promise as a durable therapy. Immune-related adverse events (irAEs), a side effect of ICIs, may serve as an indicator of beneficial response. We investigated the relationship between irAEs and clinical outcomes in patients with advanced UC who received ICI. MATERIALS AND METHODS: In this retrospective study, we investigated 70 patients with advanced UC treated with ICIs at Winship Cancer Institute from 2015 to 2020. Data on patients were collected through chart review. Cox's proportional hazard model and logistic regression were applied to estimate the association with overall survival (OS), progression-free survival (PFS), and clinical benefit (CB). The possible lead-time bias was handled in extended Cox regression models. RESULTS: The median age of the cohort was 68. Over one-third (35%) of patients experienced an irAE, with skin being the most frequent organ involved (12.9%). Patients that experienced at least one irAE had significantly enhanced OS (HR: 0.38, 95% CI, 0.18-0.79, P = .009), PFS (HR: 0.27, 95% CI, 0.14-0.53, P < .001), and CB (OR: 4.20, 95% CI, 1.35-13.06, P = .013). Patients who experienced dermatologic irAEs also had significantly greater OS, PFS, and CB. CONCLUSION: Of patients with advanced UC that had undergone ICI therapy, those who had irAEs, especially dermatologic irAEs, had significantly greater OS, PFS, and CB. These results may suggest that irAE's may serve as an important marker of durable response to ICI therapy in urothelial cancer. The findings of this study need to be validated with larger cohort studies in the future.

Bromocriptine monotherapy overcomes prostate cancer chemoresistance in preclinical models.

Chemoresistance is a major obstacle in the clinical management of metastatic, castration-resistant prostate cancer (PCa). It is imperative to develop novel strategies to overcome chemoresistance and improve clinical outcomes in patients who have failed chemotherapy. Using a two-tier phenotypic screening platform, we identified bromocriptine mesylate as a potent and selective inhibitor of chemoresistant PCa cells. Bromocriptine effectively induced cell cycle arrest and activated apoptosis in chemoresistant PCa cells but not in chemoresponsive PCa cells. RNA-seq analyses revealed that bromocriptine affected a subset of genes implicated in the regulation of the cell cycle, DNA repair, and cell death. Interestingly, approximately one-third (50/157) of the differentially expressed genes affected by bromocriptine overlapped with known p53-p21- retinoblastoma protein (RB) target genes. At the protein level, bromocriptine increased the expression of dopamine D2 receptor (DRD2) and affected several classical and non-classical dopamine receptor signal pathways in chemoresistant PCa cells, including adenosine monophosphate-activated protein kinase (AMPK), p38 mitogen-activated protein kinase (p38 MAPK), nuclear factor kappa B  (NF-κB), enhancer of zeste homolog 2 (EZH2), and survivin. As a monotherapy, bromocriptine treatment at 15 mg/kg, three times per week, via the intraperitoneal route significantly inhibited the skeletal growth of chemoresistant C4-2B-TaxR xenografts in athymic nude mice. In summary, these results provided the first preclinical evidence that bromocriptine is a selective and effective inhibitor of chemoresistant PCa. Due to its favorable clinical safety profiles, bromocriptine could be rapidly tested in PCa patients and repurposed as a novel subtype-specific treatment to overcome chemoresistance.

Treatment Response to Lycopene in Recurrent Prostate Cancer Confirmed on 18 F-Fluciclovine PET/CT.

ABSTRACT: 18 F-fluciclovine (Axumin; Blue Earth Diagnostics, Ltd, Oxford, United Kingdom) PET has shown value in detecting biochemical recurrent prostatic cancer. Lycopene, a plant-based carotenoid, is reported to have potential inhibitory effect on prostate cancer, as a complementary treatment. We report a case of biochemically recurrent prostate cancer showing treatment response to lycopene as seen on an 18 F-fluciclovine PET/CT correlating with serum prostate-specific antigen response.

Evaluation of patients of vaccine side effects after the COVID-19 vaccine.

OBJECTIVE: Postvaccine side effects were evaluated in patients presenting to our emergency department with complaints of vaccine side effects after taking COVID-19 vaccine, and new unknown side effects ranging from mild complaints to life-threatening risks, and frequency of all side effects were investigated. This study aimed to establish a scientific resource to identify the potential side effects of the vaccine. METHODS: Patients' demographic information, clinical characteristics, epicrisis reports, COVID-19 disease and vaccination histories, vital values, and blood values were examined. The SPSS 20.0 package program was used for statistical evaluation. p<0.05 was considered statistically significant. RESULTS: Notably, 13.1% of patients presenting to the emergency department started to have complaints after taking Sinovac vaccine, whereas 86.9% of them had complaints after taking BioNTech vaccine. Also, 36.9% of patients stated that they had COVID-19. All patients had a Glasgow coma scale score of 15 during admission. No patient was hospitalized, ventilator was not needed, and all patients were discharged. While the most common presenting complaint to the emergency department after vaccination was fatigue in 29.7%, the most common diagnoses after examination in the emergency department were myalgia in 32.1% and upper respiratory tract infection in 28.6%. CONCLUSION: Results and conclusions of our study will guide healthcare workers and patients on the side effects of COVID-19 vaccine.

Impact of 18 F-Fluciclovine PET/CT Findings on Failure-Free Survival in Biochemical Recurrence of Prostate Cancer Following Salvage Radiation Therapy.

PURPOSE: We aimed to evaluate the impact of 18 F-fluciclovine PET/CT imaging on failure-free survival (FFS) post-salvage radiotherapy (SRT) for prostate cancer (PCa) recurrence. METHODS: Seventy-nine patients were recruited in a phase 2/3 clinical trial to undergo 18 F-fluciclovine PET/CT before SRT for PCa. Four patients with extrapelvic disease were excluded. All patients were followed up at regular intervals up to 48 months. Treatment failure was defined as a serum prostate-specific antigen level of ≥0.2 ng/mL above the nadir after SRT, confirmed with an additional measurement, requiring systemic treatment or clinical progression. Failure-free survival was computed and compared between patients grouped according to 18 F-fluciclovine PET/CT imaging findings. RESULTS: Eighty percent (60/75) of patients had a positive finding on 18 F-fluciclovine PET/CT, of which 56.7% (34/60) had prostate bed-only uptake, whereas 43.3% (26/60) had pelvic nodal ± bed uptake. Following SRT, disease failure was detected in 36% (27/75) of patients. There was a significant difference in FFS between patients who had a positive versus negative scan (62.3% vs 92.9% [ P < 0.001] at 36 months and 59.4% vs 92.9% [ P < 0.001] at 48 months). Similarly, there was a significant difference in FFS between patients with uptake in pelvic nodes ± bed versus prostate bed only at 36 months (49.8% vs 70.7%; P = 0.003) and at 48 months (49.8% vs 65.6%; P = 0.040). Failure-free survival was also significantly higher in patients with either negative PET/CT or prostate bed-only disease versus those with pelvic nodal ± prostate bed disease at 36 (78% vs 49.8%, P < 0.001) and 48 months (74.4% vs 49.8%, P < 0.001). CONCLUSIONS: Findings on pre-SRT 18 F-fluciclovine PET/CT imaging, even when acted upon to optimize the treatment decisions and treatment planning, are predictive of post-SRT FFS in men who experience PCa recurrence after radical prostatectomy. A negative 18 F-fluciclovine PET/CT is most predictive of a lower risk of failure, whereas the presence of pelvic nodal recurrence portends a higher risk of SRT failure.

Evaluation of patients of vaccine side effects after the COVID-19 vaccine

SUMMARY OBJECTIVE: Postvaccine side effects were evaluated in patients presenting to our emergency department with complaints of vaccine side effects after taking COVID-19 vaccine, and new unknown side effects ranging from mild complaints to life-threatening risks, and frequency of all side effects were investigated. This study aimed to establish a scientific resource to identify the potential side effects of the vaccine. METHODS: Patients' demographic information, clinical characteristics, epicrisis reports, COVID-19 disease and vaccination histories, vital values, and blood values were examined. The SPSS 20.0 package program was used for statistical evaluation. p<0.05 was considered statistically significant. RESULTS: Notably, 13.1% of patients presenting to the emergency department started to have complaints after taking Sinovac vaccine, whereas 86.9% of them had complaints after taking BioNTech vaccine. Also, 36.9% of patients stated that they had COVID-19. All patients had a Glasgow coma scale score of 15 during admission. No patient was hospitalized, ventilator was not needed, and all patients were discharged. While the most common presenting complaint to the emergency department after vaccination was fatigue in 29.7%, the most common diagnoses after examination in the emergency department were myalgia in 32.1% and upper respiratory tract infection in 28.6%. CONCLUSION: Results and conclusions of our study will guide healthcare workers and patients on the side effects of COVID-19 vaccine.

Differences in Failure-Free Survival After Salvage Radiotherapy Guided by Conventional Imaging Versus 18F-Fluciclovine PET/CT in Postprostatectomy Patients: A Post Hoc Substratification Analysis of the EMPIRE-1 Trial.

The EMPIRE-1 (Emory Molecular Prostate Imaging for Radiotherapy Enhancement 1) trial reported a survival advantage in recurrent prostate cancer salvage radiotherapy (SRT) guided by 18F-fluciclovine PET/CT versus conventional imaging. We performed a post hoc analysis of the EMPIRE-1 cohort stratified by protocol-specified criteria, comparing failure-free survival (FFS) between study arms. Methods: EMPIRE-1 randomized patients to SRT planning via either conventional imaging only (bone scanning plus abdominopelvic CT or MRI) (arm A) or conventional imaging plus 18F-fluciclovine PET/CT (arm B). Randomization was stratified by prostate-specific antigen (PSA) level (<2.0 vs. ≥ 2.0 ng/mL), adverse pathology, and androgen-deprivation therapy (ADT) intent. We subdivided patients in each arm using the randomization stratification criteria and compared FFS between patient subgroups across study arms. Results: Eighty-one and 76 patients received per-protocol SRT in study arms A and B, respectively. The median follow-up was 3.5 y (95% CI, 3.0-4.0). FFS was 63.0% and 51.2% at 36 and 48 mo, respectively, in arm A and 75.5% at both 36 and 48 mo in arm B. Among patients with a PSA of less than 2 ng/mL (mean, 0.42 ± 0.42 ng/mL), significantly higher FFS was seen in arm B than arm A at 36 mo (83.2% [95% CI, 70.0-91.0] vs. 66.5% [95% CI, 51.6-77.8], P < 0.001) and 48 mo (83.2% [95% CI, 70.0-91.0] vs. 56.2% [95% CI, 40.5-69.2], P < 0.001). No significant difference in FFS between study arms in patients with a PSA of at least 2 ng/mL was observed. Among patients with adverse pathology, significantly higher FFS was seen in arm B than arm A at 48 mo (68.9% [95% CI, 52.1-80.8] vs. 42.8% [95% CI, 26.2-58.3], P < 0.001) though not at the 36-mo follow-up. FFS was higher in patients without adverse pathology in arm B versus arm A (90.2% [95% CI, 65.9-97.5] vs. 73.1% [95% CI, 42.9-89.0], P = 0.006) at both 36 and 48 mo. Patients in whom ADT was intended in arm B had higher FFS than those in arm A, with the difference reaching statistical significance at 48 mo (65.2% [95% CI, 40.3-81.7] vs. 29.1 [95% CI, 6.5-57.2], P < 0.001). Patients without ADT intent in arm B had significantly higher FFS than patients in arm A at 36 mo (80.7% [95% CI, 64.9-90.0] vs. 68.0% [95% CI, 51.1-80.2]) and 48 mo (80.7% [95% CI, 64.9-90.0] vs. 58.6% [95% CI, 41.0-72.6]). Conclusion: The survival advantage due to the addition of 18F-fluciclovine PET/CT to SRT planning is maintained regardless of the presence of adverse pathology or ADT intent. Including 18F-fluciclovine PET/CT to SRT leads to survival benefits in patients with a PSA of less than 2 ng/mL but not in patients with a PSA of 2 ng/mL or higher.

Baseline Neutrophil-to-Eosinophil Ratio Is Associated with Outcomes in Metastatic Renal Cell Carcinoma Treated with Immune Checkpoint Inhibitors.

BACKGROUND: Biomarkers have the potential to guide treatment selection and clinical care in metastatic renal cell carcinoma (mRCC) in an expanding treatment landscape. We report baseline neutrophil-to-eosinophil ratios (NER) in patients with mRCC treated with immune checkpoint inhibitors (CPIs) and their association with clinical outcomes. METHODS: We conducted a retrospective review of patients with mRCC treated with CPIs at Winship Cancer Institute from 2015 to 2020 in the United States of America (USA). Demographics, disease characteristics, and laboratory data, including complete blood counts (CBC) were described at the initiation of CPIs. Clinical outcomes were measured as overall survival (OS), progression-free survival (PFS), and clinical benefit (CB) associated with baseline lab values. RESULTS: A total of 184 patients were included with a median follow-up time of 25.4 months. Patients with baseline NER were categorized into high or low subgroups; high group was defined as NER >49.2 and low group was defined as NER <49.2 with 25% of patients in the high NER group. Univariate analyses (UVA) and multivariable analyses (MVA) identified decreased overall survival (OS) associated with elevated NER. In MVA, patients with a high baseline NER group had a hazard ratio (HR) of 1.68 (95%CI, 1.01-2.82, P = .048) for OS; however, there was no significant difference between groups for PFS. Clinical benefit was seen in 47.3% of patients with low baseline NER and 40% with high NER. CONCLUSIONS: We conclude that elevated baseline NER may be associated with worse clinical outcomes in mRCC. Although results require further validation, NER is a feasible biomarker in patients with CPI-treated mRCC.

Modulation of inflammation by phytochemicals to enhance efficacy and reduce toxicity of cancer chemotherapy.

Treatment of cancer with chemotherapeutic drugs is associated with numerous adverse effects as well as the eventual development of resistance to chemotherapy. There is a great need for complementary therapies such as botanicals and nutritional supplements with little or no side effects that prevent resistance to chemotherapy and reduce its adverse effects. Inflammation plays a major role in the development of chemoresistance and the adverse effects of chemotherapy. Phytochemicals have well-established anti-inflammatory effects; thus, they could be used as complementary therapies along with chemotherapy to increase its efficacy and reduce its toxicity. Botanical compounds inhibit the NF-κB signaling pathway, which plays an important role in the generation of inflammation, chemotherapy resistance, and modulation of cell survival and apoptosis. Botanicals have previously been studied extensively for their cancer chemopreventive activities and are generally considered safe for human consumption. The present review focuses on the modulation of inflammation by phytochemicals and their role in increasing the efficacy and reducing the toxicity of cancer chemotherapy.

Durable complete response for oligometastatic renal cell carcinoma with immune checkpoint inhibition and cytoreductive nephrectomy in a Jehovah's witness: A case report.

The role of cytoreductive nephrectomy in patients with metastatic renal cell carcinoma is a subject of debate. We report a durable complete response in a 62-year-old man Jehovah's Witness with metastatic clear cell renal cell carcinoma who received two cycles of nivolumab/ipilimumab followed by radical nephrectomy and metastasectomy of known pulmonary disease site, both without a clinical need for perioperative blood transfusions. The patient continues to be without evidence of disease and without additional need for systemic therapy over a year after his radical nephrectomy. The case highlights that cytoreductive nephrectomy continues to play a role in the era of immune checkpoint inhibitors.

Prognostic Evaluation of Metastatic Castration Resistant Prostate Cancer and Neuroendocrine Prostate Cancer with [68Ga]Ga DOTATATE PET-CT.

Objectives: Prostate cancer is well known to express high levels of somatostatin receptors and preliminary data suggests that PET imaging with the somatostatin analog, [68Ga]Ga-DOTATATE, may allow for whole body staging of patients with metastatic castration resistant prostate cancer (mCRPC) and neuroendocrine prostate cancer (NePC). This study explores the utility of [68Ga]Ga-DOTATATE PET-CT to identify metastatic deposits in men with mCRPC and NePC and prognosticate disease progression. Methods: [68Ga]Ga-DOTATATE PET-CT was performed in 17 patients with mCRPC and of those, 2/17 had NePC. A semiquantitative analysis with standardized uptake values (SUV) (e.g., SUVmax, SUVmean) was performed for each metastatic lesion and reference background tissues. [68Ga]Ga-DOTATATE uptake in metastatic deposits was further classified as: mild (less than liver), moderate (up to liver average), or marked (greater than liver). Serial prostate-specific antigen measurements and patient survival were followed up to 3 years after PET imaging to assess response to standard of care treatment. Results: All patients had at least one metastatic lesion with identifiable [68Ga]Ga-DOTATATE uptake. Marked [68Ga]Ga-DOTATATE uptake was found in 7/17 patients, including both NePC patients, and all were non-responders to systemic therapy and died within the follow up period, with a mean time to death of 8.1 months. Three patients had mild [68Ga]Ga-DOTATATE uptake, and all were responders to systemic therapy and were alive 36 months after [68Ga]Ga-DOTATATE imaging. Conclusions: [68Ga]Ga-DOTATATE is able to identify mCRPC and NePC metastatic deposits, and lesions with [68Ga]Ga-DOTATATE uptake > liver may portend poor outcomes in patients with mCRPC.