Ali Raza Khaki, MD

All Publications

• Patterns and timing of perioperative blood transfusion and association with outcomes after radical cystectomy. Urologic oncology Diamantopoulos, L. N., Sekar, R. R., Holt, S. K., Khaki, A. R., Miller, N. J., Gadzinski, A., Nyame, Y. A., Vakar-Lopez, F., Tretiakova, M. S., Psutka, S. P., Gore, J. L., Lin, D. W., Schade, G. R., Hsieh, A. C., Lee, J. K., Yezefski, T., Schweizer, M. T., Cheng, H. H., Yu, E. Y., True, L. D., Montgomery, R. B., Grivas, P., Wright, J. L. 2021

  Abstract

  BACKGROUND: Perioperative blood transfusion (PBT) has been associated with worse outcomes across tumor types, including bladder cancer. We report our institutional experience with PBT utilization in the setting of radical cystectomy (RC) for patients with bladder cancer, exploring whether timing of PBT receipt influences perioperative and oncologic outcomes.METHODS: Consecutive patients with bladder cancer treated with RC were identified. PBT was defined as red blood cell transfusion during RC or the postoperative admission. Clinicopathologic and peri and/or postoperative parameters were extracted and compared between patients who did and did not receive PBT using Mann Whitney U Test, chi-square, and log-rank test. Overall (OS) and recurrence-free survival (RFS) were estimated with the Kaplan Meier method. Univariate/multivariate logistic and Cox proportional hazards regression were used to identify variables associated with postoperative and oncologic outcomes, respectively.RESULTS: The cohort consisted of 747 patients (77% men; median age 67 years). Median follow-up was 61.5 months (95% CI 55.8-67.2) At least one postoperative complication (90-day morbidity) occurred in 394 (53%) patients. Median OS and RFS were 91.8 months (95% CI: 76.0-107.6) and 66.0 months (95% CI: 48.3-83.7), respectively. On multivariate analysis, intraoperative, but not postoperative, BT was independently associated with shorter OS (HR: 1.74, 95% CI: 1.32-2.29) and RFS (HR: 1.55, 95%CI: 1.20-2.01), after adjusting for relevant clinicopathologic variables. PBT (intra- or post- operative) was significantly associated with prolonged postoperative hospitalization ≥10 days.CONCLUSIONS: Intraoperative BT was associated with inferior OS and RFS, and PBT overall was associated with prolonged hospitalization following RC. Further studies are needed to validate this finding and explore potential causes for this observation.

  View details for DOI 10.1016/j.urolonc.2021.01.009

  View details for PubMedID 33551249

• Immune checkpoint inhibitors in advanced upper and lower tract urothelial carcinoma: a comparison of outcomes. BJU international Esagian, S. M., Khaki, A. R., Diamantopoulos, L. N., Carril-Ajuria, L., Castellano, D., De Kouchkovsky, I., Park, J. J., Alva, A., Bilen, M. A., Stewart, T. F., McKay, R. R., Santos, V. S., Agarwal, N., Jain, J., Zakharia, Y., Morales-Barrera, R., Devitt, M. E., Nelson, A., Hoimes, C. J., Shreck, E., Gartrell, B. A., Sankin, A., Tripathi, A., Zakopoulou, R., Bamias, A., Rodriguez-Vida, A., Drakaki, A., Liu, S., Kumar, V., Lythgoe, M. P., Pinato, D. J., Murgic, J., Fröbe, A., Joshi, M., Isaacsson Velho, P., Hahn, N., Alonso Buznego, L., Duran, I., Moses, M., Barata, P., Galsky, M. D., Sonpavde, G., Yu, E. Y., Msaouel, P., Koshkin, V. S., Grivas, P. 2021

  Abstract

  To compare clinical outcomes between patients with locally advanced (unresectable) or metastatic urothelial carcinoma (aUC) in the upper and lower urinary tract receiving immune checkpoint inhibitors (ICIs).We performed a retrospective cohort study collecting clinicopathological, treatment, and outcome data for patients with aUC receiving ICIs from 2013 to 2020 across 24 institutions. We compared the objective response rate (ORR), overall survival (OS), and progression-free survival (PFS) between patients with upper and lower tract UC (UTUC, LTUC). Uni- and multivariable logistic and Cox regression were used to assess the effect of UTUC on ORR, OS, and PFS. Subgroup analyses were performed stratified based on histology (pure, mixed) and line of treatment (first line, subsequent line).Out of a total of 746 eligible patients, 707, 717, and 738 were included in the ORR, OS, and PFS analyses, respectively. Our results did not contradict the hypothesis that patients with UTUC and LTUC had similar ORRs (24% vs 28%; adjusted odds ratio [aOR] 0.73, 95% confidence interval [CI] 0.43-1.24), OS (median 9.8 vs 9.6 months; adjusted hazard ratio [aHR] 0.93, 95% CI 0.73-1.19), and PFS (median 4.3 vs 4.1 months; aHR 1.01, 95% CI 0.81-1.27). Patients with mixed-histology UTUC had a significantly lower ORR and shorter PFS vs mixed-histology LTUC (aOR 0.20, 95% CI 0.05-0.91 and aHR 1.66, 95% CI 1.06-2.59), respectively).Overall, patients with UTUC and LTUC receiving ICIs have comparable treatment response and outcomes. Subgroup analyses based on histology showed that those with mixed-histology UTUC had a lower ORR and shorter PFS compared to mixed-histology LTUC. Further studies and evaluation of molecular biomarkers can help refine patient selection for immunotherapy.

  View details for DOI 10.1111/bju.15324

  View details for PubMedID 33556233

• Loose Regulatory Standards Portend a New Era of Imprecision Oncology. Cancer investigation Khaki, A. R. 2021: 1–4

  Abstract

  Precision oncology has revolutionized the therapeutic landscape of oncology and is a goal for cancer drug development. However, lenient drug approvals by the United States Food and Drug Administration under the auspices of precision oncology are setting up this therapeutic approach to fail. In this commentary, I review two recent FDA drug approvals (pembrolizumab for tumor mutation burden-high solid tumors and olaparib for castration-resistant prostate cancer with deleterious homologous recombination repair mutations) where the FDA indication is broader than the studied population. I explain how these broad approvals stray from principles of precision oncology and can cause harm to patients.

  View details for DOI 10.1080/07357907.2020.1851705

  View details for PubMedID 33290099

• A New Prognostic Model in Patients with Advanced Urothelial Carcinoma Treated with First-line Immune Checkpoint Inhibitors. European urology oncology Khaki, A. R., Li, A., Diamantopoulos, L. N., Miller, N. J., Carril-Ajuria, L., Castellano, D., De Kouchkovsky, I., Koshkin, V., Park, J., Alva, A., Bilen, M. A., Stewart, T., Santos, V., Agarwal, N., Jain, J., Zakharia, Y., Morales-Barrera, R., Devitt, M., Nelson, A., Hoimes, C. J., Shreck, E., Gartrell, B. A., Sankin, A., Tripathi, A., Zakopoulou, R., Bamias, A., Rodriguez-Vida, A., Drakaki, A., Liu, S., Kumar, V., Lythgoe, M. P., Pinato, D. J., Murgic, J., Fröbe, A., Joshi, M., Isaacsson Velho, P., Hahn, N., Alonso Buznego, L., Duran, I., Moses, M., Barata, P., Galsky, M. D., Sonpavde, G., Yu, E. Y., Shankaran, V., Lyman, G. H., Grivas, P. 2021

  Abstract

  While immune checkpoint inhibitors (ICIs) are approved in the first-line (1L) setting for cisplatin-unfit patients with programmed death-ligand 1 (PD-L1)-high tumors or for platinum (cisplatin/carboplatin)-unfit patients, response rates remain modest and outcomes vary with no clinically useful biomarkers (except for PD-L1).We aimed to develop a prognostic model for overall survival (OS) in patients receiving 1L ICIs for advanced urothelial cancer (aUC) in a multicenter cohort study.Patients treated with 1L ICIs for aUC across 24 institutions and five countries (in the USA and Europe) outside clinical trials were included in this study.We used a stepwise, hypothesis-driven approach using clinician-selected covariates to develop a new risk score for patients receiving ICIs in the 1L setting. Demographics, clinicopathologic data, treatment patterns, and OS were collected uniformly. Univariate Cox regression was performed on 18 covariates hypothesized to be associated with OS based on published data. Variables were retained for multivariate analysis (MVA) if they correlated with OS (p < 0.2) and were included in the final model if p < 0.05 on MVA. Retained covariates were assigned points based on the beta coefficient to create a risk score. Stratified median OS and C-statistic were calculated.Among 984 patients, 357 with a mean age of 71 yr were included in the analysis, 27% were female, 68% had pure UC, and 13% had upper tract UC. Eastern Cooperative Oncology Group performance status ≥2, albumin <3.5 g/dl, neutrophil:lymphocyte ratio >5, and liver metastases were significant prognostic factors on MVA and were included in the risk score. C index for new 1L risk score was 0.68 (95% confidence interval 0.65-0.71). Limitations include retrospective nature and lack of external validation.We developed a new 1L ICI risk score for OS based on data from patients with aUC treated with ICIs in the USA and Europe outside of clinical trials. The score components highlight readily available factors related to tumor biology and treatment response. External validation is being pursued.With multiple new treatments under development and approved for advanced urothelial carcinoma, it can be difficult to identify the best treatment sequence for each patient. The risk score may help inform treatment discussions and estimate outcomes in patients treated with first-line immune checkpoint inhibitors, while it can also impact clinical trial design and endpoints. TAKE  HOME MESSAGE: A new risk score was developed for advanced urothelial carcinoma treated with first-line immune checkpoint inhibitors. The score assigned Eastern Cooperative Oncology Group performance status ≥2, albumin <3.5 g/dl, neutrophil:lymphocyte ratio >5, and liver metastases each one point, with a higher score being associated with worse overall survival.

  View details for DOI 10.1016/j.euo.2020.12.006

  View details for PubMedID 33423945

• Gender Differences in Faculty Rank and Subspecialty Choice among Academic Medical Oncologists. Cancer investigation Graham, L. S., Sokolova, A. O., Khaki, A. R., Wu, Q. V., Davidson, N. E. 2021; 39 (1): 21–24

  Abstract

  Gender parity within academic oncology is important. We hypothesized that gender differences exist in subspecialty choice and academic rank among medical oncologists. We performed a cross-sectional study of adult medical oncologists at the top 15 cancer centers. Gender, rank, subspecialty (breast, thoracic, gastrointestinal, and genitourinary) and board certification year were recorded. 570 medical oncologists were identified (60% men; 40% women). More women practice breast oncology (OR 3.1, p < 0.001), but less practice genitourinary oncology (OR 0.37, p < 0.001). 22% of women were full professors vs 34% of men (OR 0.55, p = 0.001). Gender differences persist in academic adult medical oncology.

  View details for DOI 10.1080/07357907.2020.1846191

  View details for PubMedID 33131319

• Utilization of COVID-19 treatments and clinical outcomes among patients with cancer: A COVID-19 and Cancer Consortium (CCC19) cohort study. Cancer discovery Rivera, D. R., Peters, S., Panagiotou, O. A., Shah, D. P., Kuderer, N. M., Hsu, C., Rubinstein, S. M., Lee, B. J., Choueiri, T. K., de Lima Lopes, G., Grivas, P., Painter, C. A., Rini, B. I., Thompson, M. A., Arcobello, J., Bakouny, Z., Doroshow, D. B., Egan, P. C., Farmakiotis, D., Fecher, L. A., Friese, C. R., Galsky, M. D., Goel, S., Gupta, S., Halfdanarson, T. R., Halmos, B., Hawley, J. E., Khaki, A. R., Lemmon, C. A., Mishra, S., Olszewski, A. J., Pennell, N. A., Puc, M. M., Revankar, S. G., Schapira, L., Schmidt, A., Schwartz, G. K., Shah, S. A., Wu, J. T., Xie, Z., Yeh, A. C., Zhu, H., Shyr, Y., Lyman, G. H., Warner, J. L. 2020

  Abstract

  Among 2,186 US adults with invasive cancer and laboratory-confirmed SARS-CoV-2 infection, we examined the association of COVID-19 treatments with 30-day all-cause mortality, and factors associated with treatment. Logistic regression with multiple adjustments (e.g., comorbidities, cancer status, baseline COVID-19 severity) was performed. Hydroxychloroquine with any other drug was associated with increased mortality versus treatment with any COVID-19 treatment other than hydroxychloroquine or untreated controls; this association was not present with hydroxychloroquine alone. Remdesivir had numerically reduced mortality versus untreated controls that did not reach statistical significance. Baseline COVID-19 severity was strongly associated with receipt of any treatment. Black patients were approximately half as likely to receive remdesivir as white patients. While observational studies can be limited by potential unmeasured confounding, our findings add to the emerging understanding of patterns of care for patients with cancer and COVID-19 and support evaluation of emerging treatments through prospective controlled trials inclusive of this population.

  View details for DOI 10.1158/2159-8290.CD-20-0941

  View details for PubMedID 32699031

• Clinical impact of COVID-19 on patients with cancer (CCC19): a cohort study. Lancet (London, England) Kuderer, N. M., Choueiri, T. K., Shah, D. P., Shyr, Y., Rubinstein, S. M., Rivera, D. R., Shete, S., Hsu, C. Y., Desai, A., de Lima Lopes, G., Grivas, P., Painter, C. A., Peters, S., Thompson, M. A., Bakouny, Z., Batist, G., Bekaii-Saab, T., Bilen, M. A., Bouganim, N., Larroya, M. B., Castellano, D., Del Prete, S. A., Doroshow, D. B., Egan, P. C., Elkrief, A., Farmakiotis, D., Flora, D., Galsky, M. D., Glover, M. J., Griffiths, E. A., Gulati, A. P., Gupta, S., Hafez, N., Halfdanarson, T. R., Hawley, J. E., Hsu, E., Kasi, A., Khaki, A. R., Lemmon, C. A., Lewis, C., Logan, B., Masters, T., McKay, R. R., Mesa, R. A., Morgans, A. K., Mulcahy, M. F., Panagiotou, O. A., Peddi, P., Pennell, N. A., Reynolds, K., Rosen, L. R., Rosovsky, R., Salazar, M., Schmidt, A., Shah, S. A., Shaya, J. A., Steinharter, J., Stockerl-Goldstein, K. E., Subbiah, S., Vinh, D. C., Wehbe, F. H., Weissmann, L. B., Wu, J. T., Wulff-Burchfield, E., Xie, Z., Yeh, A., Yu, P. P., Zhou, A. Y., Zubiri, L., Mishra, S., Lyman, G. H., Rini, B. I., Warner, J. L. 2020

  Abstract

  Data on patients with COVID-19 who have cancer are lacking. Here we characterise the outcomes of a cohort of patients with cancer and COVID-19 and identify potential prognostic factors for mortality and severe illness.In this cohort study, we collected de-identified data on patients with active or previous malignancy, aged 18 years and older, with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection from the USA, Canada, and Spain from the COVID-19 and Cancer Consortium (CCC19) database for whom baseline data were added between March 17 and April 16, 2020. We collected data on baseline clinical conditions, medications, cancer diagnosis and treatment, and COVID-19 disease course. The primary endpoint was all-cause mortality within 30 days of diagnosis of COVID-19. We assessed the association between the outcome and potential prognostic variables using logistic regression analyses, partially adjusted for age, sex, smoking status, and obesity. This study is registered with ClinicalTrials.gov, NCT04354701, and is ongoing.Of 1035 records entered into the CCC19 database during the study period, 928 patients met inclusion criteria for our analysis. Median age was 66 years (IQR 57-76), 279 (30%) were aged 75 years or older, and 468 (50%) patients were male. The most prevalent malignancies were breast (191 [21%]) and prostate (152 [16%]). 366 (39%) patients were on active anticancer treatment, and 396 (43%) had active (measurable) cancer. At analysis (May 7, 2020), 121 (13%) patients had died. In logistic regression analysis, independent factors associated with increased 30-day mortality, after partial adjustment, were: increased age (per 10 years; partially adjusted odds ratio 1·84, 95% CI 1·53-2·21), male sex (1·63, 1·07-2·48), smoking status (former smoker vs never smoked: 1·60, 1·03-2·47), number of comorbidities (two vs none: 4·50, 1·33-15·28), Eastern Cooperative Oncology Group performance status of 2 or higher (status of 2 vs 0 or 1: 3·89, 2·11-7·18), active cancer (progressing vs remission: 5·20, 2·77-9·77), and receipt of azithromycin plus hydroxychloroquine (vs treatment with neither: 2·93, 1·79-4·79; confounding by indication cannot be excluded). Compared with residence in the US-Northeast, residence in Canada (0·24, 0·07-0·84) or the US-Midwest (0·50, 0·28-0·90) were associated with decreased 30-day all-cause mortality. Race and ethnicity, obesity status, cancer type, type of anticancer therapy, and recent surgery were not associated with mortality.Among patients with cancer and COVID-19, 30-day all-cause mortality was high and associated with general risk factors and risk factors unique to patients with cancer. Longer follow-up is needed to better understand the effect of COVID-19 on outcomes in patients with cancer, including the ability to continue specific cancer treatments.American Cancer Society, National Institutes of Health, and Hope Foundation for Cancer Research.

  View details for DOI 10.1016/S0140-6736(20)31187-9

  View details for PubMedID 32473681

• Plasmacytoid Urothelial Carcinoma: Response to Chemotherapy and Oncologic Outcomes BLADDER CANCER Diamantopoulos, L. N., Khaki, A., Grivas, P., Gore, J. L., Schade, G. R., Hsieh, A. C., Lee, J. K., Yezefski, T., Yu, E. Y., Schweizer, M. T., Cheng, H. H., Psutka, S. P., Lin, D. W., Tretiakova, M. S., Vakar-Lopez, F., Montgomery, R. B., Wright, J. L. 2020; 6 (1): 71–81

  View details for DOI 10.3233/BLC-190258

  View details for Web of Science ID 000523301600008

• Impact of performance status on treatment outcomes: A real-world study of advanced urothelial cancer treated with immune checkpoint inhibitors. Cancer Khaki, A. R., Li, A., Diamantopoulos, L. N., Bilen, M. A., Santos, V., Esther, J., Morales-Barrera, R., Devitt, M., Nelson, A., Hoimes, C. J., Shreck, E., Assi, H., Gartrell, B. A., Sankin, A., Rodriguez-Vida, A., Lythgoe, M., Pinato, D. J., Drakaki, A., Joshi, M., Isaacsson Velho, P., Hahn, N., Liu, S., Alonso Buznego, L., Duran, I., Moses, M., Jain, J., Murgic, J., Baratam, P., Barata, P., Tripathi, A., Zakharia, Y., Galsky, M. D., Sonpavde, G., Yu, E. Y., Shankaran, V., Lyman, G. H., Grivas, P. 2020; 126 (6): 1208–16

  Abstract

  Immune checkpoint inhibitors (ICIs) represent an appealing treatment for patients with advanced urothelial cancer (aUC) and a poor performance status (PS). However, the benefit of ICIs for patients with a poor PS remains unknown. It was hypothesized that a poor Eastern Cooperative Oncology Group (ECOG) PS (≥2 vs 0-1) would correlate with shorter overall survival (OS) in patients receiving ICIs.In this retrospective cohort study, clinicopathologic, treatment, and outcome data were collected for patients with aUC who were treated with ICIs at 18 institutions (2013-2019). The overall response rate (ORR) and OS were compared for patients with an ECOG PS of 0 to 1 and patients with an ECOG PS ≥ 2 at ICI initiation. The association between a new ICI in the last 30 and 90 days of life (DOL) and death location was also tested.Of the 519 patients treated with ICIs, 395 and 384 were included in OS and ORR analyses, respectively, with 26% and 24% having a PS ≥ 2. OS was higher in those with a PS of 0 to 1 than those with a PS ≥ 2 who were treated in the first line (median, 15.2 vs 7.2 months; hazard ratio [HR], 0.62; P = .01) but not in subsequent lines (median, 9.8 vs 8.2 months; HR, 0.78; P = .27). ORRs were similar for patients with a PS of 0 to 1 and patients with a PS ≥ 2 in both lines. Of the 288 patients who died, 10% and 32% started ICIs in the last 30 and 90 DOL, respectively. ICI initiation in the last 30 DOL was associated with increased odds of death in a hospital (odds ratio, 2.89; P = .04).Despite comparable ORRs, ICIs may not overcome the negative prognostic role of a poor PS, particularly in the first-line setting, and the initiation of ICIs in the last 30 DOL was associated with hospital death location.

  View details for DOI 10.1002/cncr.32645

  View details for PubMedID 31829450

  View details for PubMedCentralID PMC7050422

• Histological Subtypes and Response to PD-1/PD-L1 Blockade in Advanced Urothelial Cancer: A Retrospective Study. The Journal of urology Miller, N. J., Khaki, A. R., Diamantopoulos, L. N., Bilen, M. A., Santos, V., Agarwal, N., Morales-Barrera, R., Devitt, M., Nelson, A., Hoimes, C. J., Shreck, E., Assi, H., Gartrell, B. A., Sankin, A., Rodriguez-Vida, A., Lythgoe, M., Pinato, D. J., Drakaki, A., Joshi, M., Isaacsson Velho, P., Hahn, N., Liu, S., Alonso Buznego, L., Duran, I., Moses, M., Jain, J., Murgic, J., Barata, P., Tripathi, A., Zakharia, Y., Galsky, M. D., Sonpavde, G., Yu, E. Y., Lyman, G. H., Grivas, P. 2020; 204 (1): 63–70

  Abstract

  Urinary tract cancer can be pure urothelial carcinoma, pure nonurothelial carcinoma or variant urothelial carcinoma (defined here as mixed urothelial carcinoma). Little is known regarding outcomes for patients with variant urothelial carcinoma receiving immune checkpoint inhibitors. We hypothesized that variant urothelial carcinoma does not compromise immune checkpoint inhibitor efficacy in patients with advanced urothelial carcinoma.We performed a retrospective cohort study across 18 institutions. Demographic, clinicopathological, treatment and outcomes data were collected for patients with advanced urothelial carcinoma who received immune checkpoint inhibitors. Patients were divided into pure vs variant urothelial carcinoma subgroups, with variant urothelial carcinoma further divided by type of variant (ie squamous, neuroendocrine etc). We compared overall response rate using univariate and multivariate logistic regression and progression-free survival and overall survival using Kaplan-Meier and univariate and multivariate Cox proportional hazards.Overall 519 patients were identified, with 395, 406 and 403 included in overall response rate, overall survival and progression-free survival analyses, respectively. Overall response rate to immune checkpoint inhibitors between patients with pure vs variant urothelial carcinoma was comparable (28% vs 29%, p=0.90) without significant differences for individual subtypes vs pure urothelial carcinoma. Median overall survival for patients with pure urothelial carcinoma was 11.0 months vs 10.1 months for variant urothelial carcinoma (p=0.60), but only 4.6 months for patients with neuroendocrine features (9 patients, HR 2.75, 95% CI 1.40-5.40 vs pure urothelial carcinoma, p=0.003). Median progression-free survival was 4.1 months for pure vs 5.2 months for variant urothelial carcinoma (p=0.43) and 3.7 months for neuroendocrine features (HR 1.87, 95% CI 0.92-3.79 vs pure urothelial carcinoma, p=0.09).Overall response rate to immune checkpoint inhibitors was comparable across histological types. However, overall survival was worse for patients with tumors containing neuroendocrine features. Variant urothelial carcinoma should not exclude patients from receiving immune checkpoint inhibitors.

  View details for DOI 10.1097/JU.0000000000000761

  View details for PubMedID 31971495

  View details for PubMedCentralID PMC7289665

• Central Nervous System Metastasis in Patients With Urothelial Carcinoma: Institutional Experience and a Comprehensive Review of the Literature. Clinical genitourinary cancer Diamantopoulos, L. N., Khaki, A. R., Sonpavde, G. P., Venur, V. A., Yu, E. Y., Wright, J. L., Grivas, P. 2020; 18 (3): e266–e276

  Abstract

  Central nervous system (CNS) metastasis in patients with urothelial carcinoma (UC) is uncommon and poorly understood. We aimed to explore the clinical behavior and outcomes of this unique patient population.We performed a retrospective analysis of patients with UC and CNS metastasis, treated in our institution (2006-2018), along with an exploratory patient-point meta-analysis of a similar patient population derived from a comprehensive literature review. Data regarding diagnosis, management, and outcomes were extracted. Overall survival, time to CNS metastasis (TTCM), and residual survival (RS) from CNS involvement to death were calculated (Kaplan-Meier method). Cox regression was used for testing key clinicopathologic associations.We identified 20 "institutional" and 154 "literature" patients with adequate data granularity for analysis. Median TTCM was 17.7 (institutional cohort) and 10 (literature cohort) months. Most patients who developed CNS metastases had previous non-CNS metastasis (15/20 [75%] and 103/154 [67%], respectively). CNS lesions without previous history of metastasis were identified in 5/20 (25%) and 33/154 (21%) cases and those patients had a shorter TTCM. CNS lesions in the absence of known UC history were also documented in 18/154 (12%) literature cases. Multifocal CNS disease was associated with shorter RS in both cohorts in univariate, but not multivariate, analysis.We observed a variability in disease presentation and course, with a subset of patients showing an early predilection for CNS insult, potentially reflecting a diverse underlying biology. Genomic profiling studies, elucidating the molecular landscape, and driving future treatments should be considered in this setting.

  View details for DOI 10.1016/j.clgc.2019.11.008

  View details for PubMedID 32178979

  View details for PubMedCentralID PMC7272305

• Untangling the Multidisciplinary Care Web: Streamlining Care Through an Immune-Related Adverse Events (IRAE) Tumor Board. Targeted oncology Kennedy, L. C., Wong, K. M., Kamat, N. V., Khaki, A. R., Bhatia, S., Thompson, J. A., Grivas, P. 2020; 15 (4): 541–48

  Abstract

  Immune-related adverse events (IRAEs) are becoming increasingly common as the use of immune checkpoint inhibitors expands into more tumor types and treatment settings. Although the majority of IRAEs are mild and can be managed in the outpatient setting by the medical oncologist, severe IRAEs can be life threatening and often require complex care coordination among multiple providers. These providers include a variety of non-oncology specialists who have interest and expertise in managing IRAEs. Multiple systems-based solutions have been proposed in the literature, but these need to be tailored to the needs and resources of each practice setting. In this article, we highlight the challenges of IRAE care by presenting an illustrative case from our institution. We then describe the format and structure of the IRAE Tumor Board established at the University of Washington/Seattle Cancer Care Alliance/Fred Hutchinson Cancer Research Center. Finally, we discuss how this tumor board attempts to address clinical issues related to complex IRAE presentations and provide IRAE education.

  View details for DOI 10.1007/s11523-020-00739-5

  View details for PubMedID 32710246

  View details for PubMedCentralID PMC7489785

• Immunotherapy-based combination strategies for advanced urothelial cancer: A long quest. Cancer Khaki, A. R., Agarwal, N., Pal, S. K., Grivas, P. 2020; 126 (20): 4446–50

  Abstract

  Despite longer survival with immune checkpoint inhibitors targeting programmed cell death protein 1 (PD-1)/programmed cell death-ligand 1 (PD-L1), metastatic urothelial carcinoma remains lethal. There is an unmet need to further improve the efficacy of these agents. In their phase 2 trial, Zhang et al. evaluated the combination of pembrolizumab (a PD-1 inhibitor) plus acalabrutinib (a novel agent inhibiting an enzyme considered relevant to immunotherapy resistance) based on strong rationale but did not demonstrate clinical benefit compared with pembrolizumab alone. Future trials that examine such promising rational combinations may be able to evaluate selected patients based on validated biomarkers to optimize benefit in an endless pursuit of personalizing therapies.

  View details for DOI 10.1002/cncr.33068

  View details for PubMedID 32757318

• Comparison of Health Care Utilization at the End of Life Among Patients With Cancer in Alberta, Canada, Versus Washington State. JCO oncology practice Khaki, A. R., Xu, Y., Cheung, W. Y., Li, L., Fedorenko, C., Grivas, P., Ramsey, S., Shankaran, V. 2020; 16 (12): e1543–e1552

  Abstract

  Aggressive care at the end of life (EOL) can lead to unnecessary suffering and health care costs for patients with cancer. Despite geographic proximity and cultural similarities, we hypothesize that EOL care is more intense in the United States multipayer system versus the Canadian single-payer system. We compared health care utilization at EOL among patients with cancer in Alberta, Canada, with those in Washington state in the United States.Adult patients with American Joint Committee on Cancer stage II to IV solid tumors who died between 2014 and 2016 in Alberta and between 2015 and 2017 in Washington were identified from regional population-based cancer registries linked to treatment and hospitalization records (Alberta) and health claims from major regional insurance plans (Washington). The proportion of patients receiving chemotherapy and having multiple emergency department (ED) visits, or intensive care unit (ICU) admissions in the last 30, 60, and 90 days of life (DOL) in Alberta and Washington were determined and compared using two-sample z-test and multivariable logistic regression (α = .006 after Bonferroni correction).Of patients, 11,177 in Alberta and 12,807 in Washington were included. Patients were similar in age (median, 71 v 72 year), with more patients in Washington with no comorbidities. More patients in Washington were treated with chemotherapy (12.6% v 6.6%; adjusted OR [aOR], 2.74), had multiple ED visits (16.2% v 12.1%; aOR, 1.40), and ICU admissions (23.7% v 3.9%; aOR, 14.27) in the last 30 DOL. Utilization was also higher in Washington in the last 60 and 90 DOL and among those with stage IV disease and those age 65 years and older.Utilization of chemotherapy, ED visits, and ICU admissions near EOL was higher in Washington versus Alberta. Future studies to characterize drivers of aggressive EOL care may help improve cancer care for patients in the United States and Canada.

  View details for DOI 10.1200/OP.20.00217

  View details for PubMedID 32804586

  View details for PubMedCentralID PMC7735039

• Response to Neoadjuvant Chemotherapy and Survival in Micropapillary Urothelial Carcinoma: Data From a Tertiary Referral Center and the Surveillance, Epidemiology, and End Results (SEER) Program. Clinical genitourinary cancer Diamantopoulos, L. N., Holt, S. K., Khaki, A. R., Sekar, R. R., Gadzinski, A., Nyame, Y. A., Vakar-Lopez, F., Tretiakova, M. S., Psutka, S. P., Gore, J. L., Lin, D. W., Schade, G. R., Hsieh, A. C., Lee, J. K., Yezefski, T., Schweizer, M. T., Cheng, H. H., Yu, E. Y., True, L. D., Montgomery, R. B., Grivas, P., Wright, J. L. 2020

  Abstract

  Micropapillary urothelial carcinoma (MPC) is a rare urothelial carcinoma variant with conflicting data guiding clinical practice. In this study, we explored oncologic outcomes in relation to neoadjuvant chemotherapy (NAC) in a retrospective cohort of patients with MPC, alongside data from Surveillance, Epidemiology, and End Results (SEER)-Medicare.We retrospectively identified patients with MPC or conventional urothelial carcinoma (CUC) without any variant histology undergoing radical cystectomy (RC) in our institution (2003-2018). SEER-Medicare was also queried to identify patients diagnosed with MPC (2004-2015). Clinicopathologic data and treatment modalities were extracted. Overall survival (OS) was estimated with the Kaplan-Meier method. Mann-Whitney-Wilcoxon and chi-square tests were used for comparative analysis and Cox regression for identifying clinical covariates associated with OS.Our institutional database yielded 46 patients with MPC and 457 with CUC. In SEER-Medicare, 183 patients with MPC were identified, and 63 (34%) underwent RC. In the institutional cohort, patients with MPC had significantly higher incidence of cN+ (17% vs. 8%), pN+ stage (30% vs. 17%), carcinoma-in-situ (43% vs. 25%), and lymphovascular invasion (30% vs. 16%) at RC versus those with CUC (all P < .05). Pathologic complete response (ypT0N0) to NAC was 33% for MPC and 35% for CUC (P = .899). Median OS was lower for institutional MPC versus CUC in univariate analysis (43.6 vs. 105.3 months, P = .006); however, MPC was not independently associated with OS in the multivariate model. Median OS was 25 months in the SEER MPC cohort for patients undergoing RC, while NAC was not associated with improved OS in that group.Pathologic response to NAC was not significantly different between MPC and CUC, while MPC histology was not an independent predictor of OS. Further studies are needed to better understand biological mechanisms behind its aggressive features as well as the role of NAC in this histology variant.

  View details for DOI 10.1016/j.clgc.2020.10.002

  View details for PubMedID 33160889

• Use of Real-World Electronic Health Records to Estimate Risk, Risk Factors, and Disparities for COVID-19 in Patients With Cancer. JAMA oncology Desai, A., Khaki, A. R., Kuderer, N. M. 2020

  View details for DOI 10.1001/jamaoncol.2020.5461

  View details for PubMedID 33300955

• Effect of Xpert MTB/RIF on clinical outcomes in routine care settings: individual patient data meta-analysis LANCET GLOBAL HEALTH Di Tanna, G., Khaki, A., Theron, G., McCarthy, K., Cox, H., Mupfumi, L., Trajman, A., Zijenah, L., Mason, P., Durovni, R., Bara, W., Hoelscher, M., Clowes, P., Mangu, C., Chanda, D., Pym, A., Mwaba, P., Cobelens, F., Nicol, M. P., Dheda, K., Churchyard, G., Fielding, K., Metcalfe, J. Z., Bandason, T. 2019; 7 (2): E191–E199

  Abstract

  Xpert MTB/RIF, the most widely used automated nucleic acid amplification test for tuberculosis, is available in more than 130 countries. Although diagnostic accuracy is well documented, anticipated improvements in patient outcomes have not been clearly identified. We performed an individual patient data meta-analysis to examine improvements in patient outcomes associated with Xpert MTB/RIF.We searched PubMed, Embase, ClinicalTrials.gov, and the Pan African Clinical Trials Registry from inception to Feb 1, 2018, for randomised controlled trials (RCTs) comparing the use of Xpert MTB/RIF with sputum smear microscopy as tests for tuberculosis diagnosis in adults (aged 18 years or older). We excluded studies of patients with extrapulmonary tuberculosis, and studies in which mortality was not assessed. We used a two-stage approach for our primary analysis and a one-stage approach for the sensitivity analysis. To assess the primary outcome of cumulative 6-month all-cause mortality, we first performed logistic regression models (random effects for cluster randomised trials, with robust SEs for multicentre studies) for each trial, and then pooled the odds ratio (OR) estimates by a fixed-effects (inverse variance) or random-effects (Der Simonian Laird) meta-analysis. We adjusted for age and gender, and stratified by HIV status and previous tuberculosis-treatment history. The study protocol has been registered with PROSPERO, number CRD42014013394.Our search identified 387 studies, of which five RCTs were eligible for analysis. 8567 adult clinic attendees (4490 [63·5%] of 7074 participants for whom data were available were HIV-positive) were tested for tuberculosis with Xpert MTB/RIF (Xpert group) versus sputum smear microscopy (sputum smear group), across five low-income and middle-income countries (South Africa, Brazil, Zimbabwe, Zambia, and Tanzania). The primary outcome (reported in three studies) occurred in 182 (4·5%) of 4050 patients in the Xpert group and 217 (5·3%) of 4093 patients in the smear group (pooled adjusted OR 0·88, 95% CI 0·68-1·14 [p=0·34]; for HIV-positive individuals OR 0·83, 0·65-1·05 [p=0·12]). Kaplan-Meier estimates showed a lower rate of death (12·73 per 100 person-years in the Xpert group vs 16·38 per 100 person-years in the sputum smear group) for HIV-positive patients (hazard ratio 0·76, 95% CI 0·60-0·97; p=0·03). The risk of bias was assessed as reasonable and the statistical heterogeneity across studies was low (I2<20% for the primary outcome).Despite individual patient data analysis from five RCTs, we were unable to confidently rule in nor rule out an Xpert MTB/RIF-associated reduction in mortality among outpatients tested for tuberculosis. Reduction in mortality among HIV-positive patients in a secondary analysis suggests the possibility of population-level impact.US National Institutes of Health.

  View details for DOI 10.1016/S2214-109X(18)30458-3

  View details for Web of Science ID 000456441300022

  View details for PubMedID 30683238

  View details for PubMedCentralID PMC6366854

• Clinical Risk During the Evaluation of Genomic Risk for Hormone-Sensitive Breast Cancer: Ignoring Valuable Data. Journal of the National Comprehensive Cancer Network : JNCCN Khaki, A. R., Gadi, V. K., Prasad, V. 2019; 17 (12): 1456–58

  View details for DOI 10.6004/jnccn.2019.7363

  View details for PubMedID 31805524

• Association of Renin and Aldosterone With Ethnicity and Blood Pressure: The Multi-Ethnic Study of Atherosclerosis AMERICAN JOURNAL OF HYPERTENSION Rifkin, D. E., Khaki, A. R., Jenny, N. S., McClelland, R. L., Budoff, M., Watson, K., Ix, J. H., Allison, M. A. 2014; 27 (6): 801–10

  Abstract

  Although variations in plasma renin activity (PRA) and aldosterone have been examined in whites and blacks, the association of these hormones with blood pressure in multiethnic populations has not been described.We measured PRA and aldosterone in 1,021 participants in the Multi-Ethnic Study of Atherosclerosis not taking antihypertensives and examined the association between ethnicity and PRA/aldosterone and the association between PRA/aldosterone with systolic blood pressure (SBP).Average age was 62 (SD = 9) years, and 49% of participants were women. Median PRA was 0.51 (interquartile range (IQR) = 0.29-0.87) ng/ml/hour, and median aldosterone was 12.6 (IQR = 9.1-17.1) ng/dl. After age and sex adjustment, compared with whites, blacks had 28% lower PRA and 17.4% lower aldosterone, and Hispanics had 20.1% higher PRA but similar aldosterone levels. After multivariable adjustment, compared with whites, only Hispanic ethnicity independently associated with higher PRA (0.18ng/ml/hour; 95% confidence interval (CI) = 0.06-0.31). Blacks had lower aldosterone (-1.7ng/dl; 95% CI = -3.2 to -0.2) compared with whites. After multivariable adjustment, PRA was associated with lower SBP in whites (-3.2mm Hg; 95% CI = -5.2 to -1.2 per standardized unit PRA), Chinese (-3.5mm Hg; 95% CI = -6.2 to -0.80 per standardized unit), and Hispanics (-2.3mm Hg; 95% CI = -4.1 to -0.6 per standardized unit) but not blacks. Aldosterone was associated with higher SBP only in Hispanics (2.5mm Hg; 95% CI = 0.4-4.5 per SD).Compared with whites, blacks have lower aldosterone and Hispanics have higher PRA. Aldosterone had significant associations with higher SBP in Hispanics compared with other groups, a finding that may suggest a different mechanism of hypertension.

  View details for DOI 10.1093/ajh/hpt276

  View details for Web of Science ID 000336527400006

  View details for PubMedID 24436325

  View details for PubMedCentralID PMC4017931