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  • 1
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    Interplay of Immunosuppression and Immunotherapy Among Patients With Cancer and COVID-19
    American Medical Association (AMA) ; 2023
    In:  JAMA Oncology Vol. 9, No. 1 ( 2023-01-01), p. 128-
    Details
    In: JAMA Oncology, American Medical Association (AMA), Vol. 9, No. 1 ( 2023-01-01), p. 128-
    Abstract: Cytokine storm due to COVID-19 can cause high morbidity and mortality and may be more common in patients with cancer treated with immunotherapy (IO) due to immune system activation. Objective To determine the association of baseline immunosuppression and/or IO-based therapies with COVID-19 severity and cytokine storm in patients with cancer. Design, Setting, and Participants This registry-based retrospective cohort study included 12 046 patients reported to the COVID-19 and Cancer Consortium (CCC19) registry from March 2020 to May 2022. The CCC19 registry is a centralized international multi-institutional registry of patients with COVID-19 with a current or past diagnosis of cancer. Records analyzed included patients with active or previous cancer who had a laboratory-confirmed infection with SARS-CoV-2 by polymerase chain reaction and/or serologic findings. Exposures Immunosuppression due to therapy; systemic anticancer therapy (IO or non-IO). Main Outcomes and Measures The primary outcome was a 5-level ordinal scale of COVID-19 severity: no complications; hospitalized without requiring oxygen; hospitalized and required oxygen; intensive care unit admission and/or mechanical ventilation; death. The secondary outcome was the occurrence of cytokine storm. Results The median age of the entire cohort was 65 years (interquartile range [IQR], 54-74) years and 6359 patients were female (52.8%) and 6598 (54.8%) were non-Hispanic White. A total of 599 (5.0%) patients received IO, whereas 4327 (35.9%) received non-IO systemic anticancer therapies, and 7120 (59.1%) did not receive any antineoplastic regimen within 3 months prior to COVID-19 diagnosis. Although no difference in COVID-19 severity and cytokine storm was found in the IO group compared with the untreated group in the total cohort (adjusted odds ratio [aOR] , 0.80; 95% CI, 0.56-1.13, and aOR, 0.89; 95% CI, 0.41-1.93, respectively), patients with baseline immunosuppression treated with IO (vs untreated) had worse COVID-19 severity and cytokine storm (aOR, 3.33; 95% CI, 1.38-8.01, and aOR, 4.41; 95% CI, 1.71-11.38, respectively). Patients with immunosuppression receiving non-IO therapies (vs untreated) also had worse COVID-19 severity (aOR, 1.79; 95% CI, 1.36-2.35) and cytokine storm (aOR, 2.32; 95% CI, 1.42-3.79). Conclusions and Relevance This cohort study found that in patients with cancer and COVID-19, administration of systemic anticancer therapies, especially IO, in the context of baseline immunosuppression was associated with severe clinical outcomes and the development of cytokine storm. Trial Registration ClinicalTrials.gov Identifier: NCT04354701
    Type of Medium: Online Resource
    ISSN: 2374-2437
    URL: Article
    DOI: 10.1001/jamaoncol.2022.5357
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2023
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  • 2
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    Systemic Anticancer Therapy and Thromboembolic Outcomes in Hospitalized Patients With Cancer and COVID-19
    American Medical Association (AMA) ; 2023
    In:  JAMA Oncology
    Details
    In: JAMA Oncology, American Medical Association (AMA)
    Abstract: Systematic data on the association between anticancer therapies and thromboembolic events (TEEs) in patients with COVID-19 are lacking. Objective To assess the association between anticancer therapy exposure within 3 months prior to COVID-19 and TEEs following COVID-19 diagnosis in patients with cancer. Design, Setting, and Participants This registry-based retrospective cohort study included patients who were hospitalized and had active cancer and laboratory-confirmed SARS-CoV-2 infection. Data were accrued from March 2020 to December 2021 and analyzed from December 2021 to October 2022. Exposure Treatments of interest (TOIs) (endocrine therapy, vascular endothelial growth factor inhibitors/tyrosine kinase inhibitors [VEGFis/TKIs], immunomodulators [IMiDs] , immune checkpoint inhibitors [ICIs], chemotherapy) vs reference (no systemic therapy) in 3 months prior to COVID-19. Main Outcomes and Measures Main outcomes were (1) venous thromboembolism (VTE) and (2) arterial thromboembolism (ATE). Secondary outcome was severity of COVID-19 (rates of intensive care unit admission, mechanical ventilation, 30-day all-cause mortality following TEEs in TOI vs reference group) at 30-day follow-up. Results Of 4988 hospitalized patients with cancer (median [IQR] age, 69 [59-78] years; 2608 [52%] male), 1869 had received 1 or more TOIs. Incidence of VTE was higher in all TOI groups: endocrine therapy, 7%; VEGFis/TKIs, 10%; IMiDs, 8%; ICIs, 12%; and chemotherapy, 10%, compared with patients not receiving systemic therapies (6%). In multivariable log-binomial regression analyses, relative risk of VTE (adjusted risk ratio [aRR] , 1.33; 95% CI, 1.04-1.69) but not ATE (aRR, 0.81; 95% CI, 0.56-1.16) was significantly higher in those exposed to all TOIs pooled together vs those with no exposure. Among individual drugs, ICIs were significantly associated with VTE (aRR, 1.45; 95% CI, 1.01-2.07). Also noted were significant associations between VTE and active and progressing cancer (aRR, 1.43; 95% CI, 1.01-2.03), history of VTE (aRR, 3.10; 95% CI, 2.38-4.04), and high-risk site of cancer (aRR, 1.42; 95% CI, 1.14-1.75). Black patients had a higher risk of TEEs (aRR, 1.24; 95% CI, 1.03-1.50) than White patients. Patients with TEEs had high intensive care unit admission (46%) and mechanical ventilation (31%) rates. Relative risk of death in patients with TEEs was higher in those exposed to TOIs vs not (aRR, 1.12; 95% CI, 0.91-1.38) and was significantly associated with poor performance status (aRR, 1.77; 95% CI, 1.30-2.40) and active/progressing cancer (aRR, 1.55; 95% CI, 1.13-2.13). Conclusions and Relevance In this cohort study, relative risk of developing VTE was high among patients receiving TOIs and varied by the type of therapy, underlying risk factors, and demographics, such as race and ethnicity. These findings highlight the need for close monitoring and perhaps personalized thromboprophylaxis to prevent morbidity and mortality associated with COVID-19–related thromboembolism in patients with cancer.
    Type of Medium: Online Resource
    ISSN: 2374-2437
    URL: Article
    DOI: 10.1001/jamaoncol.2023.2934
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2023
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  • 3
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    Association Between Androgen Deprivation Therapy and Mortality Among Patients With Prostate Cancer and COVID-19
    American Medical Association (AMA) ; 2021
    In:  JAMA Network Open Vol. 4, No. 11 ( 2021-11-12), p. e2134330-
    Details
    In: JAMA Network Open, American Medical Association (AMA), Vol. 4, No. 11 ( 2021-11-12), p. e2134330-
    Type of Medium: Online Resource
    ISSN: 2574-3805
    URL: Article
    DOI: 10.1001/jamanetworkopen.2021.34330
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2021
    detail.hit.zdb_id: 2931249-8
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  • 4
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    Impact of COVID-19 in patients on active melanoma therapy and with history of melanoma
    Springer Science and Business Media LLC ; 2023
    In:  BMC Cancer Vol. 23, No. 1 ( 2023-03-23)
    Details
    In: BMC Cancer, Springer Science and Business Media LLC, Vol. 23, No. 1 ( 2023-03-23)
    Abstract: COVID-19 particularly impacted patients with co-morbid conditions, including cancer. Patients with melanoma have not been specifically studied in large numbers. Here, we sought to identify factors that associated with COVID-19 severity among patients with melanoma, particularly assessing outcomes of patients on active targeted or immune therapy. Methods Using the COVID-19 and Cancer Consortium (CCC19) registry, we identified 307 patients with melanoma diagnosed with COVID-19. We used multivariable models to assess demographic, cancer-related, and treatment-related factors associated with COVID-19 severity on a 6-level ordinal severity scale. We assessed whether treatment was associated with increased cardiac or pulmonary dysfunction among hospitalized patients and assessed mortality among patients with a history of melanoma compared with other cancer survivors. Results Of 307 patients, 52 received immunotherapy (17%), and 32 targeted therapy (10%) in the previous 3 months. Using multivariable analyses, these treatments were not associated with COVID-19 severity (immunotherapy OR 0.51, 95% CI 0.19 – 1.39; targeted therapy OR 1.89, 95% CI 0.64 – 5.55). Among hospitalized patients, no signals of increased cardiac or pulmonary organ dysfunction, as measured by troponin, brain natriuretic peptide, and oxygenation were noted. Patients with a history of melanoma had similar 90-day mortality compared with other cancer survivors (OR 1.21, 95% CI 0.62 – 2.35). Conclusions Melanoma therapies did not appear to be associated with increased severity of COVID-19 or worsening organ dysfunction. Patients with history of melanoma had similar 90-day survival following COVID-19 compared with other cancer survivors.
    Type of Medium: Online Resource
    ISSN: 1471-2407
    URL: Article
    DOI: 10.1186/s12885-023-10708-6
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2041352-X
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  • 5
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    Surgical Outcome Results From SWOG S1505 : A Randomized Clinical Trial of mFOLFIRINOX Versus Gemcitabine/Nab-paclitaxel for Perioperative Treatment of Resectable Pancreatic Ductal Adenocarcinoma
    Ovid Technologies (Wolters Kluwer Health) ; 2020
    In:  Annals of Surgery Vol. 272, No. 3 ( 2020-09), p. 481-486
    Details
    In: Annals of Surgery, Ovid Technologies (Wolters Kluwer Health), Vol. 272, No. 3 ( 2020-09), p. 481-486
    Abstract: The optimal neoadjuvant therapy for resectable pancreatic ductal adenocarcinoma (PDA) and the impact on surgical outcomes remains unclear. Methods: S1505 (NCT02562716) was a randomized phase II study of perioperative chemotherapy with mFOLFIRINOX (Arm 1) or gemcitabine/nab-paclitaxel (Arm 2). Measured parameters included resection rate, margin positivity, pathologic response, and toxicity. Results: Between 2015 and 2018, 147 patients were randomized. Of these, 44 (30%) were deemed ineligible (43 by central review). Of the 103 eligible patients, 77 (76%) completed preoperative therapy and underwent surgery; reasons patients did not undergo surgery included toxicity related to preoperative therapy (n = 9), progression (n = 9), or other (n = 7). Of the 77, 73 (95%) underwent successful resection; 21 (29%) required vascular reconstruction, 62 (85%) had negative (R0) margins, and 24 (33%) had a complete or major pathologic response to therapy. The grade 3–5 postoperative complication rate was 16%. Of the 73 patients completing surgery, 57 (78%) started and 46 (63%) completed postoperative therapy. This study represents the first prospective trial evaluating modern systemic therapy delivered in a neoadjuvant/perioperative format for resectable PDA. Conclusions: We have demonstrated: (1) Based on the high percentage of enrolled, but ineligible patients, it is clear that adherence to strict definitions of resectable PDA is challenging; (2) Patients can tolerate modern systemic therapy and undergo successful surgical resection without prohibitive perioperative complications; (3) Completion of adjuvant therapy in the perioperative format is difficult; (4) Major pathologic response rate of 33% is encouraging.
    Type of Medium: Online Resource
    ISSN: 0003-4932 , 1528-1140
    URL: Article
    DOI: 10.1097/SLA.0000000000004155
    RVK:
    XA 23900
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
    detail.hit.zdb_id: 2641023-0
    detail.hit.zdb_id: 2002200-1
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  • 6
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    Molecular testing in metastatic colorectal adenocarcinoma cytology cell pellets
    Wiley ; 2019
    In:  Diagnostic Cytopathology Vol. 47, No. 11 ( 2019-11), p. 1132-1137
    Details
    In: Diagnostic Cytopathology, Wiley, Vol. 47, No. 11 ( 2019-11), p. 1132-1137
    Abstract: Mutational status for KRAS , NRAS , and BRAF genes should be performed on all colorectal carcinoma (CRC) specimens in order to guide targeted therapy selection for metastatic disease. Mutations are typically assessed via polymerase chain reaction and/or next generation sequencing (NGS) on formalin‐fixed paraffin‐embedded tissues. With minimally invasive diagnostic methodologies, the cytology cell pellet obtained by fine‐needle aspiration (FNA) can serve as an alternative source of tumor deoxyribonucleic acid. Methods An electronic record review of the cytopathology files (CoPathPlus, Cerner Corp., North Kansas City, Missouri) from September 1, 2015 through December 31, 2018 was conducted. All cytology specimens obtained via FNA and diagnosed as metastatic CRC on which NGS was performed were included. NGS for KRAS , NRAS , and BRAF mutations using the AmpliSeq Cancer Hotspot Panel v2.0 kit (Thermo Fisher Scientific, Waltham, Massachusetts) was performed on cytology cell pellets. Results Forty‐eight cases were identified. Forty‐six of 48 specimens (96%) were adequate for molecular testing. Of those adequate specimens, proportion of malignant cells in the sample ranged from 5% to 95% (mean 46%). Twenty‐seven of 48 cases (56%) were positive for clinically relevant mutations. Twenty‐four of 27 cases (89%) were positive for KRAS mutations, with exon 2 most frequently involved (22/24 cases, 92%). Two of 27 cases (7%) were positive for NRAS mutations and one case (1/27, 4%) was positive for a BRAF mutation involving codon 594. Conclusion Mutational analysis performed on cytology cell pellets serves as a useful means of gathering clinically actionable information on tumor mutation status in metastatic CRC.
    Type of Medium: Online Resource
    ISSN: 8755-1039 , 1097-0339
    URL: Issue
    URL: Article
    DOI: 10.1002/dc.v47.11
    DOI: 10.1002/dc.24275
    Language: English
    Publisher: Wiley
    Publication Date: 2019
    detail.hit.zdb_id: 2001251-2
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  • 7
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    CTNI-04. ACTIVITY OF LAROTRECTINIB IN TROPOMYOSIN RECEPTOR KINASE (TRK) FUSION CANCER PATIENTS WITH CENTRAL NERVOUS SYSTEM (CNS) METASTASES
    Oxford University Press (OUP) ; 2020
    In:  Neuro-Oncology Vol. 22, No. Supplement_2 ( 2020-11-09), p. ii41-ii42
    Details
    In: Neuro-Oncology, Oxford University Press (OUP), Vol. 22, No. Supplement_2 ( 2020-11-09), p. ii41-ii42
    Abstract: NTRK gene fusions occur in a range of tumor types, including those with CNS metastases. Larotrectinib, a highly selective FDA- and EMA- approved TRK inhibitor, demonstrated an objective response rate (ORR) of 79% across various cancers (Hong et al. Lancet Oncol. 2020). We report data on patients with TRK fusion cancer with CNS metastases treated with larotrectinib. METHODS Patients with solid tumors with CNS metastases at baseline harboring an NTRK gene fusion enrolled in two clinical trials (NCT02122913 and NCT02576431) were identified. Response was assessed by the investigator per RECIST v1.1. RESULTS As of July 15, 2019, 14 patients with CNS-metastases were enrolled: lung cancer (n=7), thyroid cancer (n=4), melanoma (n=2), and non-secretory breast cancer (n=1). Median age was 53 years (range 25–76). Including all sites of disease, the ORR was 71% (95% CI 42–92%): ten patients had a partial response (PR), two had stable disease (SD), and two had progressive disease (lung and melanoma). Of the three patients with measurable intracranial disease at baseline, the best intracranial response was 1 complete response, 1 PR, and 1 SD. Median duration of response for all patients was 14.8 months (range 1.9+ to 17.4+), median progression-free survival was 9.9 months (range 1.4 to 19.3+), and median overall survival was 27.8 months (range 1.4+ to 27.8). Treatment duration ranged from 1.4 to 25.0 months; six patients continued treatment beyond progression (lasting between 0.1+ and 8.5 months). Treatment-emergent adverse events (TEAEs) were mainly Grade 1 and 2; Grade 3 TEAEs occurred in seven patients (50%), with one (myalgia) attributed to larotrectinib (7%). There were no Grade 4 TEAEs. CONCLUSIONS Larotrectinib was highly active and well tolerated in TRK fusion cancer patients with CNS metastases. These results support testing for NTRK gene fusions across all cancers, including in patients with CNS metastases.
    Type of Medium: Online Resource
    ISSN: 1522-8517 , 1523-5866
    URL: Article
    DOI: 10.1093/neuonc/noaa215.171
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 2094060-9
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  • 8
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    Toxicity study of gemcitabine, oxaliplatin, and bevacizumab, followed by 5-fluorouracil, oxaliplatin, bevacizumab, and radiotherapy, in patients with locally advanced pancreatic cancer
    Springer Science and Business Media LLC ; 2013
    In:  Cancer Chemotherapy and Pharmacology Vol. 71, No. 6 ( 2013-6), p. 1485-1491
    Details
    In: Cancer Chemotherapy and Pharmacology, Springer Science and Business Media LLC, Vol. 71, No. 6 ( 2013-6), p. 1485-1491
    Type of Medium: Online Resource
    ISSN: 0344-5704 , 1432-0843
    URL: Article
    DOI: 10.1007/s00280-013-2147-4
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2013
    detail.hit.zdb_id: 1458488-8
    SSG: 15,3
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  • 9
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    Prospective Clinical Study of Precision Oncology in Solid Tumors
    Oxford University Press (OUP) ; 2016
    In:  JNCI: Journal of the National Cancer Institute Vol. 108, No. 3 ( 2016-3)
    Details
    In: JNCI: Journal of the National Cancer Institute, Oxford University Press (OUP), Vol. 108, No. 3 ( 2016-3)
    Type of Medium: Online Resource
    ISSN: 1460-2105 , 0027-8874
    URL: Article
    DOI: 10.1093/jnci/djv332
    RVK:
    XA 10000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2016
    detail.hit.zdb_id: 2992-0
    detail.hit.zdb_id: 1465951-7
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  • 10
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    Molecular profile of hepatocellular carcinoma (HCC) in older versus younger adults: Does age matter?
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 4_suppl ( 2022-02-01), p. 477-477
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 4_suppl ( 2022-02-01), p. 477-477
    Abstract: 477 Background: HCC is increasingly prevalent in older adults with rising incidence and an aging population worldwide. Retrospective studies show older patients with HCC may have an increased survival compared to younger patients. However, data is lacking regarding the genomic and biologic differences, that if identified, would potentially change how we treat this disease in younger vs. older patients. Hence, there is a need to better characterize the molecular landscape of the disease in an age-specific manner. We analyzed the association of age with genomic alterations and therapeutic response to sorafenib in a cohort of advanced HCC that had undergone comprehensive molecular profiling. Methods: 487 HCC samples (excluding variants) were analyzed using Next Generation Sequencing (592 gene panel, NextSeq), Whole Exome and Whole Transcriptome Sequencing (NovaSeq), and IHC at Caris Life Sciences (Phoenix, AZ). PD-L1 positivity was determined by IHC (SP-142 clone, cutoff ≥1, 1%). Tumor mutational burden (TMB) was a measure of total somatic mutations per Mb. Immune cell populations were determined by Microenvironment Cell Population (MCP) counter analysis of RNA expression data. Overall survival (OS) calculated from tissue collection to last contact and time on treatment (TOT) with sorafenib were extracted from insurance claims and calculated using Kaplan-Meier curves. Statistical analysis was done using Chi-square, Fisher Exact and Wilcoxon rank sum tests, with p values adjusted for multiple comparisons and q 〈 0.05. Results: Differences in the molecular landscape of HCC stratified by patient age were assayed using a ternary classification based on 1 standard deviation from the mean age (mean age=65; 〈 53: A1 (n=51), 53-77: A2 (n=361), 〉 77: A3 (n=75)). With age, mutational frequencies in CTNNB1 (A1=13.04%, A2=33.43%, A3=38.24%) and TERT (A1=25%, A2=68.84%, A3=76.92%) increased, while ATM (A1=6.52%, A2=0.93%, A3=1.49%) decreased (p 〈 0.05, q 〉 0.05). There were fold increases in median TMB (A2/A1=1.33, A3/A1=1.33, p 〈 0.01), LAG3 (A2/A1=1.75, A3/A1=1.93 p 〈 0.01), CTLA4 (A2/A1=2.05, A3/A1=2.15, p 〈 0.05) expression; median cell fractions of CD8+ T cells (A2/A1=1.37, A3/A1=1.50, p 〈 0.05) & B cells (A3/A1=3.01 p 〈 0.05) increased while cancer associated fibroblasts (A1/A2=0.62, A1/A3=0.69, p 〈 0.01) decreased with age. PD-L1 was not statistically significant. While there was no change in OS, reduced TOT with sorafenib was observed in patients aged 〉 65 (p=0.013). Conclusions: Increased alterations in oncogenic drivers and estimates of CD8+ T cells and B cells were observed in the elderly population with HCC. The enhanced presence of co-inhibitory molecules suggests potential immune evasion. While we observed reduced TOT with sorafenib, additional studies are needed to elucidate the impact of molecular alterations on outcomes with sorafenib and newer therapies (i.e. immunotherapy) in older adults.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2022.40.4_suppl.477
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
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