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  • 1
    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
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2041352-X
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  • 2
    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
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2023
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  • 3
    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
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2023
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  • 4
    In: Journal of Urology, Ovid Technologies (Wolters Kluwer Health), Vol. 209, No. Supplement 4 ( 2023-04)
    Type of Medium: Online Resource
    ISSN: 0022-5347 , 1527-3792
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
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  • 5
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 34, No. 29 ( 2016-10-10), p. 3511-3517
    Abstract: Ado-trastuzumab emtansine (T-DM1) is currently approved for treatment in patients with human epidermal growth factor receptor 2 (HER2)–positive, metastatic breast cancer (MBC) who previously received trastuzumab and a taxane. However, there are no data on the activity of T-DM1 in patients who received prior pertuzumab, which is now included as standard first-line therapy. The goal of this study was to assess the efficacy of T-DM1 in routine clinical practice in a contemporary patient population that received both prior trastuzumab and pertuzumab. Patients and Methods We identified all patients with HER2-positive MBC who received T-DM1 after trastuzumab and pertuzumab between March 1, 2013, and July 15, 2015, via electronic pharmacy records and departmental databases at three institutions: MD Anderson Cancer Center, Smilow Cancer Hospital at Yale, and The James Cancer Hospital at the Ohio State University. We reviewed medical records of each case to confirm treatment sequencing and outcome. Results Of patients, 82 were identified and 78 were available for outcome analysis; 32% received T-DM1 as first- and second-line line therapy, and 48% received it as fourth-line treatment or later. Rate of prolonged duration on therapy, defined as duration on therapy ≥ 6 months, was 30.8% (95% CI, 20.6% to 41.1%), and tumor response rate was 17.9% (95% CI, 9.4% to 26.4%). Median duration on therapy was 4.0 months (95% CI, 2.7 to 5.1; range, 0 to 22.5 months). T-DM1 was discontinued for disease progression in 84% of patients and for toxicity in 10%. Conclusion Tumor response rates were lower than in prior reports of trastuzumab-resistant, HER2-positive MBC, but one third of patients received therapy with T-DM1 for ≥ 6 months, which suggests a clinically relevant benefit in patients who received prior pertuzumab.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2016
    detail.hit.zdb_id: 2005181-5
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  • 6
    In: Journal for ImmunoTherapy of Cancer, BMJ, Vol. 8, No. 1 ( 2020-03), p. e000538-
    Abstract: There is limited experience regarding the safety and efficacy of checkpoint inhibitors (CPI) in patients with autoimmune disorders (AD) and advanced urological cancers as they are generally excluded from clinical trials due to risk of exacerbations. Methods This multicenter retrospective cohort analysis of patients with advanced renal cell cancer (RCC) and urothelial cancer (UC) with pre-existing AD treated with CPI catalogued the incidence of AD exacerbations, new immune-related adverse events (irAEs) and clinical outcomes. Competing risk models estimated cumulative incidences of exacerbations and new irAEs at 3 and 6 months. Results Of 106 patients with AD (58 RCC, 48 UC) from 10 centers, 35 (33%) had grade 1/2 clinically active AD of whom 10 (9%) required corticosteroids or immunomodulators at baseline. Exacerbations of pre-existing AD occurred in 38 (36%) patients with 17 (45%) requiring corticosteroids and 6 (16%) discontinuing CPI. New onset irAEs occurred in 40 (38%) patients with 22 (55%) requiring corticosteroids and 8 (20%) discontinuing CPI. Grade 3/4 events occurred in 6 (16%) of exacerbations and 13 (33%) of new irAEs. No treatment-related deaths occurred. Median follow-up was 15 months. For RCC, objective response rate (ORR) was 31% (95% CI 20% to 45%), median time to treatment failure (TTF) was 7 months (95% CI 4 to 10) and 12-month overall survival (OS) was 78% (95% CI 63% to 87%). For UC, ORR was 40% (95% CI 26% to 55%), median TTF was 5.0 months (95% CI 2.3 to 9.0) and 12-month OS was 63% (95% CI 47% to 76%). Conclusions Patients with RCC and UC with well-controlled AD can benefit from CPI with manageable toxicities that are consistent with what is expected of a non-AD population. Prospective study is warranted to comprehensively evaluate the benefits and safety of CPI in patients with AD.
    Type of Medium: Online Resource
    ISSN: 2051-1426
    Language: English
    Publisher: BMJ
    Publication Date: 2020
    detail.hit.zdb_id: 2719863-7
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  • 7
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  American Society of Clinical Oncology Educational Book , No. 42 ( 2022-07), p. 94-99
    In: American Society of Clinical Oncology Educational Book, American Society of Clinical Oncology (ASCO), , No. 42 ( 2022-07), p. 94-99
    Abstract: With sophisticated mobile and wearable technologies available, there has been interest in leveraging these devices to help gather and analyze patient-generated health data (PGHD). This information could be used to better address health concerns, aid in treatment decision-making, and guide interventional strategies to improve outcomes. Among PGHD, electronic patient-reported outcomes, direct reports of patient experience usually collected via validated scales and questionnaires, are increasingly integrated into routine clinical practice to monitor patient status. Electronic patient-reported outcomes have been shown to improve outcomes, including symptom control, quality of life, and overall survival, in several clinical trials. Electronic patient-reported outcome collection is now being implemented across broader clinical practice settings but with limited evaluation of impact thus far. Wearable devices and mobile apps provide opportunities to collect additional PGHD, including continuous physiologic measures, and to generate algorithms with which to monitor patients with cancer and guide interventions. In this article, we discuss several topics related to PGHD and technology, including electronic patient-reported outcomes, mobile apps, and wearable devices and how their introduction into oncology care has the potential to improve the collection and use of PGHD in the future. We also highlight the challenges and future directions needed for mobile and wearable technologies to provide meaningful information that can be acted upon and thus can improve oncologic care.
    Type of Medium: Online Resource
    ISSN: 1548-8748 , 1548-8756
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2431126-1
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  • 8
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 6_suppl ( 2022-02-20), p. 390-390
    Abstract: 390 Background:The concept of primary systemic therapy has gained increasing traction in the management of metastatic and locally advanced Renal Cell Carcinoma (RCC). Most series have evaluated the use of tyrosine-kinase inhibitors, however, with the emergence of immune checkpoint inhibitor therapy as first line agents in advanced RCC, further assessment of efficacy is warranted. We examined the effects of immunotherapy (IO) combinations on the primary tumor and consequent surgical quality and short-term oncological outcomes. Methods: We conducted a multi-center, retrospective analysis of patients with advanced/metastatic RCC having received IO followed by Radical (RN) or partial nephrectomy (PN). Primary outcome was achievement of Bifecta (composite outcome of complete resection and no 30-day post-operative complications). Predictors for achievement of Bifecta were assessed with logistic regression multivariable analysis. Secondary outcomes were change in maximal tumor dimension, RENAL nephrometry score and disease progression. Kaplan-Meier analysis was used to assess progression-free survival (PFS) for Bifecta and non-Bifecta patients. Results: We identified 52 patients with advanced RCC across 9 institutions who were eligible. The median age was 63 years and 60.4% were males. Median tumor size at diagnosis was 9.3 cm. 19.6% had T4 disease and 75% had AJCC Stage IV disease. IO treatment resulted in significant reductions in median tumor size (-25.4%; 9.7 cm vs. 7.3cm p = 0.0129) and RENAL nephrometry score (9 to 8, p = 0.032). 43 (83%) of patients underwent RN and (9) 17% had PN. Median tumor size was smaller for PN (8 vs. 4.1 cm, p 〈 0.001), and 30 day complication rates were higher (p = 0.024). Bifecta was achieved in 39 patients [33/42 (78.6%) RN and 6/9 (67%) PN, p = 0.264). Predictors for achievement of Bifecta were younger age (OR 1.06, p = 0.01), increasing reduction in tumor size (OR 1.187, p 〈 0.001), and shorter time between therapy and surgery (OR 1.07, p 〈 0.001). Kaplan-Meier analysis demonstrated longer median time to progression in the Bifecta-positive group compared to patients who failed to achieve Bifecta (75 vs. 30 months, p = 0.04). Conclusions: Pre-surgical therapy resulted in tumor size and complexity reduction. Tumor size reduction was predictive for achievement of Bifecta, which was associated with improved short term oncological outcomes. To our knowledge, this is the first series evaluating the effect of neoadjuvant systemic therapy on the primary tumor prior to surgical intervention.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
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  • 9
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 6_suppl ( 2022-02-20), p. 334-334
    Abstract: 334 Background: IO, either as combination therapy in the frontline or monotherapy in the second line, has improved outcomes for patients with advanced RCC. With the movement away from upfront CN, limited data are available on the outcomes of patients who receive IO with delayed CN. In this study, we characterized the pathologic and survival outcomes for patients who received IO followed by CN. Methods: We conducted a multi-center, retrospective analysis of patients with advanced/metastatic RCC having received IO combination or monotherapy followed by CN. An IRB-approved and HIPAA-compliant registry was used to collect data from the electronic medical record. Our primary endpoint was the degree of pathologic downstaging comparing baseline clinical T stage to pathologic T stage following IO. Secondary endpoints included investigator assessed response using RECIST principals, progression-free survival (PFS), and overall survival (OS). Results: We identified53 patients with advanced RCC across 9 institutions who were eligible for the study. The median age was 63 years, 72% were white, and 60% were male. 81% of patients had clear cell histology, 11% had sarcomatoid differentiation, and 75% presented with de novo metastatic disease. Baseline IMDC risk is as follows: 4% favorable, 55% intermediate, and 26% poor risk with 15% unknown. 23% had bone metastases and 23% had liver metastases at baseline. Lines of therapy prior to CN was 1 line in 74% of patients, 2 lines in 25%, and 3 lines in 2%. For the line of IO therapy immediately preceding CN, 49% received nivolumab+ipilimumab, 30% received IO monotherapy, and 21% received combination IO/VEGF therapy. The median duration of therapy prior to surgery was 11.3 months (range 0.38-47.8). 28% of patients discontinued treatment after CN for observation. Best overall response prior to CN was stable disease in 25% of patients, partial response in 60%, and progressive disease in 4% with 11% unknown. Following receipt of IO-based treatment, 38% of patients exhibited downstaging from the baseline clinical T stage to the CN pathological T stage (Table). 11% of patients had no residual disease at CN. For pathologic outcomes, 85% of patients had negative margins, 75% had necrosis present, and the median tumor size at CN was 6.5 cm. The median PFS was 11.3 months and median OS was 25.7 months for the overall cohort. Conclusions: IO-based strategies demonstrate efficacy in the renal primary in patients with advanced RCC. T stage downstaging was demonstrated in 38% of patients with 11% having a complete pathologic response in the renal primary following IO administration. Biomarker studies on baseline and CN tissue will further elucidate molecular predictors of response and resistance to IO therapy.[Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
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  • 10
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 16_suppl ( 2022-06-01), p. e16517-e16517
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. e16517-e16517
    Abstract: e16517 Background: Body composition (comp) is an increasingly recognized prognostic indicator in patients with cancer, but there are limited data regarding body comp measurements in patients with metastatic renal cell carcinoma (mRCC) treated with immune checkpoint inhibitors. The goal of this study was to assess baseline body comp measurements and rates of sarcopenia in patients with mRCC receiving ipilimumab + nivolumab (ipi/nivo) as first-line systemic therapy and examine potential associations with overall survival (OS). Methods: We conducted a retrospective analysis of all patients with mRCC treated with first line ipi/nivo at Duke Cancer Center prior to June 1, 2021, who had a CT scan within 6 weeks of ipi/nivo initiation. CT images were segmented and measured with Automatic Body composition Analyser using Computed tomography image Segmentation (ABACS) software (Voronoi Health Analytics). Areas of skeletal muscle (SM), subcutaneous fat (SF), and visceral fat (VF) at the level of the 3rd lumbar vertebra were measured and converted to indices by dividing by height (m 2 ) (Area SMI, SFI, VFI). Volumes of SM, SF, and VF between the 1st and 5th lumbar vertebrae were measured and converted to indices by dividing by the height of the measured slab (Volume SMI, SFI, VFI). Sarcopenia was defined as SMI 〈 55cm 2 /m 2 in men and 〈 39cm 2 /m 2 in women based on prior studies. Medical records were retrospectively reviewed to identify demographic and oncologic details. Effects of body comp measures on overall survival were assessed using Cox proportional hazard models, which were adjusted for IMDC risk, age, and sex. Results: 104 patients met study criteria and had an analyzable baseline CT scan. Median age was 62 (range 37 – 81). 71% of patients were male. Median body mass index (BMI) was 27.2 (range 17.8 – 43.6). IMDC risk score was 12% favorable, 63% intermediate, 20% poor, and 5% unknown. Median follow up time was 19.98 months. Median survival was 39.79 months (95% CI 27.01, NA). 1-year survival rate was 0.81 [95% CI 0.73, 0.89] and 2-year survival rate was 0.68 [95% CI 0.59, 0.79] . 77 of 104 patients (74%) met the definition of sarcopenia prior to treatment. No body comp measurements were associated with OS. Effects of body comp measurements on overall survival are shown in table 1. Conclusions: Baseline body comp measures were not associated with OS in a population of patients with mRCC receiving ipi/nivo as first-line systemic therapy. Changes in body comp over time may instead be of interest as potential biomarkers for OS in patients with mRCC receiving ipi/nivo. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
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