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1.
BMC Health Serv Res ; 24(1): 196, 2024 Feb 13.
Article in English | MEDLINE | ID: mdl-38350945

ABSTRACT

BACKGROUND: The United States envisions a 90% reduction in HIV infections by 2030. However, the COVID-19 pandemic disrupted the HIV continuum and disproportionately affected access to social and health services for people at the highest vulnerability. This study shows how stakeholders in the State of Michigan handled disruptions and their key recommendations. As a case study, this study adds to the literature about preparedness for future pandemics. METHODS: We interviewed 33 statewide Michigan HIV/AIDS Council members-practitioners, researchers, and community representatives, guiding service planning, improvement, and resource allocations, measuring group cohesiveness using a tested scale. We measured group cohesiveness as a proxy for how individual opinions reflected those of the Council as a group. We used qualitative questions to assess: (1) how the COVID-19 pandemic disrupted HIV prevention; (2) how disruptions were handled; and (3) recommendation to help address disruptions now and in the future. Using thematic analysis, we coded the interviews. RESULTS: We found a high degree of cohesiveness. Participants agreed that the pandemic disrupted HIV prevention services (e.g., HIV testing, PrEP education, referrals to primary care, etcetera) offered by community organizations, hospital clinics, and health departments across the state. In response, they developed online and curbside services to maintain HIV services, abate social isolation, and address structural issues like lack of food and public transportation. We organized results in four categories: (1) HIV service disruptions (e.g., "Housing for women and children who are fleeing a legal situation"); (2) Responses to disruptions (e.g., "Some of them, we would say, hey, weather permitting, we'll come out to your car"); (3) Minoritized groups disproportionately affected (e.g., "Especially in my community, to get people if there's ever a vaccine, Black people are going to be the last people to take it"); and (4) Recommendations (below). CONCLUSIONS: The pandemic unsettled and further exacerbated every aspect of HIV service provision. The main recommendation was to overhaul communication systems between government and organizations offering HIV services to mitigate disruptions and improve the chances of achieving a 90% reduction.


Subject(s)
Acquired Immunodeficiency Syndrome , COVID-19 , HIV Infections , Child , Female , Humans , HIV Infections/epidemiology , HIV Infections/prevention & control , Pandemics/prevention & control , COVID-19/epidemiology , COVID-19/prevention & control , Advance Directives
3.
Cancer Immunol Immunother ; 72(11): 3839-3850, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37733060

ABSTRACT

BACKGROUND: Optimal duration of treatment (DoT) with immune checkpoint inhibitors (ICI) in metastatic cancers remains unclear. Many patients, especially those without radiologic complete remission, develop progressive disease after ICI discontinuation. Extending DoT with ICI may potentially improve efficacy outcomes but presents major logistical and cost challenges with standard frequency dosing (SFD). Receptor occupancy data supports reduced frequency dosing (RFD) of anti-PD-1 antibodies, which may represent a more practical and economically viable option to extend DoT. METHODS: We conducted a retrospective study of patients with metastatic melanoma and Merkel cell carcinoma (MCC), who received ICI at RFD administered every 3 months, after initial disease control at SFD. We evaluated efficacy, safety, and cost-savings of the RFD approach in this cohort. RESULTS: Between 2014 and 2021, 23 patients with advanced melanoma (N = 18) or MCC (N = 5) received anti-PD-1 therapy at RFD. Median DoT was 1.1 years at SFD and 1.2 years at RFD. The 3 year PFS after start of RFD was 73% in melanoma and 100% in MCC patients, which compare favorably to historical control rates. In the subset of 15 patients who received at least 2 years of therapy, total savings amounted to $1.1 million in drug costs and 384 h saved despite the extended DoT (median 3.4 years), as compared to the calculated cost of 2 years at SFD. CONCLUSIONS: ICI administration at RFD can allow extension of treatment duration, while preserving efficacy and reducing logistical and financial burden. RFD approach deserves further exploration in prospective clinical trials.


Subject(s)
Carcinoma, Merkel Cell , Immune Checkpoint Inhibitors , Melanoma , Skin Neoplasms , Humans , Carcinoma, Merkel Cell/drug therapy , Duration of Therapy , Melanoma/drug therapy , Prospective Studies , Retrospective Studies , Skin Neoplasms/drug therapy , Immune Checkpoint Inhibitors/therapeutic use
4.
Cancers (Basel) ; 15(14)2023 Jul 19.
Article in English | MEDLINE | ID: mdl-37509333

ABSTRACT

Localized renal cell carcinoma is primarily managed surgically, but this disease commonly presents in highly comorbid patients who are poor operative candidates. Less invasive techniques, such as cryoablation and radiofrequency ablation, are effective, but require percutaneous or laparoscopic access, while generally being limited to cT1a tumors without proximity to the renal pelvis or ureter. Active surveillance is another management option for small renal masses, but many patients desire treatment or are poor candidates for active surveillance. For poor surgical candidates, a growing body of evidence supports stereotactic ablative radiotherapy (SABR) as a safe and effective non-invasive treatment modality. For example, a recent multi-institution individual patient data meta-analysis of 190 patients managed with SABR estimated a 5.5% five-year cumulative incidence of local failure with one patient experiencing grade 4 toxicity, and no other grade ≥3 toxic events. Here, we discuss the recent developments in SABR for the management of localized renal cell carcinoma, highlighting key concepts of appropriate patient selection, treatment design, treatment delivery, and response assessment.

5.
J Clin Oncol ; 41(21): 3712-3723, 2023 07 20.
Article in English | MEDLINE | ID: mdl-37192435

ABSTRACT

PURPOSE: Compared with people living without HIV (PWOH), people living with HIV (PWH) and cancer have traditionally been excluded from immune checkpoint inhibitor (ICI) trials. Furthermore, there is a paucity of real-world data on the use of ICIs in PWH and cancer. METHODS: This retrospective study included PWH treated with anti-PD-1- or anti-PD-L1-based therapies for advanced cancers. Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS). Objective response rates (ORRs) were measured per RECIST 1.1 or other tumor-specific criteria, whenever feasible. Restricted mean survival time (RMST) was used to compare OS and PFS between matched PWH and PWOH with metastatic NSCLC (mNSCLC). RESULTS: Among 390 PWH, median age was 58 years, 85% (n = 331) were males, 36% (n = 138) were Black; 70% (n = 274) received anti-PD-1/anti-PD-L1 monotherapy. Most common cancers were NSCLC (28%, n = 111), hepatocellular carcinoma ([HCC]; 11%, n = 44), and head and neck squamous cell carcinoma (HNSCC; 10%, n = 39). Seventy percent (152/216) had CD4+ T cell counts ≥200 cells/µL, and 94% (179/190) had HIV viral load <400 copies/mL. Twenty percent (79/390) had any grade immune-related adverse events (irAEs) and 7.7% (30/390) had grade ≥3 irAEs. ORRs were 69% (nonmelanoma skin cancer), 31% (NSCLC), 16% (HCC), and 11% (HNSCC). In the matched mNSCLC cohort (61 PWH v 110 PWOH), 20% (12/61) PWH and 22% (24/110) PWOH had irAEs. Adjusted 42-month RMST difference was -0.06 months (95% CI, -5.49 to 5.37; P = .98) for PFS and 2.23 months (95% CI, -4.02 to 8.48; P = .48) for OS. CONCLUSION: Among PWH, ICIs demonstrated differential activity across cancer types with no excess toxicity. Safety and activity of ICIs were similar between matched cohorts of PWH and PWOH with mNSCLC.


Subject(s)
Carcinoma, Hepatocellular , Carcinoma, Non-Small-Cell Lung , HIV Infections , Head and Neck Neoplasms , Liver Neoplasms , Lung Neoplasms , Male , Humans , Middle Aged , Female , Immune Checkpoint Inhibitors/adverse effects , Retrospective Studies , Squamous Cell Carcinoma of Head and Neck , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , HIV Infections/drug therapy
6.
J Assoc Nurses AIDS Care ; 34(2): 216-220, 2023.
Article in English | MEDLINE | ID: mdl-36662654

ABSTRACT

ABSTRACT: Injectable cabotegravir and rilpivirine (CAB/RPV), administered bimonthly by a medical provider, is convenient and improves privacy and medication management. One year after approval, myriad implementation barriers threaten the access and sustainability of this life-saving innovation: (1) eligibility issues (viral suppression, drug resistance, and failed oral regimens); (2) injection requires medical provider and transportation to facility; (3) strict medication adherence; (4) life challenges-mental health, homelessness, joblessness; and (5) lack of insurance and high cost. Universal implementation of CAB/RPV calls for social, human, and health organizations to partner and provide HIV continuum of care and prevention services to facilitate CAB/RPV access and maintenance and for transparent health insurance billing practices to abate uncertainty concerning CAB/RPV's classification as a pharmaceutical or medical benefit and related cost implications.


Subject(s)
Acquired Immunodeficiency Syndrome , Anti-HIV Agents , HIV Infections , Humans , Rilpivirine/therapeutic use , Anti-HIV Agents/therapeutic use , HIV Infections/drug therapy , HIV Infections/prevention & control , Anti-Retroviral Agents/therapeutic use , Acquired Immunodeficiency Syndrome/drug therapy
7.
J Am Acad Dermatol ; 88(4): 831-840, 2023 04.
Article in English | MEDLINE | ID: mdl-36610687

ABSTRACT

BACKGROUND: Melanoma survival literature predominantly represents patients >65 years of age. Study of younger patients may reveal potential age-group-specific differences in survival outcome. OBJECTIVE: Identify factors associated with differences in melanoma survival in 2 age groups, adolescents and young adults (AYAs; ages 15-39) and older adults (ages 40-64). METHODS: This population-based registry study included all cases (n = 81,597) of cutaneous melanoma diagnosed at ages 15 to 64 from 2004 to 2015 in California. Age-group-specific multivariable Cox hazard regressions were used. RESULTS: In the adjusted, age-group-specific models, AYA patients with stage IV melanoma had worse survival (hazard ratio: 20.39, 95% CI: 13.30-31.20) than was observed among older adults (hazard ratio: 10.79, 95% CI: 9.33-12.48). Thicker tumors and public insurance were also associated with worse survival for AYAs than observed in models for older adults. AYAs experienced better survival when detected at earlier stages. LIMITATIONS: Registry data do not routinely collect behavioral information or family history of melanoma. CONCLUSIONS: Survival was much worse for AYAs with stage IV melanoma than observed among older adults. To improve AYA survival, early melanoma detection is critical. Greater awareness, suspicion, and screening for AYA melanoma may disrupt delays in diagnosis and reduce the excess burden of mortality from stage IV melanoma in young patients.


Subject(s)
Melanoma , Skin Neoplasms , Humans , Adolescent , Young Adult , Aged , Adult , Middle Aged , Proportional Hazards Models , Insurance, Health , Registries
8.
Oncologist ; 28(3): 268-275, 2023 03 17.
Article in English | MEDLINE | ID: mdl-36302223

ABSTRACT

BACKGROUND: Widespread implementation of immune checkpoint inhibitors (ICI) and targeted therapies for metastatic melanoma has led to a decline in melanoma-related mortality but increased healthcare costs. We aimed to determine how healthcare utilization varied by systemic, non-adjuvant melanoma treatment from 2016 to 2020. PATIENTS AND METHODS: Adults with presumed stage IV metastatic melanoma receiving systemic therapy from 2016 to 2020 were identified in Optum, a nationwide commercial claims database. Treatment groups were nivolumab, pembrolizumab, ipilimumab+nivolumab (combination-ICI), or BRAF+MEK inhibitor (BRAFi+MEKi) therapy. Outcomes included hospitalizations, days hospitalized, emergency room (ER) visits, outpatient visits, and healthcare costs per patient per month (pppm). Multivariable regression models were used to analyze whether cost and utilization outcomes varied by treatment group, with nivolumab as reference. RESULTS: Among 2018 adult patients with metastatic melanoma identified, mean (SD) age was 67 (15) years. From 2016 to 2020, nivolumab surpassed pembrolizumab as the most prescribed systemic melanoma therapy while combination-ICI and BRAFi+MEKi therapies remained stable. Relative to nivolumab, all other therapies were associated with increased total healthcare costs (combination-ICI: ß = $47 600 pppm, 95%CI $42 200-$53 100; BRAFi+MEKi: ß = $3810, 95%CI $365-$7260; pembrolizumab: ß = $6450, 95%CI $4420-$8480). Combination-ICI and BRAFi+MEKi therapies were associated with more inpatient hospital days. CONCLUSIONS: Amid the evolving landscape of systemic therapy for advanced melanoma, nivolumab monotherapy emerged as the most used and least costly systemic treatment from 2016 to 2020. Its sharp increase in use in 2018 and lower costs relative to pembrolizumab may in part be due to earlier adoption of less frequent dosing intervals.


Subject(s)
Melanoma , Nivolumab , Aged , Humans , Delivery of Health Care , Health Care Costs , Ipilimumab/therapeutic use , Melanoma/pathology , Nivolumab/therapeutic use , Patient Acceptance of Health Care , Middle Aged
9.
Urol Oncol ; 41(1): 51.e25-51.e31, 2023 01.
Article in English | MEDLINE | ID: mdl-36441070

ABSTRACT

BACKGROUND: Cytoreductive nephrectomy (CN) for the treatment of metastatic renal cell carcinoma (mRCC) was called into question following the publication of the CARMENA trial. While previous retrospective studies have supported CN alongside targeted therapies, there is minimal research establishing its role in conjunction with immune checkpoint inhibitor (ICI) therapy. OBJECTIVE: To evaluate the association between CN and oncological outcomes in patients with mRCC treated with immunotherapy. MATERIALS AND METHODS: A multicenter retrospective cohort study of patients diagnosed with mRCC between 2000 and 2020 who were treated at the Seattle Cancer Care Alliance and The Ohio State University and who were treated with ICI systemic therapy (ST) at any point in their disease course. Overall survival (OS) was estimated using Kaplan Meier analyses. Multivariable Cox proportional hazards models evaluated associations with mortality. RESULTS: The study cohort consisted of 367 patients (CN+ST n = 232, ST alone n = 135). Among patients undergoing CN, 30 were deferred. Median survivor follow-up was 28.4 months. ICI therapy was first-line in 28.1%, second-line in 17.4%, and third or subsequent line (3L+) in 54.5% of patients. Overall, patients who underwent CN+ST had longer median OS (56.3 months IQR 50.2-79.8) compared to the ST alone group (19.1 months IQR 12.8-23.8). Multivariable analyses demonstrated a 67% reduction in risk of all-cause mortality in patients who received CN+ST vs. ST alone (P < 0.0001). Similar results were noted when first-line ICI therapy recipients were examined as a subgroup. Upfront and deferred CN did not demonstrate significant differences in OS. CONCLUSIONS: CN was independently associated with longer OS in patients with mRCC treated with ICI in any line of therapy. Our data support consideration of CN in well selected patients with mRCC undergoing treatment with ICI.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Humans , Carcinoma, Renal Cell/drug therapy , Carcinoma, Renal Cell/surgery , Cytoreduction Surgical Procedures , Immune Checkpoint Inhibitors/pharmacology , Immune Checkpoint Inhibitors/therapeutic use , Retrospective Studies , Kidney Neoplasms/drug therapy , Kidney Neoplasms/surgery , Nephrectomy
10.
Bone Marrow Transplant ; 58(4): 353-359, 2023 04.
Article in English | MEDLINE | ID: mdl-36575360

ABSTRACT

Post-transplant lymphoproliferative disorder (PTLD) is a leading cause of cancer death in solid organ transplant recipients (SOTRs). Relapsed or refractory (R/R) PTLD portends a high risk of death and effective management is not well established. CD19-targeted CAR-T cell therapy has been utilized, but the risks and benefits are unknown. We report the first case of diffuse large B-cell lymphoma (DLBCL) PTLD treated with lisocabtagene maraleucel and present a systematic literature review of SOTRs with PTLD treated with CD19 CAR-T therapy. Our patient achieved a complete response (CR) with limited toxicity but experienced a CD19+ relapse 8 months after infusion despite CAR-T persistence. Literature review revealed 14 DLBCL and 2 Burkitt lymphoma PTLD cases treated with CD19 CAR-T cells. Kidney (n = 12), liver (n = 2), heart (n = 2), and pancreas after kidney (n = 1) transplant recipients were analyzed. The objective response rate (ORR) was 82.4% (14/17), with 58.5% (10/17) CRs and a 6.5-month median duration of response. Among kidney transplant recipients, the ORR was 91.7% (11/12). Allograft rejection occurred in 23.5% (4/17). No graft failure occurred. Our analysis suggests that CD19 CAR-T therapy offers short-term effectiveness and manageable toxicity in SOTRs with R/R PTLD. Further investigation through larger datasets and prospective study is needed.


Subject(s)
Epstein-Barr Virus Infections , Lymphoma, Large B-Cell, Diffuse , Lymphoproliferative Disorders , Organ Transplantation , Receptors, Chimeric Antigen , Humans , Antigens, CD19 , Immunotherapy, Adoptive/adverse effects , Lymphoma, Large B-Cell, Diffuse/therapy , Lymphoma, Large B-Cell, Diffuse/pathology , Lymphoproliferative Disorders/etiology , Lymphoproliferative Disorders/therapy , Neoplasm Recurrence, Local , Organ Transplantation/adverse effects , Transplant Recipients
11.
Article in English | MEDLINE | ID: mdl-38389649

ABSTRACT

The COVID-19 pandemic saw the disruption of HIV/STI testing services at crucial student-oriented spaces at the University of Michigan, including the Spectrum Center, an LGBTQ+ event and education space, and Wolverine Wellness, a well-being initiative through the University Health Services, alongside massive disruptions to testing seen elsewhere around the country (Zapata et al., 2022). HIV/STI testing resumed in October during the Fall 2021 semester at the University of Michigan at Wolverine Wellness and Spectrum Center. At the Spectrum Center, the oldest LGBTQ+ college center in the country, I had the unique opportunity to partner with professional and student staff to foster an environment sensitive to cultural needs, including awareness of how sexual and gender identity intersects with student sexual health and well-being. Additionally, at both sites, COVID-19 protocols from the state and university were also established in the new workflow of testing services. The re-introduction of HIV/STI testing services through student-oriented sites at the University of Michigan required a reassessment of work flow standards and engagement with the campus student population.

12.
Cancers (Basel) ; 14(23)2022 Nov 30.
Article in English | MEDLINE | ID: mdl-36497395

ABSTRACT

Merkel cell carcinoma (MCC), an aggressive neuroendocrine skin cancer, has a high rate (20%) of distant metastasis. Within a prospective registry of 582 patients with metastatic MCC (mMCC) diagnosed between 2003-2021, we identified 9 (1.5%) patients who developed cardiac metastatic MCC (mMCC). We compared overall survival (OS) between patients with cardiac and non-cardiac metastases in a matched case-control study. Cardiac metastasis was a late event (median 925 days from initial MCC diagnosis). The right heart was predominantly involved (8 of 9; 89%). Among 7 patients treated with immunotherapy, 6 achieved a complete or partial response of the cardiac lesion. Among these 6 responders, 5 received concurrent cardiac radiotherapy (median 20 Gray) with immunotherapy; 4 of 5 did not have local disease progression or recurrence in the treated cardiac lesion. One-year OS was 44%, which was not significantly different from non-cardiac mMCC patients (45%, p = 0.96). Though it occurs relatively late in the disease course, cardiac mMCC responded to immunotherapy and/or radiotherapy and was not associated with worse prognosis compared to mMCC at other anatomic sites. These results are timely as cardiac mMCC may be increasingly encountered in the era of immunotherapy as patients with metastatic MCC live longer.

13.
Fed Pract ; 39(Suppl 3): S56-S62, 2022 Aug.
Article in English | MEDLINE | ID: mdl-36426106

ABSTRACT

Background: In patients with multiple myeloma, thrombotic microangiopathy is a rare adverse event associated with proteasome inhibitors, such as bortezomib, carfilzomib, and ixazomib. Case Presentation: Two patients with multiple myeloma who presented with carfilzomib-induced thrombotic microangiopathy received eculizumab with subsequent stabilization of renal function. Conclusions: Given the overall rarity of this adverse event, the simultaneous presentation of these 2 cases was unexpected. These cases underscores the need for heightened awareness in clinical practice of thrombotic microangiopathy. The potential role of eculizumab as a therapeutic treatment in the setting of thrombotic microangiopathy requires further investigation.

15.
Cancer Cell ; 40(4): 393-409.e9, 2022 04 11.
Article in English | MEDLINE | ID: mdl-35413271

ABSTRACT

CD4+ T cells that recognize tumor antigens are required for immune checkpoint inhibitor efficacy in murine models, but their contributions in human cancer are unclear. We used single-cell RNA sequencing and T cell receptor sequences to identify signatures and functional correlates of tumor-specific CD4+ T cells infiltrating human melanoma. Conventional CD4+ T cells that recognize tumor neoantigens express CXCL13 and are subdivided into clusters expressing memory and T follicular helper markers, and those expressing cytolytic markers, inhibitory receptors, and IFN-γ. The frequency of CXCL13+ CD4+ T cells in the tumor correlated with the transcriptional states of CD8+ T cells and macrophages, maturation of B cells, and patient survival. Similar correlations were observed in a breast cancer cohort. These results identify phenotypes and functional correlates of tumor-specific CD4+ T cells in melanoma and suggest the possibility of using such cells to modify the tumor microenvironment.


Subject(s)
CD8-Positive T-Lymphocytes , Melanoma , Animals , Antigens, Neoplasm/genetics , CD4-Positive T-Lymphocytes , Humans , Macrophages , Melanoma/genetics , Mice , Tumor Microenvironment
16.
J Natl Compr Canc Netw ; 20(4): 406-416.e11, 2022 04.
Article in English | MEDLINE | ID: mdl-35390767

ABSTRACT

Chronic immunosuppression in solid organ transplant recipients (SOTRs) leads to an increased risk of a wide variety of cancers. Immune checkpoint inhibitor (ICI) therapy is indicated for many of these; however, the risks and benefits of ICI use in the SOTR population have not been well characterized. We performed a systematic literature review identifying 119 reported cases of ICI use among SOTRs. Treatments used included PD-1 inhibition (75.6%), CTLA-4 inhibition (12.6%), PD-L1 inhibition (1.7%), and combination and/or sequential ICI therapy (10.1%). The most common cancers included cutaneous melanoma (35.3%), hepatocellular carcinoma (22.7%), and cutaneous squamous cell carcinoma (18.5%). The overall objective response rate (ORR) was 34.5%, with a median duration of response of 8.0 months. Ongoing response was seen in 21.0%. Cutaneous squamous cell carcinoma had significantly better ORR compared with other cancer types (68.2% vs 26.8%; odds ratio [OR], 5.85; P =.0006). Factors associated with improved ORR included increasing time from transplant to ICI (OR, 1.09; P =.008) and preemptive reduction in intensity of the graft maintenance immunosuppressive regimen (50.0% vs 18.5%; OR, 4.40; P =.0088). Rejection occurred in 41.2%, graft failure in 23.5%, and immune-related adverse events in 18.5%. Factors significantly associated with allograft rejection included allograft PD-L1 positivity (100% vs 0%; P<.0001) and absence of tacrolimus in the immunosuppressive regimen (48.7% vs 25.6%; OR, 0.36; P =.019). The most common cause of death was progressive malignancy (64.0%), followed by graft failure (24.0%). Our analysis provides current benchmark data to help inform management of SOTRs with advanced cancers that are reflected by our patient cohort. Biomarker development, more robust datasets, and prospective study of concomitant immunosuppression management may help refine decision-making in this complex scenario in the future. Close coordination of care between the medical oncologist and transplant specialist is encouraged to help optimize treatment outcomes.


Subject(s)
Carcinoma, Squamous Cell , Melanoma , Organ Transplantation , Skin Neoplasms , B7-H1 Antigen/metabolism , Carcinoma, Squamous Cell/epidemiology , Humans , Immune Checkpoint Inhibitors/adverse effects , Melanoma/etiology , Organ Transplantation/adverse effects , Prospective Studies , Skin Neoplasms/drug therapy , Skin Neoplasms/etiology
17.
Cancer Med ; 11(16): 3106-3114, 2022 08.
Article in English | MEDLINE | ID: mdl-35304832

ABSTRACT

BACKGROUND: Immune checkpoint inhibitor/tyrosine kinase inhibitor (ICI/TKI) combinations are a new standard of care for the initial treatment of metastatic renal cell carcinoma (mRCC). Their efficacy and toxicity beyond the first-line setting remain poorly defined. METHODS: We retrospectively reviewed charts for 85 adults with mRCC of any histology receiving combination of ICI/TKI in any line of treatment at two academic centers as of 05/01/2020. We collected clinical, pathological, and treatment-related variables. Outcomes including objective response rate (ORR), progression-free survival (PFS), and toxicity were analyzed via descriptive statistics and the Kaplan-Meier method. RESULTS: Patients received pembrolizumab, nivolumab, avelumab, or nivolumab-ipilimumab, with concurrent use of sunitinib, axitinib, pazopanib, lenvatinib, or cabozantinib. Thirty-three patients received first-line ICI/TKI therapy, while 52 received ≥ second-line ICI/TKI. The efficacy of ICI/TKI therapy decreased with increasing lines of treatment (ORR: 56.7%, 37.5%, 21.4%, and 21%; median PFS [mPFS]: 15.2, 14.2, 10.1, and 6.8 months, for first, second, third, and ≥ fourth line therapy, respectively). In the ≥ second-line setting, ICI/TKI was most useful in patients who received ICI only, with an ORR of 50% and a mPFS of 9.1 months. Efficacy was limited in patients who received both TKI and ICI previously, with an ORR of 20% and a mPFS of 5.5 months. Overall, ≥ second-line ICI/TKI was tolerable with 25 of 52 (52%) patients developing grade ≥3 adverse events. CONCLUSIONS: ICI/TKI combination therapy is feasible and safe beyond the first-line setting. Prior treatment history appears to impact efficacy but has a lesser effect on safety/tolerability.


Subject(s)
Carcinoma, Renal Cell , Immune Checkpoint Inhibitors , Kidney Neoplasms , Protein-Tyrosine Kinases , Adult , Carcinoma, Renal Cell/drug therapy , Carcinoma, Renal Cell/pathology , Humans , Immune Checkpoint Inhibitors/therapeutic use , Kidney Neoplasms/drug therapy , Kidney Neoplasms/pathology , Nivolumab/therapeutic use , Protein-Tyrosine Kinases/antagonists & inhibitors , Retrospective Studies
18.
Support Care Cancer ; 30(5): 3829-3838, 2022 May.
Article in English | MEDLINE | ID: mdl-35034197

ABSTRACT

BACKGROUND: Sleep problems (SP) are common in cancer patients but have not been previously assessed in patients receiving immune checkpoint inhibitors (ICI). METHODS: We collected questionnaire data on sleep apnea risk, insomnia, and general sleep patterns. We used an adjusted multivariate Poisson regression to calculate prevalence ratios (PRs) and associated 95% confidence intervals (CIs) for associations between these SP and metastatic versus localized cancer stage (M1 vs. M0), and adjusted logistic regression models to calculate ORs for associations between SP with the number of ICI infusions completed (6 + vs. < 6). RESULTS: Among 32 patients who received ICI treatment, the prevalence of low, intermediate, and high-risk OSA risk was 36%, 42%, and 21%, respectively. Overall, 58% of participants reported clinically significant insomnia. We did not find a significant association between intermediate or high risk OSA (vs. low risk) and metastatic cancer status (PR = 1.01 (95% CI: 0.28, 3.67)). Patients in the cohort who reported taking > 15 min to fall asleep were 3.6 times more likely to be diagnosed with metastatic cancer compared to those reporting shorter sleep latency (95% CI (1.74, 7.35)). We did not find a significant association between SP and number of ICI infusions completed. CONCLUSION: Our data associating sleep apnea risk, insomnia, and sleep patterns with more advanced cancer encourages further exploration in larger-scale observational studies and suggests interventional clinical trials focused on sleep quality improvement that could result in better outcomes for these patients.


Subject(s)
Neoplasms , Sleep Apnea, Obstructive , Sleep Initiation and Maintenance Disorders , Humans , Neoplasms/complications , Pilot Projects , Polysomnography , Sleep Apnea, Obstructive/epidemiology , Sleep Initiation and Maintenance Disorders/complications , Sleep Initiation and Maintenance Disorders/etiology
20.
J Patient Rep Outcomes ; 5(1): 91, 2021 Sep 15.
Article in English | MEDLINE | ID: mdl-34524558

ABSTRACT

BACKGROUND: Patient reported outcomes (PROs) have been associated with improved symptom management and quality of life in patients with cancer. However, the implementation of PROs in an academic clinical practice has not been thoroughly described. Here we report on the execution, feasibility and healthcare utilization outcomes of an electronic PRO (ePRO) application for cancer patients at an academic medical center. METHODS: We conducted a randomized trial comparing an experimental ePRO arm to standard of care in patients with advanced cancer in the thoracic, gastrointestinal, and genitourinary oncology groups at Stanford Cancer Center from March 2018 to November 2019. We describe the pre-implementation, implementation, and post-implementation phases of the ePRO arm, technological barriers, electronic health record (EHR) integration, clinician burden, and patient data privacy and security. Feasibility was pre-specified to be at least 70% completion of all questionnaires. Acceptability was based on patient and clinician feedback. Ambulatory healthcare utilization was assessed by reviewing numbers of phone messages, electronic portal messages, and referrals for supportive care. RESULTS: Of 617 ePRO questionnaires sent to 72 patients, 445 (72%) were completed. Most clinicians (87.5%) and patients (93%) felt neutral or positive about the ePRO tool's ease of use. Exposure to ePRO did not cause a measurable change in ambulatory healthcare utilization, with a median of less than two phone messages and supportive care referrals, and 5-6 portal messages. CONCLUSIONS: Web-based ePRO tools for patients with advanced cancer are feasible and acceptable without increasing clinical burden. Key lessons include the importance of pilot testing, engagement of stakeholders at all levels, and the need for customization by disease group. Future directions for this work include completion of EHR integration, expansion to other centers, and development of integrated workflows for routine clinical practice.

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