Systemic Anticancer Therapy at the End of Life-Changes in Usage Pattern in the Immunotherapy Era.
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ABSTRACT:
SUBMITTER: Canavan ME
PROVIDER: S-EPMC9585458 | biostudies-literature | 2022 Dec
REPOSITORIES: biostudies-literature
Publications
Systemic Anticancer Therapy at the End of Life-Changes in Usage Pattern in the Immunotherapy Era.
Canavan Maureen E ME Wang Xiaoliang X Ascha Mustafa S MS Miksad Rebecca A RA Calip Gregory S GS Gross Cary P CP Adelson Kerin B KB
JAMA oncology 20221201 12
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Project description:BackgroundNovel systemic anticancer therapies (SACT) in the form of targeted and immunotherapies are increasingly replacing traditional chemotherapy. Little is known about the impact of novel SACT on healthcare resource utilization (HCRU) at the end of life.MethodologyA retrospective review of patients attending a tertiary cancer center in Toronto, Canada, with advanced solid or hematological malignancies who died in 2019. Demographic and cancer data, SACT use, HCRU (emergency room [ER] visits, acute/intensive care unit [ICU] admission, and place of death) were retrieved and compared between those who received SACT in their last 30 days of life and those who did not. Chi-squared tests or Quasi-Poisson regression calculated HCRU expressed as percentages or rate ratios (RR). Univariate and multivariable logistic regression identified factors independently associated with SACT use.ResultsOf 443 patients included, 88 (20%) received SACT in the last 30 days of life, with 42 (48%) receiving targeted therapies and 10 (11%) immunotherapy. Factors associated with SACT use included younger age (p = 0.016), breast (p < 0.001), lung (p = 0.047), hematological malignancies (p = 0.002), fewer comorbidities (p = 0.039), and novel SACT (p = 0.006). Receipt of SACT was associated with a higher frequency of ER visits (55% vs. 36% who did not receive SACT, p = 0.001), acute hospitalizations (68% vs. 47%, p < 0.001), ICU admissions (18% vs. 7%, p = 0.003), and death in hospital (45% vs. 30%, p = 0.008).ConclusionNovel SACT use at the end of life is high and is strongly associated with HCRU. Future studies should explore the impact of advance care planning and palliative care referrals on SACT use.
| S-EPMC11626481 | biostudies-literature
Project description:BackgroundSystemic anticancer treatment (SACT) for advanced cancer patients with limited prognosis before death is associated with high toxicity and reduced quality of life. Guidelines discourage this approach as low-value care. However, a significant number of patients continue to receive SACT in the last 30 days of life.Materials and methodsA retrospective study was carried out at the University Hospital Krems, encompassing the analysis of patients who were diagnosed with a solid tumor and died between 2017 and 2021, with a particular focus on the use of end-of-life (EOL) SACT.ResultsA total of 685 patients were included in the study. SACT was applied in 342 (49.9%) patients, of whom 143 (41.8%, total population: 20.9%) patients received SACT within the last 30 days of life. Median time from last SACT to death was 44.5 days. The analysis of potential factors impacting the administration of EOL SACT revealed the following significant findings: type of SACT [P < 0.001, targeted therapy odds ratio (OR) 5.09, 95% confidence interval (CI) 2.26-11.48; chemotherapy/targeted therapy OR 3.60, 95% CI 1.47-8.82; immune checkpoint inhibitor OR 2.32, 95% CI 1.37-3.92], no referral to palliative care (PC) (P = 0.009, OR 1.86, 95% CI 1.16-2.96), no admission to PC ward (P < 0.001, OR 2.70, 95% CI 1.67-4.35), and poor Eastern Cooperative Oncology Group (ECOG) performance status (≥2, P < 0.001, OR 3.35, 95% CI 1.93-5.83).ConclusionThe timing of SACT near the EOL is significantly influenced by several factors, including the type of SACT, referral to PC services, admission to PC unit, and ECOG performance status. These findings underscore the complexity of treatment decisions in advanced cancer care and highlight the need for personalized, patient-centered approaches that consider both clinical and patient-related factors to optimize care at the EOL.
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Project description:ImportanceMelanoma treatment has evolved during the past decade with the adoption of adjuvant and palliative immunotherapy and targeted therapies, with an unclear impact on health care costs and outcomes in routine practice.ObjectiveTo examine changes in health care costs, overall survival (OS), and time toxicity associated with primary treatment of melanoma.Design, setting, and participantsThis cohort study assessed a longitudinal, propensity score (PS)-matched, retrospective cohort of residents of Ontario, Canada, aged 20 years or older with stages II to IV cutaneous melanoma identified from the Ontario Cancer Registry from January 1, 2018, to March 31, 2019. A historical comparison cohort was identified from a population-based sample of invasive melanoma cases diagnosed from the Ontario Cancer Registry from January 1, 2007, to December 31, 2012. Data analysis was performed from October 17, 2022, to March 13, 2023.ExposuresEra of melanoma diagnosis (2007-2012 vs 2018-2019).Main outcomes and measuresThe primary outcomes were mean per-capita health care and systemic therapy costs (Canadian dollars) during the first year after melanoma diagnosis, time toxicity (days with physical health care contact) within 1 year of initial treatment, and OS. Standardized differences were used to compare costs and time toxicity. Kaplan-Meier methods and Cox proportional hazards regression were used to compare OS among PS-matched cohorts.ResultsA PS-matched cohort of 731 patients (mean [SD] age, 67.9 [14.8] years; 437 [59.8%] male) with melanoma from 2018 to 2019 and 731 patients (mean [SD] age, 67.9 [14.4] years; 440 [60.2%] male) from 2007 to 2012 were evaluated. The 2018 to 2019 patients had greater mean (SD) health care (including systemic therapy) costs compared with the 2007 to 2012 patients ($47 886 [$55 176] vs $33 347 [$31 576]), specifically for stage III ($67 108 [$57 226] vs $46 511 [$30 622]) and stage IV disease ($117 450 [$79 272] vs $47 739 [$37 652]). Mean (SD) systemic therapy costs were greater among 2018 to 2019 patients: stage II ($40 823 [$40 621] vs $10 309 [$12 176]), III ($55 699 [$41 181] vs $9764 [$12 771]), and IV disease ($79 358 [$50 442] vs $9318 [$14 986]). Overall survival was greater for the 2018 to 2019 cohort compared with the 2007 to 2012 cohort (3-year OS: 74.2% [95% CI, 70.8%-77.2%] vs 65.8% [95% CI, 62.2%-69.1%], hazard ratio, 0.72 [95% CI, 0.61-0.85]; P < .001). Time toxicity was similar between eras. Patients with stage IV disease spent more than 1 day per week (>52 days) with physical contact with the health care system by 2018 to 2019 (mean [SD], 58.7 [43.8] vs 44.2 [26.5] days; standardized difference, 0.40; P = .20).Conclusions and relevanceThis cohort study found greater health care costs in the treatment of stages II to IV melanoma and substantial time toxicity for patients with stage IV disease, with improvements in OS associated with the adoption of immunotherapy and targeted therapies. These health system-wide data highlight the trade-off with adoption of new therapies, for which there is a greater economic burden to the health care system and time burden to patients but an associated improvement in survival.
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Project description:Radiation therapy controls local disease but also prompts the release of tumor-associated antigens and stress-related danger signals that primes T cells to promote tumor regression at unirradiated sites known as the abscopal effect. This may be enhanced by blocking inhibitory immune signals that modulate immune activity through a variety of mechanisms. Indeed, abscopal responses have occurred in patients with lung cancer or melanoma when given anti-CTLA4 antibody and radiation. Other approaches involve expanding and reinfusing T or NK cells or engineered T cells to express receptors that target specific tumor peptides. These approaches may be useful for immunocompromised patients receiving radiation. Preclinical and clinical studies are testing both immune checkpoint-based strategies and adoptive immunotherapies with radiation.
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Project description:Metastatic melanoma is a fatal malignancy with a high mortality and morbidity. Since the early 1970s, available medical therapies were limited in improving survival. Surgery represented the best chance for a cure. However, surgery could only be offered to selected patients. The current landscape of treatment has radically evolved since the introduction of targeted and immunotherapies including BRAF and MEK inhibitors, and checkpoint blockers, like PD-1 and CTLA-4 antibodies. These new therapies have seen survival rates matching, and in some cases surpassing, that of surgery. Anti-PD1 and CTLA-4 combination treatments are associated with severe side effects and BRAF and MEK inhibitor combinations may trigger initial tumour responses but prolonged use have resulted in the development of resistant tumour clones and disease relapse. This review examines the role of pulmonary metastasectomy for lung metastasis from malignant melanoma in the current landscape of effective targeted therapy and immunotherapy.
| S-EPMC8107521 | biostudies-literature
Project description:Urothelial carcinoma (UC) is a common cancer associated with a poor prognosis in patients with advanced disease. Platinum-based chemotherapy has remained the cornerstone of systemic anticancer treatment for many years, and recent developments in the treatment landscape have improved outcomes. In this review, we provide an overview of systemic treatment for UC, including clinical data supporting the current standard of care at each point in the treatment pathway and author interpretations from a UK perspective. Neoadjuvant cisplatin-based chemotherapy is recommended for eligible patients with muscle-invasive bladder cancer and is preferable to adjuvant treatment. For first-line treatment of advanced UC, platinum-eligible patients should receive cisplatin- or carboplatin-based chemotherapy, followed by avelumab maintenance in those without disease progression. Among patients unable to receive platinum-based chemotherapy, immune checkpoint inhibitor (ICI) treatment is an option for those with programmed death ligand 1 (PD-L1)-positive tumours. Second-line or later treatment options depend on prior treatment, and enfortumab vedotin is preferred after prior ICI and chemotherapy, although availability varies between countries. Additional options include rechallenge with platinum-based chemotherapy, an ICI, or non-platinum-based chemotherapy. Areas of uncertainty include the optimal number of first-line chemotherapy cycles for advanced UC and the value of PD-L1 testing for UC.
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Project description:The ability of tumors to evade detection by the immune system via inducing immunosuppression prompted the therapeutic development of immune checkpoint inhibitors. In our recent review, we discussed findings from preclinical and clinical investigations of these agents utilized in combination with radiation inducing abscopal (systemic) antitumor effects.
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Project description:Novel systemic therapies for advanced melanoma improve survival, but carry potential serious side effects and high costs. This study aimed to assess the timing and use of systemic therapies in the months before death. Patients diagnosed with advanced melanoma (July 2017-June 2020) who died before July 2020 were selected from the Netherlands Cancer Registry. We evaluated the timing of systemic therapies within 30 days and 3 months before death, and studied patient and tumor characteristics associated with systemic therapy use between diagnosis and death. Out of 1097 patients 68% received systemic therapy. Almost 25% and 10% started a new therapy within 90 days and within 30 days before death, respectively. Female sex, elevated LDH, BRAF mutation, poor ECOG performance status (≥3), and high comorbidity index reduced the odds of receiving immune therapy. Poor performance status and high comorbidity decreased the odds for both therapies. A considerable number of patients started systemic therapy shortly before death, emphasizing the importance of considering potential benefits and drawbacks through shared decision-making.
| S-EPMC11483958 | biostudies-literature
Project description:PurposeAnticancer drug use at the end of life places potential extra burdens on patients and the healthcare system. Previous articles show variability in methods and outcomes; thus, their results are not directly comparable. This scoping review describes the methods and extent of anticancer drug use at end of life.MethodsSystematic searches in Medline and Embase were conducted to identify articles reporting anticancer drug use at the end of life.ResultsWe selected 341 eligible publications, identifying key study features including timing of research, disease status, treatment schedule, treatment type, and treatment characteristics. Among the subset of 69 articles of all cancer types published within the last 5 years, we examined the frequency of anticancer drug use across various end of life periods.ConclusionThis comprehensive description of publications on anticancer drug use at end of life underscores the importance of methodological factors when designing studies and comparing outcomes.
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Project description:Radiotherapy (RT) is effective at cytoreducing tumours and until relatively recently the focus in radiobiology has been on the direct effects of RT on the tumour. Increasingly, however, the effect of RT on the tumour vasculature, tumour stroma and immune system are recognized as important to the overall outcome. RT is known to lead to the induction of immunogenic cell death (ICD), which can generate tumour-specific immunity. However, systemic immunity leading to "abscopal effects" resulting in tumour shrinkage outside of the RT treatment field is rare, which is thought to be caused by the immunosuppressive nature of the tumour microenvironment. Recent advances in understanding the nature of this immunosuppression and therapeutics targeting immune checkpoints such as programmed death 1 has led to durable clinical responses in a range of cancer types including malignant melanoma and non-small-cell lung cancer. The effects of RT dose and fraction on the generation of ICD and systemic immunity are largely unknown and are currently under investigation. Stereotactic ablative radiotherapy (SABR) provides an opportunity to deliver single or hypofractionated large doses of RT and potentially increase the amount of ICD and the generation of systemic immunity. Here, we review the interplay of RT and the tumour microenvironment and the rationale for combining SABR with immunomodulatory agents to generate systemic immunity and improve outcomes.
| S-EPMC5124813 | biostudies-other