Safety and efficacy of combined radiotherapy, immunotherapy and targeted agents in elderly patients: A literature review

Belgioia, Liliana; Desideri, Isacco; Errico, Angelo; Franzese, Ciro; Daidone, Antonino; Marino, Lorenza; Fiore, Michele; Borghetti, Paolo; Greto, Daniela; Fiorentino, Alba

doi:10.1016/j.critrevonc.2018.11.009

Cited by 28 publications

(13 citation statements)

References 74 publications

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“…However, the accumulated experience with SRS for this specific patient population is based on few reports using LINAC or GammaKnife-based SRS [15][16][17][18]. As the OS after cancer diagnosis is on the rise due to new therapeutic regimens, the role of radiosurgery will become more important for the treatment of the elderly [2,[7][8][9][10].…”

Section: Discussionmentioning

confidence: 99%

“…In the current era of immunotherapy or other targeted therapies, overall survival (OS) has increased; thus, the demand for less toxic alternatives than WBRT and the need for retreatment with radiosurgery for local progression or for new cerebral lesions is on the rise [2,7,8]. It has been postulated that in the near future, 70% of new cancer diagnoses per year will be reported among the elderly [9,10]. Consequently, clinicians are facing a larger population of aging patients.…”

Section: Introductionmentioning

confidence: 99%

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Efficacy and safety of CyberKnife radiosurgery in elderly patients with brain metastases: a retrospective clinical evaluation

et al. 2020

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Background Stereotactic radiosurgery (SRS) has been increasingly applied for up to 10 brain metastases instead of whole brain radiation therapy (WBRT) to achieve local tumor control while reducing neurotoxicity. Furthermore, brain-metastasis incidence is rising due to the increasing survival of patients with cancer. Our aim was to analyze the efficacy and safety of CyberKnife (CK) radiosurgery for elderly patients. Methods We retrospectively identified all patients with brain metastases ≥ 65 years old treated with CK-SRS at our institution since 2011 and analyzed data of primary diseases, multimodality treatments, and local therapy effect based on imaging follow-up and treatment safety. Kaplan–Meier analysis for local progression-free interval and overall survival were performed. Results We identified 97 patients (233 lesions) fulfilling the criteria at the first CK-SRS. The mean age was 73.2 ± 5.8 (range: 65.0–87.0) years. Overall, 13.4% of the patients were > 80 years old. The three most frequent primary cancers were lung (40.2%), kidney (22.7%), and malignant melanoma (15.5%). In 38.5% (47/122 treatments) multiple brain metastases were treated with the CK-SRS, with up to eight lesions in one session. The median planning target volume (PTV) was 1.05 (range: 0.01–19.80) cm3. A single fraction was applied in 92.3% of the lesions with a median prescription dose of 19 (range: 12–21) Gy. The estimated overall survivals at 3-, 6-, and 12 months after SRS were 79, 55, and 23%, respectively. The estimated local tumor progression-free intervals at 6-, 12-, 24-, 36-, and 72 months after SRS were 99.2, 89.0, 67.2, 64.6, and 64.6%, respectively. Older age and female sex were predictive factors of local progression. The Karnofsky performance score remained stable in 97.9% of the patients; only one patient developed a neurological deficit after SRS of a cerebellar lesion (ataxia, CTCAE Grade 2). Conclusions SRS is a safe and efficient option for the treatment of elderly patients with brain metastases with good local control rates without the side effects of WBRT. Older age and female sex seem to be predictive factors of local progression. Prospective studies are warranted to clarify the role of SRS treatment for elderly patients.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of CyberKnife radiosurgery in elderly patients with brain metastases: a retrospective clinical evaluation

et al. 2020

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“…It is clear that more studies considering the high incidence of tumors in the elderly are needed, and that it is important to investigate the effect of ICB antibody therapy and its associated mechanisms in the elderly. In most studies, the number of elderly patients in the ICB antibody therapy group is small and data on the safety and toxicity of ICB antibody treatment are limited; therefore, the effect of ICB antibody therapy on elderly patients has not been fully elucidated [162]. Exploring the underlying mechanisms accelerating tumor growth and affecting immunotherapy in elderly patients is a challenging and urgent need.…”

Section: Immunosenescence and Tumor Immunotherapymentioning

confidence: 99%

Immunosenescence: a key player in cancer development

et al. 2020

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Immunosenescence is a process of immune dysfunction that occurs with age and includes remodeling of lymphoid organs, leading to changes in the immune function of the elderly, which is closely related to the development of infections, autoimmune diseases, and malignant tumors. T cell–output decline is an important feature of immunosenescence as well as the production of senescence-associated secretory phenotype, increased glycolysis, and reactive oxygen species. Senescent T cells exhibit abnormal phenotypes, including downregulation of CD27, CD28, and upregulation of CD57, killer cell lectin-like receptor subfamily G, Tim-3, Tight, and cytotoxic T-lymphocyte-associated protein 4, which are tightly related to malignant tumors. The role of immunosenescence in tumors is sophisticated: the many factors involved include cAMP, glucose competition, and oncogenic stress in the tumor microenvironment, which can induce the senescence of T cells, macrophages, natural killer cells, and dendritic cells. Accordingly, these senescent immune cells could also affect tumor progression. In addition, the effect of immunosenescence on the response to immune checkpoint blocking antibody therapy so far is ambiguous due to the low participation of elderly cancer patients in clinical trials. Furthermore, many other senescence-related interventions could be possible with genetic and pharmacological methods, including mTOR inhibition, interleukin-7 recombination, and NAD+ activation. Overall, this review aims to highlight the characteristics of immunosenescence and its impact on malignant tumors and immunotherapy, especially the future directions of tumor treatment through senescence-focused strategies.

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“…One concern with combination therapies is toxicity 34. ICT is a derivative of colchicine, which is a VDA.…”

Section: Discussionmentioning

confidence: 99%

Theranostic nanoparticles enhance the response of glioblastomas to radiation

Klockow

Mohanty

et al. 2019

Nanotheranostics

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Despite considerable progress with our understanding of glioblastoma multiforme (GBM) and the precise delivery of radiotherapy, the prognosis for GBM patients is still unfavorable with tumor recurrence due to radioresistance being a major concern. We recently developed a cross-linked iron oxide nanoparticle conjugated to azademethylcolchicine (CLIO-ICT) to target and eradicate a subpopulation of quiescent cells, glioblastoma initiating cells (GICs), which could be a reason for radioresistance and tumor relapse. The purpose of our study was to investigate if CLIO-ICT has an additive therapeutic effect to enhance the response of GBMs to ionizing radiation. Methods: NSG mice bearing human GBMs and C57BL/6J mice bearing murine GBMs received CLIO-ICT, radiation, or combination treatment. The mice underwent pre-and post-treatment magnetic resonance imaging (MRI) scans, bioluminescence imaging (BLI), and histological analysis. Tumor nanoparticle enhancement, tumor flux, microvessel density, GIC, and apoptosis markers were compared between different groups using a one-way ANOVA and two-tailed Mann-Whitney test. Additional NSG mice underwent survival analyses with Kaplan-Meier curves and a log rank (Mantel-Cox) test. Results: At 2 weeks post-treatment, BLI and MRI scans revealed significant reduction in tumor size for CLIO-ICT plus radiation treated tumors compared to monotherapy or vehicle-treated tumors. Combining CLIO-ICT with radiation therapy significantly decreased microvessel density, decreased GICs, increased caspase-3 expression, and prolonged the survival of GBM-bearing mice. CLIO-ICT delivery to GBM could be monitored with MRI. and was not significantly different before and after radiation. There was no significant caspase-3 expression in normal brain at therapeutic doses of CLIO-ICT administered. Conclusion: Our data shows additive anti-tumor effects of CLIO-ICT nanoparticles in combination with radiotherapy. The combination therapy proposed here could potentially be a clinically translatable strategy for treating GBMs.

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Safety and efficacy of combined radiotherapy, immunotherapy and targeted agents in elderly patients: A literature review

Cited by 28 publications

References 74 publications

Efficacy and safety of CyberKnife radiosurgery in elderly patients with brain metastases: a retrospective clinical evaluation

Efficacy and safety of CyberKnife radiosurgery in elderly patients with brain metastases: a retrospective clinical evaluation

Immunosenescence: a key player in cancer development

Theranostic nanoparticles enhance the response of glioblastomas to radiation

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