Association between pretreatment emotional distress and neoadjuvant immune checkpoint blockade response in melanoma

Fraterman, Itske; Reijers, Irene L. M.; Dimitriadis, Petros; Broeks, Annegien; Gonzalez, M.; Menzies, A. M. M.; Lopez-Yurda, Marta; Kapiteijn, Ellen; van der Veldt, Astrid A. M.; Suijkerbuijk, Karijn P. M.; Hospers, Geke A. P.; Long, Georgina V.; Blank, Christian U.; van de Poll-Franse, Lonneke V.

doi:10.1038/s41591-023-02631-x

Cited by 15 publications

(8 citation statements)

References 78 publications

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“…Caution around medical cannabis use in patients on ICIs is advised due to previously documented adverse impact on overall survival [ 100 ••, 101 ], while VAE ( Viscum album extract) therapy studies have not highlighted any safety concerns so far [ 107 , 108 ]. Given the emerging understanding of chronic stress impact on ICI treatment outcomes [ 105 , 106 ], it is prudent to discuss stress management with patients, with mind–body modality use in ICI support being an important area for further investigation.…”

Section: Discussionmentioning

confidence: 99%

“…Two recent human studies have shown an adverse impact of pre-treatment emotional distress and chronic stress on ICI treatment outcomes in melanoma and NSCLC [ 105 ]. In a post hoc analysis of the phase 2 PRADO trial, pre-treatment emotional distress was associated with reduced major pathologic responses and 2-year recurrence-free and distant metastasis-free survival after neoadjuvant ICB treatment in patients with stage IIIB-D melanoma [ 105 ]. In the STRESS-LUNG-1 trial, chronic psychological stress was the independent prognostic factor for ORR (HR = 3.93; p < 0.001), PFS (HR = 1.59; p = 0.038), and OS (HR = 3.16; p = 0.005) in stage IIIB–IV NSCLC patients treated with first-line ICI therapy [ 106 ].…”

Section: Chronic Stress and Potential For Mind–body Therapies In Ici ...mentioning

confidence: 99%

“…Animal studies have shown that chronic stress with continuous activation of the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS) unfavourably alters the TME (tumour microenvironment) in a way that could promote tumorigenesis, invasion, progression, metastasis, and attenuation of systemic therapy effects, including anti-PD-L1 immunotherapy [102][103][104]. Two recent human studies have shown an adverse impact of pre-treatment emotional distress and chronic stress on ICI treatment outcomes in melanoma and NSCLC [105]. In a post hoc analysis of the phase 2 PRADO trial, pretreatment emotional distress was associated with reduced major pathologic responses and 2-year recurrence-free and distant metastasis-free survival after neoadjuvant ICB treatment in patients with stage IIIB-D melanoma [105].…”

Section: Chronic Stress and Potential For Mind-body Therapies In Ici ...mentioning

confidence: 99%

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Integrative Oncology Approaches to Supporting Immune Checkpoint Inhibitor Treatment of Solid Tumours

Fuller-Shavel,

Krell

2024

Curr Oncol Rep

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Purpose of Review The goal of this review was to examine the role and practical applications of integrative oncology strategies in supporting immune checkpoint inhibitor (ICI) treatment of adult solid tumours. Recent Findings Beyond tumour-intrinsic factors, several patient-associated factors affect ICI response, including germline genetics, systemic inflammation, the gut microbiota, and diet. Current promising supportive interventions include a Mediterranean-style diet with over 20 g of fibre, regular exercise, use of live biotherapeutics, minimisation of PPI and antibiotic use, and ensuring vitamin D repletion, with many other integrative oncology approaches under study. Caution around medical cannabis use in patients on ICIs is advised due to previously documented adverse impact on overall survival, while VAE (Viscum album extract) therapy studies have not highlighted any safety concerns so far. Summary With expanding ICI use, it is important to investigate and apply low-cost integrative oncology strategies to support better treatment outcomes and minimise adverse events. Further research may lead to pre-treatment assessment of both tumour and patient-associated biomarkers and personalised multimodal prehabilitation care plans, as well as on-treatment support with targeted nutrition, physical activity, and supplementation regimes, including both systemic inflammation and gut microbiome modulating strategies. Given the emerging understanding of chronic stress impact on ICI treatment outcomes, mind-body approaches require further investigation.

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Section: Discussionmentioning

confidence: 99%

Section: Chronic Stress and Potential For Mind–body Therapies In Ici ...mentioning

confidence: 99%

Section: Chronic Stress and Potential For Mind-body Therapies In Ici ...mentioning

confidence: 99%

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Integrative Oncology Approaches to Supporting Immune Checkpoint Inhibitor Treatment of Solid Tumours

Fuller-Shavel,

Krell

2024

Curr Oncol Rep

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“…One interesting recent discovery is that of pretreatment emotional distress (ED) as a biomarker. It is hypothesized that ED can negatively influence the patient's immune system through β-adrenergic or glucocorticoid signaling [38,39]. From the PRADO study, a post hoc analysis demonstrated that pretreatment ED was significantly associated with reduced MPR rates (46% vs. 65%, HR 0.20, p = 0.038) [39].…”

Section: Future Perspectivesmentioning

confidence: 99%

“…It is hypothesized that ED can negatively influence the patient's immune system through β-adrenergic or glucocorticoid signaling [38,39]. From the PRADO study, a post hoc analysis demonstrated that pretreatment ED was significantly associated with reduced MPR rates (46% vs. 65%, HR 0.20, p = 0.038) [39]. This remained true after correcting for other known prognostic factors, such as the interferon-gamma signature and tumor mutational burden [39].…”

Section: Future Perspectivesmentioning

confidence: 99%

Neo-Adjuvant Therapy for Metastatic Melanoma

Kuijpers,

van Akkooi

2024

Cancers

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Melanoma treatment is leading the neo-adjuvant systemic (NAS) therapy field. It is hypothesized that having the entire tumor in situ, with all of the heterogeneous tumor antigens, allows the patient’s immune system to have a broader response to the tumor in all its shapes and forms. This translates into a higher clinical efficacy. Another benefit of NAS therapy potentially includes identifying patients who have a favorable response, which could offer an opportunity for the de-escalation of the extent of surgery and the need for adjuvant radiotherapy and/or adjuvant systemic therapy, as well as tailoring the follow-up in terms of the frequency of visits and cross-sectional imaging. In this paper, we will review the rationale for NAS therapy in resectable metastatic melanoma and the results obtained so far, both for immunotherapy and for BRAF/MEKi therapy, and discuss the response assessment and interpretation, toxicity and surgical considerations. All the trials that have been reported up to now have been investigator-initiated phase I/II trials with either single-agent anti-PD-1, combination anti-CTLA-4 and anti-PD-1 or BRAF/MEK inhibition. The results have been good but are especially encouraging for immunotherapies, showing high durable recurrence-free survival rates. Combination immunotherapy seems superior, with a higher rate of pathologic responses, particularly in patients with a major pathologic response (MPR = pathologic complete response [pCR] + near-pCR [max 10% viable tumor cells]) of 60% vs. 25–30%. The SWOG S1801 trial has recently shown a 23% improvement in event-free survival (EFS) after 2 years for pembrolizumab when giving 3 doses as NAS therapy and 15 as adjuvant versus 18 as adjuvant only. The community is keen to see the first results (expected in 2024) of the phase 3 NADINA trial (NCT04949113), which randomized patients between surgery + adjuvant anti-PD-1 and two NAS therapy courses of a combination of ipilimumab + nivolumab, followed by surgery and a response-driven adjuvant regimen or follow-up. We are on the eve of neo-adjuvant systemic (NAS) therapy, particularly immunotherapy, becoming the novel standard of care for macroscopic stage III melanoma.

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Stress as a Factor Stimulating Cancer Progression and Metastasis and Increasing Cancer Mortality

Mravec

2024

Neurobiology of Cancer

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Association between pretreatment emotional distress and neoadjuvant immune checkpoint blockade response in melanoma

Cited by 15 publications

References 78 publications

Integrative Oncology Approaches to Supporting Immune Checkpoint Inhibitor Treatment of Solid Tumours

Integrative Oncology Approaches to Supporting Immune Checkpoint Inhibitor Treatment of Solid Tumours

Neo-Adjuvant Therapy for Metastatic Melanoma

Stress as a Factor Stimulating Cancer Progression and Metastasis and Increasing Cancer Mortality

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