Prospective study of cancer survival in patients with HuD-antibody-associated paraneoplastic neurological disorders

Maddison, Paul; Lang, Bethan; Thomsen, Selina; Moloney, Teresa C.; Gozzard, Paul; Chapman, Caroline; Barnard, Victoria; Ferry, Berne; Vincent, Angela

doi:10.1136/jnnp-2021-326067

Cited by 5 publications

(9 citation statements)

References 6 publications

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“…However, this finding could be partly related to the extensive stage of SCLC in most ICI-treated patients, as opposed to the chiefly limited-stage disease in Hu-Ab ICI-naive patients found both herein and elsewhere. 15 In addition, most of the present ICI-treated patients were elderly, severely disabled at diagnosis, and with evidence of multifocal nervous system involvement, factors previously reported as predictors of death in Hu-Ab–associated PNS. 10 Therefore, age, advanced cancer-related frailty, and severe neurologic presentation seem to be relevant in determining the fatality of post-ICI Hu-Ab syndromes.…”

Section: Discussionmentioning

confidence: 64%

“…10 Although all these tumors overexpress the Hu antigen, only [16][17][18][19][20][21][22].5% of patients with SCLC harbor low titers of Hu-Ab, [11][12][13] and a minority of 1-3% develop PNS. 14,15 The clinical picture of PNS associated with Hu-Ab is highly pleomorphic, with subacute sensory neuronopathy (SNN) being the most frequent presentation at diagnosis. 10 Of interest, Hu-Abs have recently been reported in a few case reports of n-irAEs, but the neurologic disorders of patients with Hu-Ab post-ICI have not thoroughly been described.…”

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confidence: 99%

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Anti-Hu Antibodies in Patients With Neurologic Side Effects of Immune Checkpoint Inhibitors

Farina

Villagrán-García

Ciano-Petersen

et al. 2023

Neurol Neuroimmunol Neuroinflamm

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Background and ObjectivesTo clinically characterize post–immune checkpoint inhibitor (ICI) Hu antibody (Ab) neurologic disorders, we analyzed Hu-Ab–positive patients with neurologic immune-related adverse events (n-irAEs) and compared them with patients with other n-irAEs, ICI-naive patients with Hu-Ab paraneoplastic neurologic syndromes (PNSs) identified in the same study center, and those with Hu-Ab n-irAEs reported elsewhere.MethodsPatients whose samples were sent to the French reference center for a suspicion of n-irAE (2015–2021) were identified; those with a final diagnosis of n-irAE and Hu-Ab were included. Control groups included patients with a final diagnosis of n-irAE occurring during the same period as the patients included (2018–2021) but without Hu-Ab, and ICI-naive patients with Hu-Ab PNS diagnosed during the same period; a systematic review was performed to identify previous reports.ResultsEleven patients with Hu-Ab and n-irAEs were included (median age, 66 years, range 44–76 years; 73% men). Ten patients had small cell lung cancer, and 1 had lung adenocarcinoma. The median follow-up from onset was 3 months (range 0.5–18 months). Compared with those with other n-irAEs (n = 63), Hu-Ab–positive patients had more frequently co-occurring involvement of both central and peripheral nervous systems (36% vs 8%,p= 0.02) and limbic (54% vs 14%,p< 0.01), brainstem (27% vs 5%,p= 0.02), and dorsal root ganglia (45% vs 5%,p< 0.01) involvement. The proportion of patients with severe disability (modified Rankin Scale score >3) at diagnosis was higher among Hu-Ab n-irAEs (91% vs 52%,p= 0.02). Patients with Hu-Ab had also poorer outcome (100% vs 28%,p< 0.01) and higher mortality (91% vs 46%,p< 0.01). There was no significant difference in terms of clinical features between Hu-Ab n-irAEs and ICI-naive Hu-Ab PNS (n = 92), but there was a poorer outcome (56/78, 71%,p< 0.01) and higher mortality (26%,p< 0.01) among the former. No significant difference was found between the patients reported herein and those in the literature.DiscussionThe presence of Hu-Ab identifies a subgroup of n-irAEs that consistently reproduce the phenotypes of Hu-Ab-related PNS, supporting the hypothesis of ICI triggering or unmasking PNS. As these patients show high disability and mortality, further studies are required to investigate the underlying immunopathogenic mechanisms and to improve the outcome of Hu-Ab n-irAEs.

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Section: Discussionmentioning

confidence: 64%

mentioning

confidence: 99%

Anti-Hu Antibodies in Patients With Neurologic Side Effects of Immune Checkpoint Inhibitors

Farina

Villagrán-García

Ciano-Petersen

et al. 2023

Neurol Neuroimmunol Neuroinflamm

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“…Regarding anti-SOX2, two other studies showed that this antibody has diagnostic value in discriminating SCLC-LEMS from non-tumour LEMS but has no relation to survival in patients with SCLC [46,47]. More recently, in a prospective study, Maddison et al reported that a higher proportion of patients survived longer than 48 months in the group with neur-Abs and neurological PNSs, even if a more limited stage was described in this group [48]. The possible role of neur-Abs as a predictive factor during immunotherapy in SCLC was investigated in a phase II study concerning ipilimumab in combination with carboplatin and etoposide.…”

Section: Serum Anti-neuronal Nuclear Antibodiesmentioning

confidence: 97%

What Are the Biomarkers for Immunotherapy in SCLC?

Longo

Catino

Montrone

et al. 2021

IJMS

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Small-cell lung cancer (SCLC) is an aggressive malignancy that exhibits a rapid doubling time, a high growth fraction, and the early development of widespread metastases. The addition of immune checkpoint inhibitors to first-line chemotherapy represents the first significant improvement of systemic therapy in several decades. However, in contrast to its effects on non-SCLC, the advantageous effects of immunotherapy addition are modest in SCLC. In particular, only a small number of SCLC patients benefit from immune checkpoint inhibitors. Additionally, biomarkers selection is lacking for SCLC, with clinical trials largely focusing on unselected populations. Here, we review the data concerning the major biomarkers for immunotherapy, namely, programmed death ligand 1 expression and tumour mutational burden. Furthermore, we explore other potential biomarkers, including the role of the immune microenvironment in SCLC, the role of genetic alterations, and the potential links between neurological paraneoplastic syndromes, serum anti-neuronal nuclear antibodies, and outcomes in SCLC patients treated with immunotherapy.

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“…Two small recent studies suggested that paraneoplastic neuropathic syndromes are associated with a poor prognosis. 21 , 22 …”

Section: Introductionmentioning

confidence: 99%

“…Two small recent studies suggested that paraneoplastic neuropathic syndromes are associated with a poor prognosis. 21,22 In this large population-based cohort study using Danish nationwide registry data, we aimed to provide precise epidemiological evidence concerning the association between GBS and subsequent the risk and prognosis of cancer, and to investigate whether GBS may be a marker of underlying occult cancer.…”

Section: Introductionmentioning

confidence: 99%

Cancer Diagnosis and Prognosis After Guillain–Barré Syndrome: A Population-Based Cohort Study

Girma

Farkas²,

Laugesen³

et al. 2022

CLEP

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Introduction It is unclear whether Guillain–Barré syndrome (GBS) can be a marker of a paraneoplastic syndrome. We examined whether GBS is associated with cancer and whether the prognosis of GBS patients with cancer differs from that of other cancer patients. Materials and Methods We conducted a population-based cohort study of patients diagnosed with GBS between 1978 and 2017 using Danish registry-data. Main outcome measures were cancer incidence and mortality after cancer diagnosis. We calculated absolute risks of a cancer diagnosis, treating death as competing risk, and standardized incidence ratios (SIRs) as measures of relative risk. We matched each GBS cancer patient with up to 10 cancer patients without a GBS diagnosis and examined the six-month survival after cancer diagnosis using Cox regression analysis. Results We identified 7897 patients (58% male, median age 57 years) with GBS. During a median follow-up of 9.5 years, the one-year risk of cancer was 2.7% (95% confidence interval (CI), 2.4–3.1). The SIR was increased throughout follow-up, but most noticeably during the first year after diagnosis (SIR: 3.35, 2.92–3.83). SIRs were particularly elevated for hematologic cancers (SIR: 8.67, 6.49–11.34), smoking-related cancers (SIR: 3.57, 2.81–4.47), and cancers of neurological origin (SIR: 8.60, 5.01–13.77). Lung cancer was the main contributor to the overall excess risk, which persisted after 36 months of follow-up (SIR: 1.17, 1.09–1.25). The mortality rate ratio comparing patients diagnosed with any cancer within one year of their GBS diagnosis and matched GBS-free cancer cohort members was 1.56 (95% CI, 1.27–1.90). Conclusion GBS patients had a three-fold increased risk of cancer diagnosis in the first year of follow-up. The absolute cancer risk was almost 3.0%. A GBS diagnosis was an adverse prognostic marker for survival following cancer diagnosis. Clinicians should consider occult cancer in patients hospitalized with GBS.

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Prospective study of cancer survival in patients with HuD-antibody-associated paraneoplastic neurological disorders

Cited by 5 publications

References 6 publications

Anti-Hu Antibodies in Patients With Neurologic Side Effects of Immune Checkpoint Inhibitors

Anti-Hu Antibodies in Patients With Neurologic Side Effects of Immune Checkpoint Inhibitors

What Are the Biomarkers for Immunotherapy in SCLC?

Cancer Diagnosis and Prognosis After Guillain–Barré Syndrome: A Population-Based Cohort Study

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