The Prognostic Value of the MCPyV Serum Antibody Test

A Dual Institutional Observational Study

David M. Miller MD, PhD
MassGeneral Cancer Center
Harvard Medical School

Disclosures

  • No relevant disclosures

AMERK Background

  • Clinical assay developed by the UW Laboratory Medicine and Pathology Team
  • Detects circulating antibodies against the common T-Ag of MCPyV
  • Seropositivity near diagnosis previously reported to be associated with decreased recurrence
    • Seropositive patients had HR 0.58 for recurrence1
  • Used by a subset of clinicians to monitor for disease recurrence
    • NPV and PPV of 99% have been reported2

1Paulson et al. Cancer 2017;123(8):1464-1474. 2Nghiem unpublished data

Primary Aim

  • The primary aim of this study was to evaluate the association between initial AMERK serostatus and survival
    • Four survival outcomes were evaluated
      • Recurrence
      • Event-free Survival (EFS)
      • MCC Specific Survival (MSS)
      • Overall Survival (OS)

Methods

  • Dual institution (MGH and BWH/DFCI) retrospective study of patients diagnosed with MCC from January 1, 2015 to September 29, 2022
  • Database lock was August 11, 2023
  • Preregistered protocol on May 14 2023 on the Center for Open Science

Baseline Patient Characteristics
Characteristic N Overall, N = 2611 95% CI AMERK Status at Diagnosis 95% CI AMERK Status at Diagnosis 95% CI
Seronegative, N = 1321 Seropositive, N = 1291
Sex 261





    Male
161 (62%) 55%, 68% 85 (64%) 56%, 72% 76 (59%) 50%, 67%
    Female
100 (38%) 32%, 45% 47 (36%) 28%, 44% 53 (41%) 33%, 50%
Age 261 74 (67, 80)
76 (70, 82) 74, 78 71 (63, 78) 68, 72
Immune Suppressed 261 42 (16%) 12%, 21% 26 (20%) 13%, 28% 16 (12%) 7.5%, 20%
Primary Site 261





    Head/Neck
97 (37%) 31%, 43% 69 (52%) 43%, 61% 28 (22%) 15%, 30%
    Upper Extremity
54 (21%) 16%, 26% 20 (15%) 9.7%, 23% 34 (26%) 19%, 35%
    Occult Primary
40 (15%) 11%, 20% 17 (13%) 7.9%, 20% 23 (18%) 12%, 26%
    Lower Extremity
35 (13%) 9.6%, 18% 10 (7.6%) 3.9%, 14% 25 (19%) 13%, 27%
    Trunk
24 (9.2%) 6.1%, 14% 15 (11%) 6.7%, 18% 9 (7.0%) 3.4%, 13%
    Buttocks
11 (4.2%) 2.2%, 7.6% 1 (0.8%) 0.04%, 4.8% 10 (7.8%) 4.0%, 14%
Clinical Stage 261





    I
108 (41%) 35%, 48% 64 (48%) 40%, 57% 44 (34%) 26%, 43%
    II
49 (19%) 14%, 24% 19 (14%) 9.1%, 22% 30 (23%) 16%, 32%
    III
89 (34%) 28%, 40% 42 (32%) 24%, 41% 47 (36%) 28%, 45%
    IV
14 (5.4%) 3.1%, 9.0% 6 (4.5%) 1.9%, 10% 8 (6.2%) 2.9%, 12%
    Not Clinically Staged
1 (0.4%) 0.02%, 2.5% 1 (0.8%) 0.04%, 4.8% 0 (0%) 0.00%, 3.6%
Pathological Stage 261





    I
46 (18%) 13%, 23% 27 (20%) 14%, 29% 19 (15%) 9.3%, 22%
    IIA
9 (3.4%) 1.7%, 6.7% 2 (1.5%) 0.26%, 5.9% 7 (5.4%) 2.4%, 11%
    IIB
3 (1.1%) 0.30%, 3.6% 2 (1.5%) 0.26%, 5.9% 1 (0.8%) 0.04%, 4.9%
    IIIA
72 (28%) 22%, 34% 32 (24%) 17%, 33% 40 (31%) 23%, 40%
    IIIB
31 (12%) 8.3%, 17% 14 (11%) 6.1%, 17% 17 (13%) 8.1%, 21%
    IV
6 (2.3%) 0.94%, 5.2% 3 (2.3%) 0.59%, 7.0% 3 (2.3%) 0.60%, 7.2%
    Not Pathologically Staged
94 (36%) 30%, 42% 52 (39%) 31%, 48% 42 (33%) 25%, 41%
Baseline ECOG 261





    0
145 (56%) 49%, 62% 66 (50%) 42%, 58% 79 (61%) 52%, 70%
    1
67 (26%) 21%, 31% 36 (27%) 20%, 36% 31 (24%) 17%, 33%
    2
31 (12%) 8.3%, 17% 18 (14%) 8.5%, 21% 13 (10%) 5.7%, 17%
    3
12 (4.6%) 2.5%, 8.1% 7 (5.3%) 2.3%, 11% 5 (3.9%) 1.4%, 9.3%
    4
1 (0.4%) 0.02%, 2.5% 1 (0.8%) 0.04%, 4.8% 0 (0%) 0.00%, 3.6%
    Not Reported
5 (1.9%) 0.71%, 4.7% 4 (3.0%) 0.98%, 8.1% 1 (0.8%) 0.04%, 4.9%
1 n (%); Median (IQR)

Baseline Patient Characteristics
Characteristic N Overall, N = 2611 95% CI AMERK Status at Diagnosis 95% CI AMERK Status at Diagnosis 95% CI
Seronegative, N = 1321 Seropositive, N = 1291
Sex 261





    Male
161 (62%) 55%, 68% 85 (64%) 56%, 72% 76 (59%) 50%, 67%
    Female
100 (38%) 32%, 45% 47 (36%) 28%, 44% 53 (41%) 33%, 50%
Age 261 74 (67, 80)
76 (70, 82) 74, 78 71 (63, 78) 68, 72
Immune Suppressed 261 42 (16%) 12%, 21% 26 (20%) 13%, 28% 16 (12%) 7.5%, 20%
Primary Site 261





    Head/Neck
97 (37%) 31%, 43% 69 (52%) 43%, 61% 28 (22%) 15%, 30%
    Upper Extremity
54 (21%) 16%, 26% 20 (15%) 9.7%, 23% 34 (26%) 19%, 35%
    Occult Primary
40 (15%) 11%, 20% 17 (13%) 7.9%, 20% 23 (18%) 12%, 26%
    Lower Extremity
35 (13%) 9.6%, 18% 10 (7.6%) 3.9%, 14% 25 (19%) 13%, 27%
    Trunk
24 (9.2%) 6.1%, 14% 15 (11%) 6.7%, 18% 9 (7.0%) 3.4%, 13%
    Buttocks
11 (4.2%) 2.2%, 7.6% 1 (0.8%) 0.04%, 4.8% 10 (7.8%) 4.0%, 14%
Clinical Stage 261





    I
108 (41%) 35%, 48% 64 (48%) 40%, 57% 44 (34%) 26%, 43%
    II
49 (19%) 14%, 24% 19 (14%) 9.1%, 22% 30 (23%) 16%, 32%
    III
89 (34%) 28%, 40% 42 (32%) 24%, 41% 47 (36%) 28%, 45%
    IV
14 (5.4%) 3.1%, 9.0% 6 (4.5%) 1.9%, 10% 8 (6.2%) 2.9%, 12%
    Not Clinically Staged
1 (0.4%) 0.02%, 2.5% 1 (0.8%) 0.04%, 4.8% 0 (0%) 0.00%, 3.6%
Pathological Stage 261





    I
46 (18%) 13%, 23% 27 (20%) 14%, 29% 19 (15%) 9.3%, 22%
    IIA
9 (3.4%) 1.7%, 6.7% 2 (1.5%) 0.26%, 5.9% 7 (5.4%) 2.4%, 11%
    IIB
3 (1.1%) 0.30%, 3.6% 2 (1.5%) 0.26%, 5.9% 1 (0.8%) 0.04%, 4.9%
    IIIA
72 (28%) 22%, 34% 32 (24%) 17%, 33% 40 (31%) 23%, 40%
    IIIB
31 (12%) 8.3%, 17% 14 (11%) 6.1%, 17% 17 (13%) 8.1%, 21%
    IV
6 (2.3%) 0.94%, 5.2% 3 (2.3%) 0.59%, 7.0% 3 (2.3%) 0.60%, 7.2%
    Not Pathologically Staged
94 (36%) 30%, 42% 52 (39%) 31%, 48% 42 (33%) 25%, 41%
Baseline ECOG 261





    0
145 (56%) 49%, 62% 66 (50%) 42%, 58% 79 (61%) 52%, 70%
    1
67 (26%) 21%, 31% 36 (27%) 20%, 36% 31 (24%) 17%, 33%
    2
31 (12%) 8.3%, 17% 18 (14%) 8.5%, 21% 13 (10%) 5.7%, 17%
    3
12 (4.6%) 2.5%, 8.1% 7 (5.3%) 2.3%, 11% 5 (3.9%) 1.4%, 9.3%
    4
1 (0.4%) 0.02%, 2.5% 1 (0.8%) 0.04%, 4.8% 0 (0%) 0.00%, 3.6%
    Not Reported
5 (1.9%) 0.71%, 4.7% 4 (3.0%) 0.98%, 8.1% 1 (0.8%) 0.04%, 4.9%
1 n (%); Median (IQR)

Association Between Serostatus & Survival

  • Associations between AMERK serostatus and the survival outcomes were assessed using:
    • Competing risks regression model for Recurrence and MSS
    • Cox proportional hazard (CoxPH) model for EFS and OS

CRR Model for Recurrence

Recurrence = β0 + β1I(Serostatus = Seropositive) + β2Age +
β3I(Sex = Male) + β4I(Clinical Stage = IIA) +
β5I(Clinical Stage = IIB) + β6I(Clinical Stage = III) +
β7I(Clinical Stage = IV) + β8I(Baseline ECOG = 1) +
β9I(Baseline ECOG = 2) + β10I(Baseline ECOG = 3) +
β11I(Baseline ECOG = Not Reported) + β12I(Immune Suppressed = Yes) +
β13I(Initial Treatment Summarized = Surgical Excision, Adjuvant RT) +
β14I(Initial Treatment Summarized = Primary-Definitive RT) +
β15I(Initial Treatment Summarized = Chemotherapy) +
β16I(Initial Treatment Summarized = Immunotherapy) + ε

Competing Risk Regression For Recurrence
Complete Case Analysis Univariable Multivariable
Characteristic1 N SHR 95% CI SHR 95% CI p-value
Serostatus





    Seronegative 119 — — — —
    Seropositive 120 0.49 0.31, 0.76 0.48 0.30, 0.78 0.003
Sex





    Female 92 — — — —
    Male 147 1.75 1.07, 2.85 1.54 0.92, 2.57 0.10
Age 239 1.03 1.01, 1.05 1.01 0.98, 1.04 0.5
Clinical Stage





    I 105 — — — —
    IIA 36 1.45 0.78, 2.71 1.94 0.99, 3.80 0.053
    IIB 11 1.82 0.68, 4.89 1.82 0.65, 5.07 0.3
    III 77 1.61 0.98, 2.65 1.80 1.00, 3.26 0.051
    IV 10 0.68 0.17, 2.75 0.96 0.19, 4.92 >0.9
Immunocompromised





    No 201 — — — —
    Yes 38 1.43 0.85, 2.42 1.21 0.67, 2.16 0.5
Baseline ECOG





    0 141 — — — —
    1 62 1.85 1.13, 3.02 1.69 1.00, 2.85 0.049
    2-4 36 2.44 1.39, 4.30 1.56 0.76, 3.20 0.2
Initial Treatment





    Surgery Alone 30 — — — —
    Surgical Excision, Adjuvant Radiation 126 0.58 0.30, 1.10 0.66 0.35, 1.25 0.2
    Primary-Definitive Radiation 41 1.47 0.72, 3.00 1.25 0.57, 2.75 0.6
    Chemotherapy 4 1.05 0.28, 4.02 0.86 0.26, 2.78 0.8
    Immunotherapy 38 0.59 0.27, 1.31 0.50 0.21, 1.17 0.11
1 Observations: 239, Events: 83, DoF: 14, EPDF: 5.9

Competing Risk Regression For Recurrence
Complete Case Analysis Univariable Multivariable
Characteristic1 N SHR 95% CI SHR 95% CI p-value
Serostatus





    Seronegative 119 — — — —
    Seropositive 120 0.49 0.31, 0.76 0.48 0.30, 0.78 0.003
Sex





    Female 92 — — — —
    Male 147 1.75 1.07, 2.85 1.54 0.92, 2.57 0.10
Age 239 1.03 1.01, 1.05 1.01 0.98, 1.04 0.5
Clinical Stage





    I 105 — — — —
    IIA 36 1.45 0.78, 2.71 1.94 0.99, 3.80 0.053
    IIB 11 1.82 0.68, 4.89 1.82 0.65, 5.07 0.3
    III 77 1.61 0.98, 2.65 1.80 1.00, 3.26 0.051
    IV 10 0.68 0.17, 2.75 0.96 0.19, 4.92 >0.9
Immunocompromised





    No 201 — — — —
    Yes 38 1.43 0.85, 2.42 1.21 0.67, 2.16 0.5
Baseline ECOG





    0 141 — — — —
    1 62 1.85 1.13, 3.02 1.69 1.00, 2.85 0.049
    2-4 36 2.44 1.39, 4.30 1.56 0.76, 3.20 0.2
Initial Treatment





    Surgery Alone 30 — — — —
    Surgical Excision, Adjuvant Radiation 126 0.58 0.30, 1.10 0.66 0.35, 1.25 0.2
    Primary-Definitive Radiation 41 1.47 0.72, 3.00 1.25 0.57, 2.75 0.6
    Chemotherapy 4 1.05 0.28, 4.02 0.86 0.26, 2.78 0.8
    Immunotherapy 38 0.59 0.27, 1.31 0.50 0.21, 1.17 0.11
1 Observations: 239, Events: 83, DoF: 14, EPDF: 5.9

Cox Regression for Event-Free Survival
Complete Case Analysis Univariable Multivariable
Characteristic1 N HR 95% CI HR 95% CI p-value
Serostatus




0.008
    Seronegative 127 — — — —
    Seropositive 128 0.56 0.39, 0.83 0.58 0.38, 0.87
Age 255 1.04 1.02, 1.06 1.02 1.0, 1.04 0.13
Sex




0.037
    Female 98 — — — —
    Male 157 1.77 1.17, 2.69 1.57 1.02, 2.41
Clinical Stage




0.027
    I 106 — — — —
    IIA 36 1.49 0.84, 2.66 2.09 1.12, 3.88
    IIB 11 1.45 0.57, 3.71 1.39 0.53, 3.64
    III 88 1.89 1.22, 2.93 2.16 1.30, 3.59
    IV 14 1.93 0.86, 4.33 2.30 0.85, 6.25
Immune Suppressed




0.8
    No 213 — — — —
    Yes 42 1.33 0.83, 2.12 1.06 0.65, 1.74
Baseline ECOG




0.021
    0 145 — — — —
    1 66 1.95 1.26, 3.02 1.78 1.13, 2.81
    2-4 44 3.02 1.89, 4.81 1.83 1.05, 3.19
Initial Treatment




0.038
    Surgery Alone 33 — — — —
    Surgical Excision, Adjuvant Radiation 126 0.45 0.26, 0.78 0.48 0.26, 0.88
    Primary-Definitive Radiation 46 1.36 0.76, 2.43 0.97 0.51, 1.85
    Chemotherapy 4 0.71 0.16, 3.06 0.50 0.11, 2.24
    Immunotherapy 45 0.81 0.43, 1.53 0.49 0.23, 1.07
    Hospice 1 3.88 0.51, 29.5 3.80 0.46, 31.1
1 Observations: 255, Events: 111, DoF: 15, EPDF: 7.4, AIC: 1126.6

Cox Regression for Overall Survival
Complete Case Analysis Univariable Multivariable
Characteristic1 N HR 95% CI HR 95% CI p-value
Serostatus




0.081
    Seronegative 127 — — — —
    Seropositive 128 0.57 0.34, 0.93 0.62 0.36, 1.07
Age 255 1.05 1.02, 1.08 1.01 0.98, 1.04 0.6
Sex




0.2
    Female 98 — — — —
    Male 157 1.91 1.10, 3.32 1.45 0.81, 2.59
Clinical Stage




0.070
    I 106 — — — —
    IIA 36 1.84 0.85, 4.00 2.57 1.14, 5.79
    IIB 11 1.51 0.45, 5.14 1.16 0.33, 4.13
    III 88 2.32 1.29, 4.16 2.24 1.16, 4.34
    IV 14 2.43 0.90, 6.55 1.46 0.44, 4.82
Immune Suppressed




0.5
    No 213 — — — —
    Yes 42 1.54 0.87, 2.74 1.28 0.68, 2.38
Baseline ECOG




<0.001
    0 145 — — — —
    1 66 2.68 1.48, 4.84 2.58 1.41, 4.71
    2-4 44 6.53 3.55, 12.0 5.25 2.50, 11.0
Initial Treatment




0.009
    Surgery Alone 33 — — — —
    Surgical Excision, Adjuvant Radiation 126 0.32 0.15, 0.68 0.37 0.16, 0.85
    Primary-Definitive Radiation 46 1.49 0.73, 3.07 1.04 0.46, 2.35
    Chemotherapy 4 0.49 0.06, 3.82 0.51 0.06, 4.10
    Immunotherapy 45 1.23 0.59, 2.59 1.21 0.50, 2.93
    Hospice 1 25.9 3.03, 222 20.2 2.11, 194
1 Observations: 255, Events: 66, DoF: 15, EPDF: 4.4, AIC: 628.9

Competing Risk Regression for MCC-Specific Survival
Complete Case Univariable Multivariable
Characteristic1 N SHR 95% CI SHR 95% CI p-value
Serostatus





    Seronegative 120 — — — —
    Seropositive 127 0.58 0.32, 1.07 0.63 0.32, 1.23 0.2
Sex





    Female 94 — — — —
    Male 153 2.13 1.04, 4.36 1.64 0.77, 3.46 0.2
Age 247 1.03 1.0, 1.06 1.00 0.97, 1.03 0.9
Clinical Stage





    I 102 — — — —
    IIA 35 1.37 0.42, 4.47 1.79 0.51, 6.24 0.4
    IIB 11 2.00 0.44, 9.15 1.84 0.38, 8.94 0.5
    III 85 3.53 1.64, 7.58 3.27 1.27, 8.40 0.014
    IV 14 4.89 1.65, 14.5 2.77 0.66, 11.6 0.2
Immunocompromised





    No 207 — — — —
    Yes 40 1.61 0.79, 3.27 1.55 0.72, 3.33 0.3
Baseline ECOG





    0 142 — — — —
    1 63 2.43 1.24, 4.78 2.29 1.17, 4.46 0.015
    2-4 42 3.29 1.51, 7.18 3.07 1.08, 8.70 0.035
Initial Treatment





    Surgery Alone 31 — — — —
    Surgical Excision, Adjuvant Radiation 125 0.36 0.13, 0.96 0.34 0.11, 1.03 0.056
    Primary-Definitive Radiation 42 1.24 0.47, 3.28 0.70 0.20, 2.46 0.6
    Chemotherapy 4 0.84 0.11, 6.57 0.60 0.14, 2.65 0.5
    Immunotherapy 45 1.77 0.71, 4.44 0.96 0.30, 3.13 >0.9
1 Observations: 247, Events: 43, DoF: 14, EPDF: 3.07

Sensitivity Analyses

  • Signal direction persisted when sensitivity analyses were performed:
    • removing subjects with “borderline” AMERK titers at baseline (75-150)
    • removing subjects that received systemic therapy
    • analyzing with multiple imputation

AMERK Titer Prognosic?

  • If being AMERK positive is “better” than AMERK negative, is being more positive better than less positive?
    • i.e. Is the magnitude of the initial AMERK titer prognostic?
  • Subsetted on AMERK positive patients and dichotomized on the median AMERK titer (2510)
    • Initial AMERK titer <2510 = “AMERK Low”
    • Initial AMERK titer >=2510 = “AMERK High”

Cox Regression For Event-Free Survival
Seropositive Patients Univariable Multivariable
Characteristic1 N HR 95% CI HR 95% CI p-value
AMERK High/Low




>0.9
    AMERK Low 63 — — — —
    AMERK High 65 1.79 0.98, 3.29 1.01 0.49, 2.07
Age 128 1.02 0.99, 1.05 1.03 1.00, 1.06 0.073
Sex




0.002
    Female 53 — — — —
    Male 75 3.45 1.65, 7.20 2.96 1.40, 6.29
Clinical Stage




0.025
    I 44 — — — —
    IIA 24 1.62 0.59, 4.48 1.27 0.44, 3.65
    IIB 5 1.01 0.13, 8.07 0.71 0.09, 5.75
    III 47 3.71 1.65, 8.32 3.44 1.36, 8.72
    IV 8 5.25 1.71, 16.1 3.80 1.15, 12.6
1 Observations: 128, Events: 44, DoF: 7, EPDF: 6.29

Cox Regression For Event-Free Survival
Seropositive Patients Univariable Multivariable
Characteristic1 N HR 95% CI HR 95% CI p-value
AMERK High/Low




>0.9
    AMERK Low 63 — — — —
    AMERK High 65 1.79 0.98, 3.29 1.01 0.49, 2.07
Age 128 1.02 0.99, 1.05 1.03 1.00, 1.06 0.073
Sex




0.002
    Female 53 — — — —
    Male 75 3.45 1.65, 7.20 2.96 1.40, 6.29
Clinical Stage




0.025
    I 44 — — — —
    IIA 24 1.62 0.59, 4.48 1.27 0.44, 3.65
    IIB 5 1.01 0.13, 8.07 0.71 0.09, 5.75
    III 47 3.71 1.65, 8.32 3.44 1.36, 8.72
    IV 8 5.25 1.71, 16.1 3.80 1.15, 12.6
1 Observations: 128, Events: 44, DoF: 7, EPDF: 6.29

AMERK Titer and Tumor Burden

  • Paulson et al. previously reported that higher anti-T antigen antibody titers were present at diagnosis in seropositive patients with advanced disease compared to those with localized disease1
  • We sought to evaluate the correlation between baseline titer magnitude and features associated with tumor burden
    • initial stage at diagnosis
    • primary cutaneous tumor size
    • regional lymph node basin burden
    • localized disease vs. metastatic disease

1Paulson, K. G. et al. Antibodies to Merkel Cell Polyomavirus T Antigen Oncoproteins Reflect Tumor Burden in Merkel Cell Carcinoma Patients. Cancer Research 70, 8388–8397 (2010).

Disease Extent As an Effect Modifier

  • Recognizing the link between initial AMERK serostatus and disease burden, we further investigated the potential modification of the relationship between serostatus and survival by the extent of disease at diagnosis

Cox Regression for Event-Free Survival
Complete Case Analysis Univariable Multivariable
Characteristic1 N HR2 95% CI2 p-value HR2 95% CI2 p-value
Serostatus


0.003

<0.001
    Seronegative 127 — —
— —
    Seropositive 128 0.56 0.39, 0.83
0.36 0.20, 0.66
Age 255 1.04 1.02, 1.06 <0.001 1.02 1.00, 1.04 0.12
Sex


0.005

0.055
    Female 98 — —
— —
    Male 157 1.77 1.17, 2.69
1.51 0.98, 2.32
Clinically Staged Disease Extent


0.008

0.7
    Localized 153 — —
— —
    Metastatic 102 1.66 1.14, 2.41
1.10 0.62, 1.96
Immune Suppressed


0.2

0.8
    No 213 — —
— —
    Yes 42 1.33 0.83, 2.12
1.07 0.66, 1.74
Baseline ECOG


<0.001

0.016
    0 145 — —
— —
    1 66 1.95 1.26, 3.02
1.71 1.08, 2.69
    2-4 44 3.02 1.89, 4.81
2.04 1.18, 3.56
Initial Treatment


<0.001

0.086
    Surgery Alone 33 — —
— —
    Surgical Excision, Adjuvant Radiation 126 0.45 0.26, 0.78
0.57 0.31, 1.02
    Primary-Definitive Radiation 46 1.36 0.76, 2.43
1.07 0.56, 2.06
    Chemotherapy 4 0.71 0.16, 3.06
0.82 0.18, 3.75
    Immunotherapy 45 0.81 0.43, 1.53
0.62 0.30, 1.29
    Hospice 1 3.88 0.51, 29.5
4.46 0.53, 37.3
Serostatus * Disease Extent Interaction





0.007
    Seropositive * Metastatic



3.05 1.34, 6.91
1 Observations: 255, Events: 111, DoF: 13, EPDF: 8.5, AIC: 1120.3
2 HR = Hazard Ratio, CI = Confidence Interval

Cox Regression for Event-Free Survival
Complete Case Analysis Univariable Multivariable
Characteristic1 N HR2 95% CI2 p-value HR2 95% CI2 p-value
Serostatus


0.003

<0.001
    Seronegative 127 — —
— —
    Seropositive 128 0.56 0.39, 0.83
0.36 0.20, 0.66
Age 255 1.04 1.02, 1.06 <0.001 1.02 1.00, 1.04 0.12
Sex


0.005

0.055
    Female 98 — —
— —
    Male 157 1.77 1.17, 2.69
1.51 0.98, 2.32
Clinically Staged Disease Extent


0.008

0.7
    Localized 153 — —
— —
    Metastatic 102 1.66 1.14, 2.41
1.10 0.62, 1.96
Immune Suppressed


0.2

0.8
    No 213 — —
— —
    Yes 42 1.33 0.83, 2.12
1.07 0.66, 1.74
Baseline ECOG


<0.001

0.016
    0 145 — —
— —
    1 66 1.95 1.26, 3.02
1.71 1.08, 2.69
    2-4 44 3.02 1.89, 4.81
2.04 1.18, 3.56
Initial Treatment


<0.001

0.086
    Surgery Alone 33 — —
— —
    Surgical Excision, Adjuvant Radiation 126 0.45 0.26, 0.78
0.57 0.31, 1.02
    Primary-Definitive Radiation 46 1.36 0.76, 2.43
1.07 0.56, 2.06
    Chemotherapy 4 0.71 0.16, 3.06
0.82 0.18, 3.75
    Immunotherapy 45 0.81 0.43, 1.53
0.62 0.30, 1.29
    Hospice 1 3.88 0.51, 29.5
4.46 0.53, 37.3
Serostatus * Disease Extent Interaction





0.007
    Seropositive * Metastatic



3.05 1.34, 6.91
1 Observations: 255, Events: 111, DoF: 13, EPDF: 8.5, AIC: 1120.3
2 HR = Hazard Ratio, CI = Confidence Interval

Cox Regression for Event-Free Survival
Complete Case Analysis Univariable Multivariable
Characteristic1 N HR2 95% CI2 p-value HR2 95% CI2 p-value
Serostatus


0.003

<0.001
    Seronegative 127 — —
— —
    Seropositive 128 0.56 0.39, 0.83
0.36 0.20, 0.66
Age 255 1.04 1.02, 1.06 <0.001 1.02 1.00, 1.04 0.12
Sex


0.005

0.055
    Female 98 — —
— —
    Male 157 1.77 1.17, 2.69
1.51 0.98, 2.32
Clinically Staged Disease Extent


0.008

0.7
    Localized 153 — —
— —
    Metastatic 102 1.66 1.14, 2.41
1.10 0.62, 1.96
Immune Suppressed


0.2

0.8
    No 213 — —
— —
    Yes 42 1.33 0.83, 2.12
1.07 0.66, 1.74
Baseline ECOG


<0.001

0.016
    0 145 — —
— —
    1 66 1.95 1.26, 3.02
1.71 1.08, 2.69
    2-4 44 3.02 1.89, 4.81
2.04 1.18, 3.56
Initial Treatment


<0.001

0.086
    Surgery Alone 33 — —
— —
    Surgical Excision, Adjuvant Radiation 126 0.45 0.26, 0.78
0.57 0.31, 1.02
    Primary-Definitive Radiation 46 1.36 0.76, 2.43
1.07 0.56, 2.06
    Chemotherapy 4 0.71 0.16, 3.06
0.82 0.18, 3.75
    Immunotherapy 45 0.81 0.43, 1.53
0.62 0.30, 1.29
    Hospice 1 3.88 0.51, 29.5
4.46 0.53, 37.3
Serostatus * Disease Extent Interaction





0.007
    Seropositive * Metastatic



3.05 1.34, 6.91
1 Observations: 255, Events: 111, DoF: 13, EPDF: 8.5, AIC: 1120.3
2 HR = Hazard Ratio, CI = Confidence Interval

Cox Regression for Event-Free Survival
Complete Case Analysis Univariable Multivariable
Characteristic1 N HR2 95% CI2 p-value HR2 95% CI2 p-value
Serostatus


0.003

<0.001
    Seronegative 127 — —
— —
    Seropositive 128 0.56 0.39, 0.83
0.36 0.20, 0.66
Age 255 1.04 1.02, 1.06 <0.001 1.02 1.00, 1.04 0.12
Sex


0.005

0.055
    Female 98 — —
— —
    Male 157 1.77 1.17, 2.69
1.51 0.98, 2.32
Clinically Staged Disease Extent


0.008

0.7
    Localized 153 — —
— —
    Metastatic 102 1.66 1.14, 2.41
1.10 0.62, 1.96
Immune Suppressed


0.2

0.8
    No 213 — —
— —
    Yes 42 1.33 0.83, 2.12
1.07 0.66, 1.74
Baseline ECOG


<0.001

0.016
    0 145 — —
— —
    1 66 1.95 1.26, 3.02
1.71 1.08, 2.69
    2-4 44 3.02 1.89, 4.81
2.04 1.18, 3.56
Initial Treatment


<0.001

0.086
    Surgery Alone 33 — —
— —
    Surgical Excision, Adjuvant Radiation 126 0.45 0.26, 0.78
0.57 0.31, 1.02
    Primary-Definitive Radiation 46 1.36 0.76, 2.43
1.07 0.56, 2.06
    Chemotherapy 4 0.71 0.16, 3.06
0.82 0.18, 3.75
    Immunotherapy 45 0.81 0.43, 1.53
0.62 0.30, 1.29
    Hospice 1 3.88 0.51, 29.5
4.46 0.53, 37.3
Serostatus * Disease Extent Interaction





0.007
    Seropositive * Metastatic



3.05 1.34, 6.91
1 Observations: 255, Events: 111, DoF: 13, EPDF: 8.5, AIC: 1120.3
2 HR = Hazard Ratio, CI = Confidence Interval

Summary

  • The presence of circulating antibodies to MCPyV oncoproteins is associated with improved survival outcomes
  • Initial AMERK titer correlates with tumor burden
  • Potential effect modification exists between serostatus and disease extent

Limitations

  • Regional and temporally restricted retrospective study
  • Exploratory data analysis (strict significance testing not performed)
  • Low number of events

Acknowledgements

  • AMERK Test: Paul Nghiem, Kelly Paulson and UW Laboratory Medicine & Pathology
  • AMERK at BWH/DFCI: Manisha Thakuria
  • Data Collection: Manisha Thakuria, Ann Silk, David Miller, Kevin Emerick, Howard Kaufman
  • Data Abstraction: Kayla Wright, Matt Miller, Farees Saqlain, Sophia Shalhout, David Miller
  • Study Design: David Miller, Sophia Shalhout, Manisha Thakuria, Ann Silk, David Miller, Kevin Emerick, Howard Kaufman
  • Data Analysis: David Miller
  • Biostatistical Consultation: Harrison Reeder
  • Funding: Project Data Sphere
  • Editor and reviewers at Cancer