Table 1.
Baseline characteristics of included studies.
| Lead Author, Year | Country | Sample Size | Treatment | PIV Cut-Off Value | Cut-Off Selection | Tumor Type | Tumor Stage | Adjustment Factors | Outcome | Additional Comments |
|---|---|---|---|---|---|---|---|---|---|---|
| Fucà, 2020, [32] | Italy | 438 | Tribe study: FOLFIRI + Bevacizumab vs. FOLFOXIRI + Bevacizumab Valentino study: mFOLFOX6 + Panitumumab |
390 | MSR | CRC | IV | - ECOG - Prior adjuvant treatment - Primary tumor resected - Synchronous metastases - Number of metastatic sites - Primary tumor sidedness - RAS/BRAF status - NLR - PLT - Monocyte - SII |
- PFS - OS |
PIV outperformed the other immune-inflammatory biomarkers in regression model |
| Corti, 2021, [38] | Italy | 163 | - Nivolumab plus ipilimumab (32.5%) - Nivolumab (47.3%) - Pembrolizumab (9.8%) - Dostarlimab (10.4%) |
492 | MSR | CRC | IV | - ECOG - ICI regimen |
- PFS - OS - CBR |
Early PIV increase was independently correlated with clinical benefit (aOR: 0.23, 95% CI 0.08–0.66, p = 0.007) |
| Fucà, 2021, [37] | Italy | 228 | ICI: - Nivolumab (61.3%) - Pembrolizumab (38.7%) TT: - Vemurafenib (22.0%) - Dabrafenib (2.8%) - Vemurafenib plus cobimetinib (10.1%) - Dabrafenib plus trametinib (65.1%) |
600 | MSR | Melanoma | IV | - ECOG - M substage - Metastatic sites - LDH - Steroids use |
- PFS - OS - Best response |
High PIV was associated with primary resistance to both targeted therapy (OR: 8.42; 95% CI 2.50–34.5, p < 0.001) and ICI (OR: 3.98, 95% CI 1.45–12.32, p = 0.005) |
| Guven, 2021, [39] | Turkey | 120 | - Nivolumab (78.3%) - Atezolizumab (17.5%) - Pembrolizumab (4.2%) |
513.4 | Median value | RCC, NSCLC, Melanoma, Other | IV | - ECOG - LDH levels - Liver metastasis - BMI category |
- PFS - OS |
A model combining PIV, ECOG status, and LDH levels (PILE Score) was able to predict 12-week PFS and 24-week OS |
| Ligorio, 2021, [41] | Italy | 57 | - Taxane-Transtuzumab - Pertuzumab |
285 | Median value | Breast Cancer | IV | - Number of metastatic sites - Visceral metastasis - Brain metastasis |
- PFS - OS - Response |
PIV outperformed MLR, PLR, and NLR in predicting OS |
| Sahin, 2021, [36] | Turkey | 743 | - Anthracycline plus taxane (68.6%) - Anthracycline-based regimens (27.5%) - Taxane-based regimens (3.9%) |
306.4 | ROC curve | Breast Cancer | I-IV | - Clinical T stage - NLR - MLR - PLR - ER status - Her-2 status - Ki-67 index |
- pCR - DFS - OS |
Pre-treatment PIV appears to be a predictor for pCR and survival, outperforming NLR, MLR, PLR in predicting pCR |
| Zeng, 2021, [49] | China | 53 | Control group of NCT03041311 (53 patients): carboplatin, etoposide, and atezolizumab Validation group (84 patients): - PD-1 antibody (29.8%) - PD-L1 antibody (70.2%) |
581.95 | Median value | SCLC | Extensive Stage | - LDH | - PFS - OS - DCR - DCB |
Higher PILE score was associated with worse treatment efficacy (DCR: 84.21% vs. 100%, p = 0.047, DCB rate: 10% vs. 48.5%, p = 0.060) |
| Efil, 2021, [40] | Turkey | 304 | Adjuvant chemotherapy (52%) | 491 | Median | CRC | II-III | - Age - Stage |
- DFS | A model combining PIV and CD8 + TIL density was able to predict DFS |
| Sato, 2022, [44] | Japan | 758 | Adjuvant chemotherapy (30%) | 376 | ROC curve | CRC | I-III | - Age - CA19-9 - CEA - AGR - Post-operative complication |
- RFS - OS |
A high preoperative PIV was significantly associated with depth of tumor invasion and advanced TNM stage (II, III) |
| Gambichler, 2022, [43] | Germany | 49 | N/A | 372 | ROC curve | MCC | I-III | - Age > 75 - Disease stage - Elevated CRP |
- Recurrence - OS |
An association between PIV levels and stage was present |
| Susok, 2022, [42] | Germany | 62 | - Nivolumab (38.7%) - Pembrolizumab (24.5%) - Ipilimumab (14.5%) - Nivolumab plus Ipilimumab (22.6%) |
455 | ROC curve | Melanoma | III-IV | N/A | - PFS - DSS - Best response |
SII and PIV were not significantly associated with best response to ICI treatment (p = 0.87/0.64), PFS (p = 0.73/0.91), and melanoma-specific survival (p = 0.13/0.17). |
| Chen, 2022, [45] | China | 94 | - Crizotinib (89.4%) - Alectinib (10.6%) - Ceritinib (1.0%) |
364 | Median | Lung Cancer | III-IV | - Liver metastasis | - PFS - OS |
Although PIV, NLR, PLR, and SII were associated with poor median OS, only higher PIV was independently associated with poor survival outcomes (HR = 4.70, 95% Cl: 2.00–11.02, p < 0.001). |
| Baba, 2022, [46] | Japan | 433 (Validation Cohort) | N/A | 164.6 | ROC | Esophageal Cancer | I-IV | - Preoperative therapy - Pathological stage |
- OS | The PIV-high cases were significantly associated with a low TIL status (p < 0.001) and low CD8-positive cell counts (p = 0.011) |
| Lin, 2022, [47] | China | 1312 | Adjuvant chemotherapy (81.3%) | 310.2 | MSR | Breast Cancer | I-III | - Stage (T and N) - PR status - Ki-67 - Histopathological type |
- OS | The prognostic model showed a good discriminating ability for OS prediction, with a C-index of 0.759 (95% CI 0.715–0.802) |
| Perez-Martelo, 2022, [48] | Spain | 130 | - Oxaliplatin-based regimen (74%) - Non-oxaliplatin-based regimen (26%) |
424.05 | MSR | CRC | IV | - CEA - ECOG-PS - Primary tumor location - Lymph node metastases - Primary tumor resection |
- PFS - OS - DCR - ORR |
- Baseline PIV was not correlated either with DCR or ORR |
Abbreviations: MSR: maximally selected rank statistics; ECOG: Eastern Cooperative Oncology Group; mCRC: metastatic colorectal cancer; NLR: neutrophil-to-lymphocyte ratio; PLR: platelet-to-lymphocyte ratio; PLT: platelet count; MONO: monocyte count; SII: systemic immune-inflammation index; PIV: Pan-Immune-Inflammation Value; OR: odds ratio; CBR: Clinical Benefit Rate; DCR: Disease Control Rate; DCB: durable clinical benefit; DSS: disease specific survival; TIL: tumor-infiltrating lymphocytes; ROC: Receiver Operating Characteristic; MCC: Merkel cell carcinoma; BMI: body mass index; ICI: immune checkpoint inhibitor; HR: hazard ratio; CBC: complete blood count; CRP: C-reactive protein; ER: estrogen receptor; CEA: carcinoembriyonic antigen; TT: Targeted Therapy; PR: progesterone receptor.