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Early-time-point 18F-FDG-PET/CT and other prognostic biomarkers of survival in metastatic melanoma patients receiving immunotherapy

Nezka Hribernik

Nezka Hribernik

  • Department of Medical Oncology, Institute of Oncology LjubljanaLjubljana, Slovenia
  • Faculty of Medicine, University of LjubljanaLjubljana, Slovenia
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Hribernik, Nezka
, 
Katja Strasek

Katja Strasek

Faculty of Mathematics and Physics, University of LjubljanaLjubljana, Slovenia
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Strasek, Katja
, 
Andrej Studen

Andrej Studen

  • Faculty of Mathematics and Physics, University of LjubljanaLjubljana, Slovenia
  • Experimental Particle Physics Department, Jozef Stefan InstituteLjubljana, Slovenia
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Studen, Andrej
, 
Katarina Zevnik

Katarina Zevnik

Department of Nuclear Medicine, Institute of Oncology LjubljanaLjubljana, Slovenia
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Zevnik, Katarina
, 
Katja Skalic

Katja Skalic

Department of Nuclear Medicine, Institute of Oncology LjubljanaLjubljana, Slovenia
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Skalic, Katja
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Robert Jeraj

Robert Jeraj

  • Faculty of Mathematics and Physics, University of LjubljanaLjubljana, Slovenia
  • University of Wisconsin Carbone Cancer CentreMadison, USA
  • Department of Medical Physics, University of Wisconsin-MadisonMadison, USA
  • Experimental Particle Physics Department, Jozef Stefan InstituteLjubljana, Slovenia
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Jeraj, Robert
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Martina Rebersek

Martina Rebersek

  • Department of Medical Oncology, Institute of Oncology LjubljanaLjubljana, Slovenia
  • Faculty of Medicine, University of LjubljanaLjubljana, Slovenia
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Rebersek, Martina
  
Feb 27, 2025
Early-time-point 18F-FDG-PET/CT and other prognostic biomarkers of survival in metastatic melanoma patients receiving immunotherapy's Cover Image
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Article Category: research article
Published Online: Feb 27, 2025
Page range: 43 - 53
Received: Dec 12, 2024
Accepted: Jan 04, 2025
DOI: https://doi.org/10.2478/raon-2025-0014
Keywords
© 2025 Nezka Hribernik et al., published by Sciendo
This work is licensed under the Creative Commons Attribution 4.0 International License.

FIGURE 1.

Kaplan-Meier curves show overall survival (OS) probability (A) and progression-free survival (PFS) probability (B) over time in patients with metastatic melanoma treated with immune checkpoint inhibitors. The grey shading reflects the 95% confidence interval.
Kaplan-Meier curves show overall survival (OS) probability (A) and progression-free survival (PFS) probability (B) over time in patients with metastatic melanoma treated with immune checkpoint inhibitors. The grey shading reflects the 95% confidence interval.

FIGURE 2.

Swimmer plot shows individual patient’s treatment progression in each horizontal line. Colourful bars and lines indicate type and duration of treatment, while dots indicate specific action - 18F-FDG-PET/CT imaging or reason for end-of-study (if applicable). Vertical dashed lines indicate a time when 18F-FDG-PET/CT scan should be performed for patients in this study.
Swimmer plot shows individual patient’s treatment progression in each horizontal line. Colourful bars and lines indicate type and duration of treatment, while dots indicate specific action - 18F-FDG-PET/CT imaging or reason for end-of-study (if applicable). Vertical dashed lines indicate a time when 18F-FDG-PET/CT scan should be performed for patients in this study.

FIGURE 3.

Kaplan-Meier curves showing probability of median overall survival (OS) between clinical benefit (CB) and no-CB group as classified by findings on week four (W4) 18F-FDG PET/CT. The curves are statistically significantly different (p = 0.03).
Kaplan-Meier curves showing probability of median overall survival (OS) between clinical benefit (CB) and no-CB group as classified by findings on week four (W4) 18F-FDG PET/CT. The curves are statistically significantly different (p = 0.03).

FIGURE 4.

Alluvial plot illustrates the flow of patients between different response categories on 18F-FDG PET/CT scan across four evaluation time points: at week 4 (W4), week 16 (W16), week 48 (W48) and week 96 (W96). CMR = complete metabolic response; HGR = heterogeneous response; PMD = progressive metabolic disease; PPD = pseudoprogressive disease; SMD = stable metabolic disease; PMR = partial metabolic response; n = number of patients
Alluvial plot illustrates the flow of patients between different response categories on 18F-FDG PET/CT scan across four evaluation time points: at week 4 (W4), week 16 (W16), week 48 (W48) and week 96 (W96). CMR = complete metabolic response; HGR = heterogeneous response; PMD = progressive metabolic disease; PPD = pseudoprogressive disease; SMD = stable metabolic disease; PMR = partial metabolic response; n = number of patients

FIGURE 5.

Kaplan-Meier curves show the median overall survival (OS) probability of patients with metastatic melanoma treated with immune checkpoint inhibitors according to (A) LDH level and (B) the number of organs with metastatic involvement. The shading reflects the 95% confidence interval.
Kaplan-Meier curves show the median overall survival (OS) probability of patients with metastatic melanoma treated with immune checkpoint inhibitors according to (A) LDH level and (B) the number of organs with metastatic involvement. The shading reflects the 95% confidence interval.

FIGURE 6.

Kaplan-Meyer curves of the median overall survival (OS) over time in patients with metastatic melanoma treated with immune checkpoint inhibitors according to (A) occurrence of immune-related adverse events, (B) occurrence of serious immune-related adverse events, (C) cutaneous immune-related side effects, (D) immune-related endocrine immune-related side effects. The blue and pink shading reflects the 95% confidence intervals for respecting groups.
Kaplan-Meyer curves of the median overall survival (OS) over time in patients with metastatic melanoma treated with immune checkpoint inhibitors according to (A) occurrence of immune-related adverse events, (B) occurrence of serious immune-related adverse events, (C) cutaneous immune-related side effects, (D) immune-related endocrine immune-related side effects. The blue and pink shading reflects the 95% confidence intervals for respecting groups.

FIGURE 7.

A 67-year-old male patient, diagnosed with metastatic NRAS-mutated cutaneous melanoma with lung metastases in January 2021, was treated with pembrolizumab in the first-line setting. Serial 18F-FDG PET/CT scans were obtained per the study protocol. The images above show the maximal intensity projection (MIP) on the baseline PET/CT (left), on the week 4 evaluation PET/CT (middle) and at the endpoint of the study (right). The images below show transverse sections of the lungs in different planes, revealing three FDG-avid metastatic nodules in the right lung (lower left images, red arrows), only small nodules with no FDG uptake on week 4 PET/CT (lower middle images, yellow arrows), a complete metabolic response, and no residual nodules found at the end point of the PET/CT images with persistent complete remission (lower right images).
A 67-year-old male patient, diagnosed with metastatic NRAS-mutated cutaneous melanoma with lung metastases in January 2021, was treated with pembrolizumab in the first-line setting. Serial 18F-FDG PET/CT scans were obtained per the study protocol. The images above show the maximal intensity projection (MIP) on the baseline PET/CT (left), on the week 4 evaluation PET/CT (middle) and at the endpoint of the study (right). The images below show transverse sections of the lungs in different planes, revealing three FDG-avid metastatic nodules in the right lung (lower left images, red arrows), only small nodules with no FDG uptake on week 4 PET/CT (lower middle images, yellow arrows), a complete metabolic response, and no residual nodules found at the end point of the PET/CT images with persistent complete remission (lower right images).

Patient demographics, cancer staging, treatment details, and outcomes

Characteristics No = 71 (%)
Age; mean (+/-SD) (yr) 62 ± 12
Gender
  Male 43 (61)
  Female 28 (39)
ECOG performance status
  0 30 (42)
  1 41 (58)
AJCC
  III.D 1 (1)
  M1a 16 (23)
  M1b 10 (14)
  M1c 32 (45)
  M1d 12 (17)
Anatomic site of primary
  Cutaneous 58 (82)
  Ocular 4 (6)
  Mucosal 3 (4)
  Unknown primary 6 (8)
Line of systemic treatment for metastatic disease
  1st line 63 (89)
  2nd line 8 (11)
Baseline LDH
  Elevated 23 (32)
  Normal 49 (68)
Number of organs with metastatic involvement
  1 25 (35)
  2 21 (30)
  3 11 (15)
  > 3 14 20)
Actionable mutation
  BRAF wild type 21 (30)
  BRAF V600E 28 (39)
  BRAF V600K 10 (14)
  BRAF V600 - others 1 (1)
  NRAS 11 (16)
Type of systemic treatment
  PD-1 inhibitors 47 (66)
  Combination of PD-1 and CTLA-4 inhibitors 24 (34)
Tumor response on week 4 18F-FDG PET/CT
  Complete metabolic response 3 (4)
  Partial metabolic response 12 (17)
  Stable metabolic disease 10 (14)
  Heterogenous response 6 (8)
  Possible pseudoprogression 20 (28)
  Progressive metabolic disease 17 (24)

Clinical diagnosis of immune-related adverse events

Immune-related adverse event Any grade No (%) Grade 3-5 No (%) Time to onset of irAE (mean ± SD) [weeks]
No. of pts with at least one irAE 56 (79) 13 (18) -
Number of all irAE events 144 14 144 ± 161
Gastrointestinal
  Diarrhea 14 (20) 2 (3) 31.7 ± 30.6
  Colitis 7 (10) 2 (3) 39 ± 32
  Xerostomia 2 (3) 0 30.1 ± 4.4
  Gastritis 2 (3) 0 64.4 ± 7.7
  Stomatitis 1 (1) 0 3 ± 0
Respiratory
  Pneumonitis 5 (7) 0 (0) 40.9 ± 45.7
  Sarcoid reaction 2 (3) 0 (0) 6.3 ± 0.3
Hepatic
  Increased AST/ALT 16 (23) 4 (6) 7.7 ± 8.3
Endocrine
  Hypothyroidism 10 (14) 0 12.3 ± 6
  Hyperthyroidism 7 (10) 0 7.3 ± 7.1
  Adrenal insufficiency 2 (3) 2 (3) 34.4 ± 20.1
  Diabetes mellitus 1 (1) 1 (1) 72.7 ± 0
  Pancreatitis 1 (1) 1 (1) 32.4 ± 0
Cutaneous
  Pruritus 23 (32) 0 10.7 ± 10
  Skin rash 16 (23) 0 14 ± 16.3
  Vitiligo 9 (13) 0 37.4 ± 31.6
  Poliosis of hair 1 (1) 0 34.7 ± 0
Musculoskeletal
  Arthritis 10 (14) 0 28.7 ± 27.3
  Myalgia 2 (3) 0 16.7 ± 12.3
  Arthralgia 1 (1) 0 14 ± 0
  Synovitis 1 (1) 0 65.4 ± 0
Neurological
  Encephalitis 2 (3) 1 (1) 36.4 ± 32.9
  Psychosis 1 (1) 0 25.4 ± 0
Other
  Fatigue 6 (8) 0 6.5 ± 4.9
  Hypophosphatemia 1 (1) 0 17 ± 0
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Journal Subjects:
Medicine, Clinical Medicine, Internal Medicine, Haematology, Oncology, Radiology
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