Lung Neoplasms
Conditions
Brief summary
This is a prospective diagnostic pilot study to create hypotheses regarding immunocytochemistry (ICC) PD-L1 analysis of pleural effusions in NSCLC patients as compared to the reference standard of PD-L1 immunohistochemistry (IHC). This comparison will be done to assess sensitivity and specificity of PD-L1 detection by ICC in pleural effusions.
Interventions
None listed
Sponsors
Merck Sharp & Dohme LLC
Heinrich-Heine University, Duesseldorf
Wissenschaftliches Institut Bethanien e.V
Study design
Observational model
CASE_ONLY
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Presence of malignant pleural effusion with indication for pleural puncture and thoracoscopy * Confirmed diagnosis of non-small cell lung cancer according to ERS guidelines * Written informed consent
Exclusion criteria
* Pregnancy and/or lactation * Acute and life-threatening illness (instable angina pectoris, acute pulmonary arterial embolism, myocardial infarction, etc.) * Any contraindication to undergo thoracoscopy (e.g. anticoagulation therapy which cannot be discontinued for the procedure) * Any medical, psychological or other condition impairing the patient's ability to provide informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PD-L1 Prevalence IHC | At baseline | Number/prevalence of PD-L1-positive patients according to immunohistochemistry (IHC) of pleural biopsy. |
| PD-L1 Prevalence ICC | At baseline | Number/prevalence of PD-L1-positive patients according to immunocytochemistry (ICC) of pleural aspirate |
| PD-L1 Detection in Pleural Effusion Based on All Cases With Successful PD-L1 Analysis | At baseline | Based on all cases where PD-L1 analysis was indicated and sucessful (i.e. giving definite results), the immunocytochemistry analysis of PE was compared with the immunohistochemistry analysis of pleural tissue.Two different alternatives were calculated: * PD-L1 expression with a TPS ≥50% was defined as PD-L1-positive. * PD-L1 expression with a TPS ≥1% was defined as PD-L1-positive. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PD-L1 Detection in Pleural Effusion Based on All Cases With Indication for PD-L1 Analysis | At baseline | Based on all cases where PD-L1 analysis was indicated, the immunocytochemistry analysis of PE was compared with the immunohistochemistry analysis of pleural tissue.Two different alternatives were calculated: * PD-L1 expression with a TPS ≥50% was defined as PD-L1-positive. * PD-L1 expression with a TPS ≥1% was defined as PD-L1-positive. In both instances, cases where PD-L1 analysis could not be performed were defined as negative. |
| Tumor Cell Detection in Pleural Effusion | At baseline | Comparing the immunocytochemistry (ICC) analysis of pleural effusion concerning the detection of malignant tumor cells as compared to the immunohistochemistry analysis of pleural tissue. Seven cases of ICC analysis with inconclusive results were defined as negative. |
Countries
Germany
Participant flow
Recruitment details
Clinical routine patients presenting with (suspected malignant) pleural effusion and indication for pleural puncture were considered for enrollment. Patients with confirmed malignancy of pleural effusion were actually enrolled.
Participants by arm
| Arm | Count |
|---|---|
| Malignant Pleural Effusion patients with confirmed malignant pleural effusion | 50 |
| Total | 50 |
Baseline characteristics
| Characteristic | Malignant Pleural Effusion |
|---|---|
| Age, Continuous | 72.5 years |
| BMI | 25.7 kg/m2 |
| Cancer Stage (UICC 8th ed.) IA2 | 1 Participants |
| Cancer Stage (UICC 8th ed.) IB | 1 Participants |
| Cancer Stage (UICC 8th ed.) IIB | 3 Participants |
| Cancer Stage (UICC 8th ed.) IIIA | 2 Participants |
| Cancer Stage (UICC 8th ed.) IIIB | 2 Participants |
| Cancer Stage (UICC 8th ed.) III-IV (IMIG classification) | 1 Participants |
| Cancer Stage (UICC 8th ed.) IVA | 24 Participants |
| Cancer Stage (UICC 8th ed.) IVB | 15 Participants |
| Cancer Stage (UICC 8th ed.) Unknown | 1 Participants |
| Histology Type Ambiguous histology | 2 Participants |
| Histology Type Non-Hodgkin Lymphoma | 1 Participants |
| Histology Type NSCLC - Adeno carcinoma | 33 Participants |
| Histology Type NSCLC - large-cell neuroendocrine carcinoma | 1 Participants |
| Histology Type NSCLC - Squamous cell carcinoma | 7 Participants |
| Histology Type Sarcomatoid Mesothelioma | 1 Participants |
| Histology Type SCLC | 4 Participants |
| Histology Type SCLC + Adeno carcinoma | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 50 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Sex: Female, Male Female | 17 Participants |
| Sex: Female, Male Male | 33 Participants |
| smoking status current smoker | 15 Participants |
| smoking status ex-smoker | 28 Participants |
| smoking status never | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 50 |
| other Total, other adverse events | 0 / 50 |
| serious Total, serious adverse events | 0 / 50 |
Outcome results
Primary
PD-L1 Detection in Pleural Effusion Based on All Cases With Successful PD-L1 Analysis
Based on all cases where PD-L1 analysis was indicated and sucessful (i.e. giving definite results), the immunocytochemistry analysis of PE was compared with the immunohistochemistry analysis of pleural tissue.Two different alternatives were calculated: * PD-L1 expression with a TPS ≥50% was defined as PD-L1-positive. * PD-L1 expression with a TPS ≥1% was defined as PD-L1-positive.
Time frame: At baseline
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Number of PD-L1-positive Samples in IHC | PD-L1 Detection in Pleural Effusion Based on All Cases With Successful PD-L1 Analysis | Sensitivity | 100 percent |
| Number of PD-L1-positive Samples in IHC | PD-L1 Detection in Pleural Effusion Based on All Cases With Successful PD-L1 Analysis | Specificity | 63 percent |
| Number of PD-L1-positive Samples in IHC | PD-L1 Detection in Pleural Effusion Based on All Cases With Successful PD-L1 Analysis | positive predictive value | 45 percent |
| Number of PD-L1-positive Samples in IHC | PD-L1 Detection in Pleural Effusion Based on All Cases With Successful PD-L1 Analysis | negative predictive value | 100 percent |
| Sensitivity and Specificity of PD-L1 Detection in Pleural Effusion (TPS ≥1%) | PD-L1 Detection in Pleural Effusion Based on All Cases With Successful PD-L1 Analysis | negative predictive value | 60 percent |
| Sensitivity and Specificity of PD-L1 Detection in Pleural Effusion (TPS ≥1%) | PD-L1 Detection in Pleural Effusion Based on All Cases With Successful PD-L1 Analysis | Sensitivity | 86 percent |
| Sensitivity and Specificity of PD-L1 Detection in Pleural Effusion (TPS ≥1%) | PD-L1 Detection in Pleural Effusion Based on All Cases With Successful PD-L1 Analysis | positive predictive value | 75 percent |
| Sensitivity and Specificity of PD-L1 Detection in Pleural Effusion (TPS ≥1%) | PD-L1 Detection in Pleural Effusion Based on All Cases With Successful PD-L1 Analysis | Specificity | 43 percent |
Primary
PD-L1 Prevalence ICC
Number/prevalence of PD-L1-positive patients according to immunocytochemistry (ICC) of pleural aspirate
Time frame: At baseline
Population: Pleural puncture was performed in all fifty patients. PD-L1 analysis of pleural effusion was indicated in all samples with evidence of tumor cells (n=36), excluding cases with small-cell lung cancer (n=3). Mainly due to insufficient sample material (low tumor cell count) (n=7) or technical issue (n=1), PD-L1 analysis could actually be performed in 25 pleural effusion cases.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Number of PD-L1-positive Samples in IHC | PD-L1 Prevalence ICC | PD-L1 expression with a TPS ≥ 1% was defined as PD-L1-positive | PD-L1 positive | 19 Participants |
| Number of PD-L1-positive Samples in IHC | PD-L1 Prevalence ICC | PD-L1 expression with a TPS ≥ 1% was defined as PD-L1-positive | PD-L1 negative | 6 Participants |
| Number of PD-L1-positive Samples in IHC | PD-L1 Prevalence ICC | PD-L1 expression with a TPS ≥ 50% was defined as PD-L1-positive | PD-L1 positive | 13 Participants |
| Number of PD-L1-positive Samples in IHC | PD-L1 Prevalence ICC | PD-L1 expression with a TPS ≥ 50% was defined as PD-L1-positive | PD-L1 negative | 12 Participants |
Primary
PD-L1 Prevalence IHC
Number/prevalence of PD-L1-positive patients according to immunohistochemistry (IHC) of pleural biopsy.
Time frame: At baseline
Population: Thoracoscopy was performed in all fifty patients. PD-L1 analysis of pleural tissue was indicated in all samples with evidence of tumor cells (n=40), excluding cases with small-cell lung cancer (n=2). Mainly due to insufficient sample material (low tumor cell count) (n=3), PD-L1 analysis could actually be performed in 35 pleural tissue cases.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Number of PD-L1-positive Samples in IHC | PD-L1 Prevalence IHC | PD-L1 expression with a TPS ≥ 1% was defined as PD-L1-positive | PD-L1 positive | 21 Participants |
| Number of PD-L1-positive Samples in IHC | PD-L1 Prevalence IHC | PD-L1 expression with a TPS ≥ 1% was defined as PD-L1-positive | PD-L1 negative | 14 Participants |
| Number of PD-L1-positive Samples in IHC | PD-L1 Prevalence IHC | PD-L1 expression with a TPS ≥ 50% was defined as PD-L1-positive | PD-L1 positive | 8 Participants |
| Number of PD-L1-positive Samples in IHC | PD-L1 Prevalence IHC | PD-L1 expression with a TPS ≥ 50% was defined as PD-L1-positive | PD-L1 negative | 27 Participants |
Secondary
PD-L1 Detection in Pleural Effusion Based on All Cases With Indication for PD-L1 Analysis
Based on all cases where PD-L1 analysis was indicated, the immunocytochemistry analysis of PE was compared with the immunohistochemistry analysis of pleural tissue.Two different alternatives were calculated: * PD-L1 expression with a TPS ≥50% was defined as PD-L1-positive. * PD-L1 expression with a TPS ≥1% was defined as PD-L1-positive. In both instances, cases where PD-L1 analysis could not be performed were defined as negative.
Time frame: At baseline
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Number of PD-L1-positive Samples in IHC | PD-L1 Detection in Pleural Effusion Based on All Cases With Indication for PD-L1 Analysis | Sensitivity | 71 percent |
| Number of PD-L1-positive Samples in IHC | PD-L1 Detection in Pleural Effusion Based on All Cases With Indication for PD-L1 Analysis | Specificity | 71 percent |
| Number of PD-L1-positive Samples in IHC | PD-L1 Detection in Pleural Effusion Based on All Cases With Indication for PD-L1 Analysis | positive predictive value | 42 percent |
| Number of PD-L1-positive Samples in IHC | PD-L1 Detection in Pleural Effusion Based on All Cases With Indication for PD-L1 Analysis | negative predictive value | 89 percent |
| Sensitivity and Specificity of PD-L1 Detection in Pleural Effusion (TPS ≥1%) | PD-L1 Detection in Pleural Effusion Based on All Cases With Indication for PD-L1 Analysis | negative predictive value | 64 percent |
| Sensitivity and Specificity of PD-L1 Detection in Pleural Effusion (TPS ≥1%) | PD-L1 Detection in Pleural Effusion Based on All Cases With Indication for PD-L1 Analysis | Sensitivity | 71 percent |
| Sensitivity and Specificity of PD-L1 Detection in Pleural Effusion (TPS ≥1%) | PD-L1 Detection in Pleural Effusion Based on All Cases With Indication for PD-L1 Analysis | positive predictive value | 71 percent |
| Sensitivity and Specificity of PD-L1 Detection in Pleural Effusion (TPS ≥1%) | PD-L1 Detection in Pleural Effusion Based on All Cases With Indication for PD-L1 Analysis | Specificity | 64 percent |
Secondary
Tumor Cell Detection in Pleural Effusion
Comparing the immunocytochemistry (ICC) analysis of pleural effusion concerning the detection of malignant tumor cells as compared to the immunohistochemistry analysis of pleural tissue. Seven cases of ICC analysis with inconclusive results were defined as negative.
Time frame: At baseline
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Number of PD-L1-positive Samples in IHC | Tumor Cell Detection in Pleural Effusion | Sensitivity | 83 percent |
| Number of PD-L1-positive Samples in IHC | Tumor Cell Detection in Pleural Effusion | Specificity | 70 percent |
| Number of PD-L1-positive Samples in IHC | Tumor Cell Detection in Pleural Effusion | positive predictive value | 92 percent |
| Number of PD-L1-positive Samples in IHC | Tumor Cell Detection in Pleural Effusion | negative predictive value | 50 percent |