Fast and accurate staging is essential for choosing treatment for non–small-cell lung cancer (NSCLC). The purpose of this randomized study was to evaluate the clinical effect of combined positron-emission tomography and computed tomography (PET–CT) on preoperative staging of NSCLC. We randomly assigned patients who were referred for preoperative staging of NSCLC to either conventional staging plus PET–CT or conventional staging alone. Patients were followed until death or for at least 12 months. The primary end point was the number of futile thoracotomies, defined as any one of the following: a thoracotomy with the finding of pathologically confirmed mediastinal lymph-node involvement (stage IIIA [N2]), stage IIIB or stage IV disease, or a benign lung lesion; an exploratory thoracotomy; or a thoracotomy in a patient who had recurrent disease or death from any cause within 1 year after randomization. From January 2002 through February 2007, we randomly assigned 98 patients to the PET–CT group and 91 to the conventional-staging group. Mediastinoscopy was performed in 94% of the patients. After PET–CT, 38 patients were classified as having inoperable NSCLC, and after conventional staging, 18 patients were classified thus. Sixty patients in the PET–CT group and 73 in the conventional-staging group underwent thoracotomy (P=0.004). Among these thoracotomies, 21 in the PET–CT group and 38 in the conventional-staging group were futile (P=0.05). The number of justified thoracotomies and survival were similar in the two groups. The use of PET–CT for preoperative staging of NSCLC reduced both the total number of thoracotomies and the number of futile thoracotomies but did not affect overall mortality. (ClinicalTrials.gov number, NCT00867412.)

Intratumor heterogeneity may contribute to the ambiguous clinical results on PD-L1 status as a predictor for immunotherapy response in patients with HNSCC. This decreases the utility of PD-L1 expression from single tumour biopsies as a predictive biomarker. In this prospective study, intratumor heterogeneity of PD-L1 expression in HNSCC was investigated with both Tumour Proportion Score (TPS) and Combined Positive Score (CPS). Thirty-three whole surgical specimens from 28 patients with HNSCC were included. PD-L1 expression in six random core biopsies from each surgical specimen was used to assess the concordance between multiple biopsies and the negative predictive value of a single negative core biopsy. With 1% cut off, 36% of the specimens were concordant with TPS and 52% with CPS. With a 50% cut-off value the concordance was 70% with TPS and 55% with CPS. Defining a tumour as positive if just a single-one of the biopsies was positive, the negative predictive value (NPV) of a single negative core biopsy was 38.9 and 0% (1% cut off), and 79.9% and 62.8% (50% cut off) for TPS and CPS, respectively. In conclusion, PD-L1 positivity varies markedly within the tumour, both with TPS and CPS, challenging the utility of this biomarker.

Background: Small-cell lung cancer (SCLC) accounts for 15%–20% of all lung cancer cases. Accurate and fast staging is mandatory when choosing treatment, but current staging procedures are time consuming and lack sensitivity. Patients and methods: A prospective study was designed to examine the role of combined positron emission tomography/computed tomography (PET/CT) compared with standard staging (CT, bone scintigraphy and immunocytochemical assessment of bone marrow biopsy) of patients with SCLC. Thirty-four consecutive patients were included. Twenty-nine patients received initial PET/CT. Results: PET/CT caused change of stage in 5/29 (17%). Excluding patients with unconfirmed findings or pleural effusion, the sensitivity for accurate staging of patients with extensive disease was the following: for standard staging 79%, PET 93% and PET/CT 93%. Specificity was 100%, 83% and 100%, respectively. Conclusion: The results from this first study on PET/CT in SCLC indicates that PET/CT can simplify and perhaps even improve the accuracy of the current staging procedure in SCLC. A larger clinical trial, preferably with consequent histological confirmation in case of discordance, however, is warranted.