Predicting programmed death-ligand 1 (PD-L1) expression with fluorine-18 fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) metabolic parameters in resectable non-small cell lung cancer.

BACKGROUND: Programmed death-ligand 1 (PD-L1) expression is a predictive biomarker for immunotherapy in non-small cell lung cancer (NSCLC). PD-L1 and glucose transporter 1 expression are closely associated, and studies demonstrate correlation of PD-L1 with glucose metabolism. AIM: The aim of this study was to investigate the association of fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG-PET/CT) metabolic parameters with PD-L1 expression in primary lung tumour and lymph node metastases in resected NSCLC. METHODS: We conducted a retrospective analysis of 210 patients with node-positive resectable stage IIB-IIIB NSCLC. PD-L1 tumour proportion score (TPS) was determined using the DAKO 22C3 immunohistochemical assay. Semi-automated techniques were used to analyse pre-operative [18F]FDG-PET/CT images to determine primary and nodal metabolic parameter scores (including max, mean, peak and peak adjusted for lean body mass standardised uptake values (SUV), metabolic tumour volume (MTV), total lesional glycolysis (TLG) and SUV heterogeneity index (HISUV)). RESULTS: Patients were predominantly male (57%), median age 70 years with non-squamous NSCLC (68%). A majority had negative primary tumour PD-L1 (TPS < 1%; 53%). Mean SUVmax, SUVmean, SUVpeak and SULpeak values were significantly higher (p < 0.05) in those with TPS ≥ 1% in primary tumour (n = 210) or lymph nodes (n = 91). However, ROC analysis demonstrated only moderate separability at the 1% PD-L1 TPS threshold (AUCs 0.58-0.73). There was no association of MTV, TLG and HISUV with PD-L1 TPS. CONCLUSION: This study demonstrated the association of SUV-based [18F]FDG-PET/CT metabolic parameters with PD-L1 expression in primary tumour or lymph node metastasis in resectable NSCLC, but with poor sensitivity and specificity for predicting PD-L1 positivity ≥ 1%. CLINICAL RELEVANCE STATEMENT: Whilst SUV-based fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography metabolic parameters may not predict programmed death-ligand 1 positivity ≥ 1% in the primary tumour and lymph nodes of resectable non-small cell lung cancer independently, there is a clear association which warrants further investigation in prospective studies. TRIAL REGISTRATION: Non-applicable KEY POINTS: • Programmed death-ligand 1 immunohistochemistry has a predictive role in non-small cell lung cancer immunotherapy; however, it is both heterogenous and dynamic. • SUV-based fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG-PET/CT) metabolic parameters were significantly higher in primary tumour or lymph node metastases with positive programmed death-ligand 1 expression. • These SUV-based parameters could potentially play an additive role along with other multi-modal biomarkers in selecting patients within a predictive nomogram.

Multimodality Treatment and Salvage Surgery for the Treatment of Lung Cancer.

Lung cancer remains the leading cause of cancer deaths in the United Kingdom. For locally advanced disease, multimodality treatment is recommended, which includes a combination of chemotherapy, radiotherapy, surgery and, more recently immunotherapy. Options depend on the resectability of the cancer and there has been debate about the optimal treatment strategy: surgery may be planned to follow chemoradiotherapy (CRT), be offered for residual disease after CRT, or given as salvage therapy for patients treated with CRT who have later relapse of their disease. We conducted a retrospective analysis of all patients who underwent CRT and surgical resection under a single surgical team and performed a descriptive study after dividing the patients into these three groups. For the planned trimodality group, 30-day mortality this was 7% (n = 1) and 1-year survival was 78.6%; the residual disease group had a 30-day mortality rate of 0% and 1-year survival of 81.3%; for the salvage group, the figures were 0% and 62.5%, respectively. The median overall survival of the study population was 35.8 months. Median overall survival in the trimodality group was 35.4 months (20.1-51.7 interquartile range IQR), for the residual group was 34.2 months (18.5-61.0 IQR). and for the salvage group was 35.8 months (32.4-52.7 IQR).).

GPs have key role in managing men with testicular cancer.

Testicular cancer accounts for 1% of all malignancies in males. However, it is the most frequently occurring solid tumour in men between the ages of 15 and 34 years. Testicular germ cell tumours are classified into two main types: pure seminomas and non-seminomas which are also called non-seminomatous germ cell tumours (NSGCTs). NSGCTs are more clinically aggressive than seminomas so those patients who have both seminoma and non-seminoma components are managed according to NSGCT guidelines. Testicular tumours have excellent cure rates, even in those with metastases, as they are extremely sensitive to chemotherapy and radiotherapy. Early diagnosis is, however, very important as treatment is more successful and less intensive, and long-term health consequences can be minimised. Treatment options include surgery, chemotherapy, radiotherapy, or a combination of the above, depending on the histology, presence of tumour markers and radiological staging. In most patients, there is recovery of spermatogenesis two years after completion of chemotherapy but in all patients, sperm banking should be offered before chemotherapy. The risk of developing a secondary malignancy is increased in patients treated for testicular cancer. Men who have been treated with infradiaphragmatic radiotherapy or chemotherapy also have an increased incidence of cardiovascular disease and metabolic syndrome. Patients should be screened for cardiovascular risk factors, given healthy lifestyle advice and advised not to smoke.

Cytoreductive nephrectomy: past, present and future.

Cytoreductive nephrectomy (CN) is an integral part of the treatment of patients with metastatic renal cell carcinoma. Improved survival has been shown with CN and IFN-α. The introduction of targeted therapy for metastatic renal cell carcinoma has raised important questions regarding the role of CN. The majority of patients who were enrolled in the Phase III studies of targeted therapies had undergone prior nephrectomy. Thus, the benefit of these agents has largely been demonstrated in a nephrectomized population. CARMENA and SURTIME, important Phase III studies examining the role and timing of CN, are ongoing. Until new evidence is available, CN is a reasonable approach in selected patients with a resectable primary tumor and good performance status.

The molecular genetics of colorectal cancer.

Colorectal cancer is a common but heterogeneous disease, which arises through the accumulation of genetic mutations. Knowledge of the molecular basis of colorectal cancer has advanced at a rapid pace in recent years, reflecting progress made in the field of genomic medicine. Targeted therapies have come into mainstream use, and the exciting prospect of treatment regimens tailored to the mutation profile of individual tumours is beginning to emerge. In order to understand the development and application of the next generation of colorectal cancer treatments, it is important that gastroenterologists have a working knowledge of the pathological mechanisms that drive the disease. This review examines our current understanding of the molecular genetics of colorectal carcinogenesis.

The role of metastasectomy in renal cell carcinoma.

Despite significant advances in the systemic treatment of metastatic renal cell carcinoma, long-term survival remains low. A potential way to improve outcomes in selected cases is the use of metastasectomy, which is part of the multimodal treatment of this disease. Although the evidence supporting this approach is limited, we believe it is a reasonable option for certain patients. This review summarizes the evidence supporting this approach.