ABSTRACT
Background This review was implemented to examine the impact of bone metastasis on the prognosis of non-small cell lung cancer patients (NSCLC) treated with immune checkpoint inhibitors (ICIs). Methods A literature search was conducted in the PubMed, CENTRAL, Web of Science, and Embase databases up to 4th September 2022. Multivariable adjusted data were pooled in a random-effects model. Results 13 studies were included. On a combined analysis of 10 studies, it was noted that bony metastasis was associated with poor overall survival (OS) in NSCLC patients treated with ICIs (HR: 1.55 95% CI 1.24, 1.94 I2 = 69% p = 0.001). Meta-analysis of seven studies showed that bony metastasis was not associated with poor progression-free survival (PFS) in NSCLC patients treated with ICIs (HR: 1.31 95% CI 0.85, 2.01 I2 = 85% p = 0.22). Meta-regression analysis using the moderator's age, male gender, smoking history, squamous histology, and ICI as 1st line therapy for the outcome OS was not statistically significant. Conclusion The presence of bone metastasis is a predictor of poor OS in NSCLC treated with ICIs. However, PFS does not seem to be influenced by the presence of bone metastasis. Clinicians should prioritize the management of NSCLC patients with bone metastasis and explore the use of combination therapies to achieve optimal results. Further studies taking into account different combination therapies for such patients would strengthen the evidence (AU)
Subject(s)
Humans , Male , /therapeutic use , Neoplasms, Bone Tissue/drug therapy , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , PrognosisABSTRACT
Nicotinamide phosphoribosyltransferase (NAMPT) and nicotinic acid phosphoribosyltransferase (NAPRT) are rate-limiting enzymes in the NAD+ synthesis pathway. Chondrosarcoma is a malignant cartilage forming bone tumor, in which mutations altering isocitrate dehydrogenase-1 and -2 (IDH1 and IDH2) activity have been identified as potential driver mutations. Vulnerability for NAD+ depletion has been reported for IDH1/2-mutant cells. Here, the potency of NAMPT inhibitors as a treatment of chondrosarcoma was explored. Eleven chondrosarcoma cell lines were treated with NAMPT inhibitors, in which the effect on cell viability, colony formation, and 3D collagen invasion was assessed. The expression level of NAMPT and NAPRT transcripts in chondrosarcoma cells was determined by qRT-PCR. Methylation of the NAPRT promoter was evaluated using a previously published dataset of genome-wide methylation. In addition, a methylation dataset was used to determine methylation of the NAPRT promoter in 20 IDH1/2-mutated cartilage tumors. Chondrosarcoma cells showed a dose-dependent decrease in cell viability, 3D collagen invasion, and colony formation upon treatment with NAMPT inhibitors, in which nearly half of the cell lines demonstrated absolute IC50s in the low nanomolar range. Increasing IC50s correlated to increasing NAPRT expression levels and decreasing NAPRT promoter methylation. No correlation between IDH1/2 mutation status and sensitivity for NAMPT inhibitors was observed. Strikingly, higher methylation of the NAPRT promoter was observed in high-grade versus low-grade chondrosarcomas. In conclusion, this study identified NAMPT as a potential target for treatment of chondrosarcoma.Implications: Chondrosarcoma patients, especially those of high histologic grade with lower expression and hypermethylation of NAPRT, may benefit from inhibition of the NAD synthesis pathway. Mol Cancer Res; 15(12); 1714-21. ©2017 AACR.
Subject(s)
Chondrosarcoma/genetics , Cytokines/genetics , Isocitrate Dehydrogenase/genetics , Neoplasms, Bone Tissue/genetics , Nicotinamide Phosphoribosyltransferase/genetics , Pentosyltransferases/genetics , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Chondrosarcoma/drug therapy , Chondrosarcoma/pathology , Cytokines/antagonists & inhibitors , Enzyme Inhibitors/administration & dosage , Gene Expression Regulation, Neoplastic/drug effects , Humans , Mutation , NAD/antagonists & inhibitors , NAD/biosynthesis , NAD/genetics , Neoplasm Invasiveness/genetics , Neoplasms, Bone Tissue/drug therapy , Neoplasms, Bone Tissue/pathology , Nicotinamide Phosphoribosyltransferase/antagonists & inhibitors , Pentosyltransferases/antagonists & inhibitors , Promoter Regions, Genetic/drug effects , Signal Transduction/drug effectsABSTRACT
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Subject(s)
Humans , Male , Adult , Chondrosarcoma/complications , Chondrosarcoma/diagnosis , Chondrosarcoma/metabolism , Neoplasms, Bone Tissue/chemically induced , Neoplasms, Bone Tissue/diagnosis , Neoplasms, Bone Tissue/drug therapy , Lymph Nodes , Chondrosarcoma/chemistry , Chondrosarcoma/classification , Chondrosarcoma/secondary , Neoplasms, Bone Tissue/chemistry , Neoplasms, Bone Tissue/classification , Neoplasms, Bone Tissue/complications , Lymph Nodes/abnormalities , Lymph Nodes/growth & developmentABSTRACT
No disponible
No disponible
Subject(s)
Humans , Male , Adult , Enterobacteriaceae/pathogenicity , Enterobacteriaceae Infections/etiology , Catheterization, Central Venous/adverse effects , Sarcoma, Ewing/complications , Cross Infection/etiology , Enterobacteriaceae/isolation & purification , Enterobacteriaceae Infections/microbiology , Sarcoma, Ewing/drug therapy , Sarcoma, Ewing/radiotherapy , Neoplasms, Bone Tissue/complications , Neoplasms, Bone Tissue/drug therapy , Neoplasms, Bone Tissue/radiotherapy , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Lung Neoplasms/complications , Pelvic Bones/pathology , Immunocompromised HostABSTRACT
OPINION STATEMENT: Primary spinal neoplasms are rare tumors that can lead to significant morbidity secondary to local bone destruction and invasion into adjacent neurological and vascular structures. These tumors represent a clinical challenge to even the most experienced physicians and require a multidisciplinary approach to ensure optimal patient outcomes. This review will discuss the most common primary bone tumors and focus on recent surgical, medical, and radiation treatment advances.
Subject(s)
Spinal Neoplasms/therapy , Adolescent , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bone Cysts, Aneurysmal/therapy , Child , Chordoma/surgery , Combined Modality Therapy , Disease Management , Embolization, Therapeutic , Giant Cell Tumors/radiotherapy , Giant Cell Tumors/surgery , Giant Cell Tumors/therapy , Hemangioma/therapy , Hematopoietic Stem Cell Transplantation , Humans , Interdisciplinary Communication , Middle Aged , Neoplasms, Bone Tissue/drug therapy , Neoplasms, Bone Tissue/radiotherapy , Neoplasms, Bone Tissue/surgery , Neoplasms, Plasma Cell/drug therapy , Neoplasms, Plasma Cell/surgery , Spinal Neoplasms/diagnosis , Spinal Neoplasms/drug therapy , Spinal Neoplasms/radiotherapy , Spinal Neoplasms/surgery , Young AdultABSTRACT
INTRODUCTION: Infection associated with prosthesis used after tumor resection is a common and serious complication. The purpose of the current retrospective study was to describe the course of infection in patients with a tumor endoprosthesis and the determination of risk factors associated with failed limb salvage. MATERIAL AND METHODS: 30 patients with an infection associated with a tumor endoprosthesis were investigated with regard to treatment strategies, number and type of revision operations, duration of hospital stay, determination of risk factors associated with failed limb salvage and final outcome. RESULTS: Limb salvage related to the complication infection was achieved in 19 patients (63.3%). Two-stage reimplantation of an endoprosthesis was successful in 14 patients but subsequently failed in one patient. Out of 11 patients where limb salvage failed, an amputation was performed in 6 patients, a rotationplasty in 4, and stump lengthening procedure in 1 patient. A poor soft tissue condition was a significant (P<0.05) risk factor for failed limb salvage. No patient receiving chemotherapy with a poor soft tissue condition had limb salvage surgery. The mean number of revision operations per patients was 2.6. The mean duration of hospital stay was 68 days. CONCLUSION: Infection associated with prosthesis is a serious complication and is involved with long hospitalization. Limb salvage failed mostly in the case of a poor soft tissue condition. In these cases repeated revision surgery should be avoided and ablative surgery recommended at an early stage. Rotationplasty is an alternative to amputation in the case of an infection of the proximal or distal part of the femur.
