Results of a Single Institution Experience with Dose-Escalated Chemoradiation for Locally Advanced Unresectable Non-Small Cell Lung Cancer

Abstract

BackgroundWe determined factors associated with morbidity and outcomes of a series of non-small cell lung cancer (NSCLC) patients treated with dose-escalated chemoradiotherapy at the University of Pittsburgh Lung Cancer Program.Methods and materialsThe records of 170 stage III NSCLC patients treated with definitive intent were retrospectively reviewed. All patients received four-dimensional CT simulation scan and had respiratory gating if tumor movement exceeded 5 mm. Overall survival (OS), locoregional control (LRC), and freedom from distant metastasis (FFDM) were calculated using log-rank and Cox regression analysis.ResultsFor the present series of patients, median follow-up was 36.6 months, median survival 27.4 months, and the 2- and 4-year OS was 56.0 and 30.7%, respectively. The 4-year LRC and FFDM were 43.9 and 40.7%, respectively. No benefit was associated with irradiation doses above 66 Gy in OS (p = 0.586), LRC (p = 0.440), or FFDM (p = 0.230). On univariate analysis, variables associated with worse survival included: clinical stage IIIB (p = 0.037), planning target volume (PTV) over 450 cc (p < 0.001), heart V30 over 40% (p = −0.048), and esophageal mean dose over 20% (p = 0.024), V5 (p = −0.015), and V60 (p = −0.011). On multivariable analysis, PTV above 450 cc (52.2 vs. 25.3 months, p < 0.001) and esophageal V60 >20% (43.8 vs. 21.3 months, p = −0.01) were associated with lower survival. Grade 2 or higher acute lung toxicity and esophagitis were detected in 9.5 and 59.7%, respectively of patients. Grade 2 or higher acute lung toxicity was reduced if lung V5 was ≤65 (7.4 vs. 23.8%, p = 0.03). Grade 2 or higher acute esophagitis was reduced if V60 ≤ 20% (62 vs. 81.3%, p = 0.018). The use of intensity-modulated radiation therapy was more frequent in stage IIIB compared to stage IIIA patients (56.5 vs. 39.5%, p = 0.048) and was associated with a higher lung V5 and V10.ConclusionThe outcomes of a program of dose-escalated chemoradiotherapy for unresectable stage IIIA and IIIB NSCLC patients were consistent with other studies and showed no benefit to radiation doses above 66 Gy. Furthermore, maintaining low esophageal V60 and lung V5 were associated with lower morbidity and mortality.

Oncogenic KRAS suppresses store-operated Ca 2+ entry and I CRAC through ERK pathway-dependent remodelling of STIM expression in colorectal cancer cell lines

“…As such, dysregulated Ca 2+ signalling pathways contribute to the altered activity of cell processes underlying cancer [14,16–19]. Of particular note, Ca 2+ signals are necessary to sustain the cell cycle at specific checkpoints such as G 1 /S and G 2 /M transitions [20,21] and mitochondrial Ca 2+ overload is a key event in activating the apoptotic cascade [22]. Cell migration and invasion associated with tumour metastasis are also regulated by Ca 2+ [23–26].…”

A neoepitope derived from a novel human germline APC gene mutation in familial adenomatous polyposis shows selective immunogenicity

“…Cancer immunotherapy triggers a patient’s immune system to destroy tumor cells by recognizing tumor-derived neoantigens [ 16 ][ 17 ]. Cancer immunotherapy drugs, such as checkpoint inhibitors, have improved the overall survival of patients with advanced stage cancers, particularly melanoma, non-small cell lung cancer, head and neck cancer and renal cancer [ 18 ][ 19 ][ 20 ]. Cytotoxic T cells recognize tumors as foreign because the latter express tumor-specific neoantigens derived from genetically altered proteins expressed by the tumor cells.…”

The Molecular and Phenotypic Basis of the Glioma Invasive Perivascular Niche

“…Current consensus in the glioma field suggests that GSC are located within two main compartments; firstly, GSC could be located where hypoxia is evident, and pseudopalisading glioma cells (a pathognomonic feature observed by light microscopy during histopathological diagnosis of GBM) are gathered with this characteristic form around the necrotic regions in the glioma core [ 65 ]; the second compartment is located around blood vessels that are present in the periphery of the tumour to form the perivascular satellitosis as discussed above. Most studies using patient-derived tissue usually involve a single specimen for each tumour per patient, which is usually taken surgically from the core region of the glioma.…”