Background
Circulating tumor DNA (ctDNA) in cerebrospinal fluid (CSF) has become a promising surrogate for genomic profiling of central nervous system tumors. However, suboptimal ctDNA detection rates from CSF limit its clinical utility. Thus precise screening of suitable patients is needed to maximize the clinical benefit.
Patients and methods
Between February 2017 and December 2020, 66 newly diagnosed non-small-cell lung cancer (NSCLC) patients with brain parenchymal metastases were prospectively enrolled as a training cohort and 30 additional patients were enrolled as an external validation cohort. CSF samples and matched primary tumor tissues were collected before treatment and subjected to next-generation sequencing (NGS). The imageological characteristics of patients’ brain tumors were evaluated by radiologists using enhanced magnetic resonance imaging images. The clinical and imageological characteristics were evaluated by complete subsets regression, Akaike information criteria, and Bayesian information criteria methods to establish the prediction model. A nomogram was then built for CSF ctDNA detection prediction.
Results
The somatic mutation detection rate of genes covered by our targeted NGS panel was significantly lower in CSF ctDNA (59.09%) than tumor tissue (91.84%). The T
size
(diameter of the largest intracranial lesion) and LVD
min
(minimum lesion–ventricle distance for all intracranial lesions) were significantly associated with positive CSF ctDNA detection, and thus, were selected to establish the prediction model, which achieved an area under the ROC curve (AUC) of 0.819 and an accuracy of 0.800. The model’s predictive ability was further validated in the independent external cohort (AUC of 0.772, accuracy of 0.767) and by internal cross-validation. The CSF ctDNA detection rate was significantly improved from 58.18% (32/55) to 81.81% (27/33) in patients after model selection (
P
= 0.022).
Conclusions
This study developed a regression model to predict the probability of detecting CSF ctDNA using the phenotypic characteristics of metastatic brain lesions in NSCLC patients, thus, maximizing the benefits of CSF liquid biopsies.
Methods: A retrospective multicenter chart review of 604 patients with NPC who underwent CCRT from May 2005 to November 2014 was conducted (265 in the PEG group, and 339 in the non-PEG group). Baseline characteristics, weight loss outcome and treatment tolerance were examined and compared between the two groups. Risk factors of more than 10% weight loss during CCRT were assessed by multivariate analysis. Results: We found significantly more T3-T4 tumors (P ¼ 0.03), cisplatin-based regimen (P ¼ 0.01), and less body weight before CCRT (P ¼ 0.04) in the PEG group. Seventy-seven percent of patients in PEG group completed the planned cycles of chemotherapy, whereas only 48% of patients in the non-PEG group did (P < 0.0001). Moreover, lower percentage of weight loss during CCRT detected in the PEG group as compared to the non-PEG group, 8.9þ/-8.0 kilograms (kgs) and 12.5þ/-8.6 kgs, respectively (P < 0.0001). Multivariate analysis showed that obese patients (body mass index (BMI) > 25) (P < 0.0001), carboplatin-based regimen (P < 0.0001), 3-weekly chemotherapy (P ¼ 0.01), and non-prophylactic PEG (P < 0.0001) were significantly related to 10% weight loss during CCRT. Conclusions: Prophylactic PEG is strongly recommended for patients with NPC undergoing CCRT. Significant weight loss during CCRT should be cautiously aware for patients with obesity, receiving carboplatin or 3-weekly chemotherapy regimen and those without prophylactic PEG, hence intensive nutritional supplement is highly suggested for these groups of patients.
7689 Background: Nadaplatin is a 2nd generation platinum compound created in Japan. It also has been used in China for recent years and shown treatment effect in several kinds of cancer including lung cancer. However, no randomized clinical trial has been done compared with cisplatin when combined with paclitaxol in treating non-small cell lung cancer. This prospective clinical study is to investigate the treatment effect, long term survival, side effect and quality of life (QOL) of NSCLC patients treated with nadaplatin combined with paclitaxol controlled with cisplatin combined with paclitaxol. Methods: NSCLC patients with stage IIIB or IV were randomized into two groups: TN group- nadaplatin 30 mg/m2 d1–3, paclitaxol 175 mg/m2 d1, repeated every 4 weeks; TP group- DDP30 mg/m2 d1–3, paclitaxol 175 mg/m2 d1, repeated every 4 weeks. The treatment effect, 1 and 2 year survival and the side effect were observed. The functional assessment of cancer therapy-lung (FACT-L) was used to evaluate the quality of life (QOL). Results: Sixty patients were enrolled and 57 were assessable with 30 in TN group and 27 in TP group. The overall response rate were 43.3% vs 48.1% (P=0.716), and the disease control rate were 86.7% vs 88.8% in TN and TP group (P=0.799), respectively. The median survival time were 14.3 vs 13.0 months, and the 1 and 2 year survival were 62.5% vs 59.1%, 0% vs 5.8% in TN and TP group (P=0.839), respectively. Neutropenia and thrombocytopenia were similar in TN and TP group whereas more patients in TP group suffered from anemia (38.5% vs 17.5%, P=0.001), nausea and vomiting (68.0% vs 34.7% with grade 1 and 2, 14.6% vs 0.9% with grade 3 and 4, P=0.000), fatigue (35.9% vs 14.1% P=0.000) and peripheral neurotoxicity (50.0% vs 21.9%, calculated by case, p=0.023). In the FACT-L assessment, the relationship with doctor, the emotional well-being and the lung cancer related symptom were similarly improved in both TN and TP group whereas physical well-being was improved only in TN group. Conclusions: Nadaplatin combined with paclitaxol is an effective treatment regimen for NSCLC patients. When compared with similar regimen using cisplatin, the response rate and survival were similar; however, nadaplatin regimen shows superiority in some aspects of side effects and QOL. No significant financial relationships to disclose.
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