IMPORTANCE Exhaled breath is an attractive option for cancer detection. A sensitive and reliable breath test has the potential to greatly facilitate diagnoses and therapeutic monitoring of lung cancer.OBJECTIVE To investigate whether the breath test is able to detect lung cancer using the highly sensitive high-pressure photon ionization time-of-flight mass spectrometry (HPPI-TOFMS). DESIGN, SETTING, AND PARTICIPANTSThis diagnostic study was conducted with a prospectivespecimen collection, retrospective-blinded evaluation design. Exhaled breath samples were collected before surgery and detected by HPPI-TOFMS. The detection model was constructed by support vector machine (SVM) algorithm. Patients with pathologically confirmed lung cancer were recruited from Peking University People's Hospital, and healthy adults without pulmonary noncalcified nodules were recruited from Aerospace 731 Hospital. Data analysis was performed from August to October 2020. EXPOSURES Breath testing and SVM algorithm. MAIN OUTCOMES AND MEASURESThe detection performance of the breath test was measured by sensitivity, specificity, accuracy, and area under the receiver-operating characteristic curve (AUC). RESULTSExhaled breath samples were from 139 patients with lung cancer and 289 healthy adults, and all breath samples were collected and tested. Of all participants, 228 (53.27%) were women and the mean (SD) age was 57.0 (11.4) years. After clinical outcomes were ascertained, all participants were randomly assigned into the discovery data set (381 participants) and the blinded validation data set (47 participants). The discovery data set was further broken into a training set (286 participants) and a test set (95 participants) to construct and test the detection model. The detection model reached a mean (SD) of 92.97% (4.64%) for sensitivity, 96.68% (2.21%) for specificity, and 95.51%(1.93%) for accuracy in the test set after 500 iterations. In the blinded validation data set (47 participants), the model revealed a sensitivity of 100%, a specificity of 92.86%, an accuracy of 95.74%, and an AUC of 0.9586. CONCLUSIONS AND RELEVANCEThis diagnostic study's results suggest that a breath test with HPPI-TOFMS is feasible and accurate for lung cancer detection, which may be useful for future lung cancer screenings.
Background: Computed tomography guided transthoracic needle aspiration (CT-TTNA) and endobronchial ultrasonography with guide sheath (EBUS-GS) transbronchial lung biopsy are important methods for the diagnosis of peripheral pulmonary lesions (PPLs). Without enough evidence, it is controversial which is a better choice for diagnosing PPLs. In this study, we hypothesized that the complication rate of EBUS-GS would be lower than CT-TTNA and the diagnostic accuracy of EBUS-GS were not inferior to CT-TTNA. Methods: This study was a retrospective analysis of a prospective registry with propensity matching.Patients with PPLs were divided into EBUS-GS group and CT-TTNA group according to patients' intent to treatment. Pathological results and procedure related complications of EBUS-GS and CT-TTNA were recorded. Propensity score matching(PSM) was used to eliminate the intergroup bias. Diagnostic yields and complications of two groups were compared. Subgroup analysis was performed to conclude the indications of different procedures. Results: A total of 187 patients (CT-TTNA: 130; EBUS-GS: 57) were enrolled. After propensity score matching, 54 paired patients were included. Diagnostic yield was 81% (44/54) for EBUS-GS and 87% (47/54) for CT-TTNA (P=0.43), respectively. Diagnostic sensitivity in malignancy was 93% (42/45) for CT-TTNA and 79% (37/47) for EUBS-GS (P=0.04). Subgroup analysis revealed that the sensitivity of CT-TTNA was significantly higher in diagnosing of lesions close to the chest wall (100% vs. 80%, P=0.04), and bronchus sign on CT was a predictive factor for accurate diagnosis by EBUS-GS. The overall complication rate was 13% (7/54) for CT-TTNA group, which was not significantly higher than that of EBUS-GS group (2%, P=0.06). Subgroup analysis showed that patients combined with pulmonary comorbidities and lesions apart from chest wall were risk factors for complications of CT-TTNA. Conclusions: Both of the two procedures are effective for the diagnosis of PPLs, but CT-TTNA has a higher diagnostic sensitivity for malignancy. EBUS-GS has fewer complications, and it is more suitable for patients combined with pulmonary comorbidities and lesions with bronchus signs.
For osteosarcoma that progresses following first-line chemotherapy, prognosis remains poor although anti-angiogenesis tyrosine kinase inhibitors (TKIs) have been verified to prolong progression-free survival. Apatinib has led to positive responses in the treatment of refractory osteosarcoma. However, it demonstrates only short-lived activity, and the disease control rate of musculoskeletal lesions is worse compared with that of pulmonary lesions. This treatment failure has been partly overcome by the addition of ifosfamide and etoposide (IE). The present study retrospectively compared the activity of apatinib + IE in relapsed or refractory osteosarcoma in two sarcoma centres in China. The included patients had received a combination of apatinib 500 mg (orally) daily and the IE regimen (n=33) between June 3 2017 and July 17 2020. The tumour burden was considerable in these patients: 16/33 (48.5%) Patients had lung and musculoskeletal lesions, and 31/33 (93.9%) patients had progressed to two lines of therapies at baseline. With a median follow-up duration of 28.4 [interquartile range (IQR), 16.1-38.3] months, 21/33 (63.6%) patients had objective responses, and the median event-free survival was 11.4 (IQR, 6.7-18.4) months. The median overall survival time was 19.8 (IQR, 13.1-30.6) months. At the last follow-up, 16/33 patients had tumour downstaging, and all lesions had been completely resected. For osteosarcoma with multiple sites of metastasis, apatinib + IE demonstrated clinically meaningful antitumor activity and delayed disease progression in patients with recurrent or refractory osteosarcoma after failure of chemotherapy. This combination with manageable toxicity deserves further investigation in prospective trials.
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