02662nas a2200493   4500000000100000000000100001008004100002260001500043653003000058653002100088653001500109100001300124700001300137700001100150700001600161700001200177700001200189700001700201700001700218700002100235700001600256700001600272700001300288700001400301700001500315700001500330700001600345700001200361700001600373700001300389700001200402700001600414700001400430700001400444700001600458700001400474700001500488700001700503245010200520856005500622300000900677520146800686022001402154       2024                            d  c2024-04-1610aCancer of unknown primary10aCancer screening10ametastasis1 aFei Tian1 aDong Liu1 aNa Wei1 aQianqian Fu1 aLin Sun1 aWei Liu1 aXiaolong Sui1 aKathryn Tian1 aGenevieve Nemeth1 aJingyu Feng1 aJingjing Xu1 aLin Xiao1 aJunya Han1 aJingjie Fu1 aYinhua Shi1 aYichen Yang1 aJia Liu1 aChunhong Hu1 aBin Feng1 aYan Sun1 aYunjun Wang1 aGuohua Yu1 aDalu Kong1 aMeiyun Wang1 aWencai Li1 aKexin Chen1 aXiangchun Li00aPrediction of tumor origin in cancers of unknown primary origin with cytology-based deep learning  uhttps://www.nature.com/articles/s41591-024-02915-w  a1-113 aCancer of unknown primary (CUP) site poses diagnostic challenges due to its elusive nature. Many cases of CUP manifest as pleural and peritoneal serous effusions. Leveraging cytological images from 57,220 cases at four tertiary hospitals, we developed a deep-learning method for tumor origin differentiation using cytological histology (TORCH) that can identify malignancy and predict tumor origin in both hydrothorax and ascites. We examined its performance on three internal (n = 12,799) and two external (n = 14,538) testing sets. In both internal and external testing sets, TORCH achieved area under the receiver operating curve values ranging from 0.953 to 0.991 for cancer diagnosis and 0.953 to 0.979 for tumor origin localization. TORCH accurately predicted primary tumor origins, with a top-1 accuracy of 82.6% and top-3 accuracy of 98.9%. Compared with results derived from pathologists, TORCH showed better prediction efficacy (1.677 versus 1.265, P < 0.001), enhancing junior pathologists’ diagnostic scores significantly (1.326 versus 1.101, P < 0.001). Patients with CUP whose initial treatment protocol was concordant with TORCH-predicted origins had better overall survival than those who were administrated discordant treatment (27 versus 17 months, P = 0.006). Our study underscores the potential of TORCH as a valuable ancillary tool in clinical practice, although further validation in randomized trials is warranted.  a1546-170X