Background and purpose:Both prostate-specific membrane antigen(PSMA)positron emission tomography/computed tomography(PET/CT)and circulating tumor DNA(ctDNA)sequencing outcomes serve as references for therapeutic decision-making in hormone-sensitive prostate cancer(HSPC)treatment.This study aimed to analyze the association between PSMA PET/CT-derived parameters and ctDNA characteristics in patients with HSPC.Methods:HSPC patients who received PSMA PET/CT and ctDNA sequencing at an interval of less than 2 weeks and with complete medical records were retrospectively included in Fudan University Shanghai Cancer Center.Patients with active malignancies other than prostate cancer and those with histological features supporting a diagnosis of pure neuroendocrine carcinoma or small cell carcinoma were excluded.This study was approved by the Ethics Committee of Fudan University Shanghai Cancer Center(Ethics number:1909207-12).The correlation between PSMA PET/CT-derived parameters,including the maximum standardized uptake value(SUVmax),total tumor volume(TTV),total lesion uptake(TLU)and ctDNA fraction(ctDNA%)was evaluated using the Spearman correlation coefficient.Results:A total of 60 HSPC patients were included,with TP53(3.3%),BRCA2(3.3%)and ATM(3.3%)being the most common mutated genes.In the correlation analysis,a significant correlation was observed between ctDNA%and SUVmax levels(Spearman's rho=0.272,P=0.036);however,no significant correlation was found between ctDNA%and TLU(Spearman's rho=0.160,P=0.222)or TTV(Spearman's rho=0.162,P=0.215).Conclusion:There was a significant correlation between SUVmax and ctDNA%,suggesting that patients with high PSMA uptake lesions were more likely to receive combined targeted therapy than patients with no PSMA positive lesions and patients with low PSMA uptake lesions,which provided a certain reference for the formulation of individualized treatment plans.

Objective:To investigate the clinicopathological features and prognosis of patients with penile cancer.Methods:The clinical data of 362 patients with penile cancer who underwent surgery in Fudan University Shanghai Cancer Center from January 2005 to December 2020 were retrospectively analyzed. The mean age was (57.0±0.7) years. According to the clinical N stage classification, 239 patients were in N 0 stage, 57 patients in N 1 stage, 37 patients in N 2 stage, and 29 patients in N 3 stage. All these patients had no metastasis. Based on tumor size and location, 50 patients underwent extended circumcision, 283 patients underwent partial penectomy, and 29 patients underwent total penectomy. One hundred and eighty-three patients underwent inguinal lymphadenectomy and 47 patients underwent pelvic lymphadenectomy. Tumor pathology, tumor size, HPV subtype, postoperative pathological stage, overall survival (OS) and prognosis were analyzed. The Kaplan-Meier analysis and multivariate Cox regression analysis were used to analyse the factors which could affect the survival of patients. 5-year OS rate of these patients were also calculated. Results:In the pathological T classification, 137 cases were in T 1a stage, 24 cases in T 1b stage, 51 cases in T 2 stage, 136 cases in T 3 stage, and 14 cases in T 4 stage. In the pathological N classification, 235 cases were in N 0 stage, 54 cases in N 1 stage, 31 cases in N 2 stage and 42 cases in N 3 stage. The most common tumor type was squamous cell carcinoma (300 cases, 83%), followed by verrucous carcinoma (40 cases, 11%), sarcomatoid carcinoma(7 cases), carcinoma in situ (6 cases), basal-like carcinoma (6 cases), and adenosquamous carcinoma (3 cases). The most common tumor grade was mild (160 cases, 44%), followed by moderate differentiation (130 cases, 36%), poor differentiation (46 cases, 13%), and unclear differentiation (26 cases). The tumor sizes were < 3 cm in 135 patients and ≥ 3 cm in 142 patients. The tumor size was unclear in 85 patients. 173 cases (48%) were HPV positive and 189 cases (52%) were HPV negative. The Kaplan-Meier analysis showed the 5-year OS rate of HPV-positive group was higher than that of HPV-negative group (79% vs. 72%) but no significant difference was found ( P=0.09). The 5-year OS rate of patients whose tumor ≥ 3 cm (69%) was lower than those tumor < 3 cm (85%) and significant difference could be found ( P = 0.02). The 5-year OS rate of wild and moderate and poor grade were 85%, 70% and 58%, and significant difference could be found in the three groups ( P<0.01). The 5-year OS rates of patients with stage T 1a, T 1b, T 2, T 3and T 4 were 90%, 67%, 71%, 68% and 37% respectively( P<0.01). The 5-year OS rates of patients with stage N 0, N 1, N 2, and N 3 were 91%, 62%, 57%, and 30%, respectively( P<0.01). N stage could significantly affect the prognosis. The 5-year OS rate of T 1b patients was lower than that of T 1a and T 2 stage (67% vs. 90% vs. 71%, P=0.003). Of the 24 patients with T 1b stage, 17 cases received inguinal lymphadenectomy and 7 cases not. The 5-year OS rate of T 1b who received lymphadenectomy, who not and T 2 group were 73%, 57% and 71% respectively ( P=0.22). Multivariate Cox analysis showed that N stage ( HR =4.55, 95% CI 2.64-7.85, P<0.01) and tumor grade ( HR =2.09, 95% CI 1.09-4.02, P=0.03) were independent factors which could affect the prognosis. Conclusions:N stage and tumor grade were independent factors which could affect the prognosis. The poorer the tumor grade, the worse the prognosis. Inguinal lymphadenectomy could improve the prognosis of patients with T 1b stage.

Objective:To investigate the clinicopathological features and prognosis of patients with penile cancer.Methods:The clinical data of 362 patients with penile cancer who underwent surgery in Fudan University Shanghai Cancer Center from January 2005 to December 2020 were retrospectively analyzed. The mean age was (57.0±0.7) years. According to the clinical N stage classification, 239 patients were in N 0 stage, 57 patients in N 1 stage, 37 patients in N 2 stage, and 29 patients in N 3 stage. All these patients had no metastasis. Based on tumor size and location, 50 patients underwent extended circumcision, 283 patients underwent partial penectomy, and 29 patients underwent total penectomy. One hundred and eighty-three patients underwent inguinal lymphadenectomy and 47 patients underwent pelvic lymphadenectomy. Tumor pathology, tumor size, HPV subtype, postoperative pathological stage, overall survival (OS) and prognosis were analyzed. The Kaplan-Meier analysis and multivariate Cox regression analysis were used to analyse the factors which could affect the survival of patients. 5-year OS rate of these patients were also calculated. Results:In the pathological T classification, 137 cases were in T 1a stage, 24 cases in T 1b stage, 51 cases in T 2 stage, 136 cases in T 3 stage, and 14 cases in T 4 stage. In the pathological N classification, 235 cases were in N 0 stage, 54 cases in N 1 stage, 31 cases in N 2 stage and 42 cases in N 3 stage. The most common tumor type was squamous cell carcinoma (300 cases, 83%), followed by verrucous carcinoma (40 cases, 11%), sarcomatoid carcinoma(7 cases), carcinoma in situ (6 cases), basal-like carcinoma (6 cases), and adenosquamous carcinoma (3 cases). The most common tumor grade was mild (160 cases, 44%), followed by moderate differentiation (130 cases, 36%), poor differentiation (46 cases, 13%), and unclear differentiation (26 cases). The tumor sizes were < 3 cm in 135 patients and ≥ 3 cm in 142 patients. The tumor size was unclear in 85 patients. 173 cases (48%) were HPV positive and 189 cases (52%) were HPV negative. The Kaplan-Meier analysis showed the 5-year OS rate of HPV-positive group was higher than that of HPV-negative group (79% vs. 72%) but no significant difference was found ( P=0.09). The 5-year OS rate of patients whose tumor ≥ 3 cm (69%) was lower than those tumor < 3 cm (85%) and significant difference could be found ( P = 0.02). The 5-year OS rate of wild and moderate and poor grade were 85%, 70% and 58%, and significant difference could be found in the three groups ( P<0.01). The 5-year OS rates of patients with stage T 1a, T 1b, T 2, T 3and T 4 were 90%, 67%, 71%, 68% and 37% respectively( P<0.01). The 5-year OS rates of patients with stage N 0, N 1, N 2, and N 3 were 91%, 62%, 57%, and 30%, respectively( P<0.01). N stage could significantly affect the prognosis. The 5-year OS rate of T 1b patients was lower than that of T 1a and T 2 stage (67% vs. 90% vs. 71%, P=0.003). Of the 24 patients with T 1b stage, 17 cases received inguinal lymphadenectomy and 7 cases not. The 5-year OS rate of T 1b who received lymphadenectomy, who not and T 2 group were 73%, 57% and 71% respectively ( P=0.22). Multivariate Cox analysis showed that N stage ( HR =4.55, 95% CI 2.64-7.85, P<0.01) and tumor grade ( HR =2.09, 95% CI 1.09-4.02, P=0.03) were independent factors which could affect the prognosis. Conclusions:N stage and tumor grade were independent factors which could affect the prognosis. The poorer the tumor grade, the worse the prognosis. Inguinal lymphadenectomy could improve the prognosis of patients with T 1b stage.

Objective:To investigate the effects of different intensity of lighting on normal refractive development and form deprivation myopia (FDM) in guinea pigs.Methods:A total of 108 healthy 3-week-old guinea pigs were divided into normal refractive development guinea pigs ( n=54) and FDM guinea pigs ( n=54). FDM models were prepared in FDM animals by occlusion of the left eyes using an opaque mask, and the bilateral eyes were open in the normal refractive development guinea pigs.The guinea pigs were randomized to low (20 lx), normal(300 lx), and high intensity-lighting (5 000 lx) groups with a 12-hour light/12-hour dark cycle for 6 consecutive weeks under LED light.The ocular biometry was performed in a two-week interval.Axial length (AL) and dilated diopter were measured by A-scan ultrasonography and retinoscopy, respectively, and were compared after different lighting durations, and the change trends of them in normal refractive development and FDM guinea pigs were evaluated. Results:The AL values were not significantly different among low, normal and high intensity-lighting groups ( Fgroup=0.365, P=0.697), and the AL was gradually prolonged over the lighting duration ( Ftime=353.750, P<0.001). The diopters showed a statistically significant difference among different intensity-lighting groups ( Fgroup=3.576, P=0.034). The diopter in high intensity-lighting for 4 weeks was (+ 2.75±2.15) D, which was significantly higher than (0.41±3.07) D in the normal refrective development guinea pigs ( P<0.001). In the FDM guinea pigs, both AL and diopter were not significantly different among low, normal and high intensity-lighting groups ( Fgroup=0.105, P=0.900; Fgroup=0.973, P=0.387), and significant differences were seen in AL and diopter among three groups ( Ftime=408.302, 27.407; both at P<0.001). The diopter in FDM eyes of low intensity-lighting for 2 weeks was (+ 2.35±1.95) D, which was higher than (+ 1.90±0.97) D before lighting, with no statistically significant difference between them ( P>0.05). The AL was shortest and the AL change was smallest in normal refractive development guinea pigs of high intensity-lighting group.The diopter change in FDM guinea pigs of the low intensity-lighting group was significantly smaller than that in the normal intensity-lighting group ( P<0.001), with a transient hyperopia drift. Conclusions:The 5 000 lx lighting can slow down the development toward myopia in the normal refractive development eyes, and 20 lx lighting tends to delay the progression FDM eyes with a hyperopic shift after lighting for 2 weeks.

Objective:To observe the efficacy and safety of radium-223 in metastatic castration resistant prostate cancer (mCRPC) with bone metastasis.Methods:The clinical data of 48 patients with mCRPC treated with radium-223(55 kBq/kg, once every 4 weeks, planned to use for 6 cycles)from February 2021 to May 2022 were analyzed retrospectively. All patients had symptomatic bone metastasis without visceral metastasis, which the number of bone metastasis was more than one site.They were all classified as IVb stage. The average age was 70.5 (ranging 49-90) years. The median PSA was 44.70(ranging 0.15-1 864.00) ng/ml. The median ALP was 162 (ranging 43-1 589) U/L. The median time from mCRPC diagnosis to radium-223 use was 10 (ranging 3-47) months. 9, 18 and 11 patients had received first-line, second-line and third-line treatment for mCRPC before enrollment respectively, 10 patients had received at least fourth-line treatment. 38 (79.1%), 31 (64.5%), 30 (62.5%) and 7 (14.6%) patients had used abiraterone, enzalutamide, docetaxel and olaparib before enrollment. The probability of PSA level decrease >30%, ALP level decrease >30%, symptom improvement rate, median overall survival (OS), as well as the occurrence of treatment-related adverse reactions and the reasons for withdraw treatment were analyzed.Results:The median follow-up time was 8 (ranging 1-16) months. 11 patients completed all 6 courses of treatment. The median number of completed courses was 4 (ranging 1-6). 27 patients (56.2%) received radium-223 and bone protection drugs (Bisphosphate/ Denosumab). PSA decreased by >30% was recorded in 10 patients (20.8%) and ALP decreased by >30% was recorded in 25 patients (52.1%). 23 cases (47.9%) reported bone pain relief during treatment. Among the 9 patients who had received first-line of mCRPC previously, 6 cases (66%) had relief of bone pain symptoms, and 4 cases (44%) had a decrease of PSA >30%. Among the 18 patients who had previously received second-line mCRPC treatment, 11 cases (61%) had relief of bone pain symptoms, and 4 cases (22%) had a decrease of PSA >30%. Among the 21 patients who had received third-line or more mCRPC treatment in the past, 6 (28.5%) had symptom relief, and 2 (9.5%) had PSA decrease >30%. The median overall survival (OS) was not reached, and the OS was estimated to be 12.5 months using the Kaplan-Meier method. The most common hematological adverse effects were thrombocytopenia (15 cases, 31.2%; grade 3 in 6 cases and grade 4 in 0), followed by leucopenia (11 cases, 22.9%; grade 3 in 4 cases and grade 4 in 1 case) and anemia (8 cases, 16.7%; grade 3 in 3 cases and grade 4 in 0). Non-hematological adverse reactions included fever in 1 case (2.1%), constipation in 4 cases (8.3%), nausea and vomiting in 10 cases (20.8%), diarrhea in 7 cases (14.6%), dizziness in 1 case (2.1%) and fatigue in 11 cases (22.9%). Seven cases were discontinued due to intolerable adverse reactions (median 2 courses), 14 cases were discontinued due to disease progression or death (median 2 courses), and 5 cases were discontinued due to other reasons (median 1 course).Conclusions:Radium-223 has a good performance in symptom control for mCRPC patients who have previously received first-line or second-line therapy. Due to the high incidence of hematological adverse reactions, more attention should be paid to the changes of hemogram during the treatment, and timely treatment should be carried out to improve the drug tolerance of patients.