Safety and efficacy of radiotherapy combined with chemotherapy for recurrent metastatic renal pelvic and ureteral carcinoma.

PURPOSE: To retrospectively investigate the safety and efficacy of radiotherapy combined with chemotherapy for recurrent metastatic renal pelvic and ureteral carcinoma. METHODS: 109 patients were enrolled in this study, including 44 patients in the radiochemotherapy group and 65 patients in the chemotherapy group. Propensity score matching (PSM) was used to balance the baseline characteristics of the two groups by 1:1 matching. Kaplan-Meier method was used to calculate PFS and OS. Cox regression model was used for multivariate analysis. The side effects were evaluated by CTCAE v5.0 RESULTS: The median follow-up time was 14.5 months. Multivariate analysis showed that radiotherapy was a good independent prognostic factor for OS (HR: 0.327, 95% CI 0.157-0.680, P = 0.003). After matching, there were 40 patients in both groups, and the median PFS and OS in the radiochemotherapy group were longer than those in the chemotherapy group (PFS: 10.4 vs. 6.7 months, P = 0.035; OS: 43.5 vs. 18.8 months, P < 0.001). In addition, in the radiochemotherapy group, patients treated with radiotherapy before first-line chemotherapy failure had a longer PFS than those treated with radiotherapy after chemotherapy failure (median PFS: 15.7 vs. 6 months, P = 0.003). There was no significant difference in the incidence of grade 3-4 toxicities between the two groups (52.3% vs. 50.8%, P = 0.878). CONCLUSION: For patients with recurrent metastatic renal pelvic and ureteral carcinoma, radiotherapy combined with chemotherapy is well tolerable and expected to bring long-term survival benefits, and the benefits of early interventional radiotherapy may be more obvious.

ICAM-1 orchestrates the abscopal effect of tumor radiotherapy.

Compelling evidence indicates that radiotherapy (RT) has a systemic inhibitory effect on nonirradiated lesions (abscopal effect) in addition to the ablation of irradiated tumors. However, this effect occurs only in rare circumstances in clinical practice, and mechanisms underlying the abscopal effect of RT are neither fully understood nor therapeutically utilized. Here we identified that intercellular adhesion molecule-1 (ICAM-1), an inducible glycoprotein of the immunoglobulin superfamily, is up-regulated in nonirradiated tumors responsive to RT. ICAM-1 expression in preclinical animal models can be noninvasively detected by optical imaging and positron emission tomography (PET) using near-infrared fluorescence dye- and 64Cu-labeled imaging probes that we synthesized, respectively. Importantly, the expression levels of ICAM-1 determined by quantitative PET imaging showed a strong negative linear correlation with the growth of nonirradiated tumors. Moreover, genetic or pharmacologic up-regulation of ICAM-1 expression by either an intratumoral injection of engineered recombinant adenovirus or systemic administration of a Toll-like receptor 7 agonist-capsulated nanodrug could induce markedly increased abscopal responses to local RT in animal models. Mechanistic investigation revealed that ICAM-1 expression can enhance both the activation and tumor infiltration of CD8+ T cells to improve the responses of the nonirradiated tumors to RT. Together, our findings suggest that noninvasive PET imaging of ICAM-1 expression could be a powerful means to predict the responses of nonirradiated tumors to RT, which could facilitate the exploration of new combination RT strategies for effective ablation of primary and disseminated lesions.

Extracting laboratory test information from paper-based reports.

BACKGROUND: In the healthcare domain today, despite the substantial adoption of electronic health information systems, a significant proportion of medical reports still exist in paper-based formats. As a result, there is a significant demand for the digitization of information from these paper-based reports. However, the digitization of paper-based laboratory reports into a structured data format can be challenging due to their non-standard layouts, which includes various data types such as text, numeric values, reference ranges, and units. Therefore, it is crucial to develop a highly scalable and lightweight technique that can effectively identify and extract information from laboratory test reports and convert them into a structured data format for downstream tasks. METHODS: We developed an end-to-end Natural Language Processing (NLP)-based pipeline for extracting information from paper-based laboratory test reports. Our pipeline consists of two main modules: an optical character recognition (OCR) module and an information extraction (IE) module. The OCR module is applied to locate and identify text from scanned laboratory test reports using state-of-the-art OCR algorithms. The IE module is then used to extract meaningful information from the OCR results to form digitalized tables of the test reports. The IE module consists of five sub-modules, which are time detection, headline position, line normalization, Named Entity Recognition (NER) with a Conditional Random Fields (CRF)-based method, and step detection for multi-column. Finally, we evaluated the performance of the proposed pipeline on 153 laboratory test reports collected from Peking University First Hospital (PKU1). RESULTS: In the OCR module, we evaluate the accuracy of text detection and recognition results at three different levels and achieved an averaged accuracy of 0.93. In the IE module, we extracted four laboratory test entities, including test item name, test result, test unit, and reference value range. The overall F1 score is 0.86 on the 153 laboratory test reports collected from PKU1. With a single CPU, the average inference time of each report is only 0.78 s. CONCLUSION: In this study, we developed a practical lightweight pipeline to digitalize and extract information from paper-based laboratory test reports in diverse types and with different layouts that can be adopted in real clinical environments with the lowest possible computing resources requirements. The high evaluation performance on the real-world hospital dataset validated the feasibility of the proposed pipeline.

Development of a nomogram predicting metastatic disease and the assessment of NCCN, AUA and EAU guideline recommendations for bone imaging in prostate cancer patients.

PURPOSE: We identified the risk predictors related to prostate cancer (PCa) metastasis using contemporary data in a community setting. Then, we assessed the performance of indications for bone imaging recommended from the NCCN, AUA and EAU guidelines. METHODS: Using the Surveillance, Epidemiology, and End Results database (2010-2015), we collected clinicopathological information from PCa patients. The associated risk factors found by multivariate analyses were used to establish forest plots and nomograms for distant metastasis (DM) and bone(s)-only metastasis (BM). We next evaluated the NCCN, AUA and EAU guidelines indications for the discovery of certain subgroups of patients who should receive bone imaging. RESULTS: A total of 120,136 patients were eligible for analysis, of which 96.7% had no metastasis. The odds ratios of positive DM and BM results were 13.90 times and 15.87 times higher in patients with a histologic grade group (GG) 5 than in the reference group. The concordance index of the nomograms based on race, age, T/N stage, PSA, GG, percentage of positive scores for predicting DM and BM was 0.942 and 0.928, respectively. Performance of the NCCN, AUA and EAU guidelines was high and relatively similar in terms of sensitivity (93.2-96.9%) and negative predictive value (99.8-99.9%). NCCN guidelines had the highest accuracy, specificity and positive likelihood ratio, while negative likelihood ratio was lowest in AUA guideline. CONCLUSION: Histologic GG 5 was the foremost factor for DM and BM. NCCN-based recommendations may be more rational in clinical practice. Nomograms predicting metastasis demonstrate high accuracy.

Dosimetric feasibility of stereotactic ablative radiotherapy in pulmonary vein isolation for atrial fibrillation using intensity-modulated proton therapy.

PURPOSE: To evaluate dosimetric properties of intensity-modulated proton therapy (IMPT) for simulated treatment planning in patients with atrial fibrillation (AF) targeting left atrial-pulmonary vein junction (LA-PVJ), in comparison with volumetric-modulated arc therapy (VMAT) and helical tomotherapy (TOMO). METHODS: Ten thoracic 4D-CT scans with respiratory motion and one with cardiac motion were used for the study. Ten respiratory 4D-CTs were planned with VMAT, TOMO, and IMPT for simulated AF. Targets at the LA-PVJ were defined as wide-area circumferential ablation line. A single fraction of 25 Gy was prescribed to all plans. The interplay effects from cardiac motion were evaluated based on the cardiac 4D-CT scan. Dose-volume histograms (DVHs) of the ITV and normal tissues were compared. Statistical analysis was evaluated via one-way Repeated-Measures ANOVA and Friedman's test with Bonferroni's multiple comparisons test. RESULTS: The median volume of ITV was 8.72cc. All plans had adequate target coverage (V23.75Gy  ≥ 99%). Compared with VMAT and TOMO, IMPT resulted in significantly lower dose of most normal tissues. For VMAT, TOMO, and IMPT plans, Dmean of the whole heart was 5.52 ± 0.90 Gy, 5.89 ± 0.78 Gy, and 3.01 ± 0.57 Gy (P < 0.001), mean dose of pericardium was 4.74 ± 0.76 Gy, 4.98 ± 0.62 Gy, and 2.59 ± 0.44 Gy (P < 0.001), and D0.03cc of left circumflex artery (LCX) was 13.96 ± 5.45 Gy, 14.34 ± 5.91 Gy, and 8.43 ± 7.24 Gy (P < 0.001), respectively. However, no significant advantage for one technique over the others was observed when examining the D0.03cc of esophagus and main bronchi. CONCLUSIONS: IMPT targeting LA-PVJ for patients with AF has high potential to reduce dose to surrounding tissues compared to VMAT or TOMO. Motion mitigation techniques are critical for a particle-therapy approach.

Pattern and risk factors of local recurrence after nephroureterectomy for upper tract urothelial carcinoma.

PURPOSE: This study aims to identify predictive local recurrence risk factors and site-specific local recurrence pattern of upper tract urothelial carcinoma (UTUC) with different primary tumor locations. METHODS: Three hundred and eighty-nine UTUC patients with radical nephroureterectomy were included in this study. Univariate and multivariate Cox proportional hazards regressions were performed to measure the risk of local recurrence. We also mapped the position of local recurrence sites stratified by primary tumor locations. RESULTS: A total of 73 patients (18.7%) developed local recurrence within a median follow-up of 41 months (range, 3-80 months). For patients with local recurrence, the median interval of local recurrence was 9 months. Ureter tumor, multifocality, T stage, G grade, lymph node metastasis (LNM), lymph node dissection (LND), and lymph vascular invasion (LVI) were all significantly associated with increased local recurrence by univariable analyses (P < 0.05). Only multifocality, T3-4, G3, and LNM remained independent predictors of increased local recurrence by multivariable analyses. Adjuvant radiotherapy could reduce the local recurrence (HR = 0.177; 95% CI 0.064-0.493, P = 0.001). Patients with local recurrence had poorer cancer-specific survival (4-year cancer-specific survival rate 36 ± 7.5% vs 88.4 ± 2.2%, P = 0.000). We evaluated local recurrence pattern stratified by tumor locations. Para-aortic lymph node region was the most common recurrence area for all the patients. Left-sided UTUC had more than 70% recurrent lymph nodes in the left para-aortic region (LPA). For right-sided UTUC patients, recurrent para-aortic lymph nodes distributed in the LPA (33.3%), aortocaval (AC) (41.5%), and right paracaval (RPC) (25.2%) regions. Recurrence in the internal and external iliac regions was only found in the distal ureter group (P < 0.05). Renal pelvic fossa recurrence was only found in renal pelvic tumor (22.2%, P = 0.007). The ureter tumor bed recurrence rate was higher for ureter patients (P = 0.001). CONCLUSIONS: Multifocality, T3-4, G3, and LNM are predictors of higher local recurrence rate of UTUC. Adjuvant radiotherapy can reduce local recurrence rate. Local recurrence patterns are different according to primary tumor locations.

Cordyceps sinensis Promotes the Growth of Prostate Cancer Cells.

BACKGROUND: This study aims to test whether Cordyceps sinensis (CS), the most expensive Asian nutrient supplement might stimulate growth of prostate cancer cells. METHODS: Impact of CS on growth of prostate cancer was determined in vivo and in vitro. RESULTS: Firstly, the serum testosterone level was significantly elevated in mice fed CS. Prostate glands were significantly enlarged (weight index 0.53 ± 0.04 mg/g vs. 0.31 ± 0.04 mg/g, P = 0.006). Furthermore, cell viability was increased twofold in the androgen-responsive prostate cancer cell line (VCaP) after CS treatment. This promoting effect disappeared after bicalutamide was added. In addition, serum prostate-specific antigen (PSA) in mice bearing VCaP xenografts was significantly elevated (0.66 ± 0.04 ng/ml vs. 0.26 ± 0.06 ng/ml, P < 0.001) after treatment with CS. Finally, VCaP tumors in mice treated with CS grew much faster (479.2 ± 78.74 mm3 vs. 283 ± 58.97 mm3, P = 0.074). However, the above promoting effects of CS were not observed in parallel studies using the PC-3 cell line which lacks AR expression. CONCLUSIONS: These results suggest that CS promotes growth of prostate cancer cells by increasing production of testosterone and stimulating the AR-dependent pathway. Additional studies are required to see whether CS is safely consumed by patients with prostate cancer.

The role of definitive chemoradiotherapy versus surgery as initial treatments for potentially resectable esophageal carcinoma.

BACKGROUND: We performed a meta-analysis to compare the efficacy of definitive chemoradiotherapy (dCRT) and esophagectomy as initial treatments for potentially resectable esophageal cancer. METHODS: To assess both strategies, the combined odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Thirteen studies (N = 2071; dCRT = 869 and surgery = 1202) were included. In all, 90.39% of the patients were diagnosed with esophageal squamous cell carcinoma (ESCC). RESULTS: The 2-year (OR = 1.199, 95% CI 0.922-1.560; P = 0.177) and 5-year overall survival (OS) rates (OR = 0.947, 95% CI 0.628-1.429; P = 0.796) were not significantly different. No significant differences were identified in the 2-year OS among patients with stage I disease (OR = 1.397, 95% CI 0.740-2.638; P = 0.303) or stage II-III (OR = 0.418, 95% CI 0.022-7.833; P = 0.560). Patients with lymph node metastases tended to have a better 5-year OS when treated with dCRT than with surgery (OR = 0.226, 95% CI 0.044-1.169; P = 0.076); however, the difference between the two methods was not significant. Western patients who received dCRT had poorer prognoses than patients who underwent surgery (OR = 1.522, 95% CI 1.035-2.238; P = 0.033). dCRT and surgery led to similar 5-year progression-free survival rates (OR = 1.06, 95% CI 0.79-1.42; P = 0.70). CONCLUSIONS: dCRT and surgery are equally effective as initial treatments for potentially resectable esophageal cancer. These results apply primarily to Asian populations as they have an increased incidence of ESCC.

HMGN5 knockdown sensitizes prostate cancer cells to ionizing radiation.

BACKGROUND: High Mobility Group N (HMGN) proteins are a family of chromatin structural proteins that specifically bind to nucleosome core particles. HMGN5 is a novel and characteristic member of the HMGN protein family. We have previously found that HMGN5 is upregulated in prostate cancer and its downregulation had been demonstrated to induce apoptosis and G2-M cell cycle arrest. METHODS: The radiosensitization effect of HMGN5 knockdown on PC3 and DU145 cells was assessed using clonogenic assay, flow cytometry, and comet assay. The DNA double-strand break (DSB) repair kinetics of HMGN5 knockdown and control cells after radiation exposure was evaluated using immunocytofluorescence. The mitochondrial reactive oxygen species (ROS) levels were estimated using Dihydrorhodamine 123 (DHR 123) probes. Expression of mitochondrial antioxidant MnSOD was measured by real-time PCR and Western blot. The expression of antiapoptotic proteins Bcl-2 and Bcl-xL as well as cleavage of caspase-3, caspase-9, and PARP were also measured using Western blot. RESULTS: HMGN5 knockdown cells exhibit decreased clonogenic survival and increased apoptosis rate in response to 2-8 Gy ionizing radiation (IR). Loss of HMGN5 does not affect the DSB repair kinetics after radiation exposure. HMGN5 knockdown cells demonstrated increased mitochondrial ROS level and suppressed induction of MnSOD upon radiation compared with control cells upon radiation. Further, MnSOD knockdown resulted in inhibited cell viability as well as increased mitochondrial ROS level and apoptosis upon radiation in PC3 and DU145 cells. Finally, HMGN5 knockdown cells showed significantly decreased levels of antiapoptotic proteins Bcl-2 and Bcl-xL as well as increased cleavage of caspase-3, caspase-9, and PARP compared with control cells after radiation. CONCLUSIONS: HMGN5 knockdown sensitizes prostate cancer cells to ionizing radiation, and the radiosensitization effect may be partially mediated through suppressed induction of MnSOD and enhanced activation of apoptosis pathway in response to IR.

[Effect of two dose fractionations on postoperative radiotherapy of keloid: an analysis of 107 patients].

OBJECTIVE: To observe the preventive effect of two fractionations for postoperative radiotherapy of keloid and discuss the optimal way for postoperative radiotherapy. METHODS: We enrolled 107 consecutive keloid patients with 139 lesions from August 2011 to October 2012 in Department of Radiation Oncology of Peking University First Hospital. There were 114 lesions (the largest lesion part will be accounted if there are several lesions in the single body area) into the curative effect of the statistics. All the patients received irradiation after operation within 24 hours. The patients were divided into two groups: 5 Gy/f for continuous 4 days (5 Gy group); 4 Gy/f for continuous 5 days (4 Gy group). The lesions were treated by 6 MeV-E by Varian 21EX medical linear accelerator made in America. The irradiation field was surgical incision plus 1 cm in radial directions. One centimeter bolus was put on the skin to attain the therapeutical dose of skin surface. The total dose for each lesion was 20 Gy. The treatment effect of keloid was classified into cure, excellence and recurrence, referring to Darzi's standard. Effectivity means the sum of cure and excellence. SPSS 14.0 was used to statistically analyze the data. RESULTS: The total effective rate for 5 Gy group was 90.7% (49/54) and 66.7% (40/60) for 4 Gy group (P = 0.001). The lesions were divided into three regions according to the tension of the skin: ear/face/neck region, chest wall/shoulder/back region and other regions. The treatment effects of 5 Gy group and 4 Gy group were 94.1% (16/17) vs. 85.0% (17/20) for ear/face/neck region, 89.7% (26/29) vs. 60.0% (18/30) for chest wall/shoulder/back region and 87.5% (7/8) vs. 50.0% (5/10) for other regions. Significant difference was found in chest wall/shoulder/back region (P = 0.009). No obvious toxicities occurred in any group. CONCLUSION: Postoperative radiation therapy within 24 hours of 5 Gy/f for continuous 4 days and 4 Gy/f for continuous 5 days is effective, especially in 5 Gy/f group. It is suggested that hypofractionated radiation therapy is more effective for keloid patients, and it is also economical and convenient for patients and worth further discussing.

Breaking barriers: Stereotactic ablative proton and photon radiation therapy for renal cell carcinoma with extensive metastases: A case report.

Patients with advanced renal cancer (RCC) often have limited success with systemic therapy due to tumor heterogeneity. However, stereotactic ablative radiotherapy (SABR) has been shown to have a beneficial therapeutic effect for oligometastatic disease when used early. Despite this, current guidelines recommend the use of tyrosine kinase inhibitors (TKIs) as the first-line therapeutic agent for patients with recurrent or metastatic kidney cancer. Additionally, there is limited data on the combination of systemic treatment and SABR for extensive metastatic RCC due to concerns about high toxicity. Proton therapy offers a promising treatment option as it emits energy at a specific depth, generating high target doses while minimizing damage to normal tissue. This allows for precise treatment of various tumor lesions. In this case report, we describe a high-risk 65-year-old male with extensive pleural and thoracic lymph node metastases and 2 bone metastases of clear cell renal cancer. While the targeted therapy and immunotherapy effectively treated the bone metastases, it was not effective in treating the chest metastases, including the pleural and lymph node metastases. Thus, the patient received full-coverage radiotherapy with photon for primary renal tumor and intensity-modulated proton therapy (IMPT) for thoracic metastases. The patient showed no evidence of disease for 1 year after the initial radiotherapy, and no severe SABR-related adverse effects were observed until now. The combination of targeted therapy and immunotherapy with full-coverage radiotherapy may be a promising treatment option for selected patients with extensive metastatic renal cancer, especially as proton therapy allows for more precise control of the beam and minimal damage to normal tissue. This case has motivated us to investigate the potential advantages of administering proton therapy concurrently with systemic therapy in the management of metastatic renal cell carcinoma patients.

Integration of Multiparameter MRI into Conventional Pretreatment Risk Factors to Predict Positive Surgical Margins After Radical Prostatectomy.

INTRODUCTION/BACKGROUND: Positive surgical margins (PSMs) after radical prostatectomy (RP) can increase the risk of biochemical recurrence in prostate cancer (PCa) patients. However, the prediction of the likelihood of PSMs in patients undergoing similar surgical procedures remains a challenge. We aim to develop a predictive model for PSMs in patients undergoing non-nerve-sparing RP. PATIENTS AND METHODS: In this retrospective study, we analyzed data from PCa patients who underwent minimally invasive non-nerve-sparing RP at our hospital between June 2017 and June 2021. We identified independent risk factors associated with PSMs using clinical and MRI-based parameters in univariate and multivariate logistic regression analyzes. These factors were then used to develop a nomogram for predicting the probability of PSMs. The predictive performance was validated using calibration and receiver operating characteristic curve, area under the curve ,and decision curve analysis. RESULTS: Multivariate analyzes revealed prostate-specific antigen density, tumor size, tumor location at the apex, tumor contact length, extracapsular extension (ECE) level, and apparent diffusion coefficient value as independent risk factors. A nomogram was developed and validated with high accuracy (C-index = 0.78). Furthermore, we found that 44.2% of patients diagnosed with organ-confined disease had ECE after surgery, and 29.1% of patients with Gleason scores ≤7 had higher pathological scores. Interestingly, the tumor burden calculated from PCa biopsy cores was overestimated when compared to postoperative PCa specimens. CONCLUSION: We developed a reliable nomogram for predicting the risk of PSMs in PCa patients undergoing non-nerve-sparing RP. The study highlights the importance of incorporating these parameters in personalized surgical management.

Dosimetric comparison of IMPT vs VMAT for multiple lung lesions: an NTCP model-based decision-making strategy.

To compare the dosimetric differences in volumetric modulated arc therapy (VMAT) and intensity modulated proton therapy (IMPT) in stereotactic body radiation therapy (SBRT) of multiple lung lesions and determine a normal tissue complication probability (NTCP) model-based decision strategy that determines which treatment modality the patient will use. A total of 41 patients were retrospectively selected for this study. The number of patients with 1-6 lesions was 5, 16, 7, 6, 3, and 4, respectively. A prescription dose of 70 GyRBE in 10 fractions was given to each lesion. SBRT plans were generated using VMAT and IMPT. All the IMPT plans used robustness optimization with ± 3.5% range uncertainties and 5 mm setup uncertainties. Dosimetric metrics and the predicted NTCP value of radiation pneumonitis (RP), esophagitis, and pericarditis were analyzed to evaluate the potential clinical benefits between different planning groups. In addition, a threshold for the ratio of PTV to lungs (%) to determine whether a patient would benefit highly from IMPT was determined using receiver operating characteristic curves. All plans reached target coverage (V70GyRBE ≥ 95%). Compared with VMAT, IMPT resulted in a significantly lower dose of most thoracic normal tissues. For the 1-2, 3-4 and 5-6 lesion groups, the lung V5 was 29.90 ± 9.44%, 58.33 ± 13.35%, and 81.02 ± 5.91% for VMAT and 11.34 ± 3.11% (p < 0.001), 21.45 ± 3.80% (p < 0.001), and 32.48 ± 4.90% (p < 0.001) for IMPT, respectively. The lung V20 was 12.07 ± 4.94%, 25.57 ± 6.54%, and 43.99 ± 11.83% for VMAT and 6.76 ± 1.80% (p < 0.001), 13.14 ± 2.27% (p < 0.01), and 19.62 ± 3.48% (p < 0.01) for IMPT. The Dmean of the total lung was 7.65 ± 2.47 GyRBE, 14.78 ± 2.75 GyRBE, and 21.64 ± 4.07 GyRBE for VMAT and 3.69 ± 1.04 GyRBE (p < 0.001), 7.13 ± 1.41 GyRBE (p < 0.001), and 10.69 ± 1.81 GyRBE (p < 0.001) for IMPT. Additionally, in the VMAT group, the maximum NTCP value of radiation pneumonitis was 73.91%, whereas it was significantly lower in the IMPT group at 10.73%. The accuracy of our NTCP model-based decision model, which combines the number of lesions and PTV/Lungs (%), was 97.6%. The study demonstrated that the IMPT SBRT for multiple lung lesions had satisfactory dosimetry results, even when the number of lesions reached 6. The NTCP model-based decision strategy presented in our study could serve as an effective tool in clinical practice, aiding in the selection of the optimal treatment modality between VMAT and IMPT.

Dose-Intensified Postoperative Radiation Therapy for Prostate Cancer: Long-Term Results From the PKUFH Randomized Phase 3 Trial.

PURPOSE: In the randomized, single-center, PKUFH phase 3 trial, dose-intensified (72 Gy) radiation therapy was compared with conventional (66 Gy) radiation therapy. In a previous study, we found no significant difference in biochemical progression-free survival (bPFS) between the 2 cohorts at 4 years. In the current analysis, we provide 7-year outcomes. METHODS AND MATERIALS: Patients with stage pT3-4, positive surgical margins, or a prostate-specific antigen increase ≥0.2 ng/mL after radical prostatectomy were randomly assigned 1:1 to receive either 72 Gy in 36 fractions or 66 Gy in 33 fractions. All the patients underwent image guided intensity modulated radiation therapy. The primary endpoint was bPFS. Secondary endpoints were distant metastasis-free survival (DMFS), cancer-specific survival (CSS), and overall survival (OS) as estimated using the Kaplan-Meier method. RESULTS: Between September 2011 and November 2016, 144 patients were enrolled with 73 and 71 in the 72- and 66-Gy cohorts, respectively. At a median follow-up of 89.5 months (range, 73-97 months), there was no difference in 7-year bPFS between the 72- and 66-Gy cohorts (70.3% vs 61.2%; hazard ratio [HR], 0.73; 95% CI, 0.41-1.29; P = .274). However, in patients with a higher Gleason score (8-10), the 72-Gy cohort had statistically significant improvement in 7-year bPFS compared with the 66-Gy cohort (66.5% vs 30.2%; HR, 0.37; 95% CI, 0.17-0.82; P = .012). In addition, in patients with multiple positive surgical margins, the 72-Gy cohort had statistically significant improvement in 7-year bPFS compared with single positive surgical margin (82.5% vs 57.5%; HR, 0.36; 95% CI, 0.13-0.99; P = .037). The 7-year DMFS (88.4% vs 84.9%; HR, 0.93; 95% CI, 0.39-2.23; P = .867), CSS (94.1% vs 95.5%; HR, 1.19; 95% CI, 0.42-3.39; P = .745), and OS (92.8% vs 94.1%; HR, 1.29; 95% CI, 0.51-3.24; P = .594) had no statistical differences between the 72- and 66-Gy cohorts. CONCLUSIONS: The current 7-year bPFS results confirmed our previous findings that dose escalation (72 Gy) demonstrated no improvement in 7-year bPFS, DMFS, CSS, or OS compared with the 66-Gy regimen. However, patients with a higher Gleason score (8-10) or multiple positive surgical margins might benefit from the 72-Gy regimen, but this requires further prospective research.

Chinese quality control indices for standardized diagnosis and treatment of renal cancer (2022 edition).

Renal cancer is one of the most common malignancies of the urinary system, and the number of deaths continues to increase. The standardized management of the diagnosis and treatment of renal cancer is challenging due to the great differences in the diagnosis and treatment of renal cancer in different regions. The Renal Cancer Expert Committee of the National Cancer Quality Control Center (NCQCC) identified a lack of authoritative quality control standards as an opportunity to utilize its multidisciplinary membership to improve the standardized diagnosis and treatment of renal cancer. The Renal Cancer Expert Committee of the NCQCC aims to promote quality control and national standardization, uniformity, and normalization of renal cancer diagnosis and treatment, which ultimately improved the survival rate and quality of life of renal cancer patients. A panel of experts with renal cancer surgery, renal cancer medicine, medical imaging, pathology and radiotherapy were drawn together and determined the quality control standards for the standardized diagnosis and treatment of renal cancer. The Indices includes 20 items that cover all key areas in the diagnosis and treatment of renal cancer, such as standard diagnosis, surgery treatment, systemic treatment, and prognostic evaluation.

Crafting a Personalized Prognostic Model for Malignant Prostate Cancer Patients Using Risk Gene Signatures Discovered through TCGA-PRAD Mining, Machine Learning, and Single-Cell RNA-Sequencing.

BACKGROUND: Prostate cancer is a significant clinical issue, particularly for high Gleason score (GS) malignancy patients. Our study aimed to engineer and validate a risk model based on the profiles of high-GS PCa patients for early identification and the prediction of prognosis. METHODS: We conducted differential gene expression analysis on patient samples from The Cancer Genome Atlas (TCGA) and enriched our understanding of gene functions. Using the least absolute selection and shrinkage operator (LASSO) regression, we established a risk model and validated it using an independent dataset from the International Cancer Genome Consortium (ICGC). Clinical variables were incorporated into a nomogram to predict overall survival (OS), and machine learning was used to explore the risk factor characteristics' impact on PCa prognosis. Our prognostic model was confirmed using various databases, including single-cell RNA-sequencing datasets (scRNA-seq), the Cancer Cell Line Encyclopedia (CCLE), PCa cell lines, and tumor tissues. RESULTS: We identified 83 differentially expressed genes (DEGs). Furthermore, WASIR1, KRTAP5-1, TLX1, KIF4A, and IQGAP3 were determined to be significant risk factors for OS and progression-free survival (PFS). Based on these five risk factors, we developed a risk model and nomogram for predicting OS and PFS, with a C-index of 0.823 (95% CI, 0.766-0.881) and a 10-year area under the curve (AUC) value of 0.788 (95% CI, 0.633-0.943). Additionally, the 3-year AUC was 0.759 when validating using ICGC. KRTAP5-1 and WASIR1 were found to be the most influential prognosis factors when using the optimized machine learning model. Finally, the established model was interrelated with immune cell infiltration, and the signals were found to be differentially expressed in PCa cells when using scRNA-seq datasets and tissues. CONCLUSIONS: We engineered an original and novel prognostic model based on five gene signatures through TCGA and machine learning, providing new insights into the risk of scarification and survival prediction for PCa patients in clinical practice.

Biomarkers for Prostate Cancer: From Diagnosis to Treatment.

Prostate cancer (PCa) is a widespread malignancy with global significance, which substantially affects cancer-related mortality. Its spectrum varies widely, from slow-progressing cases to aggressive or even lethal forms. Effective patient stratification into risk groups is crucial to therapeutic decisions and clinical trials. This review examines a wide range of diagnostic and prognostic biomarkers, several of which are integrated into clinical guidelines, such as the PHI, the 4K score, PCA3, Decipher, and Prolaris. It also explores the emergence of novel biomarkers supported by robust preclinical evidence, including urinary miRNAs and isoprostanes. Genetic alterations frequently identified in PCa, including BRCA1/BRCA2, ETS gene fusions, and AR changes, are also discussed, offering insights into risk assessment and precision treatment strategies. By evaluating the latest developments and applications of PCa biomarkers, this review contributes to an enhanced understanding of their role in disease management.

Treatment-related neuroendocrine prostate cancer managed with partial stereotactic ablative radiotherapy (P-SABR) for long-term survival: a case series.

Background: The amount of treatment-related neuroendocrine prostate cancer (t-NEPC) increases after hormonal therapy, especially novel androgen receptor pathway inhibitors (ARPIs). T-NEPC is considered a hormone refractory [androgen receptor (AR)-negative] subtype of prostate cancer. Although tumors are initially responsive to platinum-based chemotherapy, the drugs are only effective for a short time. Therefore, whether or not local treatment can prolong survival is of great concern. Case Description: In this case series, we discuss 4 t-NEPC cases who were treated with partial stereotactic ablative radiotherapy (P-SABR) for bulky tumors. P-SABR is a radiotherapy regimen that is used in a SABR boost [such as 6 Gy × 4 fractions (f), 8 Gy × 3 f] prior to conventional radiotherapy to enhance the tumor biological effective dose (BED) without increasing the dose to organs at risk. All patients achieved good local control after P-SABR. For patient 1, P-SABR was used for the prostate tumor. After radiotherapy, pathological complete remission (pCR) was achieved, and the prostate lesion remained stable thus far. As of this writing, the patient has been in remission for 3 years after initial t-NEPC diagnosis. Conclusions: We describe 4 cases and indicate that P-SABR is safe and effective in the treatment of a large prostate mass and may prolong the survival of these patients.

Radiation Oncology Research in Asia: Current Status and a Peep Into the Future From the Federation of Asian Organizations for Radiation Oncology.

PURPOSE: This survey was conducted to assess the current research practices among the 14 members of the Federation of Asian Organizations for Radiation Oncology (FARO) committee, to inform measures for research capacity building in these nations. MATERIALS AND METHODS: A 19-item electronic survey was sent to two research committee members from the 14 representative national radiation oncology organizations (N = 28) that are a part of FARO. RESULTS: Thirteen of the 14 member organizations (93%) and 20 of 28 members (71.5%) responded to the questionnaire. Only 50% of the members stated that an active research environment existed in their country. Retrospective audits (80%) and observational studies (75%) were the most common type of research conducted in these centers. Lack of time (80%), lack of funding (75%), and limited training in research methodology (40%) were cited as the most common hindrances in conducting research. To promote research initiatives in the collaborative setting, 95% of the members agreed to the creation of site-specific groups, with head and neck (45%) and gynecological cancers (25%) being the most preferred disease sites. Projects focused on advanced external beam radiotherapy implementation (40%), and cost-effectiveness studies (35%) were cited as some of the potential areas for future collaboration. On the basis of the survey results, after result discussion and the FARO officers meeting, an action plan for the research committee has been created. CONCLUSION: The results from the survey and the initial policy structure may allow facilitation of radiation oncology research in the collaborative setting. Centralization of research activities, funding support, and research-directed training are underway to help foster a successful research environment in the FARO region.

Somatic and germline aberrations in homologous recombination repair genes in Chinese prostate cancer patients.

Simple summary: Somatic and germline aberrations in homologous recombinant repair (HHR) genes are associated with increased incidence and poor prognosis for prostate cancer. Through next-generation sequencing of prostate cancer patients across all clinical states from north China, here the authors identified a somatic mutational rate of 3% and a germline mutational rate of 3.9% for HRR genes using 200 tumor tissues and 714 blood specimens. Thus, mutational rates in HRR genes were lower compared with previous studies. Background: Homologous recombination repair deficiency is associated with higher risk and poorer prognosis for prostate cancer. However, the landscapes of somatic and germline mutations in these genes remain poorly defined in Chinese patients, especially for those with localized disease and those from north part of China. In this study, we explore the genomic profiles of these patients. Methods: We performed next-generation sequencing with 200 tumor tissues and 714 blood samples from prostate cancer patients at Peking University First Hospital, using a 32 gene panel including 19 homologous recombination repair genes. Results: TP53, PTEN, KRAS were the most common somatic aberrations; BRCA2, NBN, ATM were the most common germline aberrations. In terms of HRR genes, 3% (6/200) patients harbored somatic aberrations, and 3.8% (28/714) patients harbored germline aberrations. 98.0% (196/200) somatic-tested and 72.7% (519/714) germline tested patients underwent prostatectomy, of which 28.6% and 42.0% had Gleason scores ≥8 respectively. Gleason scores at either biopsy or prostatectomy were predictive for somatic aberrations in general and in TP53; while age of onset <60 years old, PSA at diagnosis, and Gleason scores at biopsy were clinical factors associated with positive germline aberrations in BRCA2/ATM. Conclusions: Our results showed a distinct genomic profile in homologous recombination repair genes for patients with prostate cancer across all clinical states from north China. Clinicians may consider to expand the prostate cancer patients receiving genetic tests to include more individuals due to the weak guiding role by the clinical factors currently available.