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.

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.

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.

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.

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.

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.

Uncovering the Secrets of Prostate Cancer's Radiotherapy Resistance: Advances in Mechanism Research.

Prostate cancer (PCa) is a critical global public health issue with its incidence on the rise. Radiation therapy holds a primary role in PCa treatment; however, radiation resistance has become increasingly challenging as we uncover more about PCa's pathogenesis. Our review aims to investigate the multifaceted mechanisms underlying radiation therapy resistance in PCa. Specifically, we will examine how various factors, such as cell cycle regulation, DNA damage repair, hypoxic conditions, oxidative stress, testosterone levels, epithelial-mesenchymal transition, and tumor stem cells, contribute to radiation therapy resistance. By exploring these mechanisms, we hope to offer new insights and directions towards overcoming the challenges of radiation therapy resistance in PCa. This can also provide a theoretical basis for the clinical application of novel ultra-high-dose-rate (FLASH) radiotherapy in the era of PCa.

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.

Contouring lumbosacral plexus nerves with MR neurography and MR/CT deformable registration technique.

Purpose: It is difficult to contour nerve structures with the naked eye due to poor differentiation between the nerve structures with other soft tissues on CT images. Magnetic resonance neurography (MRN) has the advantage in nerve visualization. The purpose of this study is to identify one MRN sequence to better assist the delineation of the lumbosacral plexus (LSP) nerves to assess the radiation dose to the LSP using the magnetic resonance (MR)/CT deformable coregistration technique. Methods: A total of 18 cases of patients with prostate cancer and one volunteer with radiation-induced lumbosacral plexopathy (RILSP) were enrolled. The data of simulation CT images and original treatment plans were collected. Two MRN sequences (Lr_NerveVIEW sequence and Cs_NerveVIEW sequence) were optimized from a published MRN sequence (3D NerveVIEW sequence). The nerve visualization ability of the Lr_NerveVIEW sequence and the Cs_NerveVIEW sequence was evaluated via a four-point nerve visualization score (NVS) scale in the first 10 patients enrolled to determine the better MRN sequence for assisting nerve contouring. Deformable registration was applied to the selected MRN sequence and simulation CT images to get fused MR/CT images, on which the LSP was delineated. The contouring of the LSP did not alter treatment planning. The dosimetric data of the LSP nerve were collected from the dose-volume histogram in the original treatment plans. The data of the maximal dose (Dmax) and the location of the maximal radiation point received by the LSP structures were collected. Results: The Cs_NerveVIEW sequence gained lower NVS scores than the Lr_NerveVIEW sequence (Z=-2.887, p=0.004). The LSP structures were successfully created in 18 patients and one volunteer with MRN (Lr_NerveVIEW)/CT deformable registration techniques, and the LSP structures conformed with the anatomic distribution. In the patient cohort, the percentage of the LSP receiving doses exceeding 50, 55, and 60 Gy was 68% (12/18), 33% (6/18), and 17% (3/18), respectively. For the volunteer with RILSP, the maximum irradiation dose to his LSP nerves was 69 Gy. Conclusion: The Lr_NerveVIEW MRN sequence performed better than the Cs_NerveVIEW sequence in nerve visualization. The dose in the LSP needs to be measured to understand the potential impact on treatment-induced neuropathy.

Outcomes of High-Dose Stereotactic Ablative Radiotherapy to All/Multiple Sites for Oligometastatic Renal Cell Cancer Patients.

BACKGROUND: Stereotactic ablative body radiotherapy (SABR) is one of the treatment options for oligometastatic renal cell carcinoma (RCC) but is limited by a lack of data to evaluate high-dose SABR to all/multiple sites. OBJECTIVE: This study retrospectively investigated the efficacy and prognostic factors of high-dose SABR for oligometastatic RCC patients. DESIGN, SETTING, AND PARTICIPANTS: Patients with oligometastatic RCC on systemic therapy were retrospectively collected. INTERVENTION(S): All patients were treated with SABR (40-50 Gy/5 fractions) for small tumors or partial-SABR (tumor center boosted with 6-8 Gy/3-5 fractions with 50-60 Gy/20-25 fractions to the whole tumor volume) for bulky tumors or tumors adjacent to critical organs. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Progression-free survival (PFS) and overall survival (OS) were calculated. RESULTS AND LIMITATIONS: In total, 35 patients were enrolled, of which 88.5% had intermediate- or high-risk disease, with 60% on second- to fourth-line systemic therapy. The median follow-up time was 17 months. The median PFS and OS times were 11.3 and 29.7 months, respectively. Univariate analysis showed that an OS benefit was found in patients who received radiation before tyrosine kinase inhibitor (TKI) failure (p = 0.006) and where there was a short time interval (

Redefine the Role of Proton Beam Therapy for the Locally-Advanced Non-Small Cell Lung Cancer Assisting the Reduction of Acute Hematologic Toxicity.

Purpose: To investigate the potential clinical benefit of utilizing intensity-modulated proton therapy (IMPT) to reduce acute hematologic toxicity for locally advanced non-small cell lung cancer (LA-NSCLC) patients and explore the feasibility of a model-based patient selection approach via the normal tissue complication probability (NTCP). Methods: Twenty patients with LA-NSCLC were retrospectively selected. Volumetric modulated arc photon therapy (VMAT) and IMPT plans were generated with a prescription dose of 60 Gy in 30 fractions. A wide range of cases with varied tumor size, location, stations of metastatic lymph nodes were selected to represent the general cancer group. Contouring and treatment planning followed RTOG-1308 protocol. Doses to thoracic vertebral bodies (TVB) and other organ at risks were compared. Risk of grade ≥ 3 acute hematologic toxicity (HT3+) were calculated based on the NTCP model, and patients with a reduction on NTCP of HT3+ from VMAT to IMPT (△NTCP_HT3+) ≥ 10% were considered to 'significantly benefit from proton therapy.' Results: Compared to VMAT, IMPT significantly reduced the dose to the TVB, the lung, the heart, the esophagus and the spinal cord. Tumor distance to TVB was significantly associated with △NTCP _HT3+ ≥ 10%. For the patients with tumor distance ≤ 0.7 cm to TVB, the absolute reduction of dose (mean, V30 and V40) to TVB was significantly lower than that in patients with tumor distance > 0.7 cm. Conclusion: IMPT decreased the probability of HT3+ compared to VMAT by reducing the dose to the TVB in LA-NSCLC patients. Patients with tumor distance to TVB less than 0.7 cm are likely to benefit most from proton over photon therapy.

Effectiveness of adjuvant radiotherapy for high recurrence risk patients with upper tract urothelial carcinoma.

PURPOSE: A recent study has shown that upper tract urothelial carcinoma (UTUC) patients with high-risk factors have a high local recurrence rate. The purpose of this work was to investigate the benefit of adjuvant radiotherapy (ART) for patients with high recurrence factors. METHODS: Four hundred twenty-four UTUC patients who received radical nephroureterectomy (RNU) in our hospital between 2010 and 2018 were reviewed. The significance of factors on cancer-specific survival (CSS) and recurrence-free survival (RFS) were assessed using Cox multivariate analysis. In patients with high recurrence factors, propensity score matching was used to adjust the confounding factors for ART. RESULTS: The median follow-up time was 40 (range 3-77) months. Multivariate analysis showed that multifocal tumor, G3, pT3/4 stage and positive lymph node (N+) were independent predictors for worse RFS. Multifocal tumor and pT3/4 stage were independent predictors of worse CSS in UTUC after surgery. A total of 286 patients with these high recurrence factors were identified: 192 (67.1%) patients received RNU only, and 94 (32.9%) patients received ART. Overall, ART did not improve CSS (ART 86.1% vs. RNU 78.5%.; P = 0.11). After propensity score matching, ART significantly improved the CSS of patients with high recurrence factors. The 3-year CSS was 73.1% in patients treated with RNU alone vs. 86.1% in patients treated with ART (P = 0.016). CONCLUSIONS: Results of our study demonstrated benefit of adjuvant radiotherapy in cancer specific survival in UTUC patients with high recurrence factors(multifocal tumor ,pT3/4,G3 and positive lymph node).

Variability of α/ß ratios for prostate cancer with the fractionation schedule: caution against using the linear-quadratic model for hypofractionated radiotherapy.

BACKGROUND: Prostate cancer (PCa) is known to be suitable for hypofractionated radiotherapy due to the very low α/ß ratio (about 1.5-3 Gy). However, several randomized controlled trials have not shown the superiority of hypofractionated radiotherapy over conventionally fractionated radiotherapy. Besides, in vivo and in vitro experimental results show that the linear-quadratic (LQ) model may not be appropriate for hypofractionated radiotherapy, and we guess it may be due to the influence of fractionation schedules on the α/ß ratio. Therefore, this study attempted to estimate the α/ß ratio in different fractionation schedules and evaluate the applicability of the LQ model in hypofractionated radiotherapy. METHODS: The maximum likelihood principle in mathematical statistics was used to fit the parameters: α and ß values in the tumor control probability (TCP) formula derived from the LQ model. In addition, the fitting results were substituted into the original TCP formula to calculate 5-year biochemical relapse-free survival for further verification. RESULTS: Information necessary for fitting could be extracted from a total of 23,281 PCa patients. A total of 16,442 PCa patients were grouped according to fractionation schedules. We found that, for patients who received conventionally fractionated radiotherapy, moderately hypofractionated radiotherapy, and stereotactic body radiotherapy, the average α/ß ratios were 1.78 Gy (95% CI 1.59-1.98), 3.46 Gy (95% CI 3.27-3.65), and 4.24 Gy (95% CI 4.10-4.39), respectively. Hence, the calculated α/ß ratios for PCa tended to become higher when the dose per fraction increased. Among all PCa patients, 14,641 could be grouped according to the risks of PCa in patients receiving radiotherapy with different fractionation schedules. The results showed that as the risk increased, the k (natural logarithm of an effective target cell number) and α values decreased, indicating that the number of effective target cells decreased and the radioresistance increased. CONCLUSIONS: The LQ model appeared to be inappropriate for high doses per fraction owing to α/ß ratios tending to become higher when the dose per fraction increased. Therefore, to convert the conventionally fractionated radiation doses to equivalent high doses per fraction using the standard LQ model, a higher α/ß ratio should be used for calculation.

Investigate the Dosimetric and Potential Clinical Benefits Utilizing Stereotactic Body Radiation Therapy With Simultaneous Integrated Boost Technique for Locally Advanced Pancreatic Cancer: A Comparison Between Photon and Proton Beam Therapy.

PURPOSE: To investigate the potential clinical benefits of using stereotactic body radiation therapy (SBRT) with simultaneous integrated boost (SIB) technique for locally advanced pancreatic cancer (LAPC) among different treatment modalities and planning strategies, including photon and proton. METHOD: A total of 19 patients were retrospectively selected in this study: 13 cases with the tumor located in the head of the pancreas and 6 cases with the tumor in the body of the pancreas. SBRT-SIB plans were generated using volumetric modulated arc therapy (VMAT), two-field Intensity Modulated Proton Therapy (IMPT), and three-field IMPT. The IMPT used the robust optimization parameters of ± 3.5% range and 5-mm setup uncertainties. Root-mean-square deviation dose (RMSD) volume histograms were used to evaluate the target coverage robustness quantitatively. Dosimetric metrics based on the dose-volume histogram (DVH), homogeneity index (HI), and normal tissue complication probability (NTCP) were analyzed to evaluate the potential clinical benefits among different planning groups. RESULTS: With a similar CTV and SIB coverage, two-field IMPT provided a lower maximum dose for the stomach (median: 18.6GyE, p<0.05) and duodenum (median: 32.62GyE, p<0.05) when the target was located in the head of the pancreas compared to VMAT and three-field IMPT. The risks of gastric bleed (3.42%) and grade ≥ 3 GI toxicity (4.55%) were also decreased. However, for the target in the body of the pancreas, VMAT showed a lower maximum dose for the stomach (median 30.93GyE, p<0.05) and toxicity of gastric bleed (median: 8.67%, p<0.05) compared to two-field IMPT and three-field IMPT, while other maximum doses and NTCPs were similar. The RMSD volume histogram (RVH) analysis shows that three-field IMPT provided better robustness for targets but not for OARs. Instead, three-field IMPT increased the Dmean of organs such as the stomach, duodenum, and intestine. CONCLUSION: The results indicated that the tumor locations could play a critical role in determining clinical benefits among different treatment modalities. Two-field IMPT could be a better option for LAPC patients whose tumors are located in the head of the pancreas. It provides lower severe toxicity for the stomach and duodenum. Nevertheless, VMAT is preferred for the body with better protection for the possibility of gastric bleed.

Oncological Outcomes of Adjuvant Radiotherapy for Partial Ureterectomy in Distal Ureteral Urothelial Carcinoma Patients.

PURPOSE: We retrospectively analyzed the oncological outcomes of T3 or G3 distal ureteral urothelial carcinoma (DUUC) underwent partial ureterectomy (PU) followed by adjuvant radiotherapy (ART). METHODS: From January 2008 to September 2019, clinical data from a total of 221 patients with pathologic T3 or G3 who underwent PU or RNU at our hospital were analyzed. 17 patients of them were treated with PU+ART, 72 with PU alone and 132 with radical nephroureterectomy (RNU). Clinicopathologic outcomes were evaluated. Survival was assessed using the Kaplan-Meier method. Cox regression addressed recurrence-free survival (RFS), metastasis-free survival (MFS), cancer specific survival (CSS) and overall survival (OS). RESULTS: Median age and follow-up time were 68 (IQR 62-76) years old and 43 (IQR 28-67) months, respectively. In univariate and multivariable analyses, no lymph node metastasis(LNM) and ART were independent prognostic factors of RFS (p=0.031 and 0.016, respectively). ART significantly improved 5-year RFS compared with the PU alone, (67.6% vs. 39.5%, HR: 2.431, 95%CI 1.210-4.883, p=0.039). There was no statistical difference in 5-year RFS between PU+ART and RNU groups (67.6% vs. 64.4%, HR=1.113, 95%CI 0.457-2.712, p=0.821). Compared with PU alone or RNU, PU+ART demonstrated no statistical difference in 5-year MFS (PU+ART 73.2%, PU 57.2%, RNU69.4%), CSS (70.7%, 55.1%, 76.6%, respectively), and OS (70.7%, 54.1%, 69.2%, respectively). CONCLUSIONS: For distal ureteral urothelial carcinoma patients with T3 or G3, adjuvant radiotherapy could significantly improve recurrence-free survival compared with partial ureterectomy alone. There was no significant difference between survival outcomes of PU+ART and radical nephroureterectomy.

Radiation therapy for nonmetastatic medically inoperable upper-tract urothelial carcinoma.

BACKGROUND: The standard management for upper urinary tract urothelial carcinoma (UTUC) is radical nephroureterectomy (RNU). However, some patients cannot undergo this procedure for several reasons, such as unresectable disease, old age, and multiple comorbidities. Our study explored the potential safety and effectiveness of radiotherapy as a curative treatment for UTUC patients unfit for surgery. METHODS: The data of patients treated with radiotherapy between December 2017 and November 2019 were retrospectively reviewed. For the literature review, computerized PubMed Medline, Index Medicus, and Web of Science databases and reference lists from the identified publications of interest were used. And "upper-tract urothelial carcinoma" and "radiotherapy" were used as key words in the search. RESULTS: We describe 8 patients with UTUC who were treated with radiotherapy. The median follow-up time was 13.5 months (range, 8.6-30.9 months). Local tumor control was achieved in all patients. However, distant metastases were observed in 2 patients with T3-4/N+ status. One patient had T4 status and the other had N2+ status. The patients died of tumor progression at 15.0 and 17.7 months. In addition, the other 6 patients who were still alive had relatively early-stage tumors without nodal involvement. Regarding acute toxicity, according to the CTCAE v5.0, mild side effects were noted, including grade 1 nausea and diarrhea. Four patients developed mild anemia, generally of grade 1-2. One patient experienced grade 3 anemia, but it was manageable and improved with symptomatic support. In addition, no grade 4 acute or late toxicities were observed. No significant long-term impairment of renal function occurred. CONCLUSIONS: For patients with nonmetastatic UTUC who are not suitable for surgery, radiotherapy is a safe treatment and can achieve good local tumor control.

Population-Based Comparison of Different Risk Stratification Systems Among Prostate Cancer Patients.

BACKGROUND: It is not known which risk stratification system has the best discrimination ability for predicting prostate cancer death. METHODS: We identified patients with non-metastatic primary prostate adenocarcinoma diagnosis between 2004 and 2015 using the Surveillance, Epidemiology, and End Results database. Patients were categorized in different risk groups using the three frequently used risk stratification systems of the National Comprehensive Cancer Network guideline (NCCN-g), American Urological Association guideline (AUA-g), and European Association of Urology guideline (EAU-g), respectively. Associations between risk classification and prostate cancer-specific mortality (PCSM) were determined using Kaplan-Meier analyses and multivariable regression with Cox proportional hazards model. Area under the receiver operating characteristics curve (AUC) analyses were used to test the discrimination ability of the three risk grouping systems. RESULTS: We analyzed 310,062 patients with a median follow-up of 61 months. A total of 36,368 deaths occurred, including 6,033 prostate cancer deaths. For all the three risk stratification systems, the risk groups were significantly associated with PCSM. The AUC of the model relying on NCCN-g, AUA-g, and EAU-g risk stratification systems for PCSM at specifically 8 years were 0.818, 0.793, and 0.689 in the entire population; 0.819, 0.795, and 0.691 in Whites; 0.802, 0.777, and 0.681 in Blacks; 0.862, 0.818, and 0.714 in Asians; 0.845, 0.806, and 0.728 in Chinese patients. Regardless of the age, marital status, socioeconomic status, and treatment modality, AUC of the model relying on NCCN-g and AUA-g for PCSM was greater than that relying on EAU-g; AUC of the model relying on NCCN-g system was greater than that of the AUA-g system. CONCLUSIONS: The NCCN-g and AUA-g risk stratification systems perform better in discriminating PCSM compared to the EAU-g system. The discrimination ability of the NCCN-g system was better than that of the AUA-g system. It is recommended to use NCCN-g to evaluate risk groups for prostate cancer patients and then provide more appropriate corresponding treatment recommendations.

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.

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.