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.

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.

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 (

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.

Potential of Mitochondrial Genome Editing for Human Fertility Health.

Mitochondrial DNA (mtDNA) encodes vital proteins and RNAs for the normal functioning of the mitochondria. Mutations in mtDNA leading to mitochondrial dysfunction are relevant to a large spectrum of diseases, including fertility disorders. Since mtDNA undergoes rather complex processes during gametogenesis and fertilization, clarification of the changes and functions of mtDNA and its essential impact on gamete quality and fertility during this process is of great significance. Thanks to the emergence and rapid development of gene editing technology, breakthroughs have been made in mitochondrial genome editing (MGE), offering great potential for the treatment of mtDNA-related diseases. In this review, we summarize the features of mitochondria and their unique genome, emphasizing their inheritance patterns; illustrate the role of mtDNA in gametogenesis and fertilization; and discuss potential therapies based on MGE as well as the outlook in this field.

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.

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.

Study on phonon spectra and heat capacities of CL-20/MTNP cocrystal and co-formers by density functional theory method.

The phonon spectra and heat capacities of 2, 4, 6, 8, 10, 12-hexanitrohexaazaisowurtzitane/1-methyl-3, 4, 5-trinitropyrazole (CL-20/MTNP) cocrystal and co-formers were calculated in the framework of DFT. By analyzing the phonon density of states (DOS), the energy flow directions and trigger bonds of cocrystal and co-formers have been obtained and the microscopic physical nature was revealed for thermal decomposition mechanism, detonation performance, and sensitivity. For CL-20/MTNP cocrystal, the phonon number of "doorway" modes and the characteristic vibrational frequencies Δωd are between those of its co-formers, which can provide the microscopic understanding for the ordering of impact sensitivity at experiment, ε-CL-20 > CL-20/MTNP > MTNP. In CL-20/MTNP cocrystal, more phonons and stronger phonon DOS peaks of CL-20 molecules than those of MTNP molecules mean cocrystal's detonation performance is mainly dominated by CL-20 molecules. The heat capacities obtained by the Debye model rise with elevated temperatures at 0-600 K and the order is ε-CL-20 > CL-20/MTNP > MTNP. Graphical abstract The phonon spectra and heat capacities of CL-20/MTNP cocrystal and co-formers were calculated by density functional theory (DFT). In CL-20/MTNP cocrystal, the detonation performance and impact sensitivity are mainly dominated by CL-20 molecules. The broken bonds caused by energy transfer may undergo a multi-phonon pumping process.

Factors affecting the accuracy of endoscopic ultrasound-guided fine needle aspiration for the diagnosis of small (≤20 mm) pancreatic lesions.

To explore the diagnostic value of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) for small, solid or semi-solid pancreatic lesions (≤20 mm) and the factors affecting its accuracy. METHODS: Altogether 92 patients with small, solid or semi-solid pancreatic lesions who underwent EUS-FNA at the Nanjing Drum Tower Hospital from November 2009 to January 2019 were retrospectively analyzed. Univariate and multivariate analyses were used to determine the factors affecting the accuracy of EUS-FNA for detecting these lesions. RESULTS: Among the 92 cases, 56 (60.9%) were diagnosed as having malignant lesions and 36 (39.1%) as benign lesions, respectively. The overall sensitivity, specificity and accuracy of EUS-FNA for the diagnosis of small, solid or semi-solid pancreatic lesions were 71.4%, 100% and 82.6%, respectively. When considering the impact of the presence of a tissue core on the diagnosis, the sensitivity, specificity, and accuracy of EUS-FNA with tissue core compared with those based on cytology alone were 77.3% vs 50.0%; 100% vs 100%; and 86.8% vs 62.5%, respectively. The multivariate analysis showed that larger tumor size (>15-20 mm) (odds ratio [OR] 4.200, 95% confidence interval [CI] 1.21-14.53, P = 0.023) and histologic diagnosis based on tissue core (OR 4.593, 95% CI 1.03-20.47, P = 0.046) were related to a higher accuracy of EUS-FNA. Adverse events were observed in three patients, all were treated conservatively and recovered within 3 days. CONCLUSIONS: EUS-FNA is effective and safe for diagnosing small pancreatic lesions. Tumor size and presence of tissue core are related to higher accuracy of the EUS-FNA.

Toxicity and Biochemical Outcomes of Dose-Intensified Postoperative Radiation Therapy for Prostate Cancer: Results of a Randomized Phase III Trial.

PURPOSE: Our purpose was to compare toxicity and biochemical control in postprostatectomy patients treated with conventional (66 Gy) or dose-intensified (72 Gy) radiation therapy. METHODS AND MATERIALS: Patients who had stage pT3-4, positive surgical margins, or rising prostate-specific antigen ≥ 0.2 ng/mL after radical prostatectomy were randomly assigned to receive either 66 Gy in 33 fractions or 72 Gy in 36 fractions. A primary endpoint was to assess the difference in biochemical progression-free survival (bPFS) between these 2 cohorts, and secondary endpoints were to assess differences in genitourinary (GU), gastrointestinal (GI), and hematologic toxicities between these 2 cohorts. bPFS was estimated by the Kaplan-Meier method and toxicities were compared using the χ2 test. RESULTS: Between September 2011 and November 2016, 144 patients were enrolled: 71 patients to the 66 Gy cohort and 73 patients to the 72 Gy cohort. The median follow-up time was 48.5 months (range, 14-79 months). There was no difference in 4-year bPFS between the 66 Gy and 72 Gy cohorts (75.9% vs 82.6%; P = .299). However, in patients with a higher Gleason score (8-10), the 72 Gy cohort had statistically significant improvement in bPFS compared with the 66 Gy cohort (79.7% vs 55.7%; P = .049). Toxicity analysis showed no difference in ≥2 acute or late GI or GU toxicities between these 2 cohorts. A total of 48 patients were scored as urinary incontinence before radiation therapy, of which 39 (81.3%) reported incontinence recovery or stable at 1-year follow-up, and only 9 (18.8%) patients reported worsening. There was no difference between the 2 cohorts in urinary incontinence either at baseline or at 1-year follow-up. CONCLUSIONS: Dose escalation (72 Gy) demonstrated no improvement in 4-year bPFS compared with the 66 Gy regimen. However, the dose escalation was not associated with greater acute or late GU or GI toxicities and did not increase urinary incontinence.

Intra-rectal use of epinephrine in radiotherapy of prostate cancer.

Purpose: The aim of the study was to evaluate the feasibility and toxicity of intra-rectal epinephrine during prostatic radiotherapy. Materials and methods: A total of 34 patients with prostate cancer were randomized to receive daily intra-rectal epinephrine (4 mg in 40 mL, n=16) or placebo (40 mL normal saline, n=18) 5 min before daily radiotherapy. Physical examination including systolic blood pressure (SBP) and heart rate (HR) was performed before, 5 min after, and 20 min after intra-rectal use. Toxicities were graded using the Radiation Therapy Oncology Group standard. A two-sided Fisher's exact test was used to compare proportions between groups. A mixed-effects model was used to analyze multiple measurements of SBP and HR. Survival curves were calculated using the Kaplan-Meier method and compared between groups using the log-rank test. Results: All patients completed the protocol treatment and reported no cardiovascular symptoms after intra-rectal administration. There were no differences in SBP and HR between these two groups at any time point (before, 5 min after, and 20 min after epinephrine). At 5 weeks after the start of radiotherapy, the incidence of rectal toxicity≥grade 2 was 27.8% (5/18) for the control group versus 12.5% (2/16) for the epinephrine group, but was not statistically significant (p=0.4). There was no rectal toxicity≥grade 2 in these two groups beyond 2-year follow-up. The 5-year biochemical relapse-free survival was 75.0% and 72.2% for the epinephrine and control group, respectively. Conclusion: Results of this pilot randomized trial have demonstrated that intra-rectal administration of epinephrine is feasible and safe in prostatic radiotherapy. Its radio-protective effect warrants further investigation.

Optimal contouring of seminal vesicle for definitive radiotherapy of localized prostate cancer: comparison between EORTC prostate cancer radiotherapy guideline, RTOG0815 protocol and actual anatomy.

BACKGROUND: Intermediate- to-high-risk prostate cancer can locally invade seminal vesicle (SV). It is recommended that anatomic proximal 1-cm to 2-cm SV be included in the clinical target volume (CTV) for definitive radiotherapy based on pathology studies. However, it remains unclear whether the pathology indicated SV extent is included into the CTV defined by current guidelines. The purpose of this study is to compare the volume of proximal SV included in CTV defined by EORTC prostate cancer radiotherapy guideline and RTOG0815 protocol with the actual anatomic volume. METHODS: Radiotherapy planning CT images from 114 patients with intermediate- (36.8%) or high-risk (63.2%) prostate cancer were reconstructed with 1-mm-thick sections. The starting and ending points of SV and the cross sections of SV at 1-cm and 2-cm from the starting point were determined using 3D-view. Maximum (D1H, D2H) and minimum (D1L, D2L) vertical distance from these cross sections to the starting point were measured. Then, CTV of proximal SV defined by actual anatomy, EORTC guideline and RTOG0815 protocol were contoured and compared (paired t test). RESULTS: Median length of D1H, D1L, D2H and D2L was 10.8 mm, 2.1 mm, 17.6 mm and 8.8 mm (95th percentile: 13.5mm, 5.0mm, 21.5mm and 13.5mm, respectively). For intermediate-risk patients, the proximal 1-cm SV CTV defined by EORTC guideline and RTOG0815 protocol inadequately included the anatomic proximal 1-cm SV in 62.3% (71/114) and 71.0% (81/114) cases, respectively. While for high-risk patients, the proximal 2-cm SV CTV defined by EORTC guideline inadequately included the anatomic proximal 2-cm SV in 17.5% (20/114) cases. CONCLUSIONS: SV involvement indicated by pathology studies was not completely included in the CTV defined by current guidelines. Delineation of proximal 1.4 cm and 2.2 cm SV in axial plane may be adequate to include the anatomic proximal 1-cm and 2-cm SV. However, part of SV may be over-contoured.

[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.

Theoretical studies on the thermodynamic properties, densities, detonation properties, and pyrolysis mechanisms of trinitromethyl-substituted aminotetrazole compounds.

Trinitromethyl-substituted aminotetrazoles with -NH2, -NO2, -N3, and -NHC(NO2)3 groups were investigated at the B3LYP/6-31G(d) level of density functional theory. Their sublimation enthalpies, thermodynamic properties, and heats of formation were calculated. The thermodynamic properties of these compounds increase with temperature as well as with the number of nitro groups attached to the tetrazole ring. In addition, the detonation velocities and detonation pressures of these compounds were successfully predicted using the Kamlet-Jacobs equations. It was found that these compounds exhibit good detonation properties, and that compound G (D = 9.2 km/s, P = 38.8 GPa) has the most powerful detonation properties, which are similar to those of the well-known explosive HMX (1,3,5,7-tetranitro-1,3,5,7-tetrazocine). Finally, the electronic structures and bond dissociation energies of these compounds were calculated. The BDEs of their C-NO2 bonds were found to range from 101.9 to 125.8 kJ/mol(-1). All of these results should provide useful fundamental information for the design of novel HEDMs.

Theoretical investigation of a novel high density cage compound 4,8,11,14,15-pentanitro-2,6,9,13-tetraoxa-4,8,11,14,15-pentaazaheptacyclo[5.5.1.1(3,11).1(5,9)] pentadecane.

A novel polynitro cage compound 4,8,11,14,15-pentanitro-2,6,9,13-tetraoxa-4,8,11,14,15-pentaazaheptacyclo [5.5.1.1(3,11).1(5,9)]pentadecane(PNTOPAHP) has been designed and investigated at the DFT-B3LYP/6-31(d) level. Properties, such as electronic structure, IR spectrum, heat of formation, thermodynamic properties and crystal structure have been predicted. This compound is most likely to crystallize in C2/c space group, and the corresponding cell parameters are Z = 8, a = 29.78 Å, b = 6.42 Å, c = 32.69 Å, α = 90.00°, ß = 151.05°, γ = 90.00° and ρ = 1.94 g/cm(3). In addition, the detonation velocity and pressure have also been calculated by the empirical Kamlet-Jacobs equation. As a result, the detonation velocity and pressure of this compound are 9.82 km/s, 44.67 GPa, respectively, a little higher than those of 4,10-dinitro-2,6,8,12-tetraoxa-4,10-diazaisowurtzitane(TEX, 9.28 km/s, 40.72 GPa). This compound has a comparable chemical stability to TEX, based on the N-NO(2) trigger bond length analysis. The bond dissociation energy ranges from 153.09 kJ mol(-1) to 186.04 kJ mol(-1), which indicates that this compound meets the thermal stability requirement as an exploitable HEDM.

Comparison of the major malformation rate of children conceived from cryopreserved embryos and fresh embryos.

BACKGROUND: Cryopreserved embryo transfer has become indispensable in reproductive technology. More and more children are conceived from frozen-thawed embryo transfer (FET). The risk of birth defects associated with frozen-thawed embryo transfer has been evaluated and conflict results are obtained. The aim of this study was to compare the rate of major malformations in children conceived from cryopreserved embryos with that of children from fresh embryos. METHODS: A retrospective analysis was performed on children conceived from frozen-thawed embryos and fresh embryos between January 2005 and December 2008 at the Reproduction Center of the Third Hospital, Peking University. The major malformation rates were compared between two groups for all children, as well as singletons or twins, separately. The frequencies of different subtypes of malformations classified according to different organ system were also compared. RESULTS: Thirty-four of 3125 children from cryopreserved embryos had a major malformation. The malformation rate was 1.09%, which was comparable to that for children after fresh embryos transfer (1.53% (55/3604), OR: 0.71, 95%CI; 0.46-1.09). The malformation rate was also similar when the analysis was limited to children from cryopreserved embryos resulted from in vitro fertilization (IVF) (1.39%) and fresh IVF (1.3%). However, children from cryopreserved embryos resulted from intracytoplasmic sperm injections (ICSI) had much lower malformation rate than from fresh ICSI (0.63% vs.1.83%, OR: 0.34, 95%CI: 0.16-0.75). No difference was found in the incidence of major malformations in singletons from cryo ICSI (0.73%) and fresh ICSI (1.9%), or from cryo IVF (1.49%) and fresh IVF (1.67%). Similar malformation rate was found in multiples from cryo ICSI (0.52%) and fresh ICSI (1.76%), or cryo IVF (1.30%) and fresh IVF (0.90%). The distribution and risk of the subtype of malformations, such as cardiovascular, gastrointestinal, neural tube, urogenital, musculoskeletal and facial abnormalities was not different between the cryo group and fresh group. CONCLUSIONS: The major malformation rate is similar between fetuses/children conceived from cryopreserved embryos and those from fresh embryos. Large prospective and long-term follow-up studies are needed to get exact results concerning the birth defects of the children born after cryopreserved embryos.