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To evaluate the impact of prophylactic paraortic lymph node (PALN) radiation therapy (RT) on clinical outcomes in patients with International Federation of Obstetrics and Gynecology 2018 stage IIIC1 endometrial cancer (EC).A multi-institutional retrospective study included patients with International Federation of Obstetrics and Gynecology 2018 stage IIIC1 EC lymph node assessment, status postsurgical staging, followed by adjuvant chemotherapy and RT using various sequencing regimens. Overall survival (OS) and recurrence-free survival (RFS) rates were estimated by the Kaplan-Meier method. Univariable and multivariable analysis were performed by Cox proportional hazard models for RFS/OS. In addition, propensity score matching was used to estimate the effect of the radiation field extent on survival outcomes.A total of 378 patients were included, with a median follow-up of 45.8 months. Pelvic RT was delivered to 286 patients, and 92 patients received pelvic and PALN RT. The estimated OS and RFS rates at 5 years for the entire cohort were 80% and 69%, respectively. There was no difference in the 5-year OS (77% vs 87%, P = .47) and RFS rates (67% vs 70%, P = .78) between patients treated with pelvic RT and those treated with pelvic and prophylactic PALN RT, respectively. After propensity score matching, the estimated hazard ratios (HRs) of prophylactic PALN RT versus pelvic RT were 1.50 (95% confidence interval, 0.71-3.19; P = .28) for OS and 1.24 (95% confidence interval, 0.64-2.42; P = .51) for RFS, suggesting that prophylactic PALN RT does not improve survival outcomes. Distant recurrence was the most common site of first recurrence, and the extent of RT field was not associated with the site of first recurrence (P = .79).Prophylactic PALN RT was not significantly associated with improved survival outcomes in stage IIIC1 EC. Distant metastasis remains the most common site of failure despite routine use of systemic chemotherapy. New therapeutic approaches are necessary to optimize the outcomes for women with stage IIIC1 EC.

Emphasis on value-based healthcare has led to increasing use of time-driven activity-based costing (TDABC) across medical departments. When applied to brachytherapy, TDABC provides insight into differences in costs across various modes of therapy, the nuances that drive cost including institutional factors and involved personnel, and discrepancies in reimbursement which influence clinical practice. This is especially important with the new alternative payment model (APM) in radiation oncology which offers fixed reimbursement per 90-day episode of care. The TDABC model can thus be utilized to improve efficiency, optimize the role of ancillary staff in treatment planning and care delivery, and implement shorter fraction schedules when clinically appropriate to promote value-based care. Ultimately, application of this methodology could potentiate changes to practice and incentives to improve patient care. In this review, we discuss the utility and limitations of TDABC in the context of existing studies in brachytherapy which have utilized this methodology.

Background Conflicting data exists regarding the benefit of prophylactic cranial irradiation (PCI) in patients with extensive-stage small-cell lung cancer (ES-SCLC). We sought to retrospectively review outcomes of patients within our network with ES-SCLC treated with and without PCI between 2009 and 2020. Methods Endpoints assessed using the Kaplan-Meier estimator were overall survival (OS), freedom from death with uncontrolled intracranial disease (UI-DFS), brain metastasis-free survival (BMFS), and symptomatic BMFS (SBMFS). Log-rank test was performed for univariate comparison of outcomes, with Cox regression performed for univariate and multivariable analysis of OS and UI-DFS. Results Some 250 patients were determined to be eligible for PCI based on any response to upfront chemotherapy, with 46 patients excluded owing to lack of negative staging brain magnetic resonance imaging (MRI). Brain MRI was performed both at diagnosis and near completion of chemotherapy in 108 patients, with brain metastases identified near completion of chemotherapy in 17 patients (15.7%), excluding them from further analysis. Median OS in remaining eligible 187 patients was 9.0 months, with 2-year Kaplan-Meier estimate of OS of 21.9%. PCI was associated with improved UI-DFS, BMFS, and SBMFS. However, PCI was not associated with improved OS in the entire cohort or the propensity matched cohort. Conclusion Our study suggests screening with MRI following chemotherapy is important because of the identification of unsuspected brain metastases in nearly 16% of patients with response to chemotherapy. PCI is associated with reduction in brain metastases, without a demonstrable impact on OS in the era of MRI screening.

Our purpose was to evaluate the effect of sequence and type of adjuvant therapy for patients with stage IIIC endometrial carcinoma (EC) on outcomes.In a multi-institutional retrospective cohort study, patients with stage IIIC EC who had surgical staging and received both adjuvant chemotherapy and radiation therapy (RT) were included. Adjuvant treatment regimens were classified as adjuvant chemotherapy followed by sequential RT (upfront chemo), which was predominant sequence; RT with concurrent chemotherapy followed by chemotherapy (concurrent); systemic chemotherapy before and after RT (sandwich); adjuvant RT followed by chemotherapy (upfront RT); or chemotherapy concurrent with vaginal cuff brachytherapy alone (chemo-brachy). Overall survival (OS) and recurrence-free survival (RFS) rates were estimated by the Kaplan-Meier method.A total of 686 eligible patients were included with a median follow-up of 45.3 months. The estimated 5-year OS and RFS rates were 74% and 66%, respectively. The sequence and type of adjuvant therapy were not correlated with OS or RFS (adjusted P = .68 and .84, respectively). On multivariate analysis, black race, nonendometrioid histology, grade 3 tumor, stage IIIC2, and presence of adnexal and cervical involvement were associated with worse OS and RFS (all P.05). Regardless of the sequence of treatment, the most common site of first recurrence was distant metastasis (20.1%). Vaginal only, pelvic only, and paraortic lymph node (PALN) recurrences occurred in 11 (1.6%),15 (2.2 %), and 43 (6.3 %) patients, respectively. Brachytherapy alone was associated with a higher rate of PALN recurrence (15%) compared with external beam radiation therapy (5%) P.0001.The sequence and type of combined adjuvant therapy did not affect OS or RFS rates. Brachytherapy alone was associated with a higher rate of PALN recurrence, emphasizing the role of nodal radiation for stage IIIC EC. The vast proportion of recurrences were distant despite systemic chemotherapy, highlighting the need for novel regimens.

Highlights • We present the journey of an FA patient who developed metachronous bilateral breast cancers and was successfully treated with breast conserving therapy with no significant treatment related toxicity., Fanconi Anemia (FA) is a rare inherited autosomal recessive disease that results in impaired double stranded DNA repair. This leads to both increased susceptibility to various cancers, as well as hypersensitivity to radiotherapy and systemic therapy; thus, increasing the complexity of oncological treatment paradigm. Here, we present an FA patient who initially developed invasive breast cancer for which she received breast conserving treatment with no significant treatment related toxicity. This was followed by a diagnosis of high-grade ductal carcinoma-in-situ in the contralateral breast, which was managed successfully by surgery and meticulously planned adjuvant radiotherapy, with no treatment interruptions.

OBJECTIVES The brain is a rare site for sarcoma metastases. Sarcoma's radioresistance also makes standard whole-brain radiotherapy less appealing. We hypothesize that stereotactic radiation techniques (stereotactic radiosurgery [SRS]/stereotactic fractionated radiotherapy [FSRT]) may provide effective local control. MATERIALS AND METHODS This single-institution retrospective analysis evaluated our experience with linear acceleator-based SRS/FSRT for sarcoma brain metastases. Time to event analysis was estimated via Kaplan-Meier. Univariable/multivariable Cox regression analyses followed to assess the impact of patient and disease characteristics on outcomes. RESULTS Between 2003 and 2018, 24 patients were treated with 34 courses of SRS/FSRT to 58 discrete lesions. The median age at first treatment was 57 years (range: 25 to 87 y). Majority of patients had concurrent lung metastases (n=21; 88%), diagnosed spindle cell sarcoma (n=15; 25%) or leiomyosarcoma (n=12; 21%) histology, and were treated with either SRS (n=43; median dose=19 Gy, range: 15 to 24 Gy) or FSRT (n=17; 3/5 fractions, median dose=25 Gy, range: 25 to 35 Gy). With a median follow-up after brain metastasis of 7.3 months, the 6 month/12 month local control, distant brain control, and overall survival of 89%/89%, 59%/34%, and 50%/38%, respectively. All local failures were of primary spindle cell histology (P

Purpose Halcyon linear accelerators employ intensity‐modulated radiation therapy (IMRT) and stereotactic body radiation therapy (SBRT) techniques. The Halcyon offers translational, but not rotational, couch correction, which only allows a 3 degrees of freedom (3‐DOF) correction. In contrast, the TrueBeam (TB) linear accelerator offers full 6‐DOF corrections. This study aims to evaluate the difference in treatment plan quality for single thoracic or lumbar vertebral segment SBRT between the Halcyon and TB linear accelerators. In addition, this study will also investigate the effect of patient rotational setup errors on the final plan quality. Methods We analyzed 20 patients with a single‐level spine metastasis located between the T7 and L5 vertebrae near the spinal canal. The median planning target volume was 52.0 cm3 (17.9–138.7 cm3). The median tumor diameter in the axial plane was 4.6 cm (range 1.7–6.8 cm), in the sagittal plane was 3.3 cm (range 2–5 cm). The prescription doses were either 12–16 Gy in 1 fraction or 18–24 Gy in 3 fractions. All patients were treated on the TB linear accelerator with a 2.5 mm Multi‐Leaf Collimator (MLC) leaf width. Treatment plans were retrospectively created for the Halcyon, which has a 5 mm effective MLC leaf width. The 20 patients had a total of 50 treatments. Analysis of the 50 cone beam computed tomography (CBCT) scans showed average rotational setup errors of 0.6°, 1.2°, and 0.8° in pitch, yaw, and roll, respectively. Rotational error in roll was not considered in this study, as the original TB plans used a coplanar volumetric modulated arc therapy (VMAT) technique, and each 1° of roll will contribute an error of 1/360. If a plan has 3 arcs, the contribution from errors in roll will be 1° in the absence of 6‐DOF correction capabilities.

PURPOSE/OBJECTIVE(S) The optimal use of stereotactic body radiotherapy (SBRT) for the diverse group of patients with gynecologic malignancies has not been clearly defined. This multi-institutional pooled analysis aims to characterize the use of SBRT for different primary disease types and indications within the gynecologic cancer population. MATERIALS/METHODS Patients treated with SBRT at three institutions with oligometastatic (OM) disease (5 or fewer sites), oligoprogressive (OP) disease (limited areas of progression with controlled systemic disease), or progression in an eloquent area were included. Descriptive statistics were used to report patient and treatment characteristics and toxicity. Local recurrence-free survival (LRFS), distant progression-free survival (DPFS), salvage chemotherapy-free survival (CFS, excluding patients on systemic therapy at time of SBRT) and overall survival (OS) probabilities following SBRT were calculated using Kaplan-Meier methods. Associations with disease and tumor factors were examined using Cox regression methods. RESULTS One hundred forty-four patients (144) with gynecologic cancers were treated with SBRT to 206 lesions. The median age was 61 (range 46-86) and median follow up was 16.6 months (range 0.5-106.8). Patients had cancers of the uterus (n = 101), ovary (n = 67), cervix (n = 27), and vulva or vagina (n = 8). Lesions were considered OM (n = 124), OP (n = 68), or progressive in an eloquent area (n = 14). Treatment was delivered to lesions in the pelvis (n = 50), lung (n = 40), para-aortic region (n = 37), abdomen or liver (n = 36), bone (n = 31), and distant nodes (n = 10). SBRT dose ranged from 20-60Gy (median 40Gy) in 2-5 fractions. Twenty-three (11.1%) lesions recurred locally after SBRT. Median LRFS was 23.9 months (95% CI 20.2-27.5), DPFS was 10.7 months (95% CI 10.7-16.9), and OS 22.9 months (95% CI 12.8-31.3). LRFS was 73.0% and 47.8%, DPFS was 44.2% and 19.6%, and OS was at 72.9% and 46.6% 1 and 2 years respectively. Twenty-nine percent of patients received salvage systemic therapy, and median CFS was 14.1 months (95% CI 10.4-17.8). On multi-variable analysis, only higher BED (OR 0.98, P = 0.013) was associated with LRFS. Primary disease type, tumor size, dose of radiotherapy, nodal versus non-nodal target, and DFI were not significantly associated with OS or DPFS on MVA. CONCLUSION This large cohort of patients receiving SBRT for oligometastatic and oligoprogressive gynecologic cancers had excellent tumor control, and promising DPFS and OS. Local control appears to be related to SBRT dose. SBRT may have the potential to delay time to initiation of chemotherapy or targeted therapies in select gynecologic cancer populations. Further prospective studies are required to determine which primary disease types benefit most from SBRT, and to establish the optimal sequencing of SBRT with other oncologic treatments.

To retrospectively analyse the impact of prophylactic cranial irradiation (PCI) on survival and intracranial progression in patients with limited stage small cell lung cancer (LS-SCLC) in the modern era of widespread magnetic resonance imaging brain screening.Patients with LS-SCLC treated within our network between 2009 and 2020 who responded to initial therapy were stratified by receipt of PCI and stage of disease. A propensity score match analysis was carried out for stage II-III patients. Overall and neurological survival were defined as time to death and presumed death due to uncontrolled intracranial disease, respectively. Brain metastasis-free survival and symptomatic brain metastasis-free survival were defined as freedom from intracranial progression and symptomatic intracranial progression, respectively. The effect of PCI on these outcomes was assessed using Kaplan-Meier and Cox proportional hazards models.In total, 243 (69.6%) of 349 patients received PCI. On multivariate analysis in the propensity matched stage II-III cohort, PCI was a significant predictor of improved neurological survival (hazard ratio 0.23, 95% confidence interval 0.08-0.65; P = 0.01), brain metastasis-free survival (hazard ratio 0.25, 95% confidence interval 0.12-0.51; P0.01) and symptomatic brain metastasis-free survival (hazard ratio 0.21, 95% confidence interval 0.08-0.55; P0.01), but not improved overall survival. Two-year neurological survival estimates within the propensity matched cohort were 96.8% (95% confidence interval 87.6-99.2%) with PCI and 77.2% (95% confidence interval 63.0-86.4%) without PCI and 1- and 2-year estimates of incidence of brain metastases were 3.9% (95% confidence interval 1.3-11.7%) and 11.7% (95% confidence interval 5.6-23.5%) in the PCI group and 31.6% (95% confidence interval 22.1-43.9%) and 40.4% (95% confidence interval 29.2-54.0%) in the no PCI group, respectively.In the modern era of magnetic resonance imaging screening, PCI was associated with reduced incidence of intracranial progression in patients with stage II-III LS-SCLC who respond to initial therapy. This, importantly, translated to a decreased risk of neurological death within our propensity matched cohort, without significant improvement in overall survival.

Background: During the development of heart failure cardiac fuel metabolism switches from predominantly fatty acid oxidation (FAO) to increased reliance on glucose, especially glycolysis. Mechanisms responsible for the switch are poorly understood but appear to be coupled with impaired mitochondrial function. We recently demonstrated that increased glucose metabolism is required for cardiomyocytes growth during pathological remodeling. Hypothesis: Upregulation of mitochondrial ATPase inhibitory factor 1 (ATPIF1) in hypertrophied hearts suppresses ATP synthesis and shifts cardiac metabolism from fatty acid oxidation towards glucose metabolism. Methods and Results: We report that ATPIF1 expression is upregulated in cardiomyocytes and mouse hearts undergoing pathological hypertrophy. Using genetic models of ATPIF1 gain- and loss-of-function in cardiomyocytes and in mouse hearts,we find that upregulation of ATPIF1 in cardiac hypertrophy inhibits ATP synthesis. Furthermore, quantitative analysis of chemical crosslinking by mass spectrometry revealed that increased expression of ATPIF1 promoted the formation of F o F 1 -ATP synthase nonproductive tetramer. Impairment of F o F 1 -ATP synthase function in respiring mitochondria increasedROS generation resulting in transcriptional activation of glycolysis. Cardiac-specific deletion of ATPIF1 in mice prevented the switch to glycolysis in pressure overload induced cardiac hypertrophy. Conclusions: We show that upregulation of ATPIF1 drives glucose metabolism at the expense of energy supply during the pathological growth of cardiomyocytes. Our study proposes a central role of ATP synthase in toggling anabolic and catabolic metabolism during pathological remodeling, illustrating a new concept for metabolic reprogramming of the heart.

PURPOSE We compared multiple response assessment and visualization techniques for characterization of post-SRS treatment outcomes in a cohort of breast cancer patients with long median follow-up. METHODS A retrospective IRB-approved review was completed of 75 breast cancer patients treated with SRS for 271 brain metastases with median follow up of 40 months. Tumor dimensions, brain failure events, corticosteroid use, and clinical status were analyzed utilizing RANO-BM, bidimensional product (BDP), and bidimensional sum (BDS) techniques. 46/75 patients were eligible for RANO-BM assessment. Response at each post-treatment assessment were scored as PD, SD, PR, or CR, and the concordance between techniques was determined. A scoring system-based outcome metric labelled ‘average state’ was derived to estimate fractional time/response state by each assessment method. Interactive timeline displays of outcome states were generated. RESULTS The concordance of patient response states was determined using either RANO-BM, BDP or BDS among the 46 eligible patients. The overall mean and median concordance between techniques were 0.82 and 0.83, (range 0.52 – 1). The average state for the patient population post-treatment was 1.98 by RANO-BM, 2.29 by BDP, and 2.19 by BDS. For patients excluded from RANO-BM secondary to lack of measurable disease, the average state was determined to be 2.44 by BDP and 2.35 by BDS. The average state for HER2+ vs. HER2- patients was 2.21 vs. 1.75 by RANO-BM, 2.58 vs. 2 by BDP, and 2.39 vs. 1.99 by BDS. An interactive timeline view was generated to display outcome states utilizing the 3 response assessment techniques, and the impact of inclusion of non-target lesions and variable response parameters was assessed graphically. CONCLUSIONS These results characterize the concordance and the limitations of multiple outcome assessment methodologies in a post-SRS cohort with long median follow-up. The utility of a novel ‘average state’ outcome metric is demonstrated in this cohort.

Purpose The aim of this study was to assess the impact of air gaps at the cylinder surface on the rate of vaginal cuff failure (VCF) after image-guided adjuvant vaginal cuff brachytherapy (VCBT) in the treatment of high-intermediate risk (HIR) FIGO (Federation Internationale de Gynecologie et d'Obstetrique (International Federation of Gynecology and Obstetrics)) Stage I endometrial cancer. Methods and Materials A retrospective review of patients treated with image-guided VCBT from 2009 to 2016 for HIR FIGO Stage I endometrial cancer was performed. Air gaps present at the applicator surface on the first postinsertion CT were contoured. Vaginal cuff failure–free survival (VCFFS) was measured from the first fraction of VCBT to VCF. Results A total of 234 patients were identified. Air gaps were present on the first postinsertion CT scan in 82% of patients. The median number of air gaps was 2 (interquartile range [IQR] 1–3), median depth of the largest air gap was 2.7 mm (IQR 2.1–3.4 mm), and the median cumulative volume of air gaps was less than 0.1 cm3 (range Conclusions In this population, VCFFS remained high despite most patients having air gaps present on postinsertion CT scan.

Background and purpose Ureteral stenosis (US) is a known complication from image-guided brachytherapy (IGBT); however, no dosimetric parameter has been associated with ureteral toxicity. We aimed to report the rate of late grade ≥3 US after MRI-based IGBT, and to identify clinical factors and dosimetric parameters predictive for US. Materials and methods A retrospective review was performed on all cervical cancer patients treated with MRI-based IGBT between 2007 and 2017. Late grade ≥3 US was recorded according to CTCAE 4.03. The minimum dose to the maximally irradiated 0.1 cm3 of ureter (D0.1cm3) was extracted from dose-volume histograms. Binary logistic regression was performed to identify predictors of late grade ≥3 US. Results 242 patients with a median follow-up of 35.8 months (IQR, 19.2–60.8) were identified. Late grade ≥3 US occurred in 18 patients, and the actuarial 3-year rate was 7.3% (95% CI 3.3–11.3). After excluding patients with pre-existing hydronephrosis, late grade ≥3 US occurred in 11 patients with an actuarial 3-year rate of 4.4% (95% CI 1.7–7.1). Ureters with D0.1cm3 ≥77 Gy had a 28.6% incidence of late grade ≥3 US compared to 7.5% in those with D0.1cm3 Conclusion After MRI-based IGBT, there is an estimated 4.4% risk of developing late grade ≥3 US among patients without pre-existing hydronephrosis. Ureteral dose ≥77 Gy to D0.1cm3 correlates with development of late grade ≥3 US.

PURPOSE The Vienna and Venezia (Elekta) are hybrid intracavitary/interstitial brachytherapy (BT) applicators for cervical cancers unsuitable for intracavitary BT alone to improve target coverage or reduce critical organ dose. There is limited outcome data with the use of these applicators outside published experience of the EMBRACE group. We report feasibility and early outcomes with the use of these hybrid applicators at our institution. METHODS AND MATERIALS Hybrid applicators were used to treat 61 patients with cervical cancer from November 2011 to December 2019. Indications for hybrid applicator use were involvement of the vagina in 10 patients (16%), residual central or parametrial disease in 46 patients (75%), and a narrow introitus in 5 patients (9%). Toxicities were graded using the CTCAE v4.0. Outcomes were assessed with the Kaplan–Meier method. Results Median follow-up was 16 months (IQR 9–32 mos). Median HRCTV volume was 31.6 cm3 (IQR 25–48 cm3). Median HRCTV D90 was 86.1 Gy (IQR 84.3–88.0 Gy). In 54 patients with follow-up PET/CT at 3 months, complete initial imaging response locally was seen in 46 patients.Estimated 12-month Kaplan–Meier overall survival, locoregional control, distant control, and recurrence-free survival estimates were 86.9%, 80.6%, 73.8%, and 65.9%, respectively. The 12-month incidence of Grade 3+ GI/GU chronic toxicities was 5.7%, consisting of vesicovaginal fistula, rectovaginal fistula, and ureterovesical fistula. Conclusions Our single-institution data support the use of the hybrid applicators, as an alternative to traditional BT applicators when clinically warranted. Use of hybrid applicators is feasible with adequate coverage of disease in the vagina and parametrium.

After deep venous thrombosis (DVT), many patients have impaired quality of life (QOL). We aimed to assess whether pharmacomechanical catheter-directed thrombolysis (PCDT) improves short-term or long-term QOL in patients with proximal DVT and whether QOL is related to extent of DVT.The Acute Venous Thrombosis: Thrombus Removal with Adjunctive Catheter-Directed Thrombolysis (ATTRACT) trial was an assessor-blinded randomized trial that compared PCDT with no PCDT in patients with DVT of the femoral, common femoral, or iliac veins. QOL was assessed at baseline and 1 month, 6 months, 12 months, 18 months, and 24 months using the Venous Insufficiency Epidemiological and Economic Study on Quality of Life/Symptoms (VEINES-QOL/Sym) disease-specific QOL measure and the 36-Item Short Form Health Survey (SF-36) physical component summary (PCS) and mental component summary general QOL measures. Change in QOL scores from baseline to assessment time were compared in the PCDT and no PCDT treatment groups overall and in the iliofemoral DVT and femoral-popliteal DVT subgroups.Of 692 ATTRACT patients, 691 were analyzed (mean age, 53 years; 62% male; 57% iliofemoral DVT). VEINES-QOL change scores were greater (ie, better) in PCDT vs no PCDT from baseline to 1 month (difference, 5.7; P = .0006) and from baseline to 6 months (5.1; P = .0029) but not for other intervals. SF-36 PCS change scores were greater in PCDT vs no PCDT from baseline to 1 month (difference, 2.4; P = .01) but not for other intervals. Among iliofemoral DVT patients, VEINES-QOL change scores from baseline to all assessments were greater in the PCDT vs no PCDT group; this was statistically significant in the intention-to-treat analysis at 1 month (difference, 10.0; P .0001) and 6 months (8.8; P .0001) and in the per-protocol analysis at 18 months (difference, 5.8; P = .0086) and 24 months (difference, 6.6; P = .0067). SF-36 PCS change scores were greater in PCDT vs no PCDT from baseline to 1 month (difference, 3.2; P = .0010) but not for other intervals. In contrast, in femoral-popliteal DVT patients, change scores from baseline to all assessments were similar in the PCDT and no PCDT groups.Among patients with proximal DVT, PCDT leads to greater improvement in disease-specific QOL than no PCDT at 1 month and 6 months but not later. In patients with iliofemoral DVT, PCDT led to greater improvement in disease-specific QOL during 24 months.

PURPOSE/OBJECTIVE(S) Previous studies have suggested that the dose immediately outside the PTV may impact the incidence of distant metastases after stereotactic body radiation therapy (SBRT) for patients with early-stage non-small cell lung cancer. In particular, Diamant et al have reported a correlation between the mean EQD2 of a 30mm shell around the PTV and both local control and the rate of distant metastases in lung SBRT patients. In this study, we review this parameter and others in a series of patients with radiographically presumed or biopsy proven early-stage non-small cell lung cancer treated at our institution with SBRT between 2014 and 2019. MATERIALS/METHODS We reviewed the dosimetry, local control and rate of distant metastases for a series of 155 patients with 165 lesions treated with SBRT at our institution. Dosimetric parameters obtained included the prescribed dose, minimum and mean doses to the PTV, conformity index, and the mean EQD2 to a 30mm shell around the PTV, as reported by Diamant et al. Time to local progression and distant metastasis were defined from date of last fraction of SBRT to date of event, with event-free patients censored at last radiographic follow-up. All plans were calculated in the Varian Eclipse treatment planning system using the AAA algorithm and treated on conventional Linac with either IMRT or VMAT delivery. Analysis of the data was performed using IBM SPSS for Windows (version 27), with analysis of time to event via Kaplan-Meier method. Univariate analysis of outcomes based on the above dosimetric parameters was performed utilizing the log-rank test. A P-value < 0.05 was considered to be statistically significant. RESULTS No significant correlation was seen between the mean EQD2 dose to a 30mm shell around the PTV and either the local control or the rate of distant metastases in these patients. Positive predictors of reduced incidence of distant metastases were the prescribed dose of 54 Gy (vs 45-50 Gy, P < 0.01) and PTV < 22 cc (vs. ≥ 22 cc, P = 0.01). In the 45-50 Gy cohort, PTV mean dose ≥ 53 Gy (vs. < 53 Gy, P = 0.04) was associated with reduced incidence of distant metastases. Improved local control was also noted with prescribed dose of 54 Gy (vs 48-50 Gy, P = 0.01). In the 45-50 Gy cohort, PTV mean dose ≥ 53 Gy (vs. < 53 Gy, P = 0.03) was associated improved local control. No additional factors examined were significantly correlated with local control. CONCLUSION We failed to replicate the correlation of the rate of distant metastases with dose outside the PTV as reported by Diamant et al. Higher prescribed and mean dose to the PTV was correlated with both local control and reduced incidence of distant metastases. References.

PURPOSE/OBJECTIVE(S) Ureteral stenosis (US) is an underreported complication of brachytherapy for cervical cancer, with limited data regarding dose constraints to reduce risk of toxicity. Previous work from our institution demonstrated that an EQD2 ≥ 77 Gy to 0.1 cm3 of ureter correlated with development of US. We sought to determine whether we can reduce ureter dose EQD2 ≤77 Gy while maintaining similar HR-CTV coverage. We also sought to determine if anatomical factors would limit achieving ureter dose constraints. MATERIALS/METHODS We identified patients with locally advanced cervical cancer treated with external beam radiation therapy plus HDR MRI-guided brachytherapy boost without hydronephrosis at diagnosis who had single or bilateral ureter dose EQD2 ≥ 77 Gy to 0.1 cm3, regardless of subsequent US. Replan was attempted for each individual brachytherapy fraction, aiming to achieve HR-CTV D90 ≥ 80-85 Gy without significant reduction in coverage, while maintaining rectal D2cc ≤65 Gy, bowel D2cc ≤65-70 Gy, sigmoid D2cc ≤70 Gy, and bladder D2cc ≤80 Gy. Distance of each ureter from lateral margin of HR-CTV and tandem were recorded, with mean values calculated on a per patient basis. Dependent samples T-test was performed to compare highest ureteral dose from original plan to replan ureteral dose and original plan HR-CTV D90 to replan HR-CTV D90. Independent samples T-test was performed to compare the mean distance of closest ureter to HR-CTV and tandem in patients for whom ureteral dose reduction was feasible to those for whom reduction was not feasible. RESULTS 25 patients met inclusion criteria, with all patients receiving 45 Gy in 25 fractions to the pelvis plus/minus paraaortic lymph nodes and 20 of 25 patients receiving mean parametrial dose of 5.4 Gy. Replan meeting ureteral dose of ≤77 Gy was feasible in 18 of 25 patients, with significant reduction in highest mean ureteral dose from 85.3 Gy to 76.7 Gy (P < 0.001). Mean original plan HR-CTV dose of 85.06 Gy decreased by 0.94 Gy to replan dose of 84.12 Gy in successfully replanned patients. Mean distance of closest ureter to HR-CTV margin was 1.5mm in patients for whom achieving ureter dose constraints was not feasible compared to 8.2mm for patients for whom replan was feasible (P = 0.038). Mean distance of closest ureter to tandem was 14.5mm for patients whom achieving ureter dose constraints was not feasible compared to 24.7mm for patients for whom replan was feasible (P < 0.001). Replan achieved ureter dose ≤77 Gy in the majority of patients who experienced US (56%), and 100% of unilateral US cases occurred in the ureter closest to HR-CTV. CONCLUSION When ureters are contoured, optimization to reduce ureter dose to ≤77 Gy is feasible, potentially allowing for reduction in US risk without significant compromise in HR-CTV D90. Anatomic variation of ureter position may impact this optimization. Ureters may be considered as potential organs at risk during MRI-based brachytherapy treatment if visualization is feasible to reduce risk of US. AUTHOR DISCLOSURE S.A. Koerner: Stock; Novavax, Pfizer, Inovio Pharmaceuticals, Ocugen, Teladoc, ADC Therapeutics, CVS, Viatris Inc. T. Baig: None. H. Kim: None. J.L. Rodriguez-Lopez: None. A. Keller: None. S. Beriwal: None.

Purpose/Objective(s) Wait-and-watch (W&W) approach for select rectal cancer patients is gaining popularity due to the detrimental effects of surgery on patient's quality-of-life. Here, we present the oncological outcomes of patients managed by W&W approach in a large cancer center network. Materials/Methods Patients with rectal cancer who underwent neoadjuvant therapy (NAT), and had clinical complete or near complete response (cCR) were managed by W&W approach. Disease evaluation was by clinical examination, imaging, and endoscopy. Baseline characteristics including age, gender, tumor location, use of MRI for staging, maximum tumor size and stage, along with time to start and duration of NAT were examined. Kaplan-Meier estimates were used to assess local regrowth (LR), disease-free survival (DFS), and overall survival (OS). Univariate and multivariate Cox models were used to identify factors associated with LR and DFS. Results Between 2010 and 2020, 1400 patients were referred for NAT. Of these, 96 patients (6.85%) were managed by W&W approach. There was a progressive increase in the adoption of W&W. Among the current W&W cohort (N = 96), only 1 patient (1.5%) was diagnosed in 2010, whereas 21.8% and 26% of the cohort were diagnosed recently in 2018 and 2019, respectively. Median follow-up was 23 months (IQR 11,36). Median age was 65 years (IQR 57,73). 21% of the cohort were 75 years or older. Majority of the patients had MRI for staging (76%) and were noted to have low rectal tumors (65.6%). Most of the patients had T3 tumors (62.5%) and were node negative (57.4%). Long course chemoradiation (CRT) followed by 4 months of chemotherapy (41.6%) was the commonest NAT approach, while the other approaches included chemotherapy followed by CRT (25%) or CRT alone (25%). At the start of this program, few patients (16.6%) underwent trans anal excision to confirm pathological complete response. Isolated local regrowth (LR) was noted in eight patients (8.3%), and distant relapse (DR) in 3 patients (4.34%). Salvage surgery was performed in 7 LR patients, while one patient refused surgical intervention. At 1-year, LR rate was 4.7%, DFS was 92.9%, and OS was 98.7%. Similarly, at 3-years, LR rate was 11.5%, DFS was 81.7%, and OS was 92.1%. Importantly, response on MRI did not correlate with either endoscopic assessment of disease status (P > 0.99) or local regrowth (P > 0.99). Finally, tumor size within the highest tertile (> 50mm) was associated with worse LR (81.3% vs. 92.3%, P = 0.04) and DFS (73.9% vs. 85.7%, P = 0.025). In a multivariable Cox model, tumor size within the highest tertile was associated with both LR (HR 8.4, 95% CI 1.5-45.8, P = 0.01) and poor DFS (HR 5.6, 95% CI 1.4-22.0, P = 0.01) independent of age, tumor location, MRI usage, and time to start and duration of NAT. Conclusion Our data supports the use of W&W approach following NAT for select rectal patients with a clinical (near) complete response given the excellent short-term outcomes. The impact of tumor size on local regrowth and DFS should be confirmed in a prospective study.

In 2008, the Radiation Therapy Oncology Group (RTOG) published an international collaborative atlas to define the clinical target volume (CTV) for pelvic radiation therapy in the postoperative treatment of endometrial and cervical cancer. This article updates the atlas using the last decade of knowledge on target definitions, expands the atlas to include the para-aortic region and inferior obturator region and removes all references to bony landmarks. PURPOSE: Accurate target definition is critical for the appropriate application of radiation therapy. In 2008, the Radiation Therapy Oncology Group (RTOG) published an international collaborative atlas to define the clinical target volume (CTV) for intensity modulated pelvic radiation therapy in the postoperative treatment of endometrial and cervical cancer. The current project is an updated consensus of CTV definitions, with removal of all references to bony landmarks and inclusion of the para-aortic and inferior obturator nodal regions. METHODS AND MATERIALS: An international consensus guideline working group discussed modifications of the current atlas and areas of controversy. A document was prepared to assist in contouring definitions. A sample case abdominopelvic computed tomographic image was made available, on which experts contoured targets. Targets were analyzed for consistency of delineation using an expectation-maximization algorithm for simultaneous truth and performance level estimation with kappa statistics as a measure of agreement between observers. RESULTS: Sixteen participants provided 13 sets of contours. Participants were asked to provide separate contours of the following areas: vaginal cuff, obturator, internal iliac, external iliac, presacral, common iliac, and para-aortic regions. There was substantial agreement for the common iliac region (sensitivity 0.71, specificity 0.981, kappa 0.64), moderate agreement in the external iliac, para-aortic, internal iliac and vaginal cuff regions (sensitivity 0.66, 0.74, 0.62, 0.59; specificity 0.989, 0.966, 0.986, 0.976; kappa 0.60, 0.58, 0.52, 0.47, respectively), and fair agreement in the presacral and obturator regions (sensitivity 0.55, 0.35; specificity 0.986, 0.988; kappa 0.36, 0.21, respectively). A 95% agreement contour was smoothed and a final contour atlas was produced according to consensus. CONCLUSIONS: Agreement among the participants was most consistent in the common iliac region and least in the presacral and obturator nodal regions. The consensus volumes formed the basis of the updated NRG/RTOG Oncology postoperative atlas. Continued patterns of recurrence research are encouraged to refine these volumes.

Introduction To evaluate the implementation and dosimetric outcomes of magnetic resonance imaging (MRI) planning for improved target and normal tissue definition for the treatment of prostate cancer with high-dose-rate brachytherapy (HDRBT). Methods From August 2015 to October 2017, 137 unique patients with newly diagnosed localized prostate cancer underwent a total of 174 outpatient brachytherapy procedures using MRI-based treatment planning. Patients receiving brachytherapy as monotherapy underwent two separate procedures while those receiving brachytherapy as a boost after external beam radiation therapy underwent a single procedure. The target volume was defined as the prostate +/- seminal vesicles as clinically appropriate without any additional margin. Pre-treatment dose-volume histogram (DVH) goals to the target were: D90≥95%, V90≥95%, V100≥90%, V150≤30%, V200≤15%. DVH goals to organs-at-risk (OARs): urethra D.01cc ≤115%, bladder D1cc ≤75%, rectum D1cc ≤75%, neurovascular bundle D0.1cc ≤100%, penile bulb D1cc ≤100%. Procedure times were recorded at each step of the procedure, from catheter insertion to removal. Results The median target volume was 45.9 cc, the median volume receiving the prescription dose was 53.0 cc, and the median selectivity index was 0.9. The median values for target dosimetry were as follows: D90=99.9%, V90=95.7%, V100=90.1%, V150=28.1%, V200=10.5%. The median values for OAR dosimetry were: urethra D.01cc=114.3%, bladder D1cc=68.3%, rectum D1cc=51.8%, left neurovascular bundle D0.1cc=86.8%, right neurovascular bundle D0.1cc=88.5%, penile bulb D1cc=31.7%. The median time from catheter insertion to end of HDRBT delivery was four hours 14 minutes (range 2:56-9:08); total treatment package time was five hours 32 minutes (range 3:31-9:45). Conclusion Routine MRI-based treatment planning is feasible for the delivery of HDRBT for prostate cancer. We met stringent dosimetric criteria despite more objective target and normal tissue definition with MRI imaging. Treatment package time remains reasonable. We have adopted MRI as our standard imaging modality for HDRBT for prostate cancer.

Background and Objectives: The Göteborg randomised population-based prostate cancer screening trial demonstrated that Prostate Specific Antigen (PSA) based screening reduces prostate cancer deaths compared with an age matched control group. Utilising the prostate cancer detection rates from this study we have investigated the clinical and cost-effectiveness of a similar PSA-based screening strategy for an Australian population of men aged 50-69 years. Methods: A decision model that incorporated Markov processes was developed from a health system perspective.The base case scenario compared a population-based screening programme with current opportunistic screening practices. Costs, utility values, treatment patterns and background mortality rates were derived from Australian data. All costs were adjusted to reflect July 2015 Australian dollars. An alternative scenario compared systematic with opportunistic screening but with optimisation of active surveillance (AS) uptake in both groups. A discount rate of 5% for costs and benefits was utilised. Univariate and probabilistic sensitivity analyses were performed to assess the effect of variable uncertainty on model outcomes. Results: Our model very closely replicated the number of deaths from both prostate cancer and background mortality in the Göteborg study. The incremental cost per quality-adjusted life-year (QALY) for PSA screening was $AU147,528. However, for years of life gained (LYGs) PSA based screening ($AU45,890/LYG) appeared more favourable. Our alternative scenario with optimised AS improved cost-utility to $AU45,881/QALY, with screening becoming cost-effective at a 92% AS uptake rate. Both modelled scenarios were most sensitive to the utility of patients before and after intervention, and the discount rate used. Conclusion: PSA-based screening is not cost-effective compared to Australia’s assumed willingness to pay threshold of $AU50,000/QALY. It appears more cost-effective if LYGs are used as the relevant outcome, and is more cost effective than the established Australian breast cancer screening programme on this basis. Optimised utilisation of AS increases the cost-effectiveness of prostate cancer screening dramatically.

A 77-year-old man presented with watery, bloody diarrhoea, symptomatic anaemia and signs of sepsis. He was well known to our unit with a history of extensive low-grade urothelial carcinoma involving a solitary kidney. CT performed on admission demonstrated a new finding of renocolic fistula. Due to his multiple medical and surgical comorbidities conservative management was elected. He passed away after 1 year of follow-up.

The Goteborg randomised population-based prostate cancer screening trial demonstrated that prostate-specific antigen (PSA)-based screening reduces prostate cancer deaths compared with an age-matched control group. Utilising the prostate cancer detection rates from this study, we investigated the clinical and cost effectiveness of a similar PSA-based screening strategy for an Australian population of men aged 50–69 years. A decision model that incorporated Markov processes was developed from a health system perspective. The base-case scenario compared a population-based screening programme with current opportunistic screening practices. Costs, utility values, treatment patterns and background mortality rates were derived from Australian data. All costs were adjusted to reflect July 2015 Australian dollars (A$). An alternative scenario compared systematic with opportunistic screening but with optimisation of active surveillance (AS) uptake in both groups. A discount rate of 5 % for costs and benefits was utilised. Univariate and probabilistic sensitivity analyses were performed to assess the effect of variable uncertainty on model outcomes. Our model very closely replicated the number of deaths from both prostate cancer and background mortality in the Goteborg study. The incremental cost per quality-adjusted life-year (QALY) for PSA screening was A$147,528. However, for years of life gained (LYGs), PSA-based screening (A$45,890/LYG) appeared more favourable. Our alternative scenario with optimised AS improved cost utility to A$45,881/QALY, with screening becoming cost effective at a 92 % AS uptake rate. Both modelled scenarios were most sensitive to the utility of patients before and after intervention, and the discount rate used. PSA-based screening is not cost effective compared with Australia’s assumed willingness-to-pay threshold of A$50,000/QALY. It appears more cost effective if LYGs are used as the relevant outcome, and is more cost effective than the established Australian breast cancer screening programme on this basis. Optimised utilisation of AS increases the cost effectiveness of prostate cancer screening dramatically.

Objectives To compare the costs of photoselective vaporisation (PVP) and transurethral resection of the prostate (TURP) for management of symptomatic benign prostatic hyperplasia (BPH) from the perspective of a Queensland public hospital provider. Patients and Methods A decision-analytic model was used to compare the costs of PVP and TURP. Cost inputs were sourced from an audit of patients undergoing PVP or TURP across three hospitals. The probability of re-intervention was obtained from secondary literature sources. Probabilistic and multi-way sensitivity analyses were used to account for uncertainty and test the impact of varying key assumptions. Results In the base case analysis, which included equipment, training and re-intervention costs, PVP was AU$ 739 (95% credible interval [CrI] –12 187 to 14 516) more costly per patient than TURP. The estimate was most sensitive to changes in procedural costs, fibre costs and the probability of re-intervention. Sensitivity analyses based on data from the most favourable site or excluding equipment and training costs reduced the point estimate to favour PVP (incremental cost AU$ –684, 95% CrI –8319 to 5796 and AU$ –100, 95% CrI –13 026 to 13 678, respectively). However, CrIs were wide for all analyses. Conclusions In this cost minimisation analysis, there was no significant cost difference between PVP and TURP, after accounting for equipment, training and re-intervention costs. However, PVP was associated with a shorter length of stay and lower procedural costs during audit, indicating PVP potentially provides comparatively good value for money once the technology is established.

Purpose To estimate the health system costs of prostate cancer by disease risk category and treatment type over 2016 to 2025 and to identify potential strategies to contain the cost increase. Methods A Markov cohort model was developed using clinical pathways from US prostate cancer guidelines and clinical expertise. Estimates of the probabilities of various treatments and outcomes and their unit costs were sourced from systematic reviews, meta-analyses, epidemiological publications and national cost reports. Estimated costs by stage of disease, by major treatments and by age at diagnosis were reported in 2016 US dollars. One-way and probabilistic sensitivity analyses assessed potential variation in the modeled costs. Results Australia-wide costs of prostate cancer were estimated at US$270.9 million in 2016 rising to US$384.3 million in 2025, an expected increase of 42%. Of this total increase, newly diagnosed low risk cases will contribute US$32.9 million, intermediate-risk US$56.8 million, high-risk US$53.3 million and advanced US$12.6 million. For men diagnosed at age 65 with low-risk disease, lifetime costs per patient were US$14,497 for surgery, US$19,665 for radiation therapies to the primary lesion, and US$9,234 for active surveillance. For intermediate- or high-risk disease, mean costs per patient were US$34,941 for surgery plus radiation and US$31,790 for androgen deprivation therapy plus radiation while advanced cancer therapies were at US$31,574 per patient. Additional costs for managing iatrogenic disease secondary to these treatments were excluded. Conclusion Strategies for identifying patients early before cancers have spread are critical to contain the estimated 42% increase in costs over the next decade. Increased uptake of active surveillance would also lead to substantial cost-savings in the management of low-risk prostate cancer.

Langerhans' histiocytosis or histiocytosis X is a rare intrinsically benign disease producing a destructive tumor with a variable clinical presentation and an often unpredictable clinical course. Focal forms such as eosinophilic granuloma of the bone only require minimal care but the gravity of multisystem forms causing organic dysfunction sometimes require aggressive chemotherapy. Bone involvement is generally observed in children mostly boys. Both sporadic and chronic forms are noted. We report a case observed in a 17-year-old adolescent who presented an exceptional association of bony destruction of the pelvis with extended asymptomatic pulmonary involvement. The lung disease led to the initial diagnosis and optimal surgical, pathological and radiological management.

IntroductionThe large nested variant of urothelial carcinoma (LNVUC) is a newly described and rare subtype of urothelial carcinoma. It is characterised by bland cytological features and a large nested architecture similar in appearance to low grade urothelial carcinoma with an inverted growth pattern. To date only 23 cases in a single series have been described.Case ReportWe describe the case of a 59 year old male with LNVUC whose tumour was initially misdiagnosed as a non-invasive low grade urothelial carcinoma. At a subsequent re-resection, his tumour was correctly re-classified as LNVUC with extensive invasion of the muscularis propria. Radical cystectomy and formation of an ileal conduit was performed. His operative specimen revealed invasion of prostatic stroma and perivesical fat, with all surgical margins clear. He is currently free from clinical recurrence 12 months after his cystectomy.ConclusionLNVUC is a newly described and rare urothelial carcinoma subtype. It characteristically possesses bland cytological features and may mimic low grade urothelial cancer. Despite its bland appearance it behaves aggressively with invasion, metastasis and death being common.

Objective:To evaluate our unit’s theatre throughput efficiency, to identify where inefficiencies existed and consequently where the greatest improvement might be made.To identify the causes of day of surgery cancellations and how they might be avoided. Patients and Methods:A prospective audit of theatre utilisation was undertaken over a 6 month period between 05/02//2013 and 02/08/2013 at Ipswich General Hospital, QLD, Australia.Times collected were: time of patient arrival in anaesthetic bay, start time of operative procedure, end time of operative procedure, and time of patient leaving theatre.The causative factors for any delays or day of surgery cancellations were identified and recorded where possible. Results:In the six month period 26,850 sessional minutes were available for elective operating over 100 operating sessions.304 elective cases were performed, split between 21 major and 283 minor proceduresThe sessions ran overtime a cumulative 2114 minutes.Total non-operative minutes totalled 13,209 (50.3% of all available time), split between late starts 499 minutes (1.8%), early list finishes 1894 minutes (7.05%), changeover time 1869 minutes (6.9%) and anaesthetic time, 8974 minutes (33.4%)Actual operating time only compromised 50.7% of all available elective operating session time (13,614 minutes)Theatre utilisation was 91.8%.51 procedures were cancelled on the day of surgery during the audit period, representing 14.3% of all scheduled procedures.The most common reason for cancellation was lack of surgical fitness, followed by inadequate operative time. Conclusion: A significant proportion of all elective operative time was consumed by non-operative minutes.Inefficiencies existed in turnover of patients as well as over as well as underbooking of patients on elective lists.An excessive number of cases were cancelled on the day of surgery, wasting valuable operative time.A multi-parametric approach must be taken to improve operation list utilisation.

An 83-year-old man presented with severe left anterolateral thigh and knee pain for several days. He was completely unable to ambulate owing to the pain. The patient reported no history of acute back pain prior to presentation. His history initially confounded diagnosis. Subsequent investigations demonstrated a chronic contained rupture of an infrarenal aortic aneurysm with significant vertebral body erosion and obliteration of the ipsilateral psoas muscle. Proposed symptomatology was compression of the lateral femoral cutaneous nerve and its roots. The patient had multiple medical comorbidities and died of unrelated causes before his aneurysm was able to be repaired.

To profit from growing high value commodity, vegetable, and horticultural crops smallholder farmers need affordable irrigation products to get the most “crop per drop” and net income from small-plot (0.1 to 1 ha) irrigation systems. In view of this we have developed a generic Small-plot Irrigation Product (SIP) line that includes three types of drip, two types of sprinkle, and a piped surface irrigation application system. Simple to manufacture polyethylene layflat tubing of diameters between 16 mm and 75 mm and with thicknesses ranging from 125 to 900 microns is used for the pipe networks.

The LC-MS/MS shotgun proteomics workflow is widely used to identify and quantify sample peptides and proteins. The technique, however, presents a number of challenges for large-scale use, including the diverse raw data file formats output by mass spectrometers, the large false positive rate among peptide assignments to MS/MS spectra, and the loss of connectivity between identified peptides and the sample proteins that gave rise to them. Here we describe the Trans-Proteomic Pipeline, a freely available open source software suite that provides uniform analysis of LC-MS/MS data from raw data to quantified sample proteins. In a straightforward manner, users can extract MS/MS information from raw data of many instrument formats, submit them to search engines for peptide identification, validate the results to remove false hits, combine together results of multiple search engines, infer sample proteins that gave rise to the identified peptides, and perform quantitation at the peptide and protein levels.

Aircraft produce emissions and pollution harmful to humans and the environment. Though aircraft are only responsible for a small percentage of transportation industry emissions, higher concentrations of air traffic at lower altitudes around major airports cause increased local pollution levels. Current monitoring systems in place provide no accountability for emissions.

IntroductionSquamous cell carcinoma (SCC) of the bladder is a rare malignancy in Western countries accounting for only 5% of all primary bladder cancers. Chronic irritation is the predominant risk factor, with chronic infections, bladder stones and long term catheterisation common precursors. The highest incidence of SCC occurs in patients with spinal cord injuries who rely on indwelling or self-catheterisation for bladder drainage. We report a case of primary SCC of the bladder secondary to a fungal ball located in the renal pelvis.Case reportA 72 year-old lady was referred to our unit for further investigation of recurrent polymicrobial urinary tract infections associated with intermittent flank pain and complicated by sepsis. Investigations into the cause for her recurrent urinary tract infections identified a mass in her left renal pelvis. Pyeloscopy demonstrated no tumour, but a fungal ball. Attempts to clear the fungal ball via pyeloscopy resulted in recurrent intensive care unit (ICU) admission for urosepsis. Several months after her last pyeloscopy she returned with haematuria. Cystoscopy at this time revealed a large bladder mass. Biopsy revealed primary SCC of the bladder invading muscle. At cystectomy the mass had invaded pubic bone and was unresectable and a palliative ileal conduit was formed. The patient passed away less than 4 months following diagnosis.ConclusionWe report what we believe to be the first case of primary SCC of the bladder secondary to a renal pelvis fungal ball. Despite frequent surveillance of her urinary tract the tumour developed rapidly and was unresectable at diagnosis.

Objective: Current practice mandates a prostate biopsy for histological confirmation of prostate cancer prior to a radical prostatectomy. Prostate biopsy, whether performed trans-rectally or trans-perineally, is an invasive procedure which typically involves an anaesthetic and has the risks of urosepsis, bleeding and haematoma. Post-biopsy inflammatory changes can also obliterate natural tissue planes thereby potentially compromising the quality of a nerve sparing procedure and increasing positive margin rates.3T-Multi-Parametric Magnetic Resonance Imaging of the Prostate (3T mpMRI-P) is gaining increasing acceptance in the identification and localisation of prostate cancer. In experienced centres, the positive predictive value has been reported to be as high as 95%.Methods: Two patients with rising and elevated age- adjusted PSAs and palpable malignant prostate nodules on Digital Rectal Examination (DRE) underwent 3T mpMRI-P. Both patients had Prostate Imaging-Reporting and Data System (PI-RADS) 5 lesions in their peripheral zones corresponding to palpable nodules. Prostate biopsies were offered but declined by both patients. Both were satisfied that there was sufficient evidence on their PSA, DRE and 3T mpMRI-P for a diagnosis of prostate cancer without prostate biopsies and both elected to proceed to a Da Vinci Robotic Assisted Laparoscopic Radical Prostatectomy (RALRP).Results: Unilateral nerve sparing RALRPs were performed on both patients without complication. Histology demonstrated Gleason 4+4=8 and 4+3=7 prostate adenocarcinomas, with tumour volumes of 14.92cc and 4.5cc respectively.Conclusions: In appropriately counselled patients who have a high pre-test probability of prostate cancer (rising and elevated PSA, malignant nodule on DRE and a corresponding PI-RADS 5 lesion on 3T mpMRI-P), it may be appropriate to proceed to a radical prostatectomy without a tissue diagnosis if the patients have strong reservations about prostate biopsy.

In 2005, the San Juan River Dineh Water Users, Inc (SJRDWU) a newly organized water users association located on the Navajo Nation in Shiprock, NM, converted Loop Lateral, an earthen ditch, into an underground pipeline. Achievements by completing the conversion include introducing water management to an area with no formalized scheduling, improving the equitable distribution of water delivery, facilitating on-farm development improvements implemented by subsistence farmers, and bringing validity to a fledging organization whose sole purpose is to receive the transfer of operations from a tribal government. The project was completed solely by SJRDWU, an independent Navajo corporation, on Indian trust land with partial

Several water technologies that have been designed specifically for and are being marketed to resource poor farmers (smallholders) with small land holdings are presented. Both the market creation approach to development and the appropriate technologies are described. The water technologies include: treadle pumps and storage tanks to supply water for crop irrigation; and low-cost drip and mini-sprinkle irrigation systems to apply water to high value crops. The development of these efficient and affordable water technologies provides smallholders with an essential tool for intensifying their farming practices. This allows them to grow high value crops and significantly boost their farming income while also increasing crop production per unit of water used and consumed.

We present a statistical model to estimate the accuracy of peptide assignments to tandem mass (MS/MS) spectra made by database search applications such as SEQUEST. Employing the expectation maximization algorithm, the analysis learns to distinguish correct from incorrect database search results, computing probabilities that peptide assignments to spectra are correct based upon database search scores and the number of tryptic termini of peptides. Using SEQUEST search results for spectra generated from a sample of known protein components, we demonstrate that the computed probabilities are accurate and have high power to discriminate between correctly and incorrectly assigned peptides. This analysis makes it possible to filter large volumes of MS/MS database search results with predictable false identification error rates and can serve as a common standard by which the results of different research groups are compared.

Endomyocardial biopsy (EMB) remains the mainstay for the diagnosis of acute cellular rejection in cardiac transplant patients. A noninvasive alternative that would supplant or reduce the number of EMBs would be a highly desirable and cost-effective tool. To evaluate one potential alternative, a pacemaker with high resolution telemetry capabilities and two fractally coated epimyocardial leads were implanted in 30 patients at five transplant centers during the heart transplant procedure. Ventricular electrograms were recorded during intrinsic and paced activity and digitized to a laptop-based data acquisition device. Electrograms were recorded at frequent intervals and systematically on days when EMBs were performed. The electrogram data were then transferred via the Internet to a central data processing site. Clinical patient management was blinded to the electrogram results and varied considerably among the five centers. Using EMB together with clinical assessment of the transplant revealed 18 cases of clinically significant rejection beyond postoperative day 27 that required antirejection therapy. The normalized parameter values extracted from the electrogram recordings during pacing (the ventricular evoked response) that were associated with significant rejection were statistically lower (86% +/- 16% versus 96% +/- 22%, P < 0.005). The application of a single-threshold diagnosis model to the parameter values allowed detection of significant rejection with a negative predictive value of 98%. This analysis also showed that as many as 55% of the routine surveillance EMBs could have been eliminated had the pacemaker monitoring technique been used as a screening tool prior to EMB. A prospective study should further define the role of this technique in the detection and management of cardiac transplant patients.

The purpose of this note is to comment on some models for the mechanical properties of tendon and to draw attention to a misprint in an earlier paper, Diamant et al , (1972), to which we were contributors. In the study published in 1972 we and our coauthors at Case Western Reserve University, Cleveland, Ohio, presented optical and mechanical evidence for a planar zig-zag model of the basic load-bearing structure in rat-tail tendon interpreting the mechanical deformation by the theory of the extensible elastica. Because of an unfortunate misprint in the published paper, the validity of the elastica model has been called into question, and other theories explaining the load deformation behaviour of tendon have been proposed (Lanir 1978; Comninou & Yannas 1976).

Tail tendons from Fischer and Sprague-Dawly albino rats of ages from 2 weeks to 3 years were investigated under the polarizing microscope as regards structure and deformation behaviour. Periodically extinguishing bands were observed along the otherwise featureless tendons. By analysing the behaviour of this extinction pattern under appropriate rotations of the tendon, it could be deduced that the orientation of the basic birefringent units varies periodically along the tendon and that this periodic pattern corresponds to a planar arrangement of the anisotropic entities. All the relevant parameters of this periodic structure could be determined in a representative manner from polarizing optics alone. Subdivision of the tendons revealed regularly undulating or rather crimped subunits in good correspondence to what has been deduced from the extinction bands in the intact tendons. The crimp angle was found to decrease while the periodicity increased - in approximate proportion to the length of the tail - with the age of the rat implying constancy of crimp number during the life time of the animal. On elongation the periodicity was gradually removed. The calculated fibre elongation necessary to eliminate the crimp was in good agreement with observation for mature rats but was larger for young rats implying the simultaneous stretching of the fibre itself. Stress-strain properties of tendons were measured and models for crimp straightening were tested. It was found that a model containing inflexible hinges, corresponding to the ‘elastica’ problem in mechanics gave reasonable fit with experiment. Analysis of stress-strain data on this basis leads to a basic load bearing unit, the diameter of which increases from 100 to 500 nm with the age of the animal. Implications of these findings for the structure and properties of the tendons, also in relation to ageing are pointed out.