Change In Lesion Size Research Articles

PSUN21 Adrenal Incidentaloma: Is Interval Scanning Warranted?

Abstract Background Adrenal incidentaloma (AI) is an increasingly recognised finding, with pressure on healthcare systems. Earlier guidelines recommended interval scanning and testing to ensure stability. However, the recent European guidelines do not recommend the need for repeat scanning if initial assessment is reassuring. Aim To explore the utility of this guidance on need for interval scanning of benign AI. Methods A retrospective unselected review of AI cases seen in our unit before the launch of the European guidelines was conducted. At that time, a local protocol was in use to characterise scan and test adrenal functions at baseline, and at two years, the scan and endocrine tests were repeated. We compared the baseline scan results with those at two-years. Results We collected data on 54 patients initially identified between 2011 and 2016. Of these, 31 had left-sided lesions, 15 had right-sided lesions and 8 bilateral. Of the left-sided lesions, 16 increased in size over the 2.2-year follow-up period, 4 decreased in size and 17 remained the same. Of the right-sided lesions, 3 increased in size over the follow-up period, 6 decreased in size and 13 remained the same. Of those that increased (left- or right-sided), the largest increase was 5mm. Taking 2 mm as the cut-off for a significant change: on the left, 32/37 (86%) had a change ≤2mm (P<0. 001 for no increase). On the right, 21/22 (95%) had a change ≤2mm (P<0. 001). Using a ≤5% increase as cut-off: 28/37 on the left (P=0. 028) and 20/22 on the right (p<. 001) showed ≤5% increase. There was no statistical difference in change in lesion size in terms of laterality, being indeterminate on initial scanning, gender, age or initial size on presentation. Conclusion We found that there was no significant change in size after two years. Therefore, our data support the European guidelines that repeat scanning is unnecessary. This should be reassuring to patients and provide a more cost-effective service. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

Outcomes of Intraplaque Verapamil Injection for Treatment of Peyronie’s Disease

Objective: To determine the outcomes of intraplaque verapamil injection for treatment of Peyronie's disease. Aim:The purpose of this study is to evaluate the outcomes & efficacy of intraplaque verapamil injection in Peyronie’s disease management. Methods: The quasi experimental study was conducted from July 2018 to July 2019 on a group of 26 subjects suffering from Peyronie's disease. After detailed history, complete physical and genital examination, the diagnosis was confirmed. After informed consent, questionnaires regarding pain and sexual satisfaction of patients were filled. All patients received verapamil injections on weekly basis for a period of 10 weeks. After that, all necessary variables were recorded and data analyzed using SPSS version 16. Results: Most of the patients in our study were in the age group of 30-65 years. 26.9 % patients were in the range of 51-55 years old. 53.8% patients got no effect of intralesional injection of verapamil on pain while pain relieved in 38.5% of patients & 7.7% patients experienced an increased in pain intensity after 10 weeks of intralesional injection of verapamil. 61.5%of patients satisfied with their sexual life after 10 week of injections & 30.8% of patients remained unsatisfied with their sexual life while in 7.7%of patients symptoms aggravated. 53.8% of patients experienced no change in size of lesion and curvature of penis, while 30.8% got less than 50% reduction in size of lesion while 15.4% of patients got more than 50% reduction in size after 10 weeks. Practical implication: We can easily find the efficacy of Verapamil injection for management of Peyronie’s disease. Conclusion: This study concluded the efficacy of Verapamil injection for management of Peyronie’s disease disease causes significant decrease in size of lesion and improvement in sexual activity. Keywords: Peyronie’s disease, Improvement, Lesions, Significant

Model-free dynamic contrast-enhanced MRI analysis: differentiation between active tumor and necrotic tissue in patients with glioblastoma.

Treatment response assessment in patients with high-grade gliomas (HGG) is heavily dependent on changes in lesion size on MRI. However, in conventional MRI, treatment-related changes can appear as enhancing tissue, with similar presentation to that of active tumor tissue. We propose a model-free data-driven method for differentiation between these tissues, based on dynamic contrast-enhanced (DCE) MRI. The study included a total of 66 scans of patients with glioblastoma. Of these, 48 were acquired from 1 MRI vendor and 18 scans were acquired from a different MRI vendor and used as test data. Of the 48, 24 scans had biopsy results. Analysis included semi-automatic arterial input function (AIF) extraction, direct DCE pharmacokinetic-like feature extraction, and unsupervised clustering of the two tissue types. Validation was performed via (a) comparison to biopsy result (b) correlation to literature-based DCE curves for each tissue type, and (c) comparison to clinical outcome. Consistency between the model prediction and biopsy results was found in 20/24 cases. An average correlation of 82% for active tumor and 90% for treatment-related changes was found between the predicted component and population-based templates. An agreement between the predicted results and radiologist's assessment, based on RANO criteria, was found in 11/12 cases. The proposed method could serve as a non-invasive method for differentiation between lesion tissue and treatment-related changes.

Assessing Treatment Response after Lung SABR: An Evaluation of the Predictive Value of RECIST Criteria

<h3>Purpose/Objective(s)</h3> Response Evaluation Criteria In Solid Tumors (RECIST) – version 1.1 is a commonly used framework to assess treatment response. However, response assessment after lung stereotactic ablative radiotherapy (SABR) can be difficult due to radiation-induced lung changes. The goal of this study was to assess how frequently lung lesions treated with SABR triggered RECIST criteria for recurrence and to correlate RECIST findings with actual treatment outcomes. <h3>Materials/Methods</h3> We reviewed patients who were treated with lung SABR between 2010-2015. Prescribed dose was 54-60 Gy in 3-8 fractions. Both primary lung and metastatic lesions were included. All lesion measurements were based on maximum diameter on CT axial slices. After treatment, progressive disease (PD) by RECIST was based on strict RECIST criteria and defined as: 1) increase of ≥ 20% compared to post-treatment minimum and 2) ≥ 5 mm absolute increase. The final assessment of recurrence was based on subsequent changes in lesions size after PD by RECIST and, when available, PET scan and/or pathology. When assessing subsequent changes in lesion size, stability (≤ 20% change) in size for at least one year or a decrease (> 20%) in size indicated no recurrence, while subsequent growth (> 20%) indicated recurrence. The assessment of lesion response by the treating radiation oncologist (RO) in the clinical record was also recorded when available. <h3>Results</h3> A total of 85 patients, with 88 lesions, met inclusion criteria. 75 of these lesions were lung primaries, the remainder were metastases. Median patient age was 79 years (IQR: 73-85) and mean lesion size was 2.1 ± 0.9 cm. Median follow-up was 52 months (IQR: 33-68). 66% (58/88) of treated lesions met criteria for PD by RECIST. However, on final assessment only 10% (9/88) were found to have recurrence. The positive predictive value (PPV) of RECIST criteria was 0.16. In the subset of patients with primary lung tumors only, 64% (48/75) were classified as PD by RECIST, but only 12% (9/75) were categorized as recurrence on final assessment. PPV was 0.19. The predictive value of RECIST was lower when PD by RECIST was triggered ≤ 12 vs. > 12 months post-treatment (PPV 0.08 vs. PPV 0.21). Median time to PD by RECIST was 19 months (IQR: 12-27) for those with recurrence vs. 15 months (IQR: 8-24) for those without recurrence on final assessment (p=0.13). Assessment by treating RO was only available for 57% (50/88) of cases, but concordance with final study assessment was 0.85, translating to an overall predictive accuracy of 94% (47/50). <h3>Conclusion</h3> Using strict RECIST criteria, two-thirds of patients treated with lung SABR met criteria for PD. However, on further follow-up only a minority of these patients were felt to have recurrence, leading to a poor PPV for RECIST criteria in this setting. Further work is needed to develop validated criteria for designation of recurrence after lung SABR.

The Changes in Size of Periapical Lesions after Root Canal Treatments Assessed by Digital Periapical Radiography and Cone-Beam Computed Tomography: A 2-Years Prospective Clinical Study.

Background and Objectives: There is limited information regarding comparison of long-term dynamics of periapical bone destruction estimated by digital periapical radiography (DPR) and by cone-beam computed tomography (CBCT). This study aimed to compare the radiographically assessed periapical changes of endodontically treated teeth over 2 years of follow-up and to analyse disagreements in periapical lesion size estimates around the same roots using DPR and CBCT. Materials and Methods: A total of 176 endodontically treated teeth, of 128 patients with apical periodontitis, were assessed by DPR and CBCT, at baseline and after 2 years. All periapical radiolucencies were categorised by severity (S0, S1, S2, S3) concerning their size. Descriptive statistics were used to report distribution of the radiolucencies at baseline and at follow-up, and their size transitions over 2 years. Site-specific comparison of the radiolucencies identified by two methods was performed using Z test and Pearson’s chi-square test. Results: majority of the detected radiolucencies were scored as S0: 65% and 68% at baseline; 89% and 83% at follow-up, by DPR and CBCT, respectively. Site-specific score comparison showed that disagreements comprised 18% and 20% of the total number of radiolucencies detected by DPR and CBCT, respectively. There were more disagreements between DPR and CBCT within categories S1 and S2 + S3 compared to S0: at baseline, they comprised 17–33% and after two years 62–95% of all detected radiolucencies within the category. 65% of non-matching score transitions over two years occurred between S0 and S1. The CBCT-based evaluation resulted in negative treatment outcomes for 10 more root canals than the DPR-based result. Conclusions: Most remarkable disagreement between DPR and CBCT recordings was observed within the radiolucency categories S2 and S3. However, the diagnostic accuracy of both radiographic methods was questionable as it resulted in a high proportion of non-matching S0-S1 lesion transitions over 2 years.

Do body composition parameters correlate with response to targeted therapy in ER+/HER2- metastatic breast cancer patients? Role of sarcopenia and obesity.

PurposeTo investigate the association between body composition parameters, sarcopenia, obesity and prognosis in patients with metastatic ER+/HER2- breast cancer under therapy with cyclin-dependent kinase (CDK) 4/6 inhibitors.Methods92 patients with biopsy-proven metastatic ER+/HER2- breast cancer, treated with CDK 4/6 inhibitors between 2018 and 2021 at our center, were included in this retrospective analysis. Visceral Adipose Tissue (VAT), Subcutaneous Adipose Tissue (SAT) and Skeletal Muscle Index (SMI) were measured before starting therapy with CDK 4/6 inhibitors (Palbociclib, Abemaciclib or Ribociclib). Measurements were performed on a computed tomography-derived abdominal image at third lumbar vertebra (L3) level by an automatic dedicated software (Quantib body composition®, Rotterdam, Netherlands). Visceral obesity was defined as a VAT area > 130 cm2. Sarcopenia was defined as SMI < 40 cm2/m2. Changes in breast lesion size were evaluated after 6 months of treatment. Response to therapy was assessed according to RECIST 1.1 criteria. Spearman’s correlation and χ2 analyses were performed.ResultsOut of 92 patients, 30 were included in the evaluation. Of the 30 patients (mean age 53 ± 12 years), 7 patients were sarcopenic, 16 were obese, while 7 patients were neither sarcopenic nor obese. Statistical analyses showed that good response to therapy was correlated to higher SMI values (p < 0.001), higher VAT values (p = 0.008) and obesity (p = 0.007); poor response to therapy was correlated to sarcopenia (p < 0.001). Moreover, there was a significant association between sarcopenia and menopause (p = 0.021) and between sarcopenia and the persistence of axillary lymphadenopathies after treatment (p = 0.003), while the disappearance of axillary lymphadenopathies was associated with obesity (p = 0.028).ConclusionsThere is a growing interest in body composition, especially in the field of breast cancer. Our results showed an interesting correlation between sarcopenia and progression of disease, and demonstrated that VAT can positively influence the response to targeted therapy with CDK 4/6 inhibitors. Larger-scale studies are needed to confirm these preliminary results.Clinical RelevanceSarcopenia and obesity seem to predict negative outcomes in many oncologic entities. Their prevalence and impact in current breast cancer care are promising but still controversial.

Abstract P3124: Treatment Of Apoe -/- Mice With Advanced Atherosclerosis With The Senolytic Agent Abt-263 Caused Increased Mortality And Was Associated With Increased Endo-mt But Reduced Acta2 Cap Thickness And Collagen Content

Background: Plaque rupture and erosion of advanced atherosclerotic lesions resulting in ischemic heart disease or stroke are the leading worldwide cause of death. Multiple studies have shown that senescent cells are present in human atherosclerotic lesions, and recent animal studies have claimed that removing senescent cells from the lesions using senolytic agents has some beneficial effects but also limitations. Although these mouse studies have important implications for using senolytic agents to treat atherosclerosis, due to the lack of lineage tracing models and relying on markers not specific for various lesion cell types, it is difficult to ascertain the mechanisms that underline the beneficial effects shown by previous studies. Hypothesis: Treatment of western diet (WD) fed Apoe -/- mice with the senolytic agent ABT-263 (Navitoclax) will reduce lesion size and induce changes consistent with increased plaque stability including a thicker collagen-rich ACTA2 fibrous cap. Methods: SMC (Myh11-ERT2-Cre-eYFP+) and EC (Cdh5-ERT2-Cre-eYFP+) lineage tracing Apoe -/- were fed a WD for 18 weeks, followed by ABT-263 (100MG or 50MG /KG/BW) treatment for six to nine weeks on WD and analyzed for the indices of stability. Results: ABT-263 treatment did not result in changes in lesion size, lumen area, or outward remodeling of the brachiocephalic artery (BCA). However, surprisingly, ABT-263 treatment was associated with an 80% reduction in SMC (Myh11-eYFP+) but a 50-60% increase in endothelial cell (EC) contributions to lesions via EC to mesenchymal transition (EndoMT) (Chd5-eYFP+). ABT-263 treatment also reduced ACTA2 cap thickness by 50-75% and collagen content by 50%, but increased mortality by 50-60%. Conclusions: Taken together, contrary to our hypothesis, the senolytic agent ABT-263 treatment on advanced atherosclerosis showed multiple detrimental effects, including reduced indices of stability, increased Endo-MT, and increased mortality.

Outcomes of Intraplaque Verapamil Injection for Treatment of Peyronie’s Disease

Objective: To determine the outcomes of intraplaque verapamil injection for treatment of Peyronie's disease.&#x0D; Aim: The purpose of this study is to evaluate the outcomes &amp; efficacy of intraplaque verapamil injection in Peyronie’s disease management.&#x0D; Methods: The quasi experimental study was conducted from July 2018 to July 2019 on a group of 26 subjects suffering from Peyronie's disease. After detailed history, complete physical and genital examination, the diagnosis was confirmed. After informed consent, questionnaires regarding pain and sexual satisfaction of patients were filled. All patients received verapamil injections on weekly basis for a period of 10 weeks. After that, all necessary variables were recorded and data analyzed using SPSS version 16.&#x0D; Results: Most of the patients in our study were in the age group of 30-65 years. 26.9 % patients were in the range of 51-55 years old. 53.8% patients got no effect of intralesional injection of verapamil on pain while pain relieved in 38.5% of patients &amp; 7.7% patients experienced an increased in pain intensity after 10 weeks of intralesional injection of verapamil. 61.5%of patients satisfied with their sexual life after 10 week of injections &amp; 30.8% of patients remained unsatisfied with their sexual life while in 7.7%of patients symptoms aggravated. 53.8% of patients experienced no change in size of lesion and curvature of penis, while 30.8% got less than 50% reduction in size of lesion while 15.4% of patients got more than 50% reduction in size after 10 weeks.&#x0D; Conclusion: This study concluded the efficacy of Verapamil injection for management of Peyronie’s disease.

Comparison of Choi, RECIST and Somatostatin Receptor PET/CT Based Criteria for the Evaluation of Response and Response Prediction to PRRT.

Aim: The most suitable method for assessment of response to peptide receptor radionuclide therapy (PRRT) of neuroendocrine tumors (NET) is still under debate. In this study we aimed to compare size (RECIST 1.1), density (Choi), Standardized Uptake Value (SUV) and a newly defined ZP combined parameter derived from Somatostatin Receptor (SSR) PET/CT for prediction of both response to PRRT and overall survival (OS). Material and Methods: Thirty-four NET patients with progressive disease (F:M 23:11; mean age 61.2 y; SD ± 12) treated with PRRT using either Lu-177 DOTATOC or Lu-177 DOTATATE and imaged with Ga-68 SSR PET/CT approximately 10–12 weeks prior to and after each treatment cycle were retrospectively analyzed. Median duration of follow-up after the first cycle was 63.9 months (range 6.2–86.2). A total of 77 lesions (2–8 per patient) were analyzed. Response assessment was performed according to RECIST 1.1, Choi and modified EORTC (MORE) criteria. In addition, a new parameter named ZP, the product of Hounsfield unit (HU) and SUVmean (Standard Uptake Value) of a tumor lesion, was tested. Further, SUV values (max and mean) of the tumor were normalized to SUV of normal liver parenchyma. Tumor response was defined as CR, PR, or SD. Gold standard for comparison of baseline parameters for prediction of response of individual target lesions to PRRT was change in size of lesions according to RECIST 1.1. For prediction of overall survival, the response after the first and second PRRT were tested. Results: Based on RECIST 1.1, Choi, MORE, and ZP, 85.3%, 64.7%, 61.8%, and 70.6% achieved a response whereas 14.7%, 35.3%, 38.2%, and 29.4% demonstrated PD (progressive disease), respectively. Baseline ZP and ZPnormalized were found to be the only parameters predictive of lesion progression after three PRRT cycles (AUC ZP 0.753; 95% CI 0.6–0.9, p 0.037; AUC ZPnormalized 0.766; 95% CI 0.6–0.9; p 0.029). Based on a cut-off-value of 1201, ZP achieved a sensitivity of 86% and a specificity of 67%, while ZPnormalized reached a sensitivity of 86% and a specificity of 76% at a cut-off-value of 198. Median OS in the total cohort was not reached. In univariate analysis amongst all parameters, only patients having progressive disease according to MORE after the second cycle of PRRT were found to have significantly shorter overall survival (median OS in objective responders not reached, in PD 29.2 months; p 0.015). Patients progressive after two cycles of PRRT according to ZP had shorter OS compared to those responding (median OS for responders not reached, for PD 47.2 months, p 0.066). Conclusions: In this explorative study, we showed that Choi, RECIST 1.1, and SUVmax-based response evaluation varied significantly from each other. Only patients showing progressive disease after two PRRT cycles according to MORE criteria had a worse prognosis while baseline ZP and ZPnormalized performed best in predicting lesion progression after three cycles of PRRT.

Abstract 5255: Tumor heterogeneity in response to therapy and its association with outcome in patients with metastatic colorectal cancer (mCRC)

Abstract Background: Clinical benefit of therapies matched with genetic profiling remains limited in patients with mCRC, which is partially attributed to tumor heterogeneity. Compared to molecular tumor heterogeneity using modern multi-omics approach, tumor heterogeneity in response to therapy has not been adequately studied. We aimed to characterize such tumor heterogeneity and evaluate its association with outcome in patients with mCRC. Methods: We used individual patient data from a clinical trial (NCT00364013) in Project Data Sphere who received first-line FOLFOX for mCRC and had ≥2 baseline metastatic target lesions. We used standard deviations of following tumor features in an individual patient to represent tumor heterogeneity: percentage change in size of a target lesion from baseline to first radiographic evaluation (H1), average speed of such percentage change in size as defined in H1 (H2), percentage change in size of a target lesion from baseline to the time of its best response to therapy (H3), and average speed of such percentage change in size as defined in H3 (H4). Cox proportional hazards models were used to evaluate association of tumor heterogeneity with survival. Results: Mean age of 328 patients included was 61 years. Median follow-up time was 18.2 months. 85% of them had liver metastasis; 15% had lung metastasis. All tumor heterogeneity variables in response to therapy (H1-4) were higher (p&amp;lt;0.001) in patients with disease progression compared to those without. In univariate analyses, higher tumor heterogeneity H1 (HR 7.2, 95% CI 2.3-22.6), H2 (HR 3.1, 95% CI 1.7-5.7), H3 (HR 6.4, 95% CI 2.1-19.3), and H4 (HR 4.1, 95% CI 2.4-7.1) were associated with shorter progression-free survival (PFS) (p&amp;lt;0.001). H4 high group (median as cutoff) had a shorter median PFS of 7.3 months compared to H4 low group (9.1 months, p=0.005). In multivariable analysis, higher H1 (HR 8.0, 95% CI 2.2-28.9, p=0.002), H2 (HR 3.9, 95% CI 2.0-7.6, p&amp;lt;0.001), H3 (HR 6.4, 95% CI 1.9-21.9, p=0.003), or H4 (HR 5.1, 95% CI 2.9-9.1, p&amp;lt;0.001) was each associated with a shorter PFS, after adjusted for baseline number of metastatic sites, number of target lesions, tumor size, age, albumin, ECOG, and lymph node metastasis. Similar findings were found when ratio of maximal change to baseline sum of tumor size due to therapy was adjusted for and when H1-4 were calculated from liver lesions only. Higher H1 (HR 3.6, 95% CI 1.2-11.2, p=0.03), H2 (HR 1.9, 95% CI 1.1-3.4, p=0.02), H3 (HR 5.2, 95% CI 1.8-14.8, p=0.002), or H4 (HR 2.5, 95% CI 1.5-4.0, p&amp;lt;0.001) was also each associated with a shorter overall survival in multivariable analysis. Conclusion: Higher tumor heterogeneity in response to chemotherapy within an individual patient was independently associated with early disease progression and shorter survival. It could provide prognostic value complementary to existing tumor heterogeneity variables in patients with mCRC. Citation Format: Junjia Liu, Hao Xie. Tumor heterogeneity in response to therapy and its association with outcome in patients with metastatic colorectal cancer (mCRC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5255.

Abstract 4112: Patient derived organoids predict clinical response: A patient in the lab

Abstract Colorectal cancer (CRC) is the third leading cause of cancer and cancer-related death. A large fraction of the CRC patients diagnosed with de novo metastatic disease do not benefit from the standard of care but still experience substantial side effects. Therefore, there is the urgency for a new model to predict clinical response. Adult epithelial stem cell (ASC) -derived organoids are proving to be a major breakthrough in pre-clinical models. ASC-derived organoids can be developed from healthy as well as diseased tissue, including cancer lesions and therefore are often referred to as patient-derived organoids (PDOs or HUB Organoids࣪). These model is established directly from patient tissue, represent the tissue of origin and faithfully recapitulate patient disease in vitro and can be propagated for drug testing in a matter of weeks. PDOs bridges the gap between the lab and the clinic and effectively bring a “patient in the lab.” In this study we aimed to validate the predictive value of PDOs in the stratification of metastatic CRC (mCRC) patients for treatment with chemotherapeutic agents. PDOs from mCRC tissues were established following our optimized procedures and drug screening was performed. Clinical response was compared with PDO drug response and the best predicting drug response parameters (growth rate (GR), GRmax, GR50 and area under the curve) were identified. The patient response was evaluated by the percentage of change in size of the target lesions on response scans (% size change), best Response Evaluation Criteria in Solid Tumors (RECIST) response and progression-free survival (PFS). Importantly, we validated the predictive value of organoids towards fluorouracil (5-FU). We are validating these results in a large trial. Current efforts to further expand our PDO and drug sensitivity biobank will enable the implementation of the personalized HUB Organoid Technology to accurate and fast predict of the treatment response to improve clinical outcome of mCRC patients. Citation Format: Carla S. Verissimo, Lidwien Smabers, Emerens Wensink, Esmee Koedoot, Maarten Huismans, Celia Higuera Barón, Ricardo Korporaal, Emma Teal, Katerina-Chara Pitsa, Edwin van Oosten, Roshni Nair, Liselot Valkenburg, Geert Cirkel, Anneta Brousali, Jorieke Salij, René Overmeer, Manon Braat, Sjoerd Elias, Robert Vries, Onno Kranenburg, Miriam Koopman, Sylvia F. Boj, Jeanine Roodhart. Patient derived organoids predict clinical response: A patient in the lab [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 4112.

Outcomes of Intraplaque Verapamil Injection for Treatment of Peyronie’s Disease

Objective: To determine the outcomes of intraplaque verapamil injection for treatment of Peyronie’s disease. Aim: The purpose of this study is to evaluate the outcomes &amp; efficacy of intraplaque verapamil injection in Peyronie’s disease management. Methods: The quasi experimental study was conducted from July 2018 to July 2019 on a group of 26 subjects suffering from Peyronie’s disease. After detailed history, complete physical and genital examination, the diagnosis was confirmed. After informed consent, questionnaires regarding pain and sexual satisfaction of patients were filled. All patients received verapamil injections on weekly basis for a period of 10 weeks. After that, all necessary variables were recorded and data analyzed using SPSS version 16. Results: Most of the patients in our study were in the age group of 30-65 years. 26.9 % patients were in the range of 51-55 years old. 53.8% patients got no effect of intralesional injection of verapamil on pain while pain relieved in 38.5% of patients &amp; 7.7% patients experienced an increased in pain intensity after 10 weeks of intralesional injection of verapamil. 61.5%of patients satisfied with their sexual life after 10 week of injections &amp; 30.8% of patients remained unsatisfied with their sexual life while in 7.7%of patients symptoms aggravated. 53.8% of patients experienced no change in size of lesion and curvature of penis, while 30.8% got less than 50% reduction in size of lesion while 15.4% of patients got more than 50% reduction in size after 10 weeks. Conclusion: This study concluded the efficacy of Verapamil injection for management of Peyronie’s disease.

Gamma Knife radiosurgery for obsessive compulsive disorder.

Gamma Knife radiosurgical capsulotomy has been performed for over 40 years as a rarely used surgical intervention for the treatment of obsessive-compulsive disorder. Over time, the procedure has evolved in many ways with most significant modifications being made in target location, number of isocenters and prescribed dose, subsequently producing changes in lesion size and geometry. Long-term clinical response data and adverse outcomes to the earlier empiric treatment parameters have resulted in shifting the target from its initial location within the midpoint of the anterior limb of internal capsule to a currently used point that includes its most ventral portion as well as the ventral striatum. This led to the contemporary Gamma Knife ventral capsulotomy procedure that focuses on ventral capsule/ventral striatum. Many of the early studies, despite demonstrating efficacy in some patients, were complicated by clinically relevant radiation-induced adverse effects. More recent studies have demonstrated strong efficacy with diminished adverse effects with well-placed lesions created at lower radiation doses. Advances in neuroimaging technology such as diffusion tensor imaging (DTI) based fiber tracking may provide further insight into precisely targeting of the ventral capsule/striatum based on patient-specific variations in white matter connectivity.

Assessment of changes in color and size of vitiligo lesions during treatment with narrow band ultraviolet B.

Many treatment modalities have been used to stabilize vitiligo and induce repigmentation. Several methods were used to monitor the color changes inside the treated lesions such as spectroscopes and colorimeters that measure the melanin index inside the lesion. To study whether the colorimeter and point counting technique can be used as objective methods in monitoring vitiligo lesions during treatment with Nb-UVB. Twenty randomly chosen patients with non-segmental vitiligo were enrolled in this interventional study. Vitiligo disease activity score was recorded in each patient. Patients received Nb-UVB three times per week for 6months. Two lesions were chosen in each patient, and each lesion was assessed for size using point counting technique and degree of color using the Dermacatch® at the beginning of the treatment and evaluated for changes in color and size every 4weeks till the end of the treatment. After 6months of treatment, regarding the lesion size, 90% of lesions showed variable degrees of repigmentation and 10% showed increase in size, indicating increased activity of the disease, and regarding to color changes. We noticed that after one month of Nb-UVB treatment, there is marked increase in MI measurements in many lesions before any clinical improvement appeared, while at the end of treatment, inside the lesion; 95% showed an increase in melanin index and 5% showed no elevation. While the color changes outside the lesion showed 75% of lesions increased in melanin index, 15% remained unchanged and 10% of the lesions showed decrease in melanin index. Colorimeter was able to detect change in color after only one month of treatment before it was clinically apparent which means that it can be used as a prognostic tool.

A comparative clinical study of bioceramic and calcium hydroxide based root canal sealer in the treatment of non-vital permanent tooth with periapical lesion

Introduction: The use of Bioceramic sealer in the obduration of the root canal system has been expected by many of the previous studies. However, the clinical outcome has not yet been established. Objective: To compare the effectiveness of bioceramic and calcium hydroxide based root canal sealer in treatment of non-vital permanent teeth with periapical lesion (Periapical periodontitis). Materials and Methods: A total 100 mature permanent anterior teeth were selected after clinical and radiological examination which had non-vital pulp with periapical lesion. Clinically pulp vitality test, palpation and percussion test was performed maintaining standard procedure. Following cavity preparation and biomechanical preparation, each canal was obturated either with bioceramic (Endosequence BC) or calcium hydroxide based sealer (Sealapex, Kerr). All participants were evaluated immediately after obturation, at 3 and 6 months for the assessment of change in size of periapical lesion, condition of periodontal ligament space, lamina dura and incidence of post-operative pain, swelling. Statistical analysis was performed using Chi- square(X2) test and t-test. A value of p&lt;0.05 was considered as statistically significant. Results: Bioceramic was more effective in reducing the lesion size than that of calcium hydroxide. At 6 months, the mean lesion size was reduced from 3.52±0.7 to 1.30±0.462 mm in Bioceramics and from 3.48±1.07 to 1.58± 0.498 mm in sealapex treated teeth.. Furthermore, 98% of bioceramic treated teeth and 94% of sealapex treated teeth showed absence of swelling. The differences between two groups were statistically significant (p&lt;0.05). Conclusion: In this short period of study, Bioceramics based sealer seems to be more effective than calcium hydroxide based sealer in repair of periapical lesions of the nonvital teeth. Update Dent. Coll. j: 2021; 11(2): 26-31

Rationale and design of the Diet Restriction and Exercise-induced Adaptations in Metastatic breast cancer (DREAM) study: a 2-arm, parallel-group, phase II, randomized control trial of a short-term, calorie-restricted, and ketogenic diet plus exercise during intravenous chemotherapy versus usual care

BackgroundAn underlying cause of solid tumor resistance to chemotherapy treatment is diminished tumor blood supply, which leads to a hypoxic microenvironment, dependence on anaerobic energy metabolism, and impaired delivery of intravenous treatments. Preclinical data suggest that dietary strategies of caloric restriction and low-carbohydrate intake can inhibit glycolysis, while acute exercise can transiently enhance blood flow to the tumor and reduce hypoxia. The Diet Restriction and Exercise-induced Adaptations in Metastatic Breast Cancer (DREAM) study will compare the effects of a short-term, 50% calorie-restricted and ketogenic diet combined with aerobic exercise performed during intravenous chemotherapy treatment to usual care on changes in tumor burden, treatment side effects, and quality of life.MethodsFifty patients with measurable metastases and primary breast cancer starting a new line of intravenous chemotherapy will be randomly assigned to usual care or the combined diet and exercise intervention. Participants assigned to the intervention group will be provided with food consisting of 50% of measured calorie needs with 80% of calories from fat and ≤ 10% from carbohydrates for 48–72 h prior to each chemotherapy treatment and will perform 30–60 min of moderate-intensity cycle ergometer exercise during each chemotherapy infusion, for up to six treatment cycles. The diet and exercise durations will be adapted for each chemotherapy protocol. Tumor burden will be assessed by change in target lesion size using axial computed tomography (primary outcome) and magnetic resonance imaging (MRI)-derived apparent diffusion coefficient (secondary outcome) after up to six treatments. Tertiary outcomes will include quantitative MRI markers of treatment toxicity to the heart, thigh skeletal muscle, and liver, and patient-reported symptoms and quality of life. Exploratory outcome measures include progression-free and overall survival.DiscussionThe DREAM study will test a novel, short-term diet and exercise intervention that is targeted to mechanisms of tumor resistance to chemotherapy. A reduction in lesion size is likely to translate to improved cancer outcomes including disease progression and overall survival. Furthermore, a lifestyle intervention may empower patients with metastatic breast cancer by actively engaging them to play a key role in their treatment.Trial registrationClinicalTrials.gov, NCT03795493, registered 7 January, 2019.

MP22-13 PROSTATE LESION GROWTH VELOCITY ON CONSECUTIVE MRIS PREDICTS GRADE PROGRESSION

You have accessJournal of UrologyImaging/Radiology: Uroradiology II (MP22)1 Sep 2021MP22-13 PROSTATE LESION GROWTH VELOCITY ON CONSECUTIVE MRIS PREDICTS GRADE PROGRESSION Cheyenne Williams, Nitin Yerram, Michael Daneshvar, Luke P. OConnor, Jillian Egan, Patrick T. Gomella, Jeunice Owens-Walton, Nabila Khondakar, Michael Ahdoot, Maria Merino, Bradford Wood, Peter Choyke, Baris Turkbey, and Peter Pinto Cheyenne WilliamsCheyenne Williams More articles by this author , Nitin YerramNitin Yerram More articles by this author , Michael DaneshvarMichael Daneshvar More articles by this author , Luke P. OConnorLuke P. OConnor More articles by this author , Jillian EganJillian Egan More articles by this author , Patrick T. GomellaPatrick T. Gomella More articles by this author , Jeunice Owens-WaltonJeunice Owens-Walton More articles by this author , Nabila KhondakarNabila Khondakar More articles by this author , Michael AhdootMichael Ahdoot More articles by this author , Maria MerinoMaria Merino More articles by this author , Bradford WoodBradford Wood More articles by this author , Peter ChoykePeter Choyke More articles by this author , Baris TurkbeyBaris Turkbey More articles by this author , and Peter PintoPeter Pinto More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002013.13AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Multiparametric MRI (mpMRI) has demonstrated utility in diagnosing prostate cancer and selecting patients for active surveillance (AS). Additionally, among patients on AS, imaging changes over the course of surveillance may indicate pathological progression suggestive for a switch to active treatment. We explored the value of mpMRI for measuring index lesion growth velocity and changes in PI-RADS over the whole length of AS and assessed their value for predicting grade progression. METHODS: Patients with ≥2 surveillance MRIs and combined MRI-targeted and systematic biopsy were identified from a prospectively maintained AS database. Patients eligible for AS had Gleason grade group (GG) 1 or GG2 disease. Patients were included if they had consistent index lesions, defined by largest diameter, and measured across every surveillance MRI. Linear regression modeled the change in index lesion size over surveillance period in mm/year. Cox proportional hazard analysis modeled predictors of grade progression on active surveillance, and Kaplan-Meier curves compared progression risk among patients with no growth, 0-1mm/year growth and >1mm/year growth. RESULTS: Ultimately, 369 patients were included in the analysis. Median follow-up was 28 months, and patients received on average 3.1(±0.03) MRIs. Average index lesion growth rate was 0.40 (±0.05) mm/year. Grade progression was independently predicted by PSA density (OR: 1.52, CI: 1.16-1.99, p=0.003), having GG2 disease at AS enrollment (OR: 2.39, CI: 1.45-3.96, p <0.001), and index lesion growth (mm/year) (OR: 1.50, CI:1.17-1.93, p=0.001). Increase in PI-RADS was not independently predictive of progression (p>0.05); however, receiver operator curve analysis showed growth velocity+change in PI-RADS had good predictive value for progression (AUC=0.70). Median time to progression was 157 months for patients with no growth, 93 months for patients with 0-1 mm/year growth, and 49 months for patients with >1mm/year growth (log-ranked p <0.001) (Figure 1). CONCLUSIONS: Active surveillance MRI can reliably track prostate lesion growth over the course of surveillance, and growth velocity is independently associated risk of grade progression. Future use of lesion growth rate thresholds may be used to stratify patients who should switch from active surveillance to active treatment. Source of Funding: The National Institute of Health (NIH) Medical Research Scholars Program, Foundation for the NIH, NIH Intramural Research Program © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e396-e396 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Cheyenne Williams More articles by this author Nitin Yerram More articles by this author Michael Daneshvar More articles by this author Luke P. OConnor More articles by this author Jillian Egan More articles by this author Patrick T. Gomella More articles by this author Jeunice Owens-Walton More articles by this author Nabila Khondakar More articles by this author Michael Ahdoot More articles by this author Maria Merino More articles by this author Bradford Wood More articles by this author Peter Choyke More articles by this author Baris Turkbey More articles by this author Peter Pinto More articles by this author Expand All Advertisement Loading ...

SAVER: sodium valproate for the epigenetic reprogramming of high-risk oral epithelial dysplasia\u2014a phase II randomised control trial study protocol

BackgroundSodium valproate (VPA) has been associated with a reduced risk of head and neck cancer development. The potential protective mechanism of action is believed to be via inhibition of histone deacetylase and subsequent epigenetic reprogramming. SAVER is a phase IIb open-label, randomised control trial of VPA as a chemopreventive agent in patients with high-risk oral epithelial dysplasia (OED). The aim of the trial is to gather preliminary evidence of the clinical and biological effects of VPA upon OED and assess the feasibility and acceptability of such a trial, with a view to inform a future definitive phase III study.MethodsOne hundred and ten patients with high-risk OED will be recruited from up to 10 secondary care sites in the UK and randomised into either VPA or observation only for 4 months. Women of childbearing potential will be excluded due to the teratogenic properties of VPA. Tissue and blood samples will be collected prior to randomisation and on the last day of the intervention/observation-only period (end of 4 months). Clinical measurement and additional safety bloods will be taken at multiple time points during the trial. The primary outcome will be a composite, surrogate endpoint of change in lesion size, change in grade of dysplasia and change in LOH profile at 8 key microsatellite regions. Feasibility outcomes will include recruitment targets, compliance with the study protocol and adverse effects. A qualitative sub-study will explore patient experience and perception of the trial.DiscussionThe current management options for patients with high-risk OED are limited and mostly include surgical resection and clinical surveillance. However, there remains little evidence whether surgery can effectively lead to a notable reduction in the risk of oral cancer development. Similarly, surveillance is associated with concerns regarding delayed diagnosis of OED progressing to malignancy. The SAVER trial provides an opportunity to investigate the effects of a repurposed, inexpensive and well-tolerated medication as a potential chemopreventive strategy for patients with high-risk OED. The clinical and biological findings of SAVER will inform the appropriateness, design and feasibility of a definitive phase III trial.Trial registrationThe trial is registered with the European Clinical Trials Database (Eudra-CT 2018-000197-30). (http://www.isrctn.com/ISRCTN12448611). The trial was prospectively registered on 24/04/2018.

Experimental infection of Asian house geckos with Enterococcus lacertideformus demonstrates multiple disease transmission routes and the in-vivo efficacy of antibiotics

The disease caused by Enterococcus lacertideformus is multisystemic and ultimately fatal. Since its emergence, the bacterium has significantly impacted the captive breeding programs of the extinct in the wild Christmas Island Lister’s gecko (Lepidodactylus listeri) and blue-tailed skink (Cryptoblepharus egeriae). The bacterium’s pathogenicity, inability to grow in-vitro, and occurrence beyond the confines of Christmas Island necessitated the development of an experimental infection and treatment model. Asian house geckos (Hemidactylus frenatus) were challenged with a single dose of E. lacertideformus inoculum either by mouth, application to mucosal abrasion or skin laceration, subcutaneous injection, coelomic injection, or via co-housing with an infected gecko. Five healthy geckos acted as controls. Each transmission route resulted in disease in at least 40% (n = 2) geckos, expanding to 100% (n = 5) when E. lacertideformus was applied to skin laceration and mucosal abrasion groups. Incubation periods post-infection ranged between 54 and 102 days. To determine the efficacy of antibiotic treatment, infected geckos were divided into six groups (enrofloxacin 10 mg/kg, per os (PO), every 24 h (q24), amoxicillin-clavulanic acid 10 mg/kg, PO, q24, enrofloxacin 10 mg/kg combined with amoxicillin-clavulanic acid 10 mg/kg, PO, q24, rifampicin 15 mg/kg, PO, q24, clarithromycin 15 mg/kg, PO, q24, and untreated controls) for 21 days. Response to treatment was assessed by the change in lesion size, bacterial dissemination, and histological evidence of a host immune response. Irrespective of the antibiotic given, histology revealed that geckos inoculated by skin laceration were observed to have more extensive disease spread throughout the animal’s body compared to other inoculation routes. The reduction in the average surface area of gross lesions was 83.6% for geckos treated with enrofloxacin, followed by the combination therapy amoxicillin-clavulanic acid and enrofloxacin (62.4%), amoxicillin-clavulanic acid (58.2%), rifampicin (45.5%), and clarithromycin (26.5%). Lesions in geckos untreated with antibiotics increased in size between 100 and 300%. In summary, enrofloxacin and amoxicillin-clavulanic acid show promising properties for the treatment of E. lacertideformus infection in geckos. The Asian house gecko E. lacertideformus infection model therefore provides foundational findings for the development of effective therapeutic treatment protocols aimed at conserving the health of infected and at-risk reptiles.

Phase 2 Study of Carfilzomib and Bone Metabolism in Patients with Relapsed Multiple Myeloma

Background: Carfilzomib is an epoxyketone proteasome inhibitor (PI) that binds selectively and irreversibly to the constitutive proteasome and immunoproteasome. In addition to its direct cytotoxicity, PIs possess bone anabolic effect, by facilitating osteoblast differentiation, which in turn, inhibits multiple myeloma (MM) growth. However, the relative contribution of carfilzomib on direct tumor killing and bone formation has been difficult to discern when it is used in combination with other agents such as steroids, chemotherapeutics, or immunomodulatory agents (iMiDs); most of which increase bone loss.Objective: We explored the effect of single agent carfilzomib on bone metabolism and disease response in patients with relapsed MM.Methods: We conducted a phase II study of single-agent carfilzomib at 56 mg/m2 day 1, 2, 8, 9, 15, 16 of a 28 day cycle in patients with relapsed MM. Serum markers of bone resorption including carboxyterminal cross-linked telopeptide of type I collagen (ICTP) and tartrate resistant acid phosphatase 5b (TRACP 5b) and bone formation markers including N-terminal type 1 procollagen (P1NP) and osteocalcin (OC) were analyzed at baseline and 6 months after therapy, and compared using paired t-tests. Imaging using 18F-NaF PET-CT scans to monitor bone response and 8F-FDG PET-CT to measure localized tumor burden were done at baseline and 6 months post treatment. For each patient, the three sites with the highest baseline SUVs and an iliac crest (representing an uninvolved site) were selected for quantitative comparisons using paired t-test.Results: Ten patient were accrued. Average age was 70.1 +/- 6.79 (mean +/- SD) years. Median prior lines of therapy was 2. 9 were evaluable for response. Overall response rate was 77.8%: VGPR (1/9: 11%), partial response (6/9: 67%), stable disease (2/9: 22%). Median PFS was 11.5 months. Overall survival was 21.9 months. Common treatment adverse events (AE) were comparable to previous reports including diarrhea (40%), fever (40%), dyspnea (30%) and fatigue (30%). Grade 3/4 AEs, occurring in 10% each included neutropenia, thrombocytopenia, dyspnea, fatigue, vomiting, ataxia, heart failure and pulmonary edema.Serum ICTP and TRACP were elevated at baseline in 80% of subjects; means (+/- SD) of serum ICTP (14.4 +/- 3.1 ug/L) and TRACP (8.2 +/- 4.2 U/L), respectively. Both markers declined significantly after therapy (means +/- SD of serum ICTP 8.4 +/- 3.1 ug/L and TRACP (5.2 +/- 4.2 U/L); p<0.01), suggesting osteoclast suppression. Serum PINP and OC varied among subjects; 5 patients with low levels and 4 normal levels and 1 with elevated level: mean (+/- SD) of PINP 25 +/- 23 ug/L and OC (18 +/- 12 ug/L). Neither post treatment mean PINP nor OC differed significantly from baseline overall (p=0.16). However, all subjects who achieve PR or better had a more than 25% increase in PINP and OC, suggesting increased new bone formation.8F-FDG and 18F-NaF were positive in all subjects. Number of active sites and SUVs vary largely among subjects. 18F-NaF images mirrored the 8F-FDG signals, appearing as rings around the tumor sites, suggesting a bone reaction to the localized tumors. 6 of 9 subjects had post treatment PET/CTs for paired comparison. Post treatment 8F-FDG SUV of representative sites decreased significantly, while 18F-NaF SUVs varied; 58% of lesions had a decline in SUV, while 32% were unchanged and 10% were brighter, suggesting heterogeneous bone response. 18F-NaF SUVs of iliac sites decreased post treatment, suggesting a lower bone turnover overall. CT scans showed increased sclerosis at the rim of lytic lesions without significant change in lesion size, at this early time point.Conclusion: Carfilzomib at 56 mg/m2 dosing strongly inhibits bone resorption and demonstrates bone anabolic effects, in addition to cytotoxicity, in relapsed MM. Single agent use allows bone response analysis without the confounding effects of other anti-MM agents used in combination therapy. Response rates and side effects are favorable to prior reports. Serum markers of bone remodeling are useful for an assessment of overall bone metabolism while the 18F-NaF PET/CT allows assessment of both local and systemic changes but lacks specificity. Studies of osteoblast differentiation from subject's bone marrow stromal cells pre and post treatment are ongoing. Whether carfilzomib can heal bone lesions requires longer follow up. DisclosuresSuvannasankha:Celgene: Research Funding; Bristol-Myers Squibb: Research Funding; Takeda: Research Funding; Janssen Pharmaceuticals: Research Funding. Abonour:Celgene: Other: Steering committee, Research Funding; Prothena: Research Funding; Takeda: Other: Steering committee, Research Funding. Roodman:PharmaMar: Research Funding.