Unknown Grade Research Articles

Early testing and grade of the reaction are affecting factors of skin test positivity in β-Lactam allergies.

Background: β-Lactams are the most widely used antibiotic family in the world. Nevertheless, they also stand out as the primary culprits for inducing drug hypersensitivity reactions (HSR). Methods: Between May 2018 and March 2023, patients with suspected HSRs to β-lactams, who underwent skin tests (ST), were retrospectively screened. The determinants of allergenic penicillin (DAP) tests, which include penicillin minor and major determinants, clavulanic acid, and amoxicillin, along with ampicillin, sulbactam, the identified culprit drugs, and alternative cephalosporins, which include cefuroxime, ceftriaxone prick and/or intradermal tests, were administered. The analysis focused on identifying positive ST results and determining the true HSRs rates in this patient cohort. Results: Of the 147 patients, 78.9% (n = 116) were women and the median (minimum-maximum) age was 41 years (18-71 years). Mild HSRs (grades 1-2) were observed in 72.78% (n = 107), whereas 24.4% (n = 36) had severe reactions (grades 3-4) and 2.7% (n = 4) had an unknown grade. Of the patients, 64% (n = 94) experienced HSRs within the first hour after the last dose of the identified culprit drug. The overall positivity rate for all STs was 26.5% (n = 39). ST positivity rates were notably higher in individuals who had experienced HSRs within the past 6 months (p = 0.02) and those with severe anaphylaxis (p < 0.001). Conclusion: β-Lactam ST positivity is higher, especially in those with grades 3-4 reactions and consulted a physician within the first 6 months after their HSRs.

Treatment outcomes of brain metastasis from primary renal cell carcinoma in United States: A National Cancer Database analysis.

4561 Background: The advent of stereotactic radiosurgery (SRS) in treatment of brain metastasis (BM) has improved both clinical outcomes and survival in patients with BM. Recent studies suggest that immunotherapy presents a promising potential in the treatment of patients with BM. However, data regarding the effectiveness of combining SRS with immunotherapy for BM in metastatic renal cell carcinoma (RCC) remain largely unknown. We aim to delineate the impact of various treatment therapies including combination therapy for treatment of RCCBM. Methods: We queried the National Cancer Database (NCDB) to include patients with BM from mRCC from 2004 to 2020. We divided the patients into groups based on the treatment they received. Resultantly, 5 different treatment groups i.e., WRBT± immunotherapy, SRS± immunotherapy and immunotherapy alone were identified. We excluded patients with unknown treatment status. We analyzed survival outcomes using the Kaplan-Meier analysis and compared the effect of treatment modalities on survival with the log-rank test. Results: The NCDB yielded 6,446 patients diagnosed with BM from mRCC. In eligible cases, the median age was 63 years (range: 19-90+ years), 69.2% were male, 86.8% were White, 7.9% were Black, 41.9% had Medicare as primary payor, 27.7% had annual income &gt;$74,063, 79.3% belonged from metropolitan areas, 39.6% were treated at academic/research program, 68.3% had Charlson-Deyo score of 0, 44.6% had an unknown grade of the primary RCC. 1,705 (43.44%) patients who were given WBRT had a median overall survival (OS) of 5.65 months, 427 (10.88%) patients were treated with SRT + immunotherapy had an OS of 19.0 months, 987 (25.15%) patients who underwent SRT only had an OS of 9.7 months, 431 (10.98%) patients who received immunotherapy only showed an OS of 12.9 months, and 375 (9.55%) patients who underwent WBRT + immunotherapy had an OS of 12.78 months (log-rank p &lt;0.001). Conclusions: This national database analysis reveals that the combination of SRS with immunotherapy significantly increases the OS in RCCBM compared to immunotherapy, WBRT, or combination of WRBT and immunotherapy. Further prospective studies are warranted to confirm these findings. [Table: see text]

Results from the 2022 Mexican report card on physical activity for children and adolescents.

The Mexican Report Card on Physical Activity for Children and Adolescents aims to assess the prevalence of movement behaviors and opportunities to perform them. Data on 11 indicators were obtained from national health surveys, census data, government documents, websites, and published studies. Data were compared against established benchmarks, and a grade between 0 and 10 was assigned to each indicator. For Daily Behaviors, we found 34.5% of Mexican children and adolescents meet Physical Activity recommendations (Grade 3), 48.4% participate in Organized Sports (Grade 5), 35-75.8% engage in Active Play outdoors (Grade 4), 54.1% use Active Transportation (Grade 5), 43.6% spend <2 h in Sedentary Behavior per day (Grade 4), and 65-91% meet Sleep recommendations (Grade 7). Girls have lower physical activity levels and sports participation than boys of the same age. For Physical Fitness, we found 56.2-61.8% of children and adolescents have an adequate body mass index for their age (Grade 6). For Sources of Influence, we found 65-67% of parents engage in physical activity or sports in a week (Grade 7), 32.2-53.3% of basic education schools have a physical education teacher (Grade 6), and 37% of neighborhoods in Mexico have sidewalks with trees (Grade 4). Regarding Government, several policies and programs aimed at improving children physical activity were launched but their impact and allocated implementation budget are unknown (Grade 6). Mexican children and adolescents engage in low levels of movement behaviors and have limited opportunities to perform such behaviors. The grades and recommendations provided here should be considered to improve such opportunities.

Incidence of Malignant Peripheral Nerve Sheath Tumor in Saudi Arabia: A Registry-based Descriptive Analysis

Background: Malignant peripheral nerve sheath tumors (MPNSTs) refer to malignant tumors in the cells of the peripheral nerve or nerve sheath. This study was conducted to report the incidence and provide an overview of MPNSTs in Saudi Arabia due to the rarity and lack of studies on MPNSTs in the country. Methods: This retrospective cohort study of MPNSTs included all patients diagnosed with MPNSTs in Saudi Arabia between 2010 and 2020. The data was collected from the Saudi Cancer Registry (SCR) and was analyzed using John&amp;apos;s Macintosh Project (JMP) statistical software. Results: Twenty-five total with 25 MPNST cases were included in this study. The annual incidence in Saudi Arabia is 0.076 per million people. Of the patients, 15 were males (60.00%), and the median age was 36 (15–47) years. In this study, all 25 cases were diagnosed based on histopathology of the primary lesions (100.00%). For the sites of the lesions, the trunk and lower limbs were the most reported sites with six cases (24.00%) each. Regarding tumor grading, the majority had an unknown grade (18 cases, 72.00%), followed by grade II (moderately differentiated) in four cases (16.00%). Lastly, for tumor extension, 12 cases (48.00%) were localized, whereas only one case (4.00%) was distally metastasized. Conclusion: This study revealed a low incidence of MPNSTs in Saudi Arabia, providing information on gender distribution, age, geographical distribution, tumor site, grading, and tumor extension.

Graft-Versus-Host Disease (GvHD) and Steroid-Refractory GvHD after Allogeneic Hematopoietic Stem Cell Transplantation: A Large Real-World EBMT-Based Epidemiology and Treatment Pattern Study

Introduction: Graft-versus-host disease (GvHD) is a multi-systemic disorder affecting patients who undergo allogenic hematopoietic stem cell transplantation (allo-HSCT) and is associated with considerable morbidity and mortality both in its acute (a) and chronic (c) forms, particularly in patients with steroid-refractory (SR)-GvHD (Flinn AM and Gennery AR. Fac Rev 2023).Given the lack of real-life data on GvHD, this study was conducted using a large European database with the objective to provide evidence on the epidemiology and treatment patterns in patients with aGvHD, cGvHD, and SR-GvHD. Methods: This retrospective, observational cohort study was conducted between July 1, 2014 and December 31, 2020 in allo-HSCT patients registered to the European Society for Blood and Marrow Transplantation (EBMT) database. Male or female patients aged ≥12 years at index (≥18 years for SR-GvHD and ruxolitinib [RUX] cohorts) who had received ≥1 allo-HSCT during this study period (January 1, 2017 to July 1, 2019 for SR-GvHD and RUX cohorts) were included in the study population. The EBMT cohort included all allo-HSCT patients, irrespective of GvHD development post-transplant (Tx). The primary objective was to assess the cumulative incidence of aGvHD and cGvHD in patients from the EBMT cohort who met the inclusion criteria. Overall survival of patients up to 60 months was also assessed in the EBMT cohort. The SR-GvHD cohort comprised a sub-selection of GvHD patients (from selected EBMT centers) who were diagnosed with SR-aGvHD, SR-cGvHD, or both, some receiving RUX as treatment; from the SR-GvHD cohort, a sub-selection of patients who had been treated with RUX for aGvHD and/or cGvHD, irrespective of treatment line, were included in the RUX cohort. Results:In the EBMT database, 60,140 patients had received an allo-HSCT. Most patients (94.5%) underwent 1 allo-HSCT, the remaining had &amp;gt;1 procedure. The EBMT cohort included a higher proportion of male patients between 50 and 69 years (Table 1). The main indication for allo-HSCT was acute leukemia. At the time of Tx, most patients were in their early disease stage and had unrelated donors(Table 1). The cumulative incidence of aGvHD was 27.9% and 27.6%, 4 months after first and second Tx, respectively. The cumulative incidence of cGvHD was 37.4% and 29.7%, 60 months after first and second Tx, respectively. aGvHD was of grade 2-4 in 27.1% of patients, and the most affected organ was skin (33.6%, grade 2-4: 19.5%) followed by liver (4.0%, grade 2-4: 2.3%) and gut (4.6%, grade 2-4: 2.8%); however, organ involvement was not collected in many patients. The cGvHD was limited (13.6%), extensive (14.7%) or of unknown grade (3.1%). Graft failure occurred in 5.9% of patients. The overall survival of EBMT cohort patients at 60 months was 53.1% with a median follow-up time of 32.9 months. The most frequent cause of death was relapse/progression (30.6%) followed by infection (27.1%) and GvHD (19.1%). The EBMT registry contains more SR-GvHD patients but only for subset of 292 SR-GvHD patients, additional information was obtained, of which 37 (34.6%) patients were treated with RUX and 70 (65.4%) with other second-line (2L) treatment for SR-aGvHD. For SR-cGvHD, 59 (31.9%) received RUX and 126 (68.1%) other 2L treatment. Baseline characteristics were comparable between SR-GvHD and the EBMT cohort (Table 1). Within SR-GvHD treatment groups, overall, the baseline characteristics were comparable across RUX and other 2L, and consistent with the EBMT and SR-GvHD cohorts. Compared with other 2L treatment, a slightly higher proportion of RUX-treated patients were females in SR-aGvHD cohort and males in SR-cGvHD cohort. While the most common first-line treatment for aGvHD in both RUX and the other group was methylprednisolone, for SR-cGvHD, it was prednisone+cyclosporine in RUX and prednisone in the other group. Conclusion:This large retrospective real-world evidence study from the EBMT reports on patients with GvHD after allo-HSCT. The cumulative incidence of aGvHD at 4 months post-Tx and cGvHD at 60 months was similar after the first or the second Tx. Though this study provides valuable insights on the epidemiology and treatment patterns of SR-GvHD patients, interpretation of these data is limited due to the small sample size of RUX and other treatment groups compared with the EBMT cohort.

Using Public Landslide Inventories for Landslide Susceptibility Assessment at the Basin Scale: Application to the Torto River Basin (Central-Northern Sicily, Italy)

In statistical landslide susceptibility evaluation, the quality of the model and its prediction image heavily depends on the quality of the landslide inventories used for calibration. However, regional-scale inventories made available by public territorial administrations are typically affected by an unknown grade of incompleteness and mapping inaccuracy. In this research, a procedure is proposed for verifying and solving such limits by applying a two-step susceptibility modeling procedure. In the Torto River basin (central-northern Sicily, Italy), using an available regional landslide inventory (267 slide and 78 flow cases), two SUFRA_1 models were first prepared and used to assign a landslide susceptibility level to each slope unit (SLU) in which the study area was partitioned. For each of the four susceptibility classes that were obtained, 30% of the mapping units were randomly selected and their stable/unstable status was checked by remote analysis. The new, increased inventories were finally used to recalibrate two SUFRA_2 models. The prediction skills of the SUFRA_1 and SUFRA_2 models were then compared by testing their accuracy in matching landslide distribution in a test sub-basin where a high-resolution systematic inventory had been prepared. According to the results, the strong limits of the SUFRA_1 models (sensitivity: 0.67 and 0.57 for slide and flow, respectively) were largely solved by the SUFRA_2 model (sensitivity: 1 for both slide and flow), suggesting the proposed procedure as a possibly suitable modeling strategy for regional susceptibility studies.

HLA Linked Regional Differences in Donor Selection: A 9-Year Study of the Swiss Registry

Introduction: The large HLA diversity in worldwide populations is a major challenge for matched unrelated haematopoietic stem cell (HSC) donor searches. The impact of regional diversity on the effective HSC donor selection has not been documented so far for national registries. Methods: The aim of the study was to analyse the 532 consecutive work-up (WU) requests received by Swiss Blood Stem Cells (SBSC), over a 9-year period (2011–2019) with respect to criteria including the geographical origin of the donors as derived from the postal codes, countries requesting SBSC donors, HLA-matching parameters, and patients’ HLA haplotype frequencies. Results: Highly matched donors (10/10) represented 73.5% of the WU, whereas 8–9/10 mismatched donors accounted for 24.0%. The remaining donors were 7–8/8 matched (1.7%) or had an unknown matching grade (0.8%). Among the 10/10 matched patient/donor pairs with full HLA-DPB1 typing information, the rate of 11–12/12 matched donors was 73.3%. Of the 532 WU requests, 47.6% were for patients of the four neighbouring countries and for national patients. The ratio of WU requests was directly proportional to the total number of donors registered in each region (Pearson’s r = 0.977). However, for two regions (lemanic and north-eastern areas of Switzerland (CH)), the proportion of selected donors was slightly above the min-max ratio of registered donors throughout the study period. The number of WU requests differed between countries when considering donors from the northern and southern parts of the country delineated by the alpine barrier. Conclusion: This study shows the value of the SBSC registry for both national and international patients. Two countries (USA and Germany) which operate the two worldwide largest registries (>19 million donors) requested 30% of SBSC registered donors, while the Swiss transplant centres accounted for 13% of the WU requests. When considering the geographic origin of SBSC donors, we observe a correlation of WU requests with the total number of registered donors in each subregion. This finding thus supports recruitment efforts throughout all regions. Interestingly, donors from three regions (lemanic area, Zurich and Ticino) are slightly over-represented, which is possibly related to higher HLA haplotypic diversity. A focus on planning recruitment in these regions might contribute to more successful donor searches.

Using chemotherapy response by KELIM score to predict response to first line maintenance PARP inhibitor therapy in non-BRCA mutant/homologous recombination deficiency (HRD) unknown high grade serous ovarian cancer (HGSOC).

e17547 Background: Maintenance PARP inhibitor therapy after response to first line chemotherapy is now standard of care in advanced HGSOC. Niraparib is available to all patients based on the PRIMA trial data; however, the progression free survival (PFS) benefit for patients without BRCA mutations or homologous recombination deficiency (HRD) is limited. Funded HRD testing is not accessible in many countries. Patient selection for PARPi therapy in non-BRCA mutant HGSOC is challenging. The calculated CA-125 ELIMination of Rate Constant K (KELIM) score is a mathematical model developed to evaluate CA-125 kinetics during chemotherapy. KELIM has been shown to correlate with chemosensitivity, with scores ≥1 associated with better clinical outcomes. This project aims to use real-world patient data to assess if surrogate markers, such as KELIM score and/or pathological chemotherapy response score, can predict response to 1st line maintenance PARPi in the absence of funded HRD testing. Methods: A retrospective review of non-BRCA mutant HGSOC cases on first line maintenance PARPi therapy at BC Cancer, Canada between April 2020 and June 2022. Only cases confirmed to be non-BRCA mutant (by both germline and tumour testing) were included in the study. Data collection was through electronic medical records and included patient demographics, chemotherapy intent (neoadjuvant vs. adjuvant), pathological (p) chemotherapy response score (CRS), progression-free survival (PFS) defined as start of niraparib to radiological evidence of disease progression. PFS analysis was performed in all patients provided 1 full cycle had been completed. The rate of not progressing at 12 months (PFS12) was calculated. KELIM score was calculated from at least 3 CA125 values taken within 100 days from the chemotherapy start date and using a validated calculation software. Results: 70 patients met the full eligibility criteria for analysis. All patients received niraparib as PARPi therapy. Mean age was 67 years and 40 patients (57%) were ≥ 65 years. Most patients were FIGO stage 3C at presentation (56%). Median number of niraparib cycles was 10 (range 1-28). 35/70 patients (50%) had disease progression at time of data analysis with a median follow-up of 13.2 months. 59 patients had evaluable KELIM scores. pCRS was not associated with any statistically significant differences in PFS. Patients with KELIM scores ≥1 had a trend to greater PFS from niraparib vs. those with KELIM &lt;1 with median PFS of 15 months vs. 8.3 months respectively ( p=0.06). PFS12 rate was higher at 64% with KELIM scores ≥1 vs. 43% with KELIM &lt;1; ( p=0.18). Conclusions: We show that KELIM score could be a useful tool to predict PARP inhibitor response and aid clinical decision-making by oncologists and patients in the real world setting where HRD testing is unfunded.

Evaluation of the Survival Outcomes of Intestinal Adenosquamous Carcinomas Using the SEER 18 Registry: What Do We Know?

Background: Intestinal adenosquamous carcinoma (ASC) is a rare malignancy. This study evaluated overall survival of this malignancy in the small intestine, colon, and rectum. Methods: Using the Surveillance, Epidemiology, and End Results (SEER) 18 registry, we analyzed cases from 2000 through 2015 by Cox proportional hazards using univariate and multivariate analysis, adjusting for age, primary tumor site, tumor grade, and type of surgery performed to calculate the hazard ratios for overall survival. All analyses were performed on R version 4.0.5. Results: We identified 332 patients with ASC: small intestine ( n = 20, 6.02%), colon ( n = 200, 60.2%) and rectum ( n = 112, 33.7%). Age of diagnosis was significantly different between the groups: 44.5, 40, and 36, for small intestine, colon, and rectum, respectively ( p &lt; 0.05). The 5-year survival for small intestine, colon, and rectum were 5.0%, 24.9% and 42.5%, respectively ( p &lt; 0.001). Based on grade of cancer at diagnosis, overall 5-year survival was 61% for 1, 39.9% for 2, 25.9% for 3/4 tumors, and 24.1% for tumors of unknown grade with significant difference ( p = 0.006). The overall hazard ratio in poorly differentiated grade 3 tumors was 3.17 times that of well-differentiated tumors (95% CI, 1.01–9.96, p &lt; 0.05). The overall hazard ratio for death in patients without any surgical intervention was 3.33 (95% CI, 2.34–4.72, p &lt; 0.001) compared to patients who had surgery. Conclusion: There was high rate of diagnosis in advanced stages of ASC, which was associated with poor survival outcomes. Patients who underwent surgical intervention had better survival outcomes when adjusted for grade and site of tumor.

Recurring Pancreatic Neuroendocrine Tumor: Timing and Pattern of Recurrence and Current Treatment.

The objective of this study was to describe the pattern of recurrence, treatments received, as well the oncological outcomes, of pancreatic neuroendocrine tumors (PanNETs) following curative surgery. PanNETs recur in 10% to 15% of cases following surgery. Information on the natural history and management of recurring disease is lacking. Patients with PanNET that underwent curative surgery at 4 institutions between 2000 and 2019 were identified. Patients with poorly differentiated tumors, unknown tumor grade and differentiation, hereditary syndromes, unknown margin or R2 status, metastatic, and those that had neoadjuvant treatment or perioperative mortality were excluded. Clinical variables were assessed including first site of recurrence, treatment received, and survival outcomes. A total of 1402 patients were included: 957 (74%) had grade 1, 322 (25%) had grade 2, and 13 (1%) had grade 3 tumors. Median follow-up was 4.8 years (interquartile range: 2-8.2 years). Cumulative incidence of recurrence at 5 years was 13% (95% CI: 11%-15.2%) for distant disease, 1.4% (95% CI: 0.8%-2.3%) for locoregional recurrence, and 0.8% (95% CI: 0.4%-1.5%) for abdominal nodal recurrence. Patients who recurred had 2.89 increased risk of death (95% CI: 2-4.1) as compared with patients who did not recur. Therapy postrecurrence included: somatostatin analogs in 111 (61.0%), targeted therapies in 48 (26.4%), liver-directed therapies in 61 (33.5%), peptide receptor radionuclide therapy in 30 (16.5%), and surgery in 46 (25.3%) patients. Multiple treatments were used in 103 (57%) cases. After the first recurrence, 5-year overall survival was 74.6% (95% CI: 67.4%-82.5%). Recurrence following surgery is infrequent but reduces survival. Most recurrences are distant and managed with multiple therapies. Prospective studies are needed to establish strategies for surveillance and the sequence of treatment to control the disease and prolong survival.

Surgery versus radiotherapy in octogenarians with stage Ia non‑small cell lung cancer: propensity score matching analysis of the SEER database

ObjectivesTo compare overall survival (OS) and cancer-specific survival (CSS) outcomes of surgery with radiotherapy in octogenarians with stage Ia non-small cell lung cancer (NSCLC).Materials and methodsPatients aged ≥ 80 years with clinical stage Ia (T1N0M0) NSCLC between 2012 and 2017 were identified from the population-based Surveillance, Epidemiology, and End Results (SEER) database. Patients were assigned into surgery and radiotherapy groups. Multivariate Cox regression analysis was used to identify survival-associated factors. Treatment groups were adjusted by propensity score matching (PSM) analysis while OS and CSS outcomes were compared among groups by Kaplan–Meier analysis.ResultsA total of 1641 patients were identified, with 46.0% in the surgical group and 54.0% in the radiotherapy group. Compared to surgery, radiotherapy-treated patients were older, later diagnosed, had more often unmarried, more squamous cell carcinoma, more unknown grade and increased tumor sizes. Radiotherapy was associated with a significantly worse OS, compared to surgery (hazard ratio 2.426; 95% CI 2.003–2.939; P < .001). After PSM, OS (P < 0.001) and CSS (P < 0.001) were higher in the surgery group. The 1-, 3-, and 5-year OS rates of surgical and radiotherapy group were 90.0%, 76.9%, 59.9%, and 86.0%, 54.3%, 28.0%, respectively. The 1-, 3-, and 5-year CSS rates of surgical and radiotherapy group were 94.5%, 86.1%, 78.0% and 90.7%, 74.5%, 61.0%, respectively. There were no survival differences between the matched surgery without lymph node examination (LNE) and radiotherapy group, as well as between the matched surgery and radiotherapy who were recommended but refused surgery group.ConclusionsIn octogenarians with stage Ia NSCLC, surgery with lymph node dissection offers better OS and CSS outcomes than radiotherapy.

Initial observational management of hydronephrosis in infants with reduced differential renal function and non-obstructive drainage parameters

Hydronephrosis secondary to ureteropelvic junction (UPJ) obstruction is a common finding in infants with prenatally-diagnosed hydronephrosis and often results in pyeloplasty due to obstructive drainage parameters and/or renal function compromise. However, little is known regarding the natural history of hydronephrosis with reduced differential renal function (DRF) but non-obstructive drainage. We sought to explore our experience with initial observational management of these patients. A retrospective review of our institutional database of all diuretic MAG-3 renal scans obtained between 2000 and 2016 was performed. We included patients with antenatally-detected unilateral hydronephrosis≥SFU grade 2, first MAG-3 scan prior to 18months of age, DRF <40% and post-furosemide half-time (T1/2) <20min. Exclusion criteria were: hydroureter, VUR, solitary kidney, duplication anomalies. Outcomes of interest were a progression of T1/2≥20min and/or further decline in DRF >5%. Of 704 patients with unilateral hydronephrosis, 91 had DRF≤40%, of which 29 (18 boys, 11 girls) met our inclusion criteria and were followed for a mean of 2.8 years (1.4 months-6.6 years). Mean age at first sonogram was 2.3 months. 2 patients had SFU grade 2, 16 had grade 3, and 9 had grade 4 hydronephrosis, and 2 unknown grade. Median half-time on initial MAG-3 scan across all patients was 10min (3-20min). Initial MAG3 scan was performed at a median of 2.3 months of age (0.3-17 months). 22/29 patients had >1 MAG3 scan. Of the 7 remaining, 5 were lost to follow-up and 2 demonstrated improvement in hydronephrosis. Worsening drainage occurred in 10/22(45%), median final T1/2 was 45.5min 8 of these underwent pyeloplasty and 2 were lost to follow up. 4/22 patients (18%) had progressive decline in DRF (mean 8.3%, range 6-10%). 3/4 maintained non-obstructive drainage patterns and stable/improved hydronephrosis, and 1 underwent pyeloplasty. 13/18 remaining patients had stable DRF and 5 had improvement in DRF. 7(39%) of these underwent surgery for worsening drainage (Summary Figure). Overall, 7/29(24%) patientshad sufficient resolution of hydronephrosisto bedischarged from our care, 8(28%) are under continued observation, 9(31%) underwent pyeloplasty, and 5(17%) were lost to follow-up. In the observational group [median follow-up 4.5 years (3.7-6.6 years)], all 8 demonstrated improved non-obstructive drainage (T1/2 <20 minutes) and/or improvement in hydronephrosis. 4/10(40%) with DRF <35% underwent pyeloplasty versus 5/19(26%) with DRF 35-40%(p=0.67). Initial observational management of unilateral hydronephrosis with reduced DRF and nonobstructive drainage is recommended as most kidneys maintain nonobstructive drainage and do not demonstrate further decline in DRF. Even when DRF decreases, the majority remain non-obstructive. Worsening drainage over time more often leads to the decision for pyeloplasty rather than change in DRF.

Cancer-specific Mortality in T1a Renal Cell Carcinoma Treated with Local Tumor Destruction Versus Partial Nephrectomy

BackgroundLarge-scale analyses addressing cancer-specific mortality (CSM) in T1a renal cell carcinoma (RCC) patients treated with local tumor destruction (LTD), relative to partial nephrectomy (PN), are scarce. ObjectiveTo compare CSM after LTD versus PN. Design, setting, and participantsWithin the Surveillance, Epidemiology, and End Results (SEER) database (2004–2018), we identified patients with clinical T1a stage RCC treated with LTD or PN. Outcome measurements and statistical analysesAfter 1:1 ratio propensity score matching (PSM) between patients treated with LTD versus PN, competing risks regression (CRR) models addressed CSM, after adjustment for other-cause mortality (OCM) and other covariates (age, tumor size, tumor grade, and histological subtype). Results and limitationsRelative to the 35 984 PN patients, 5936 LTD patients were older and more frequently harbored unknown RCC histological subtype or unknown grade. After 1:1 PSM that resulted in 5352 LTD versus 5352 PN patients, the 10-yr CSM rate was 8.7% versus 5.5%. In multivariable CRR models, LTD was associated with higher CSM, relative to PN (hazard ratio [HR]: 1.58, p < 0.001). Subgroup analyses revealed invariably higher CSM after LTD versus PN in patients with tumor size ≤3 cm (10-yr CSM 7.2% vs 5.3%, multivariable HR: 1.47, p < 0.001) and in patients with tumor size 3.1–4 cm (10-yr CSM 11.4% vs 6.1%, multivariable HR: 1.72, p < 0.001). Lack of information regarding earlier cancer controls, retreatment, tumor location within the kidney, and type of surgery represented limitations. ConclusionsIn T1a RCC patients, LTD is invariably associated with higher CSM relative to PN, even after adjustment for OCM and all available patient and tumor characteristics, and regardless of tumor size considerations. However, the magnitude of CSM disadvantage was more pronounced in LTD patients with tumor size 3.1–4 cm than in those with tumor size ≤3 cm. Patient summaryIn patients with small renal masses, we observed higher cancer-specific death rates for local tumor destruction (LTD) than for partial nephrectomy. The LTD disadvantage was more pronounced for patients with tumor size 3.1–4 cm, but was also present in those with tumor size ≤3 cm.

A novel histogram based on the SEER database predicts overall survival in patients with high‐grade cerebellar glioma

ObjectiveHigh‐grade cerebellar gliomas are clinically challenging to treat, and there is a relative lack of large sample statistics as a prognostic criterion. In order to compare changes in patient survival under different conditions, we screened the risk factors that affecting survival in patients with high‐grade cerebellar gliomas, developed Nomograms and verified their accuracy.MethodsPatients with high‐grade cerebellar glioma from 1975 to 2016 were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database, excluding patients with no biopsy or surgery, unknown tissue type, grade, or survival data, then coded patient data for classification and processed, and a prediction group and a validation group were randomly assigned using the CARET procedure in R (4.0.2). We use univariate and multivariate Cox regression models to screen variables that were significantly related to the prognosis of patients with high‐grade cerebellar glioma, and these variables were then used to construct Nomogram. Secondly, we use the consistency index (C‐index), receiver operating characteristic curve (ROC), calibration chart and decision curve analysis (DCA) to analytically validate the accuracy of the Nomogram model. Finally, Kaplan‐Meier survival analysis was used to test the prognostic indicators of Nomogram.ResultsA total of 197 patients with high‐grade cerebellar glioma were selected from the SEER database, and the patient data were categorized and coded into a prediction group (n = 100) and a validation group (n = 97). Univariate and multivariate Cox regression models were used to obtain four statistically significant indices of age, tumor type, type of surgery, and radiation therapy, which were then used to construct Nomogram with a C‐index of 0.830 (95% CI: 0.765‐0.895) for the prediction group and 0.789 (95% CI: 0.715‐0.863) for the validation group.ConclusionNomograms have promising clinical applicability and more accurate predictive outcome. For patients with cerebellar glioma, radiotherapy and surgical resection are definitive in improving prognosis. Older patients tend to die earlier, and the pathological type is also a key factor in prognosis.

Algorithm to Identify Incident Epithelial Ovarian Cancer Cases Using Claims Data.

To create an algorithm to identify incident epithelial ovarian cancer cases in claims-based data sets and evaluate performance of the algorithm using SEER-Medicare claims data. We created a five-step algorithm on the basis of clinical expertise to identify incident epithelial ovarian cancer cases using claims data for (1) ovarian cancer diagnosis, (2) receipt of platinum-based chemotherapy, (3) no claim for platinum-based chemotherapy but claim for tumor debulking surgery, (4) removed cases with nonplatinum chemotherapy, and (5) removed patients with prior claims with personal history of ovarian cancer code to exclude prevalent cases. We evaluated algorithm performance using SEER-Medicare claims data by creating four cohorts: incident epithelial ovarian cancer, a 5% random sample of cancer-free Medicare beneficiaries, a 5% random sample of incident nonovarian cancer, and prevalent ovarian cancer cases. Using SEER tumor registry data as the gold standard, our algorithm correctly classified 89.9% of incident epithelial ovarian cancer cases (cohort n = 572) and almost 100% of cancer-free controls (n = 97,127), nonovarian cancer (n = 714), and prevalent ovarian cancer cases (n = 3,712). The overall algorithm sensitivity was 89.9%, the positive predictive value was 93.8%, and the specificity and negative predictive value were > 99.9%. Patients were more likely to be correctly classified as incident ovarian cancer if they had stage III or IV disease compared with early stage I or II disease (93.5% v 83.7%, P < .01), and grade 1-4 compared with unknown grade tumors (93.8% v 81.4%, P < .01). Our algorithm correctly identified most incident epithelial ovarian cancer cases, especially those with advanced disease. This algorithm will facilitate research in other claims-based data sets where cancer registry data are unavailable.

Modifiable risk factors associated with long-term survival in women with serous ovarian cancer: a National Cancer Database study

ObjectiveTo identify patient, clinical and hospital factors associated with long-term survival (≥10 years) in women with serous ovarian cancer.MethodsThis National Cancer Database cohort study included women with stage II–IV serous...

Machine Learning Based Prediction for the Response of Gas Discharge Tube to Damped Sinusoid Signal

In order to predict the circuit response of a Gas Discharge Tube (GDT) to an electromagnetic pulse, a “black box” model for a GDT based on a machine learning method is proposed and validated in this paper.Firstly, the machine learning model of the Elman neural network is established by taking advantage of the existing measurement data to dampen the sinusoid signal, and then the established model is adopted to predict the response waveform of an unknown injection current grade and frequency.Without considering the complex physical parameters and dynamic behavior of GDTs, the Elman neural network modeling method is simpler than the existing physical or Pspice model.Validation experiments show a good agreement between the predicted and the measured waveforms.

Abstract P1-18-16: First line aromatase inhibitor (AI) + palbociclib with randomized switch to fulvestrant + palbociclib upon detection of circulating ESR1 mutation in HR+ HER2- metastatic breast cancer patients: Global safety results of PADA-1, a UCBG-GINECO phase III trial

Abstract Background: Aromatase inhibitors (AI) in combination with a CDK 4/6 inhibitor have been established as the standard first line treatment of non AI-resistant hormone receptor-positive (HR+) HER2- metastatic breast cancer (mBC) patients (pts). ESR1 mutations are known drivers of resistance to AIs in the metastatic setting but their actionability remains unknown. The phase 3 PADA-1 trial aimed both at refining the global safety of palbociclib combined to any AI as first line treatment of HR+ HER2- mBC pts, and at evaluating the clinical benefit associated with a switch to fulvestrant-palbociclib upon detection of a rising ESR1 mutation in blood (bESR1mut). Methods: PADA-1 (NCT03079011), a multicenter, randomized, open-label, phase 3 trial, enrolled HR+ HER2- mBC pts with no prior therapy for mBC, in the absence of AI-resistance. In the first step, pts received a combination of any AI and palbociclib at standard recommended doses and underwent centralized bESR1mut screening every two months. In the second step, bESR1mut+ pts with no clinical/imaging concomitant disease progression were randomized between continuing the same therapy (standard arm) or switching to fulvestrant-palbociclib (experimental arm). The third step consisted in an optional cross-over after tumor progression for patients randomized in the standard arm. PADA-1 co-primary endpoints were global safety of the combination of palbociclib + endocrine therapy in the whole population of patients, throughout the study, with focus on hematological toxicities; and PFS in the second step. We present here the results of the global safety co-primary endpoint. Results: From 3/2017 to 01/2019, 1017 pts were accrued in 83 sites. As per 05/2021, 272 pts were still in step 1, 35 in step 2, and 8 in step 3. The overall follow-up was 33.7 months. 232 pts have deceased. 333 SAEs have been reported, including 21 grade 5, 35 grade 4, 183 grade 3, 53 grade 2, 26 grade 1 and 15 unknown grade. Among the grade 5 cases, 2 have been declared as potentially related to the underlying treatment (Death of unknown cause, pulmonary embolism). No pt died of SARS-CoV2 infection. The main hematological toxicities encountered, as well as selected non-hematological events are described in Table 1. Permanent discontinuation of the treatment due to toxicity occurred in 39 pts/1017 (3.8%). Palbociclib dose decreases occurred in 419 (41.2%) pts. Conclusion: By the number of included patients, PADA-1 is the largest prospective trial with 1st line AI and palbociclib. Data confirm the favorable safety profile of palbociclib when combined to any AI +/- switch to fulvestrant. Hematological toxicity appears limited and is mostly restricted to non-clinically significant neutropenia. Permanent discontinuation was exceptional. Detailed per-step analyses will be presented. Table 1.Adverse events (% pts)Grade 3, N (%)Grade 4, N (%)Neutropenia628 (61.8%)83 (8.2%)Febrile neutropenia4 (0.4%)0Thrombocytopenia18 (1.8%)3 (0.3%)Anemia24 (2.4%)0Lymphocytopenia58 (5.7%)5 (0.5%)Insterstitial lung disease4 (0.4%)0Liver enzymes increase (AST/ALT)5 (0.5%)0Mucositis10 (1%)0 Citation Format: Suzette Delaloge, Anne-Claire Hardy-Bessard, Thomas Bachelot, Jean-Yves Pierga, Jean-Luc Canon, Florian Clatot, Fabrice André, Thibault De La Motte Rouge, Barbara Pistilli, Florence Dalenc, Nadine Dohollou, Olivier Arsene, Thierry Petit, Cecilia Riedl, François Morvan, Adina Marti, Emma Lachaier, Mihaela Achille, Michel Gozy, Anne Escande, Dominique Mille, Fanny Trouboul, Sandrine Marques, Jerome Lemonnier, Frederique Berger, François-Clément Bidard. First line aromatase inhibitor (AI) + palbociclib with randomized switch to fulvestrant + palbociclib upon detection of circulating ESR1 mutation in HR+ HER2- metastatic breast cancer patients: Global safety results of PADA-1, a UCBG-GINECO phase III trial [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-18-16.

Abstract P1-22-06: A longitudinal cohort study of outcomes in 311 women with unresected ductal carcinoma in situ detected through the English breast screening programme

Abstract Background The variable natural history of ductal carcinoma in situ (DCIS) is poorly understood. The aim of this retrospective cohort study was to determine the outcomes of women who were diagnosed through the English National Health Service Breast Screening Programme (NHS BSP) and had no surgery for screen-detected DCIS. Method English NHS BSP databases were searched for women diagnosed with DCIS without invasive cancer on needle biopsy between 1 April 2001 and 31 March 2018 inclusive, who had no record of surgery within 6 months of diagnosis. These were cross-referenced with cancer registry data for further treatment, event information and mortality records. Details of potentially eligible women were sent to the relevant breast screening units for verification and for completion of data forms detailing clinical, radiological and pathological findings, non-surgical treatment, subsequent clinical course and outcomes. Results Data for 311 eligible women (median age 62 years) were included, with median follow-up (primary DCIS diagnosis to either surgery, development of invasive disease, death or last known to be alive) of 4.1 years (range 0.5 to 17.4 years). The median age at diagnosis was 64 years (range 47 to 90 years). Sixty (19%) women developed invasive breast cancer, 56 ipsilateral and 4 contralateral. Twenty-two women (7%) underwent surgery for DCIS (&amp;gt;6 months after diagnosis) and 86 (28%) died of other causes. Women with high or intermediate grade DCIS were significantly more likely to develop ipsilateral invasive breast cancer (iIBC) than those with low grade DCIS. 28/123 (23%) with high grade DCIS, 21/105 (20%) with intermediate grade DCIS, 5/76 (7%) with low grade DCIS and 2/7 (29%) with an unknown grade of DCIS developed iIBC. Ipsilateral invasion risk increased approximately linearly with time for at least 10 years. Women who developed iIBC were significantly younger than those who did not. This was driven primarily by a strong association among those with high grade DCIS. There was no significant difference in age between those with intermediate and low grade DCIS respectively who did or did not develop iIBC. The median baseline size of DCIS in women who developed iIBC was higher than in women who did not develop iIBC, both overall and in each of the three grade categories (median sizes - high grade 38 mm vs 29 mm, p=0.19; intermediate grade 35 mm vs 18 mm, p=0.31; low grade 18 mm vs 15 mm, p=0.38). This reached statistical significance for all grades combined: 37 mm (range 3-95) v 20 mm (range 3-200), p=0.02. Of the 262 women with a known microinvasion status, 8/25 (32%) with definite or possible microinvasion were subsequently diagnosed with ipsilateral invasive cancer compared to 38/237 (16%) without microinvasion (p=0.027). There was no significant association on univariable analysis between risk of iIBC and microcalcification as the predominant radiological feature (iIBC and microcalcification 47/258 vs iIBC and other radiological feature 7/46; p=0.83), the presence of histological necrosis (iIBC and necrosis, 14/89 vs iIBC and no necrosis, 31/157; p=0.49) or the use of ET (iIBC and ET 11/67 vs iIBC and no ET 45/244; p=0.86). Of the 51 invasive cancers that developed with a known grade, 46 (90%) were grade 2 or 3. Conclusion The findings suggest that women diagnosed with high or intermediate grade DCIS and those with microinvasion should continue to be offered surgery. For those with low grade DCIS there is a need for shared decision-making in the choice of surgery or active surveillance based on a discussion of the risks and benefits of the options as currently understood, and in the light of the low reproducibility of DCIS grading. Citation Format: Karen Clements, Anthony Maxwell, Bridget Hilton, Matthew Wallis, Cliona Kirwan, Hilary Stobart, Elena Provenzano, Nisha Sharma, Janet Litherland, Abeer Shaaban, David Dodwell, Joanne Dulson-Cox, Elinor Sawyer, Senthurun Mylvaganam, Olive Kearins, Samantha Brace-McDonnell, Sarah Pinder, Alastair Thompson. A longitudinal cohort study of outcomes in 311 women with unresected ductal carcinoma in situ detected through the English breast screening programme [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-22-06.

Correlation of circulating tumor DNA (ctDNA) with clinical outcomes in appendiceal cancers (AC).

29 Background: Appendiceal Cancers are a heterogenous group of rare tumors with distinct histopathologic and genomic alterations. These often have peritoneal spread that might not be easily detected on current imaging modalities, and conventional tumor markers may not lend diagnostic support. Hence, novel diagnostic techniques are needed. Measurement of ctDNA for recurrence risk prediction, response to therapy and and early diagnosis is a promising technique. However, limited published data exist in AC to validate the role and utility of ctDNA in clinical practice. Here we present a single institution experience of ctDNA analysis in patients with AC. Methods: ctDNA measurements of 37 pts with stage II-IV AC treated between 1/1/2019 and 9/15/2021 were reviewed retrospectively. ctDNA analysis was done using Signatera bespoke mPCR NGS assay. ctDNA results were compared to crossectional imaging, CEA levels, and clinical evaluation. Results: 19/37 patients (51%) had at least one positive ctDNA test result. Of those, 8 had testing done during the surveillance setting (two with grade 3, one with grade 2, two with grade 1, and three with unknown grade). Of those, 5 pts (62.5%) had positive ctDNA detected, while 33.33% had elevated CEA level, 25% had radiographic and 42.9% had clinical evidence of recurrence (Table). 7/14 (50%) pts had high-grade pathology and positive ct-DNA, 3/6 (50%) patients had low-grade (grade 1) pathology and positive ct-DNA findings. 4 patients had longitudinal ct-DNA measurements available which correlated well with their disease course. Median duration to recurrence (radiographic or laparoscopic) was 376 days. Median duration to the first positive ctDNA test was 370 days. Median duration to positive CEA after initial treatment was 475 days. Conclusions: Measurement of ctDNA can be a useful tool to follow disease course and to guide management decision-making in patients with AC. Prospective studies with serial measurements of ctDNA are planned. [Table: see text]