Low-stage Disease Research Articles

Analyzing factors associated with the receipt of surgery in clear cell sarcoma.

447 Background: Clear cell sarcoma (CCS) is a ultrarare soft tissue sarcoma, which is highly aggressive and associated with a poor prognosis. CCS is histologically characterized by clear cells, representative of intracellular glycogen accumulation. Primary tumors commonly arise from tendinous sheaths or aponeuroses in the upper and lower extremities—the most common site being around the ankles. Average age at diagnosis is 25 years old. 5-year survival is between 40 and 60%. CCS is the result of fusion gene EWSR1/ATF1. Multimodal therapy, including wide surgical excision with radiotherapy, is often used to treat CCS. Chemotherapy may be used if patients are not eligible for surgery. No significant study has analyzed the factors which predict the utilization of wide surgical excision. This study aims to describe the factors involved in the receipt of this surgery. Methods: The National Cancer Database (NCDB) was used to identify patients diagnosed with CCS from 2004 to 2020 using histology codes 9044 as assigned by the Commission on Cancer Accreditation program. Kaplan-Meier, ANOVA Chi-Square, and Logistic Regression tests were performed, and data were analyzed using SPSS version 27. Statistical significance was set at α = 0.05. Results: 669 patients with CCS formed the initial sample. Of these patients, 466 patients (69.7%) received a surgical procedure of the primary site. Additionally, 14 patients (2.09%) received radiation and 69 patients (10.31%) received adjuvant chemotherapy. The receipt of surgery was associated with a marked increase in median survival ( 91.5 months vs. 8.525 months; p<0.05). Surgical resection with clear margins was achieved in 409 patients (61.14%), of whom experienced improved survival compared to patients with residual tumor burden. Each additional year of age in a patient conferred a 2.4% decrease in likelihood of the patient receiving surgery. Lower stage disease was significantly more likely to be treated surgically (OR 11.4; p<0.001), while stage IV disease and abdominal primary site tumors were associated with lower rates of surgery. Facility type (academic vs. nonacademic), insurance, or distance travelled for care had no effect on rates of surgery. Conclusions: As a significant portion of CCS patients receive surgical treatment, this study confirms that tumor resection is associated with increased overall survival of patients with CCS. Improved survival with surgery correlates with clear surgical margins and full tumor resection. It appears that patients are more likely to be treated surgically if their disease is of lower stage. Patients with abdominal primary site tumors or stage IV disease are less likely to receive surgery. This research serves as the beginning of developing standardized treatment plans for CCS patients. Further studies are needed to better understand the factors involved in receiving surgery and other treatment modalities as part of CCS treatment.

Extracranial germ cell tumours: Mature and immature (1990-2015). First report by the South African Association of Paediatric Haematology Oncology (SAAPHO).

Outcomes of rare paediatric teratomas have not previously been reported nor treatment regimens standardised in low- and middle-income settings. We sought to evaluate treatment outcomes of children and adolescents with histologically confirmed extracranial germ cell tumours, both mature teratomas (MT) and immature teratomas (IT) in preparation for the development of the South African national treatment guideline. Retrospective data by folder review were collated from nine South African paediatric oncology units. Kaplan-Meier analysis with Cox regression was performed to determine 5-year overall survival (OS) and prognostic factors. From January 1990 to December 2015, 60 patients were diagnosed with MTs; 14 males (median age 2months; interquartile range [IQR]: 0-8.75months) and 46 females (median age 9months; IQR: 0-88.5months). Forty patients were diagnosed with ITs; 10 males (median age less than 1month; IQR: 0-1.75months) and 30 females (median age 4.5months; IQR: 1-162months). There were high rates of upfront surgical resections in patients with MTs (58/60; 96.6%) and ITs (36/40; 90%), and similarly satisfactory rates of complete resection in patients with both MTs (55/60; 91.7%) and ITs (32/40; 80%). The 5-year OS for the whole group was 85.4%, significantly influenced by stage: Stage I (96.9%), Stage II (100%), Stage III (38.9%) (p<.001 [MT]; p=.013 [IT]). The event-free survival (EFS) ratio for the whole cohort was 78.7%. Five-year OS for those with low-stage disease was excellent, but was poorer for patients with advanced disease. The implementation of a national treatment guideline will facilitate the standardising of surgical approaches, indications for chemotherapy and specifications for follow-up to improve survival and to collect more robust late effects data.

Impact of BCL-2 Expression on Course of Disease in Neuroblastoma.

The antiapoptotic BCL-2 protein has implications for maturation and differentiation of neural tissue and acts as a strong modulator of carcinogenesis in different tumors. Recent research focuses not only on its benefit as a prognostic factor, but also as a potential therapeutic target. The role of BCL-2 in neuroblastoma, the most common extracranial solid tumor in childhood, remains controversial. The aim of our study was to determine the gene expression level of BCL-2 in a large cohort of neuroblastoma patients and its correlation with clinical parameters. Tumor samples and clinical data were collected from 100 neuroblastoma patients treated according to the NB2004 protocol of the German Society of Pediatric Oncology and Hematology. BCL-2 gene expression levels were measured by quantitative reverse transcription polymerase chain reaction and correlated with clinical parameters. BCL-2 expression was detected in all tumor samples. Relative BCL-2 expression levels were higher in females versus males (1.839 vs. 1.342; p = 0.0143), in patients with low versus high International Neuroblastoma Staging System stage (2.051 vs. 1.463; p = 0.0206), in nonmetastatic versus metastatic disease (1.801 vs. 1.342; p = 0.0242), as well as in patients without presurgical chemotherapy (2.145 vs. 1.402; p = 0.0016), but was not associated with overall survival and MYCN amplification. Our study demonstrates the ubiquitous expression of BCL-2 in neuroblastoma and suggests the possibility for targeted therapy with BCL-2 inhibitors, even in lower-stage neuroblastoma. It also underlines the need for further research on concomitant genetic alterations for a better understanding of the impact of BCL-2 on this pediatric tumor type.

Evaluation and Clinicopathological Correlation of ALDH1 in Colorectal Adenoma with Low-/High-Grade Dysplasia and Carcinoma.

Colorectal carcinoma (CRC) stands as one of the most prevalent malignant neoplasms, carrying significant morbidity and mortality implications. Within colorectal carcinogenesis, cancer stem cells are recognized as key contributors, infusing tumors with aggressive traits, including chemoresistance. A group of enzymes known as ALDH1 exhibits stem cell properties, potentially playing a role in colorectal neoplasms. This study aims to evaluate ALDH1 expression in colonic neoplasms and its correlation with clinicopathological parameters. The research encompasses 50 consecutive cases, involving CRC (30) and colorectal adenoma (20), gathered prospectively from September 2019 to August 2021, as well as archived cases from January 2018 to August 2019. Histological examination was conducted on CRC cases to assess tumor type, grade, lymphovascular invasion, perineural invasion, mitosis, and necrosis, while colorectal adenomas were subjected to histological grading. ALDH1 immunohistochemistry was performed on both CRC and adenoma specimens. Statistical analysis utilized SPSS 20 software, employing the chi-squared test and Fischer's exact test. A higher count of adenoma cases displayed positive staining (p = 0.0005) and greater expression (p = 0.036) in comparison to carcinoma cases. The other clinicopathological parameters didn't demonstrate notable associations. Adenomas with low-grade dysplasia exhibited a higher frequency of positive ALDH1 staining and expression than those with high-grade dysplasia. In malignant cases, a higher proportion of positive staining was observed in lower-stage disease compared to higher-stage disease. The heightened staining and expression outcomes of ALDH1 in adenomas versus carcinomas, as well as their presence in lower-stage carcinomas, suggest the potential acquisition of novel mutations and the proliferation of distinct clonal stem cell subsets during disease progression. The absence of ALDH1 in adenoma/carcinoma could indicate a poorer prognosis and an increased likelihood of disease progression to a higher stage. Comprehensive multi-institutional and validation studies are needed to enhance our understanding of ALDH1's role in colorectal oncogenesis, as well as its viability as a targeted or personalized therapy option.

The diagnostic accuracy and prognostic implication of pelvic and peritoneal fluid cytology specimens in ovarian clear cell carcinoma

Ovarian clear cell carcinoma (OCCC) is a rare subtype of ovarian epithelial carcinoma. Patients with low-stage disease have an excellent prognosis, while the prognosis for those with high-stage disease is poor. Neoplastic cells in abdominopelvic washings upstages the patient to at least FIGO 1C3. Positive cytology confers a worse prognosis when compared to similar stage patients with negative cytology. This study aims to investigate the diagnostic performance of abdominopelvic fluid cytology specimens in cases with pure OCCC and reaffirm the importance of accurate cytologic detection and its impact on patient prognosis. The laboratory information system was queried to identify all patients treated for ovarian clear cell carcinoma at our institution over a period of 20 years with a companion abdominopelvic fluid cytology specimen at the time of surgical resection. Cases were sorted by the FIGO stage of the corresponding oophorectomy specimen. Cytology results, patient demographics, fluid volume, immunohistochemical results, and follow-up data were recorded. A total of 143 cases were identified. The overall detection rate was 38%, with 54 of 143 cases positive for malignancy. Cytologic detection rates increased as FIGO stages increased. Fifty percent of stage 1C cases were upstaged on cytology alone. Ascites fluids performed better among stage 1 cases compared to pelvic wash specimens (77% detection rate versus 23%). Stage 1 patients with positive cytology trended towards a worse prognosis compared to those with negative cytology. Positive cytology in low stage cases of OCCC has significant prognostic and therapeutic implications. Our large cohort further underscores the importance of accurate cytologic detection and subsequent staging in this setting.

Socioeconomic status significantly impacts childhood cancer survival in South Africa.

Significantly discrepant survival rates have been documented in single disease childhood cancer cohorts in South Africa; those from higher socioeconomic groups were shown to have a significantly lower risk of death than those from less affluent households. This study aimed to determine the impact of socioeconomic status (SES) on childhood cancer survival using pooled South African data. Five databases spanning January 2000 to December 2021 were interrogated. SES status was assigned based on a public sector annual household income classification. H0 households (formally unemployed) received free healthcare. H1, H2 and H3 (annual income > United States Dollar [USD] 19,000) households paid for healthcare relative to their income. The Spearman test assessed correlations between SES and disease stage in patients with solid tumours. Hazard ratios were determined using Cox regression modelling. The Kaplan-Meier procedure estimated overall survival (OS). A total of 1598 children were eligible for analysis; 1269 had a solid tumour with a negative correlation between SES and stage (Spearman rho=-.178; p<.001). Patients with solid tumours and lower SES showed proportionately higher numbers of stage III and IV disease (p<.01). This proportion decreased with higher SES categories. In the multivariate analyses adjusted for sex, age, tumour type and stage, higher SES was associated with lower mortality risk (p<.001), indicating that the impact of SES on survival was in excess of any effect that could be explained by lower stage disease alone. There was a strong positive correlation between race and SES (Fisher's exact tests, p<.001) across all groups and all SES strata. Five-year OS was 85.3% in children from H3 households versus 46.3% in children from H0 households (p<.001). SES significantly impacts childhood cancer survival for children with solid tumours in South Africa. SES is a robust surrogate for race in South Africa as a prognostic metric of disease outcome in childhood cancer. Advocacy to increase social support for impoverished patients is essential to achieve equitable improvements in outcomes treated with standardised national treatment guidelines.

Germline founder variant c.1998delinsTTCT in the RET oncogene: a cohort study in 15 Belgian families.

The c.1998delinsTTCT variant in the RET gene (codon 666) is linked to medullary thyroid carcinoma in Belgium. We aimed to study the clinical phenotype and the age-dependent penetrance in predictive variant carriers. Retrospective study of index patients and predictive variant carriers, identified through familial cascade testing between 2001 and 2020. The total cohort comprised 119 patients: 15 index patients, 102 heterozygous, and 2 homozygous predictive variant carriers. Among heterozygous carriers, high suspicion of clinical disease was present in 25 patients at initial evaluation and in 3 patients during follow-up. No high suspicion of clinical disease was observed during surveillance in 56 patients, and 18 patients did not proceed to screening for clinical disease. Compared to index patients, surgically treated heterozygous predictive variant carriers had a lower presurgical basal calcitonin, a lower disease stage, less need for adjuvant therapy, and higher chances of remission. In heterozygous carriers, median age at developing high suspicion of disease is 52 years (range 7-75), with a predicted penetrance of 62% (9% SE) at the age of 70 years. Two patients were identified with pheochromocytoma and 1 patient with primary hyperparathyroidism. The 2 homozygous predictive variant carriers presented with higher disease severity at first clinical evaluation. The c.1998delinsTTCT variant in the RET gene is pathogenic and associated with a moderate risk for medullary thyroid carcinoma and rarely with other multiple endocrine neoplasia type 2A (MEN2A) manifestations. Active surveillance is a possible option in heterozygous gene carriers with a negative first clinical evaluation.

Endometrial cancer diagnoses prompted by routine cervical cytology: a retrospective case study.

Endometrial cancer is the commonest gynaecological cancer in New Zealand. Some women have their diagnosis of endometrial cancer prompted by an abnormal cervical cytology screening test. When high-risk human papillomavirus (hr-HPV) testing becomes the primary test for cervical screening, this avenue of incidental diagnosis will be reduced. Therefore, our aims were to estimate the proportion of women whose diagnosis of endometrial cancer follows incidental detection on routine cervical cytology, and to understand the clinicopathologic characteristics of these cases. Retrospective analysis of patient medical records from women of cervical screening age diagnosed with endometrial cancer between 2015-2019 in the South Island of New Zealand. Of 334 women, 26 (7.8%) had endometrial cancer diagnosis prompted by abnormal cervical cytology. Most women had low-grade (17/26, 65.4%), low-stage (18/26, 69.2%) disease of endometrioid histologic subtype (21/26, 80.8%). The small cohort prevented significant correlations with clinicopathologic characteristics and outcomes. Overall, cervical cytology had low sensitivity (32.3%) for the detection of endometrial cancer in the 6 months before diagnosis. A small number of women currently have diagnoses of endometrial cancer prompted by routine cervical screening with cytology. However, the undefined clinical benefit from and poor sensitivity of cervical cytology for detecting endometrial cancer does not justify its use in screening, or opposition to hr-HPV cervical screening.

PD-L2 overexpression on tumor-associated macrophages is one of the predictors for better prognosis in lung adenocarcinoma.

Immunotherapies that target programmed cell death protein 1 (PD-1) signals are standard therapies for advanced-stage lung cancer, and the expression of programmed death-ligand 1 (PD-L1) in cancer tissue predicts immunotherapy efficacy. Although programmed death-ligand 2 (PD-L2) is expressed in cancer cells and macrophages, similar to PD-L1, its significance in lung cancer is unclear. Double immunohistochemistry analyses using anti-PD-L2 and anti-PU.1 antibodies were carried out on tissue array sections from 231 cases of lung adenocarcinoma, and PD-L2 expression in macrophages was evaluated. High PD-L2 expression in macrophages was associated with longer progression-free survival (PFS) and cancer-specific survival (CSS) and observed more often in females, non-heavy smokers, and patients with epidermal growth factor receptor (EGFR) mutations and those at a lower disease stage. Significant correlations were found more frequently in patients with EGFR mutations. Cell culture studies revealed that cancer cell-derived soluble factors induced PD-L2 overexpression in macrophages, suggesting the involvement of the JAK-STAT signaling pathway. The present findings suggest that PD-L2 expression in macrophages predicts PFS and CSS in lung adenocarcinoma without immunotherapy.

Comparison of Clinicopathologic Features and Outcomes Between Synchronous and Metachronous Bilateral Breast Cancer

Purpose: Bilateral breast cancer (BBC) can be divided into two concurrent lesions, depending on the time of occurrence of primary cancer and secondary tumors after treatment of the primary cancer. This study aimed to compare the clinicopathological characteristics and results of synchronous BBC (SBBC) and metachronous BBC (MBBC).Methods: Data of patients diagnosed with breast cancer at Wonkwang university Hospital between October 1991 and October 2021 were retrospectively reviewed. Data of 3,259 patients who were diagnosed with malignant neoplasm of the right or left breast were reviewed. The tumor was defined as SBBC when another cancer was identified as BBC simultaneously or within six months after the primary breast cancer, and as MBBC when another cancer was identified after six months. Among patients with BBC, 31 had SBBC and 32 had MBBC.Results: In SBBC patients, the median age was 59.9 years, and the condition was diagnosed 3.3 years later compared with MBBC. The primary and secondary tumors of SBBC had lower disease stage, even when diagnosed late. Except for tumor, node, and metastasis stage, MBBC showed more invasive ductal carcinoma, while SBBC showed relatively more ductal carcinoma &lt;i&gt;in situ&lt;/i&gt; in both primary and secondary tumors compared with MBBC. In addition, SBBC showed lower hormone receptor positivity rates and Ki-67 levels compared with MBBC. MBBC patients showed a higher survival rate compared with SBBC patients. MBBC is associated with higher overall survival rate compared with SBBC, and its prognosis is not worse compared with that of unilateral breast cancer. In the case of secondary tumor that develops in the contralateral breast without evidence of metastasis, the survival rate is similar to that of unilateral breast cancer, while the treatment is similar to that of primary tumor.Conclusion: As those with SBBC have a worse survival, these patients will require more medical attention; meanwhile, MBBC requires an active treatment approach that is equivalent to that for unilateral breast cancer.

Effects of PEG in patients with esophageal squamous cell carcinoma during concurrent chemoradiotherapy: a prospective study

This prospective study aimed to compare the changes in nutritional status and adverse events among patients with esophageal squamous cell carcinoma who received enteral nutrition through oral intake, PEG, and an enteral nasogastric tube (NGT) during concurrent chemoradiotherapy (CCRT). Of 141 included patients, 38, 74, and 29 patients were fed through oral intake, PEG, and NGTs, respectively. The clinical characteristics and baseline nutritional status of the 3 groups were recorded and analyzed. The Patient-Generated Subjective Global Assessment score, skeletal muscle index, and quality of life were evaluated before and after CCRT; the incidence of adverse events during feeding using PEG and NGTs was also recorded. The correlations among the different nutritional pathways and the CCRT-related adverse events (eg, radiation esophagitis and myelosuppression) were assessed. At baseline, the oral intake group had a significantly better nutritional status and lower disease stage than those in the PEG and NGT groups. However, during CCRT, the oral intake group exhibited the most significant decreases in weight and skeletal muscle index. The synchronous chemotherapy completion rate was the highest in the PEG group. Multivariate analysis showed that the planning tumor volume and oral intake and NGT feeding pathways were associated with radiation esophagitis of at least grade2. We found that PEG effectively maintained the body weight and skeletal muscle index of patients with esophageal cancer during CCRT. PEG also improved the synchronous chemotherapy completion rate and reduced the occurrence of at least grade 2 radiation esophagitis. (Clinical trial registration number: NCT04199832.).

Abstract 6689: Whole genome cell-free tumor DNA mutational signatures from blood for early detection of recurrence of low stage lung adenocarcinoma

Abstract Introduction: Lung cancer remains the leading cause of cancer-related deaths. Surgery is the best option for early lung cancer, and the role of adjuvant therapy remains controversial. Liquid biopsy offers a noninvasive approach to monitor cancer burden. Targeted sequencing of circulating cell free tumor DNA (ctDNA) in blood has shown success for diagnosis; however, low tumor burden and dynamic evolution of low stage disease is challenging for targeted panels. Thus, we hypothesized that a whole genome sequencing (WGS)-derived patient specific mutational signature from a matched tumor-normal WGS can provide sensitive and specific approach to detect mutations and copy numbers in ctDNA for monitoring of lung adenocarcinoma patients. Methods: We successfully profiled 50 Stage 1 or 2 lung adenocarcinomas. ctDNA was extracted from 1-2 mL of plasma, tumor DNA was extracted from pathology tissue and normal germline DNA from the white blood cells. WGS using was performed on matched tumor and normal DNA, and ctDNA extracted from plasma. WGS coverage was 40x for matched tumor-normal and 20x for ctDNA. We derived a personalized mutational pattern for each tumor and used an AI-based error suppression model for quantification and ultra-sensitive detection of ctDNA in plasma samples. A patient-specific personalized genome-wide compendium of somatic mutations and copy numbers was established and ctDNA tested at 3 to 18 available time points during the therapy or follow up. A personalized mutational signature for detection ctDNA from WGS was quantified and the ctDNA Tumor Fraction (TF) was compared to the clinical status and time to recurrence. Results: Tumor specific signatures were derived from matched tumor-normal samples with &amp;gt;5% tumor purity and &amp;lt;30% duplications rate. Out of all patients, 33 patients showed no recurrence and 12 recurred. Tumor-specific signatures detected the presence of the tumor signature in plasma with TF as low as 10−5. Based on positive minimal residual disease in plasma, the recurrence prediction sensitivity was 0.75 and specificity 0.82, with positive predictive value of 0.6 and negative predictive value 0.9. WGS ctDNA predicted recurrence with a median lead time of 508 days before clinical/imaging recurrence. In one case we were able to identify the second primary by deconvoluting known and novel ctDNA mutations. ctDNA mutational profiles enabled identification of smoking mutational signature matching clinical history, and APOBEC and ageing signatures as well as tumor mutational burden. Conclusions: Patient-specific WGS tumor signature from plasma derived ctDNA enables specific and ultrasensitive tracking of minimal residual disease in low stage lung adenocarcinoma patients. Molecularly positive status can be used to predict recurrence and identify patients with clinical low stage disease that may benefit from adjuvant therapy. Citation Format: Ivy Tran, Alejandro Vargas, Reid Wilkins, Isabella Pizzillo, Kenneth Tokoro, Danielle Afterman, Tomer Lauterman, Maja Kuzman, Santiago Gonzalez, Dunja Glavas, James Smadbeck, Dillon Maloney, Jurica Levatic, Samuel Phillips, Sunil Deochand, Michael Yahalom, Ryan Ptashkin, Iman Tavassoly, Zohar Donenhirsh, Eric White, Ravi Kandasamy, Ury Alon, Paz Polak, Boris Oklander, Asaf Zviran, Matija Snuderl, Harvey I. Pass. Whole genome cell-free tumor DNA mutational signatures from blood for early detection of recurrence of low stage lung adenocarcinoma. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6689.

MP56-06 PATHOLOGIC DOWNSTAGING RATE AND PREDICTIVE BIOMARKER EXPLORATION IN PATIENTS WITH BIOPSY-PROVEN CLINICALLY NODE POSITIVE BLADDER CANCER UNDERGOING CHEMOTHERAPY FOLLOWED BY RADICAL CYSTECTOMY

You have accessJournal of UrologyCME1 Apr 2023MP56-06 PATHOLOGIC DOWNSTAGING RATE AND PREDICTIVE BIOMARKER EXPLORATION IN PATIENTS WITH BIOPSY-PROVEN CLINICALLY NODE POSITIVE BLADDER CANCER UNDERGOING CHEMOTHERAPY FOLLOWED BY RADICAL CYSTECTOMY Amy Lim, Akshay Sood, Vikram Narayan, Mohammed Seif, Justin Matulay, Kelly Bree, Matt Campbell, Ashish Kamat, Colin Dinney, and Neema Navai Amy LimAmy Lim More articles by this author , Akshay SoodAkshay Sood More articles by this author , Vikram NarayanVikram Narayan More articles by this author , Mohammed SeifMohammed Seif More articles by this author , Justin MatulayJustin Matulay More articles by this author , Kelly BreeKelly Bree More articles by this author , Matt CampbellMatt Campbell More articles by this author , Ashish KamatAshish Kamat More articles by this author , Colin DinneyColin Dinney More articles by this author , and Neema NavaiNeema Navai More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003309.06AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Studies assessing the efficacy of preoperative chemotherapy in bladder cancer rarely include clinically node positive (cN+) patients. Further, the cN+ patients that are included are frequently categorized as cN+ based on imaging only. Therefore, true nodal response rates and oncological outcomes in this select patient group are generally unknown. Additionally, studies examining responder characteristics are lacking. METHODS: Data were collected retrospectively on patients with cTanyN1-3M0 bladder cancer who underwent radical cystectomy at the University of Texas MD Anderson Cancer Center (2006-2017). Complete nodal response (pN0) and bladder tumor response (pT0), recurrence free survival (RFS) and overall survival (OS) for patients with a positive lymph-node (LN) biopsy were recorded. Tissue mRNA microarray expression profiling was performed on LN and primary tumor tissue (pre-therapy) and compared among responders (pN0) and non-responders. RESULTS: Among the 120 patients identified with cTanyN1-3M0 disease, 26 (21.7%) patients had a positive LN biopsy. Induction chemotherapy was administered in all patients. Nine (34.6%) were pN0 and 9 (34.6%) were pT0 after primary chemotherapy. Seven were pT0N0. Lower stage disease on final pathology was associated with improved RFS and OS (p<0.001). Fourteen differentially expressed genes in the LNs and 68 differentially expressed genes in the bladder were predictive of pN0 response to primary chemotherapy in the LNs (FDR<0.1; Figure). CONCLUSIONS: Among cN+ patients, the true response rate to primary chemotherapy appears to be∼35%. Pathologic bladder response correlates well with nodal response. Finally, our study suggests that a panel of genes may be useful in distinguishing cN+ chemo-responders vs not, and thus could help reduce over- and undertreatment. These exploratory findings need prospective validation. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e775 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Amy Lim More articles by this author Akshay Sood More articles by this author Vikram Narayan More articles by this author Mohammed Seif More articles by this author Justin Matulay More articles by this author Kelly Bree More articles by this author Matt Campbell More articles by this author Ashish Kamat More articles by this author Colin Dinney More articles by this author Neema Navai More articles by this author Expand All Advertisement PDF downloadLoading ...

V06-08 UPPER TRACT TUMOR EN BLOC ENUCLEATION: A NOVEL APPROACH TO THE DIAGNOSIS AND MANAGEMENT OF UPPER TRACT UROTHELIAL CARCINOMA

You have accessJournal of UrologyCME1 Apr 2023V06-08 UPPER TRACT TUMOR EN BLOC ENUCLEATION: A NOVEL APPROACH TO THE DIAGNOSIS AND MANAGEMENT OF UPPER TRACT UROTHELIAL CARCINOMA Joshua Jue and Noel Armenakas Joshua JueJoshua Jue More articles by this author and Noel ArmenakasNoel Armenakas More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003274.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The identification of high grade disease and subepithelial connective tissue invasion (pT1 disease) are important prognostic factors which guide treatment options in upper tract urothelial carcinoma (UTUC). We aim to describe and demonstrate our novel en bloc enucleation technique for the endoscopic diagnosis and treatment of upper tract tumors. METHODS: We detail the instruments required for this procedure, as well as the surgical technique to perform an en bloc enucleation and specimen removal. Endoscopic video of a 2 cm renal pelvis tumor demonstrates all aspects of the technique, and histopathologic slides illustrate the diagnostic information obtained. RESULTS: A ureteral access sheath is inserted distal to the upper tract tumor, and a flexible ureteroscope is used to visualize the extent of upper tract disease and tumor characteristics. A 200 mm thulium fiber laser partially ablates the tumor surface to create an edge for tissue biopsy and post-ablation urine cytology. The tumor base is identified and the subepithelial connective tissue is carefully entered with low ablation laser settings. The correct tissue plane is extended by maintaining the ureteroscope in the subepithelial connective tissue and continuing the dissection along the entire width of the tumor base. Once the tumor is enucleated, a Nitinol stone retrieval basket is used to remove the specimen(s) and a ureteral stent is placed. CONCLUSIONS: En bloc enucleation is a safe technique that provides extensive histopathologic information in upper tract urothelial carcinoma. In cases where complete enucleation is not feasible, this procedure affords a mechanism for large caliber biopsies, enhancing diagnostic accuracy. This technique can be therapeutic in low grade and stage disease, but also offers a mechanism for large caliber biopsy if complete enucleation cannot be performed. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e511 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Joshua Jue More articles by this author Noel Armenakas More articles by this author Expand All Advertisement PDF downloadLoading ...

A fortunate presentation of intestinal obstruction secondary to a rare sarcomatoid tumour of the small bowel

Intussusception in the adult is rarely from a benign cause and is almost always pathological. Causes include carcinomas, polyps, Meckel's diverticulum, or colonic diverticulum. Common symptoms include abdominal pain, intestinal obstruction, palpable abdominal mass, gastrointestinal (GI) bleeding, and anaemia. Sarcomatoid carcinoma is a rare type of small intestinal malignancy exhibiting carcinomatous and sarcomatous features. It primarily affects older patients, mean age 57, and is 1.5 times more prevalent in men. This is an interesting case report of a patient presenting with intussusception secondary to a sarcomatoid tumour of the small bowel. Surgery is the treatment of choice in adults with intussusception due to the high malignancy potential. Furthermore, surgical resection of the affected bowel is the definitive form of therapy as small bowel sarcomatoid tumours are not responsive to chemotherapy and radiotherapy. Early surgical intervention helps reduce mortality as it allows for early staging, treatment, and monitoring of the tumour. The patient was fortunate to have presented with intussusception, facilitating early surgical intervention, and was found to have a low disease stage.

A prognostic score based on B cell and plasma cell densities compared to T cell densities in colorectal cancer

PurposeThe purpose of this study was to compare a B cell/plasma cell–based scoring system to T cell score and evaluate their prognostic value in colorectal cancer.MethodsWe used immunohistochemistry to analyze the expression of CD20, CD138, CD3, and CD8 in 221 colorectal cancer patients. CD20+ B cell and CD138+ plasma cell densities in the tumor center and invasive margin were calculated and converted into a B cell/plasma cell score. T cell score was defined similarly, using CD3+ and CD8+ T cell densities. Their associations with tumor and patient characteristics and survival were analyzed.ResultsKaplan–Meier analysis showed a high B cell/plasma cell score was associated with a tendency towards longer survival (p = 0.089), but no statistically significant association was found. High T cell score associated with longer cancer-specific survival in Kaplan–Meier analysis and multivariable Cox regression analysis (p < 0.001). Additionally, high T cell score associated with lower disease stage (p < 0.001) and lesser lymphovascular invasion (p = 0.020).ConclusionsHigh T cell score is associated with longer survival and clinicopathological factors typical to less aggressive tumors. This study did not support the additional prognostic value of B cell/plasma cell quantification.

Does uptake of specialty care affect HRQoL development in COPD patients beneficially? A difference-in-difference analysis linking claims and survey data

BackgroundThere is an evidence gap on whether the choice of specialty care beneficially affects health-related quality of life (HRQoL) in patients with chronic obstructive pulmonary disease (COPD). This study analyzes how newly initiated pulmonologist care affects the generic and disease-specific HRQoL in COPD patients over a period of 1 year.MethodsWe linked claims data with data from two survey waves to investigate the longitudinal effect of specialty care on HRQoL using linear Difference-in-Difference models based on 1:3 propensity score matched data. Generic HRQoL was operationalized by EQ-5D-5L visual analog scale (VAS), and disease-specific HRQoL by COPD assessment test (CAT). Subgroup analyses examined COPD patients with low (GOLD AB) and high (GOLD CD) exacerbation risk.ResultsIn contrast to routine care patients, pulmonologists’ patients (n = 442) experienced no significant deterioration in HRQoL (VAS − 0.0, p = 0.9870; CAT + 0.5, p = 0.0804). Models unveiled a small comparative advantage of specialty care on HRQoL (mean change: CAT − 0.8, VAS + 2.9), which was especially pronounced for GOLD AB (CAT − 0.7; VAS + 3.1).ConclusionThe uptake of pulmonologist care had a statistically significant, but not clinically relevant, beneficial impact on the development of HRQoL by slowing down overall HRQoL deterioration within 1 year. Including specialty care more appropriately in COPD management, especially at lower disease stages (GOLD AB), could thus improve patients’ health outcome.

Cancer-directed surgery brings survival benefits for patients with advanced prostate cancer: a population-based propensity-score matching study.

Purpose: The purpose of this study was to evaluate the survival benefits of cancer-directed surgery (CDS) for localized prostate cancer (PCa) as well as advanced PCa. Methods: We retrospectively used the Surveillance, Epidemiology, and End Results (SEER) database and conducted a propensity score matching (PSM) study to investigate survival benefits and influencing factors of CDS in patients with PCa, especially for those with advanced PCa. Results: 19,729 cases were included. Patients who were recommended CDS had lower stages of disease (81.01% vs. 77.32% at stages I and II, p<0.01) than those who were not recommended CDS. It was primarily age, diagnosis year, cancer stage (American Joint Committee on Cancer Staging System), Gleason score, race, and home location and prostate-specific antigen, that influenced whether CDS was recommended or not (all p<0.05). Patients with PCa had lower rates of cancer specific mortality (CSM) and overall mortality (OM) when CDS was performed (CDS performed=CDSP). The unselected patients with CDSP decreased both rates of CSM by 79% and OM by 26% (both p<0.001). CDSP also benefited the young patients (with age ≤74 years old) with stage IV disease, promoting a rate decrease by 28% in CSM and by 31% in OM (both p<0.001). Conclusions: We found a decline in CSM and OM for unselected patients with PCa and patients less than 74 years old with stage IV disease. CDS as part of a multimodal treatment concept should be considered for an alternative treatment for patients with advanced PCa.

Who Presents Where? A Population-Based Analysis of Socio-Demographic Inequalities in Head and Neck Cancer Patients' Referral Routes.

Head and neck cancers (HNC) are often late stage at diagnosis; stage is a major determinant of prognosis. The urgent cancer referral pathway (two week wait; 2WW) within England's National Health Service aims to reduce time to diagnosis. We investigated factors associated with HNC route to diagnosis. Data were obtained from the English population-based cancer registry on 66,411 primary invasive HNCs (ICD C01-14 and C31-32) diagnosed 2006-2014. Multivariable logistic regression determined the likelihood of different diagnosis routes by patients' demographic and clinical characteristics. Significant socio-demographic inequalities were observed. Emergency presentations declined over time and 2WW increased. Significant socio-demographic inequalities were observed. Non-white patients, aged over 65, residing in urban areas with advanced disease, were more likely to have emergency presentations. White males aged 55 and older with an oropharynx cancer were more likely to be diagnosed via 2WW. Higher levels of deprivation were associated with both emergency and 2WW routes. Dental referral was more likely in women, with oral cancers and lower stage disease. Despite the decline over time in emergency presentation and the increased use of 2WW, socio-demographic variation is evident in routes to diagnosis. Further work exploring the reasons for these inequalities, and the consequences for patients' care and outcomes, is urgently required.

Prognostic factors and outcomes in women with breast cancer in Slovenia in relation to step-wise implementation of organized screening.

The aim of organized breast cancer screening is early detection and reduction in mortality. Organized screening should promote equal access and reduce socio-economic inequalities. In Slovenia, organized breast cancer screening achieved complete coverage in 11-years' time. We explored whether step-wise implementation reflects in prognostic factors (earlier diagnosis and treatment) and survival of breast cancer patients in our population. Using population-based cancer registry and screening registry data on breast cancer cases from 2008-2018, we compared stage distribution and mean time to surgical treatment in (A) women who underwent at least one mammography in the organized screening programme, women who received at least one invitation but did not undergo mammography and women who did not receive any screening invitation, and in (B) women who were invited to organized screening and those who were not. We also compared net survival by stage in different groups of women according to their screening programme status. Women who underwent at least one mammography in organized screening had lower disease stage at diagnosis. Time-to-treatment analysis showed mean time to surgery was shortest in women not included in organized screening (all stages = 36.0 days vs. 40.3 days in women included in organized screening). This could be due to quality assurance protocols with an obligatory multidisciplinary approach within the organized screening vs. standard treatment pathways which can vary in different (smaller) hospitals. Higher standard of care in screening is reflected in better survival in women included in organized screening (5-years net survival for regional stage: at least one mammography in the screening programme- 96%; invitation, but no mammography- 87.4%; no invitation or mammography in the screening programme- 82.6%). Our study, which is one of the first in central European countries, shows that introduction of organized screening has temporary effects on population cancer burden indicators already during roll-out period, which should therefore be as short as possible.