Multi-institutional Retrospective Analysis Research Articles

Efficacy and Toxicity Analysis of mFOLFIRINOX in High-Grade Gastroenteropancreatic Neuroendocrine Neoplasms.

High-grade neuroendocrine neoplasms (NENs) comprise both well-differentiated grade 3 neuroendocrine tumors (G3 NETs) and poorly differentiated neuroendocrine carcinomas (NECs). Mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs) nearly always include poorly differentiated NEC as the neuroendocrine component. The efficacy and safety of frontline mFOLFIRINOX chemotherapy has never been investigated in patients with high-grade NENs. We conducted a multi-institutional retrospective analysis of patients with advanced high-grade NEN of the gastroenteropancreatic tract or of unknown origin seen between February 2016 and April 2023 who received treatment with frontline mFOLFIRINOX. A total of 35 patients were included (G3 NETs: n=2; NECs: n=25; MiNENs: n=8; stage III: n=5; stage IV: n=30). The objective response rate was 77% (complete response: 3%; partial response: 74%). Median progression-free survival was 12 months (95% CI, 9.2-16.2 months) and median overall survival was 20.6 months (95% CI, 17.2-30.6 months). No significant differences in efficacy were seen according to primary site, histopathology, and Ki-67 proliferative index. All 5 patients with stage III disease who received mFOLFIRINOX obtained an objective response and underwent radical surgery or definitive radiotherapy with curative intent, with a recurrence rate of 40%. Grade 3 or 4 adverse events were observed in 43% of patients (mainly neutropenia and diarrhea). Females were at significantly increased risk of developing severe toxicities. mFOLFIRINOX shows antitumor activity against high-grade NENs. Well-designed, prospective clinical trials are needed to assess the efficacy of mFOLFIRINOX in both the neoadjuvant and metastatic settings.

Treatment at relapse for synovial sarcoma of children and adolescents: A multi-institutional European retrospective analysis.

Though the prognosis for pediatric patients with localised synovial sarcoma (SS) is generally good, the chances of being cured after relapse are limited. This study describes a retrospective multi-institutional series of relapsing SS patients treated at six selected European referral centers for pediatric sarcoma. The study included 41 patients<21 years with relapsing SS, treated between 2002 and 2022. The analysis included patient's characteristics at first diagnosis, first-line treatments, clinical findings at relapse, and second-line treatment modalities. The first relapse occurred within 3-132 months (median 18 months) after first diagnosis and was local in 34%, metastatic in 54%, and both in 12%. Treatment at first relapse included surgery in 56% of cases, radiotherapy in 34%, and systemic therapy in 88%. In all, 36 patients received second-line medical treatment, that was chemotherapy in 32 cases (with 10 different regimens) and targeted therapy in four. No patient was included in an early-phase clinical trial as second-line therapy-line therapy. Overall response rate was 42%. Median event-free survival (EFS) was 12 months, postrelapse 5-year EFS was 15.8%. Median overall survival (OS) was 30 months, postrelapse 5-year OS was 22.2%. At the Cox's multivariable regression analysis, OS was significantly associated with time and type of relapse. Pediatric patients with relapsed SS have a poor prognosis and generally receive an individualized approach, due to the lack of a uniform standardized approach. New comprehensive strategies are needed to improve the knowledge on the biologic landscape of SS and develop tailored prospective clinical trials.

Alternative venous access sites for dual-lumen extracorporeal membrane oxygenation cannulation.

Dual-lumen cannulas for veno-venous (VV) extracorporeal membrane oxygenation (ECMO) support are typically inserted in the right internal jugular vein (RIJV); however, some scenarios can make this venous route inaccessible. This multicentre case series aims to evaluate if single-site cannulation using an alternative venous access is safe and feasible in patients with an inaccessible RIJV. We performed a multi-institutional retrospective analysis including high-volume ECMO centres with substantial experience in dual-lumen cannulation (DLC) (defined as >10 DLC per year). Three centres [Freiburg (Germany), Toronto (Canada) and Vienna (Austria)] agreed to share their data, including baseline characteristics, technical ECMO and cannulation data as well as complications related to ECMO cannulation and outcome. A total of 20 patients received alternative DLC for respiratory failure. Cannula insertion sites included the left internal jugular vein (n = 5), the right (n = 7) or left (n = 3) subclavian vein and the right (n = 4) or left (n = 1) femoral vein. The median cannula size was 26 (19-28) French. The median initial target ECMO flow was 2.9 (1.8-3.1) l/min and corresponded with used cannula size and estimated cardiac output. No procedural complications were reported during cannulation and median ECMO runtime was 15 (9-22) days. Ten patients were successfully bridged to lung transplantation (n = 5) or lung recovery (n = 5). Ten patients died during or after ECMO support. Alternative venous access sites for single-site dual-lumen catheters are a safe and feasible option to provide veno-venous ECMO support to patients with inaccessible RIJV.

Prognostic factors of conversion surgery for stage IV gastric cancer: A multi-institutional retrospective analysis.

Conversion surgery (CS) is a highly anticipated strategy for stage IV advanced gastric cancer (AGC) with a good response to chemotherapy. However, prognostic factors limiting R0 resection remain unclear. In this multi-institutional study, we investigated the clinical outcomes of CS for stage IV AGC and the prognostic factors of CS-limiting R0 resection and analyzed them according to metastatic patterns. Clinical data on 210 patients who underwent CS for stage IV AGC at six institutions between 2007 and 2017 were retrospectively retrieved. The patient background, preoperative treatment, operative outcomes, and survival times were recorded. Prognostic factors for overall and recurrence-free survival were investigated using univariate and multivariate analyses for patients who underwent R0 resection. R0 resection was achieved in 146 (70%) patients. The median survival time was 32 months, and the 3-year survival rate was 45%. Patients who achieved R0 resection had significantly longer survival than those with R1/2 resection (median survival time: 41.5 months vs. 20.7 months). Multivariate analysis identified pathological N positivity for overall and relapse-free survival and pathological T4 for relapse-free survival as significant independent poor prognostic factors of R0 resected patients. There was no significant difference in survival among the peritoneum, liver, and lymph node groups regarding the initial metastatic sites. CS with R0 resection for patients with stage IV AGC can lead to longer survival. Patients with pathological T4 and pathological N positivity were eligible for intensive adjuvant therapy after CS with R0 resection.

Stratification of Stage II Colon Cancer Using Recurrence Prediction Value: A Multi-institutional International Retrospective Study.

To create a recurrence prediction value (RPV) of high-risk factor and identify the patients with high risk of cancer recurrence. There are several high-risk factors known to lead to poor outcomes. Weighting each high-risk factor based on their association with increased risk of cancer recurrence can provide a more precise understanding of risk of recurrence. We performed a multi-institutional international retrospective analysis of patients with Stage II colon cancer patients who underwent surgery from 2010 to 2020. Patient data from a multi-institutional database were used as the Training data, and data from a completely separate international database from two countries were used as the Validation data. The primary endpoint was recurrence-free survival (RFS). A total of 739 patients were included from Training data. To validate the feasibility of RPV, 467 patients were included from Validation data. Training data patients were divided into RPV low (n = 564) and RPV high (n = 175). Multivariate analysis revealed that risk of recurrence was significantly higher in the RPV high than the RPV low (Hazard ratio (HR) 2.628; 95% confidence interval (CI) 1.887-3.660; P < 0.001). Validation data patients were divided into two groups (RPV low, n = 420) and RPV high (n = 47). Multivariate analysis revealed that risk of recurrence was significantly higher in the RPV high than the RPV low (HR 3.053; 95% CI 1.962-4.750; P < 0.001). RPV can identify Stage II colon cancer patients with high risk of cancer recurrence world-wide.

Definitive radiotherapy in patients with clinical T1N0M0 esophageal squamous cell carcinoma: A multicenter retrospective study (KROG 21–10)

PurposeTo assess the failure pattern and analyze the treatment scheme of definitive radiation therapy (RT) for T1N0M0 esophageal squamous cell carcinoma (ESCC). MethodsWe performed a multi-institutional retrospective analysis in T1N0M0 ESCC patients who underwent definitive RT from 2010 to 2019. Patterns of failure were demonstrated as in-, and out-field locoregional, and distant metastasis. In the analysis, freedom-from locoregional recurrence (FFLRR) and their association with clinicopathologic factors were evaluated. Propensity score matching in cT1b patients was done. Results168 patients were included with a median follow-up of 34.0 months, and 26 cT1a, 116 cT1b disease. The rates of 3-year all and locoregional recurrence for cT1a were 30.5% and 24.1% and those for cT1b were 27.1% and 25.9%, respectively. Among 116 cT1b patients, 69 patients received elective nodal irradiation (ENI) and 47 received involved field irradiation (IFI). After propensity score matching, the 3-year FFLRR rate was 84.5%. There was no difference between ENI and IFI in FFLRR (P = 0.831) and OS (P = 0.525). The 3-year FFLRR was 83.8% (95% Confidence interval (CI), 61.8–93.8%) in IFI group and 85.3% (95% CI, 65.1–94.3%) in ENI group. In multivariate analysis, concurrent chemotherapy use was marginally associated with FFLRR (Hazard ratio, 0.16; P = 0.064). ConclusioncT1a patients who cannot receive endoscopic resection showed similar failure rates as cT1b patients, questioning the staging accuracy and raised the need for thorough treatment like chemoradiotherapy. In cT1b patients, IFI with 50 to 60 Gy and concurrent chemotherapy could be reasonable.

Pre-Treatment Trends in Child-Pugh Score as an Indicator of Post-Treatment Survival in Patients Receiving Liver SBRT for HCC

We sought to understand the value of Child-Pugh (CP) score trends prior to undergoing stereotactic body radiation therapy (SBRT) for hepatocellular carcinoma in patients with advanced cirrhosis, as an indicator of post-treatment morbidity and mortality. We hypothesize that an uptrend in CP score prior to RT increases risk of post-treatment cirrhosis progression, or death. We retrospectively reviewed all patients who underwent definitive SBRT for HCC between 2014-2022 in our health system. Most patients were referred for treatment in the 2nd or 3rd line setting, allowing us to determine CP score at multiple points before SBRT. Response to treatment was evaluated with RECIST or mRECIST criteria. Acute treatment toxicities were assessed by CTCAE v5. OS was assessed using the Kaplan-Meier method, and differences between groups were evaluated using log-rank test. A total of 61 patients were identified, 26 had an immediate pre-SBRT CP score of A5, 11 with A6, 10 with B7, 4 with B8, 4 with B9, 5 with C10, and 1 with C11. Median prescribed dose was 40Gy in 5fx. Median OS of all patients was 24 months. When stratified by CP category, median OS for CP A was not reached (NR) at time of analysis, CP B had a median OS of 14.8mo, and CP C with 1.9mo (p < 0.01). Local control rate at 6mo was 87.5%. 5 patients (8.3%) had CTCAE grade 2 acute toxicity. 10 patients had CP score progression of 2pts or more within 6mo after treatment, and 7 patients had a cause of death attributed to end stage liver disease. Median time interval between HCC diagnosis and start of RT was 338 days. In this time interval, patients with a CP score increase of 2 pts or more prior to starting RT had a median OS of 362 days, compared to NR for patients without increase (p = 0.02). When excluding the CP A group, patients with 2 pt increase had median OS of 362 days vs 445 days (p = 0.34). Again excluding the CP A group, patients with a 1 pt increase had median OS of 362 days vs NR (p = 0.23). Of 9 patients who had a pre-RT CP score increase of 2 pts or more, 7 experienced continued CP progression after treatment. In this multi-institutional retrospective analysis, we found 24 patients with advanced CP B/C cirrhosis who underwent SBRT, none of whom received orthotopic liver transplant. While CP C patients did relatively poorly, we find that some patients with CP B cirrhosis may tolerate SBRT well with good oncologic effect. When taking pre-treatment CP score increase into consideration, we saw a trend but no statistical significance indicating that a pre-SBRT increase in CP score may be associated with worse OS after treatment among CP B/C patients. We conclude that there may be a subset of patients with advanced cirrhosis who, if well selected, are appropriate candidates for SBRT. We suggest a novel use of the CP score and pre-RT trends as an additional clinical tool to aid in decision making when selecting patients. We also suggest that patients with marked up-trending scores pre-treatment have a high likelihood of continued cirrhosis progression after treatment.

Pneumonitis in Patients Receiving Thoracic Radiotherapy and Osimertinib: A Multi-Institutional Study

IntroductionThoracic radiotherapy (TRT) is increasingly used in patients receiving osimertinib for advanced NSCLC, and the risk of pneumonitis is not established. We investigated the risk of pneumonitis and potential risk factors in this population. MethodsWe performed a multi-institutional retrospective analysis of patients under active treatment with osimertinib who received TRT between April 2016 and July 2022 at two institutions. Clinical characteristics, including whether osimertinib was held during TRT and pneumonitis incidence and grade (Common Terminology Criteria for Adverse Events version 5.0) were documented. Logistic regression analysis was performed to identify risk factors associated with grade 2 or higher (2+) pneumonitis. ResultsThe median follow-up was 10.2 months (range: 1.9–53.2). Of 102 patients, 14 (13.7%) developed grade 2+ pneumonitis, with a median time to pneumonitis of 3.2 months (range: 1.5–6.3). Pneumonitis risk was not significantly increased in patients who continued osimertinib during TRT compared with patients who held osimertinib during TRT (9.1% versus 15.0%, p = 0.729). Three patients (2.9%) had grade 3 pneumonitis, none had grade 4, and two patients had grade 5 events (2.0%, diagnosed 3.2 mo and 4.4 mo post-TRT). Mean lung dose was associated with the development of grade 2+ pneumonitis in multivariate analysis (OR = 1.19, p = 0.021). ConclusionsAlthough the overall rate of pneumonitis in patients receiving TRT and osimertinib was relatively low, there was a small risk of severe toxicity. The mean lung dose was associated with an increased risk of developing pneumonitis. These findings inform decision-making for patients and providers.

Impact of pathological response on oncological outcomes in patients with upper tract urothelial cancer receiving neo-adjuvant chemotherapy

The purpose of this study is to evaluate the rates of pathological complete response (ypT0N0/X) and pathological response (ypT1N0/X or less) in patients with upper tract urothelial cancer who were treated with neo-adjuvant chemotherapy and to examine their impact on oncological outcomes. This study is a multi-institutional retrospective analysis of patients with high-risk upper tract urothelial cancer who underwent neoadjuvant chemotherapy and radical nephroureterectomy between 2002 and 2021. Logistic regression analyses were used to investigate all clinical parameters for response after neoadjuvant chemotherapy. Cox proportional hazard models were performed to assess the effect of the response on the oncological outcomes. A total of 84 patients with UTUC who received neo-adjuvant chemotherapy were identified. Among them, 44 (52.4%) patients received cisplatin-based chemotherapy, and 22 (26.2%) patients had a carboplatin-based regimen. The pathological complete response rate was 11.6% (n=10), and the pathological response rate was 42.9% (n=36). Multifocal tumors or tumors larger than 3cm significantly reduced the odds of pathological response. In the multivariable Cox proportional hazard model, pathological response was independently associated with better overall survival (HR 0.38, p=0.024), cancer-specific survival (HR 0.24, p=0.033), and recurrence-free survival (HR 0.17, p=0.001), but it was not associated with bladder recurrence-free survival (HR 0.84, p=0.69). Pathological response after neo-adjuvant chemotherapy and radical nephroureterectomy is strongly associated with patient survival and recurrence, and it might be a good surrogate for evaluating the efficacy of neo-adjuvant chemotherapy in the future.

Outcomes in pediatric relapsed/refractory anaplastic large cell lymphoma: A multi-institutional retrospective analysis.

10032 Background: Treatment options for relapsed or refractory (R/R) anaplastic large cell lymphoma (ALCL) have increased in the era of targeted therapies such as brentuximab vedotin (BV) and Anaplastic Lymphoma Kinase (ALK)-inhibitors. However, there is no standard treatment and limited published data evaluating their use in this patient population. Methods: We conducted a retrospective, multi-institutional study of patients &lt;22 yrs old at initial diagnosis with R/R ALCL treated between 2011-2021 across 18 institutions. Results: We identified 85 patients with R/R ALCL (median age at initial diagnosis 12 yrs, 67% male, 96% ALK+). Treatment for initial diagnosis included ALCL99 (31%), ANHL12P1 + BV (32%), ANHL12P1 + crizotinib (CZ) (11%), ANHL0131 (14%), or other (13%). Median time from diagnosis to relapse was 0.7 yrs (range 0.2-10.8 yrs) with sixteen patients (18%) relapsing on initial chemotherapy. Stage at relapse for 82 ALK+ patients: I (9%), II (15%), III (41%), IV (35%). Initial re-induction regimens shown in the table. Fifty-nine (72%) patients received a hematopoietic stem cell transplant (HSCT), 11 autologous and 49 allogeneic with one receiving both. Of 59 transplanted patients, 10 relapsed (6 allo 4 auto) and 7 died. All but one of the patients who relapsed post-HSCT responded to additional therapy and remain alive. Of 23 ALK+ patients who never had a transplant, 4 patients died and 19 are alive in remission. Eleven remain on active therapy (6 CZ, 3 BV, 1 BV+CZ, 1 vinblastine) with eight off therapy. Patients who received a transplant more likely to be off therapy and alive. Duration of treatment for patients receiving BV or the ALK-inhibitor CZ varied widely (BV 1-11 yrs; CZ 2-10 yrs) with 20 patients continuing on therapy at the time of data collection. Five-year overall survival for patients with or without transplant was 91% (CI 84-99%) and 86% (CI 73-100%) respectively. Conclusions: This is the largest collection of patients with R/R ALK+ ALCL treated in the era of targeted therapy. Patients achieved excellent responses to ALK-inhibitor or BV monotherapy, but questions remain about duration of therapy. Transplant may not be necessary for all R/R patients including those with high-risk disease. [Table: see text]

“Interchangeability” of anti-PD1 antibodies in patients (pts) with metastatic melanoma (mM).

e21546 Background: PD-L1 inhibitors are the components of the standard treatment options in pts with mM. Currently, there are no data about the efficacy and safety of switching the between of different anti-PD1 antibodies in pts with mM, therefore, the aim of our study was to evaluate safety and efficacy of interchangeability of nivolumab, pembrolizumab, and prolgolimab in such population. Methods: We performed a multi-institutional retrospective analysis of pts with advanced cutaneous melanoma. Inclusion criteria were as follows: histologically confirmed cutaneous melanoma, performance status ECOG 0-2, and first-line treatment with anti-PD1 antibody and switching to another anti-PD1 antibody due to economic issues with no progressive disease after initiating of immunotherapy. Primary end-point was progression-free survival (PFS), secondary end-points were rate of all grades and grade 3-4 adverse events (CTC AE 5.0). A sample size of 87 achieves 80% power to detect an equivalence difference of 15% in 3-months PFS after change of anti-PD1 antibody using a one-sided exact test with a significance level (alpha) of 0,05. These results assume a baseline proportion of 3-months PFS 0,6 and that the actual difference is 0. Results: A total of 92 patients (52% female) were included with the median age of 65 year (28-95). Number of organs with metastases 1, 2, ≥3 were in 62 (67%), 19 (21%), and 11 (12%) of pts, respectively. Liver metastases were observed in 11% of patients. Performance status ECOG 0, 1, and 2 was in 31 (34%), 58 (63%), 3 (3,2%) pts, respectively. 56 (61%) pts received nivolumab, 18 (20%) patients received pembrolizumab, 16 (17%) patients received prolgolimab, and 2 (2%) patients received atezolizumab as first-line treatment. 19 (20,6%) pts were switched to nivolumab, 18 (19,5%) pts were switched to pembrolizumab, 57 (61,9%) pts were switched to prolgolimab, and 2 (2,1%) - to atezolizumab during first-line treatment. The median duration of treatment with first anti-PD1 antibody was 8,5 months (range 1-58 months), with second PD1-inhibitor was 4,2 months (range 1-19 months), with third anti-PD1 antibody – 2,8 months (range 1-10 months). 58 (63%) patients received 2 drugs and 34 (36%) patients received 3 drugs. Within 3 months after 1 replacement of the drug, there were 82 (89.1%) pts without progression. The efficacy was not associated with type of the switched antibodies. The frequency of all AEs and AEs is 3-4. on the first drug was 16.3% and 1.1%, when switching to the second drug - 10.8% and 0%, when switching to the third drug 3.2% and 0%. Conclusions: Our data indicate that it is possible to switch from one anti-PD1 antibody to another in first-line therapy in pts with mM without progression when limited access to anti-PD1 antibodies exists. Further randomized studies are needed to determine the efficacy of such switching strategy of ICIs.

EGFR tyrosine kinase inhibitors (TKIs) versus durvalumab (durva) following concurrent chemoradiation (CRT) in unresectable EGFR-mutant non-small-cell lung cancer (NSCLC).

8567 Background: Adjuvant osimertinib (osi) improves disease-free survival (DFS) in patients (pts) with resected, early-stage, EGFR-mutant (EGFRmut) NSCLC, yet the benefit of osi after CRT in pts with unresectable locally advanced NSCLC is unknown. Post-hoc analysis of the PACIFIC trial showed a lack of survival benefit with consolidation durva versus placebo in pts with EGFRmut NSCLC. Comparisons between consolidation durva and EGFR TKIs in unresectable EGFRmut NSCLC following CRT are lacking. Methods: We conducted a multi-institutional retrospective analysis of pts with stage III unresectable EGFRmut NSCLC (exon19 deletion, exon21 L858R), who received EGFR TKI or durva after ≥ 2 cycles of platinum-based chemotherapy plus definitive radiation therapy between 2015-2022. Baseline characteristics including age, sex, smoking history, PD-L1 status, and outcomes on DFS, overall survival (OS), and safety were collected. Multivariable (MVA) cox regression analysis was used for statistical analysis. Treatment-related adverse events (trAE) were defined using CTCAE 5.0. Results: Seventeen pts from 12 institutions received an EGFR TKI (osi, n=15; erlotinib, n=2), and 13 pts received consolidation durva. Median follow-up was 23 months. Median age of all pts was 61 years (IQR:52-72) and 76.7% were female. Most pts in both groups had never-smoked and had adenocarcinoma. All pts received ≥ 60 Gy of radiation with concurrent chemotherapy. PD-L1 expression was ≥ 50% in 1/10 (10%) pts treated with durva vs 6/13 (46.2%) treated with TKI, p=0.09. Median duration on treatment for EGFR TKI and durva was 12.2 months and 4.8 months, respectively. Pts treated with EGFR TKI had significantly longer 24-month DFS versus pts treated with durva after adjusting for stage (3A vs 3B vs 3C) (Table). Any grade tRAE occurred in 58.8% (10/17) of pts treated with EGFR TKI vs 38.5% (5/13) with durva. Grade &gt; 3 tRAE occurred in 15.4% (1 pneumonitis and 1 AST/ALT elevation) of pts treated with durva but in none of pts treated with EGFR TKI. Three pts within each arm came off treatment due to toxicity (EGFR TKI: 1 pneumonitis and 2 dermatitis; durva: 1 of each pneumonitis, Type 1 diabetes, AST/ALT elevation). Conclusions: EGFR TKI therapy after definitive CRT was associated with significantly longer DFS compared to durva in this retrospective study of pts with stage III unresectable EGFRmut NSCLC, without unanticipated safety signals. Follow-up is ongoing and OS outcomes will be evaluated subsequently. Further investigation is warranted to define the optimal therapy for locally advanced EGFRmut NSCLC. [Table: see text]

A Retrospective Multi-Institutional Cohort Analysis of Clinical Characteristics and Outcomes in Dedifferentiated Chondrosarcoma.

Dedifferentiated chondrosarcoma (DDCS) is a rare subset of chondrosarcoma. It is an aggressive neoplasm characterized by a high rate of recurrent and metastatic disease with overall poor outcomes. Systemic therapy is often used to treat DDCS; however, the optimal regimen and timing are not well defined, with current guidelines recommending following osteosarcoma protocols. We conducted a multi-institutional retrospective analysis of clinical characteristics and outcomes of patients with DDCS. Between 1 January 2004 and 1 January 2022, the databases from five academic sarcoma centers were reviewed. Patient and tumor factors, including age, sex, tumor size, site, location, the treatments rendered, and survival outcomes, were collected. Seventy-four patients were identified and included in the analysis. Most patients presented with localized disease. Surgical resection was the mainstay of therapy. Chemotherapy was used predominantly in the metastatic setting. Partial responses were low (n = 4; 9%) and occurred upon treatment with doxorubicin with cisplatin or ifosfamide and single-agent pembrolizumab. For all other regimens, stable disease was the best response. Prolonged stable disease occurred with the use of pazopanib and immune checkpoint inhibitors. DDCS has poor outcomes and conventional chemotherapy has limited benefit. Future studies should focus on defining the possible role of molecularly targeted therapies and immunotherapy in the treatment of DDCS.

Accuracy of models to prognosticate survival after surgery for pancreatic cancer in the era of neoadjuvant therapy.

Outcomes for pancreatic adenocarcinoma (PDAC) remain difficult to prognosticate. Multiple models attempt to predict survival following the resection of PDAC, but their utility in the neoadjuvant population is unknown. We aimed to assess their accuracy among patients that received neoadjuvant chemotherapy (NAC). We performed a multi-institutional retrospective analysis of patients who received NAC and underwent resection of PDAC. Two prognostic systems were evaluated: the Memorial Sloan Kettering Cancer Center Pancreatic Adenocarcinoma Nomogram (MSKCCPAN) and the American Joint Committee on Cancer (AJCC) staging system. Discrimination between predicted and actual disease-specific survival was assessed using the Uno C-statistic and Kaplan-Meier method. Calibration of the MSKCCPAN was assessed using the Brier score. A total of 448 patients were included. There were 232 (51.8%) females, and the mean age was 64.1 years (±9.5). Most had AJCC Stage I or II disease (77.7%). For the MSKCCPAN, the Uno C-statistic at 12-, 24-, and 36-month time points was 0.62, 0.63, and 0.62, respectively. The AJCC system demonstrated similarly mediocre discrimination. The Brier score for the MSKCCPAN was 0.15 at 12 months, 0.26 at 24 months, and 0.30 at 36 months, demonstrating modest calibration. Current survival prediction models and staging systems for patients with PDAC undergoing resection after NAC have limited accuracy.

MP41-07 PROPOSAL FOR RECLASSIFICATION OF UPSTAGED T1 AND T2 AND PATHOLOGICAL T3 RCC BASED ON IMPROVED ALIGNMENT OF SURVIVAL ANALYSES

You have accessJournal of UrologyCME1 Apr 2023MP41-07 PROPOSAL FOR RECLASSIFICATION OF UPSTAGED T1 AND T2 AND PATHOLOGICAL T3 RCC BASED ON IMPROVED ALIGNMENT OF SURVIVAL ANALYSES Margaret Meagher, Clara Cerrato, Dhruv Puri, Franklin Liu, Aastha Shah, Saeed Ghassemzadeh, Sohail Dhanji, Luke Wang, Dattatraya Patil, Kazutaka Saito, Yosuke Yasuda, Ryan Nasseri, Yasuhisa Fujii, Viraj Master, and Ithaar Derweesh Margaret MeagherMargaret Meagher More articles by this author , Clara CerratoClara Cerrato More articles by this author , Dhruv PuriDhruv Puri More articles by this author , Franklin LiuFranklin Liu More articles by this author , Aastha ShahAastha Shah More articles by this author , Saeed GhassemzadehSaeed Ghassemzadeh More articles by this author , Sohail DhanjiSohail Dhanji More articles by this author , Luke WangLuke Wang More articles by this author , Dattatraya PatilDattatraya Patil More articles by this author , Kazutaka SaitoKazutaka Saito More articles by this author , Yosuke YasudaYosuke Yasuda More articles by this author , Ryan NasseriRyan Nasseri More articles by this author , Yasuhisa FujiiYasuhisa Fujii More articles by this author , Viraj MasterViraj Master More articles by this author , and Ithaar DerweeshIthaar Derweesh More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003279.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Patients with pathologically upstaged tumors have worse survival outcomes than their non-upstaged matched counterparts. We sought to examine if pathologic upstaging incrementally may more rationally stratify cancer specific survival outcomes. METHODS: Multi-institutional (Emory, TMDU, UCSD) retrospective analysis of patients with renal cell carcinoma who underwent partial or radical nephrectomy between 1998-2020. Patients were divided into cT1 upstaged to pT3 (cT1/pT3), cT2 non-upstaged (cT2/pT2), cT2 upstaged to pT3 (cT2/pT3), and cT3 non-upstaged (cT3/pT3). Primary outcome was cancer specific mortality (CSM). Secondary outcomes were overall survival (OS) and recurrence free survival (RFS). Cox regression was utilized to analyze factors associated with outcomes. Kaplan Meier analysis (KMA) was performed to analyze 5-year CSM. ROC analysis was utilized to compare predictive value of AJCC 8th edition TNM staging vs proposed staging. RESULTS: 1093 patients were analyzed (283 cT1/pT3, 237 cT2/pT2, 244 cT2/pT3, and 329 cT3/pT3). Median follow-up was 25.9 months. Cox regression demonstrated that cT2/pT3 (HR 2.7, p<0.001 vs. cT1/pT3 [referent]) and cT3/pT3 (HR 2.6, p<0.001 vs. cT1/pT3 [referent]) were significantly associated with worsened CSM, while cT1/pT3 (HR 0.4, p<0.001 vs. cT3/pT3 [referent]) and cT2/pT2 (HR 0.4, p<0.001 vs. cT3/pT3 [referent]) were associated with improved CSM. Based on this, we proposed to realign cT1/pT3 with cT2/pT2 and cT2/pT3 with cT3/pT3. KMA revealed significant differences in 5-year CSM (cT1/pT3 82%, cT2/pT2 81%, cT2/pT3 67%, and cT3/pT3 60%, p<0.001). There were significant differences in 5-year OS (cT1/pT3 63%, cT2/pT2 67%, cT2/pT3 49%, and cT3/pT3 49%, p<0.001), and 5-year RFS (cT1/pT3 80%, cT2/pT2 83%, cT2/pT3 70%, and cT3/pT3 59%, p<0.001) on KMA. ROC analysis revealed an AUC of 0.529 for CSM and AUC of 0.502 for ACM using the current AJCC 8th edition TNM staging. ROC analysis revealed an AUC of 0.597 for CSM and AUC of 0.545 for our new proposal. CONCLUSIONS: Our analysis suggests that cT1 tumors pathologically upstaged to pT3 behave more similarly to pT2 tumors. Further delineation of pathologically upstaged tumors may more rationally stratify cancer specific survival outcomes to guide patient counseling and clinical decision making. Source of Funding: N/A © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e556 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Margaret Meagher More articles by this author Clara Cerrato More articles by this author Dhruv Puri More articles by this author Franklin Liu More articles by this author Aastha Shah More articles by this author Saeed Ghassemzadeh More articles by this author Sohail Dhanji More articles by this author Luke Wang More articles by this author Dattatraya Patil More articles by this author Kazutaka Saito More articles by this author Yosuke Yasuda More articles by this author Ryan Nasseri More articles by this author Yasuhisa Fujii More articles by this author Viraj Master More articles by this author Ithaar Derweesh More articles by this author Expand All Advertisement PDF downloadLoading ...

PD08-08 SHOULD ADJUVANT THERAPY BE CONSIDERED FOR POSITIVE SURGICAL MARGINS IN RENAL CELL CARCINOMA: A STAGE-BASED ANALYSIS OF IMPACT OF POSITIVE SURGICAL MARGINS ON SURVIVAL OUTCOMES USING THE INMARC REGISTRY

PD08-08 SHOULD ADJUVANT THERAPY BE CONSIDERED FOR POSITIVE SURGICAL MARGINS IN RENAL CELL CARCINOMA: A STAGE-BASED ANALYSIS OF IMPACT OF POSITIVE SURGICAL MARGINS ON SURVIVAL OUTCOMES USING THE INMARC REGISTRY

Abstract P1-02-03: Real World Treatment Patterns of Adjuvant Endocrine Therapy and Ovarian Suppression in Premenopausal HR+/HER2+ Breast Cancer

Abstract Background: Approximately 10% of breast cancers (BC) are hormone receptor positive (HR+) and HER2 positive (HER2+). Despite treatment advances in the modern era of HER2 targeted therapies for early-stage disease, there remains a risk for late relapses. However, the role of adjuvant endocrine therapy (ET) to reduce recurrence in this BC subtype is unclear. Oncologists employ clinical judgment given lack of consensus, resulting in differences in treatment patterns. The ideal endocrine agent including the role of adding ovarian suppression (OS) in premenopausal women is unknown. These patients are largely underrepresented in clinical trials such as the phase III SOFT and TEXT studies. Additionally, these trials were initiated prior to the widespread use of trastuzumab with chemotherapy, which is now standard of care for HER2+ disease. We aimed to describe real world patterns surrounding choice of adjuvant ET and clinicopathologic features which predicted treatment with OS in premenopausal women with HR+/HER2+ BC. Methods: We performed a multi-institutional retrospective analysis of premenopausal women with non-metastatic HR+/HER2+ BC in the American Society of Clinical Oncology CancerlinQ® Discovery database from January 2010 to May 2020. Electronic health record data was obtained from 74 participating academic and community oncology sites. We collected clinical data on women less than 50 years who received chemotherapy, anti-HER2 therapy (trastuzumab with or without pertuzumab), and ET. Adjuvant OS was defined as receipt of at least 6 months of goserelin or leuprolide or surgical bilateral oophorectomy. Demographics, clinical characteristics, and treatment history was collected. Patients were categorized into 1 of 4 groups based on type of adjuvant ET prescribed at treatment initiation: aromatase inhibitor (AI) + OS, OS, tamoxifen + OS, or tamoxifen. Multivariable logistic regression was conducted to assess the association between clinicopathologic features and OS use. Results: Out of 360,540 patients with invasive breast cancer in the database, 937 met inclusion criteria. Mean age was 41.7 (SD 5.9) years; 83% had stage 1 or 2 BC and 78% had node positive disease. The majority (n=818, 87%) were prescribed tamoxifen whereas only 4 (0.4%), 50 (5.3%), and 65 (6.9%) received OS, tamoxifen + OS, and AI + OS, respectively. Table 1 includes demographic and clinical characteristics of the cohort. No clinicopathologic features predicted OS use apart from age; patients ≥35 years were less likely to receive OS compared with those &amp;lt; 35 (p&amp;lt; 0.001) (table 2). Conclusion: To our knowledge, this is the first real world study evaluating OS treatment in HR+/HER2+ BC. The use of OS was uncommon; this suggests a perception of its limited benefit when added to HER2-targeted therapy. Most patients received tamoxifen as the ET of choice. Age was the only factor to predict OS treatment; high risk features including node positivity and higher stage was not associated with its use. This highlights the wide variability in real world practice surrounding the clinical indications for OS. Further investigation is warranted to characterize the utility of ET including addition of OS to prevent recurrence in premenopausal HR+/HER2+ BC. This will better inform a personalized approach to tailor therapy for optimal outcomes in this distinct BC subtype. Table 1. Demographic and clinical characteristics of study participants by endocrine therapy treatment group. Table 2. Multivariable logistic regression model of clinicopathologic characteristics to predict use of ovarian suppression. Citation Format: Jasmine S. Sukumar, Sagar Sardesai, Andy Ni, Nicole Williams, Bhuvaneswari Ramaswamy, Robert Wesolowski, Mathew A. Cherian, Daniel Stover, Margaret Gatti-Mays, Ashley C. Pariser, Preeti K. Sudheendra, Mridula A. George, maryam lustberg. Real World Treatment Patterns of Adjuvant Endocrine Therapy and Ovarian Suppression in Premenopausal HR+/HER2+ Breast Cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-02-03.

Proposal for reclassification of upstaged T1 and T2 and pathological T3 RCC based on improved alignment of survival analyses.

732 Background: Patients with pathologically upstaged tumors have worse survival outcomes than their non-upstaged matched counterparts. However, we do know that original clinical tumor staging does still predict outcomes. We sought to examine if pathologic upstaging incrementally may more rationally stratify cancer specific survival outcomes. Methods: Multi-institutional (Emory, TMDU, UCSD) retrospective analysis of patients with renal cell carcinoma who underwent partial or radical nephrectomy between 1998-2020. Patients were divided into cT1 upstaged to pT3 (cT1/pT3), cT2 non-upstaged (cT2/pT2), cT2 upstaged to pT3 (cT2/pT3), and cT3 non-upstaged (cT3/pT3). Patients were analyzed for demographics, clinical parameters, and post-surgical outcomes. Primary outcome was cancer specific mortality (CSM). Secondary outcomes were all cause mortality and recurrence free survival. Cox regression was utilized to analyze factors associated with outcomes. Kaplan Meier analysis (KMA) was performed to analyze 5-year cancer specific survival. ROC analysis was utilized to compare predictive value of AJCC 8th edition TNM staging vs proposed staging. Results: 1093 patients were analyzed (283 cT1/pT3, 237 cT2/pT2, 244 cT2/pT3, and 329 cT3/pT3). Median follow-up was 25.9 months. Cox regression demonstrated that cT2/pT3 (HR 2.7, p&lt;0.001 vs. cT1/pT3 [referent]) and cT3/pT3 (HR 2.6, p&lt;0.001 vs. cT1/pT3 [referent]) were significantly associated with worsened cancer specific mortality, while cT1/pT3 (HR 0.4, p&lt;0.001 vs. cT3/pT3 [referent]) and cT2/pT2 (HR 0.4, p&lt;0.001 vs. cT3/pT3 [referent]) were associated with improved cancer specific mortality. Based on this, we proposed to realign cT1/pT3 with cT2/pT2 and cT2/pT3 with cT3/pT3. KMA revealed significant differences in 5-year cancer specific survival (cT1/pT3 82%, cT2/pT2 81%, cT2/pT3 67%, and cT3/pT3 60%, p&lt;0.001). There were significant differences in 5-year overall survival (cT1/pT3 63%, cT2/pT2 67%, cT2/pT3 49%, and cT3/pT3 49%, p&lt;0.001), and 5-year recurrence free survival (cT1/pT3 80%, cT2/pT2 83%, cT2/pT3 70%, and cT3/pT3 59%, p&lt;0.001) on KMA. ROC analysis revealed an AUC of 0.529 for CSM and AUC of 0.502 for ACM using the current AJCC 8th edition TNM staging. ROC analysis revealed an AUC of 0.597 for CSM and AUC of 0.545 for our new proposal. Conclusions: Our analysis suggests that cT1 tumors pathologically upstaged to pT3 behave more similarly to pT2 tumors. Further delineation of pathologically upstaged tumors may more rationally stratify cancer specific survival outcomes to guide patient counseling and clinical decision making.

CT and MRI features of hepatic epithelioid haemangioendothelioma: a multi-institutional retrospective analysis of 15 cases and a literature review

ObjectiveTo improve the current imaging understanding of MRI or CT for hepatic epithelioid haemangioendothelioma (HEHE) to aid in its successful preoperative diagnosis.MethodsThe imaging features of 15 patients (median age 38.6, range 20–71; 7 M/8 F) from eight institutions with pathologically confirmed HEHE were retrospectively analysed. Additionally, the CT/MR imaging features of 180 patients in 15 literature publications were collected, analysed and compared with our case series.ResultsFifteen patients underwent CT and MRI (n = 2), CT (n = 9) or MR (n = 8) scans. A total of 92.9% (13/14) of the patients were initially diagnosed with other lesions on imaging. A total of 86.7% (13/15) were multifocal. Nodules (11/15, 73.3%) were predominantly peripheral in distribution (12/15, 80.0%). Some cases were associated with hepatic capsular retraction (13/15, 86.7%), “target signs” (8/15, 53.3%) and “lollipop signs” (5/15, 33.3%). Peripheral enhancement of various shapes in the early phase with a progressive centripetal filling was the most common pattern of enhancement (12/15, 80.0%). Abnormal vascularity was seen in 50.7% (6/15) of the patients. Suspicious tumour thromboses in the inferior vena cava were seen in 3 (20.0%) of the patients. Two of the 15 patients (13.3%) had a history of smoking.ConclusionsHEHEs have common distinctive features, including multifocal lesions that are predominantly peripheral, “target signs”, “lollipop signs”, hepatic capsular retraction and peripheral enhancement of various shapes in the early phase with progressive centripetal filling. Additional aggressive imaging features that may be valuable clues to the diagnosis can be identified by CT or MRI.

A multi-institutional retrospective pooled outcome analysis of molecularly annotated pediatric supratentorial ZFTA-fused ependymoma.

ZFTA-RELA (formerly known as c11orf-RELA) fused supratentorial ependymoma (ZFTAfus ST-EPN) has been recognized as a novel entity in the 2016 WHO classification of CNS tumors and further defined in the recent 2021 edition. ZFTAfus ST-EPN was reported to portend poorer prognosis when compared to its counterpart, YAP1 ST-EPN in some previously published series. The aim of this study was to determine the treatment outcome of molecularly confirmed and conventionally treated ZFTAfus ST-EPN patients treated in multiple institutions. We conducted a retrospective analysis of all pediatric patients with molecularly confirmed ZFTAfus ST-EPN patients treated in multiple institutions in 5 different countries (Australia, Canada, Germany, Switzerland, and Czechia). Survival outcomes were analyzed and correlated with clinical characteristics and treatment approaches. A total of 108 patients were collated from multiple institutions in 5 different countries across three continents. We found across the entire cohort that the 5- and 10-year PFS were 65% and 63%, respectively. The 5- and 10-year OS of this cohort of patients were 87% and 73%. The rates of gross total resection (GTR) were high with 84 out of 108 (77.8%) patients achieving GTR. The vast majority of patients also received post-operative radiotherapy, 98 out of 108 (90.7%). Chemotherapy did not appear to provide any survival benefit in our patient cohort. This is the largest study to date of contemporaneously treated molecularly confirmed ZFTAfus ST-EPN patients which identified markedly improved survival outcomes compared to previously published series. This study also re-emphasizes the importance of maximal surgical resection in achieving optimal outcomes in pediatric patients with supratentorial ependymoma.