T4 Disease Research Articles

Identifying care fragmentation in the management of non-metastatic muscle-invasive bladder cancer.

e13527 Background: Measuring care fragmentation facilitates exploration of breakdowns in cancer care delivery that may impact quality of care and patient outcomes. Bladder cancer often requires a multimodal approach of surgery, chemotherapy and radiation, increasing the risk of fragmented care. This study assesses the extent of care fragmentation across different inpatient facilities and examines patient characteristics associated with inpatient care fragmentation. Methods: We adapt the modified Herfindahl-Hirschman market concentration index to construct a Fragmentation Index (FI) capturing the distribution of a patient’s care across inpatient facilities. We calculate FI for the 15 months following diagnosis for non-metastatic muscle-invasive bladder cancer (MIBC) patients who underwent radical cystectomy from 2010-2016 and had at least 2 admissions during the study period. We use Pennsylvania Cancer Registry data linked to statewide facility discharge records to estimate patient-level multivariable regression models of the relationship between FI and patient demographics, disease features, rurality, area deprivation index (ADI), payer, and Commission on Cancer hospital (CoC-H) accreditation status. Results: Of 965 patients, 87.3% (n = 842) lived in urban areas, 8.9% in large towns and 3.8% rural. Approximately 8% had Medicaid and 5.7% had uninsured or unknown payer status. A majority (64%; n = 614) were age 60-79; 76% were men and 92% non-Hispanic White; 19.5% (n = 188) had T4 disease and 25% (n = 239) received neoadjuvant chemotherapy. Almost half of patients (45.3%; n = 437) had an FI of 0, indicating all admissions were at the same hospital. The mean FI was 0.254 for the total cohort and 0.464 for patients with FI > 0. Residency in a large town or rural area was associated with 0.59 (CI 0.003—0.114) and 0.14 (CI 0.060—0.220) higher FI relative to urban areas. T4 disease was associated with 0.063 higher FI (CI 0.019—0.107) relative to <T2 disease. Factors associated with lower FI included Non-White race (-0.092, CI -0.151 – -0.033) and no admissions to CoC-H (-0.138, CI -0.182 – -0.095) relative to patients admitted to at least 1 CoC-H. Patients never admitted to a CoC-H (n = 134) mostly lived in urban areas (88%) and 49% had Medicare insurance: they were disproportionately from the most disadvantaged ADI quartile in the cohort (37.3%). Conclusions: Our findings highlight that many MIBC patients receive inpatient care across at least two different hospitals. Advanced disease and patient residence in non-urban areas are associated with greater fragmentation of inpatient care. Patients who never received care at a CoC hospital experienced less fragmentation but were more likely to be relatively economically disadvantaged. Future research will investigate relationships between fragmentation and clinical outcomes to inform policy and clinical strategies aimed at optimizing patterns of care.

Post radical prostatectomy (RP) PSA outcomes following 6 vs 18 months of perioperative androgen deprivation therapy (ADT) in men with localized high risk prostate cancer (LHRPC): Results of Part 2 of a randomized phase 2 trial.

5095 Background: Patients with LHRPC have an increased risk of relapse following RP. We previously reported on Part 1 of a phase 2 trial testing neoadjuvant apalutamide, leuprolide, and abiraterone acetate plus prednisone (ALAAP) or leuprolide and abiraterone plus prednisone (LAP) for 6 months followed by RP (McKay, J Urol, 2021). We demonstrated favorable pathologic responses (tumor <5 mm) at RP in 20.3% of patients (n=24/118). Herein, we report the results of Part 2 testing adjuvant ALAAP (NCT02903368). Methods: Eligible patients had a Gleason score ≥4+3, PSA >20 ng/mL, or T3 disease (by DRE or MRI) and lymph nodes <20 mm. At Part 2, patients were randomized 1:1 to ALAAP for 12 months (Arm 2A) or observation (Arm 2B), stratified by neoadjuvant therapy and pathologic T stage (<ypT3 or ≥ypT3). The primary endpoint was biochemical progression-free survival (bPFS) at 3 years post-RP. bPFS was defined as the time from randomization to progression (PSA ≥ 0.2 ng/mL, local/distant disease on CT/MRI or bone scan, or receipt of post-RP therapy or radiation for rising PSA) or death. The Kaplan-Meier estimate of bPFS at 3 years was compared between arms using a Chi-square test (Klein, Stat Med, 2007). Secondary endpoints included safety and time to testosterone recovery (>200 ng/dL). Results: Overall, 82/118 (69%) of patients enrolled to Part 1 were randomized to Part 2. Median follow-up was 47 months post-RP. Patient preference was the main reason for non-randomization in Part 2. In the intent-to-treat analysis, the 3-year bPFS estimate was 80% (95% CI:65-90%) for Arm 2A and 72% (95% CI:56-84%) for Arm 2B, which was not statistically significant (2-sided p=0.39). Patients who achieved pathologic responses (n=14) had longer bPFS than non-responders (log-rank test two-sided p=0.03; 3-year bPFS 100% vs 72%). In per-protocol population, of 36 patients receiving Arm 2A treatment with available data, 83% had testosterone recovery and median time to recovery from therapy end was 8.7 months. For patients on observation (n=42), 95% had testosterone recovery, and median time to recovery from RP was 4.0 months. No new safety signals were observed. Conclusions: Neoadjuvant ADT in LHRPC resulted in favorable pathologic responses and 3-year bPFS in a subset of patients. As 30% of patients declined an additional 12 months of adjuvant treatment, the study was underpowered to detect a difference between 6 months vs. 18 months of treatment. Subsequent analyses will evaluate predictors of improved bPFS. Clinical trial information: NCT02903368 . [Table: see text]

Carboplatin and paclitaxel chemoradiation for localized anal cancer in patients not eligible for mitomycin and 5-fluorouracil.

e15500 Background: Anal cancer (AC) is a relatively uncommon malignancy in the United States, however, this disease continues to increase in incidence, especially in individuals over 50 years old. Current standard of care for locoregional disease includes mitomycin and 5-fluorouracil (M/5FU) with radiation. This combination is associated with significant toxicity limiting its use in those patients who are elderly or have multiple comorbidities. Carboplatin and paclitaxel (C/P) is now the preferred standard of care treatment regimen for metastatic AC. Weekly C/P has become a standard of care option in combination with radiation for locally advanced esophageal cancer. Here we evaluate the efficacy of weekly C/P chemoradiation in treating a cohort of patients unable to receive standard M/5FU chemoradiation. Methods: Subjects were consented to an IRB approved AC registry at the University of Wisconsin Carbone Cancer Center. Patients (pts) were identified to have received weekly infusional C/P concurrent with standard-dose radiation for localized AC between January 1, 2016 and December 1, 2022. Clinical response was determined based on evidence of disease on imaging or anoscopy and toxicities were graded according to CTCAE v5. Results: 8 pts (7F/1M; median age 76 (54-87)) were found to meet eligibility criteria. 6 had perianal cancers and 2 had cancers within the anal canal. 6 had T2 disease and 2 had T3 tumors. 2 had node positive disease. Dosing ranged from C (AUC 1.5-2), P (30-50mg/m2) and radiation (50.4-58 Gy). Patients completed a median of 82.5% (40%-100%) of intended treatments. Most common toxicities included leukopenia, anemia, perianal pain, and fatigue. Grade 3 or higher toxicities included neutropenia (3) of which 2 resulted in febrile neutropenia, and anemia (3). All patients had a complete clinical response. With a median follow-up of 17 mos (3-40 mos), no patients have had recurrence and all patients are still alive. Conclusions: This study demonstrates promising tolerability and efficacy for weekly C/P chemoradiation for patients with anal cancer unable to receive M/5FU. This regimen merits further investigation in prospective clinical trials.

Neoadjuvant tislelizumab, a PD-1 mAb plus nab-paclitaxel (nab-P) followed by tislelizumab plus epirubicin/cyclophosphamide (EC) for triple-negative breast cancers (TNBC): Interim analysis of clinical response in a phase 2 TREND trial.

e14623 Background: Chemo-based immunotherapy improves the prognosis of TNBC. However, the dominant population and optimal chemo-backbone of neoadjuvant immunotherapy remain undefined. Aim of TREND trial was to assess the efficacy and safety of tislelizumab in combination with nab-P and EC (nab-P-EC) in neoadjuvant therapy of TNBC. Methods: In this prospective, single-arm phase 2 clinical study, untreated TNBC patients who have clinically node-positive or at least T2 disease without distant metastasis were eligible. Before surgery, enrolled patients received tislelizumab (200 mg IV Q3W) plus weekly nab-P (100 mg/m² IV Q3W) for 12 weeks, followed by tislelizumab (200 mg IV Q3W) plus epirubicin (75 mg/m² IV Q3W) and cyclophosphamide (600 mg/m² IV Q3W) for the subsequently 12 weeks. The primary endpoint was pCR (ypT0/Tis ypN0) and secondary endpoints was objective response rate (ORR, RECIST v1.1). Combined positive score (CPS) of PD-L1 expression in pre-treatment biopsy samples was tested by PD-L1 IHC 22C3 PharmDx. Single-cell RNA sequencing, single-cell TCR sequencing, mass cytometry by time of flight, whole exome sequencing, RNA-seq and olink-assay were performed on pre- and post-treatment samples from primary tumors, metastatic lymph nodes and peripheral blood. Results: Of 43 enrolled patients from Nov 2020 to Nov 2022, 21 patients completed neoadjuvant therapy and accepted surgery in per protocol set (PPS; median age 48 years; range 25-69 years), and 16 were still on treatment. In PPS, the pCR (ypT0/is ypN0) rate was 71.43% (15/21). For different target lesions, 15 patients achieved ypT0/Tis (pCR rate = 71.43%) and 20 reached ypN0 (pCR rate = 95.24%). When stratified by CPS, pCR (ypT0/is ypN0) rate were 68.4%,72.2% and 76.9% in CPS ≥ 1, CPS ≥ 5 and CPS ≥ 10 subgroups, respectively. The ORR in PPS was 90.48% (n = 19/21, 95% CI: 68.18 - 98.33) and DCR reached 95.24% (n = 20/21, 95% CI: 74.13 - 99.75), including 9 complete response and 10 partial response. Treatment emergent adverse event (TEAE) occurred in 74.4% patients (32/43), of which 69.8% were Immune-related adverse event (irAE) (30/43). Grade ≥ 3 IrAE was 7.0% (3/43) and no treatment-related deaths were found. Conclusions: Combining tislelizumab and neoadjuvant nab-P-EC achieved favorable efficacy in TNBC, supporting that platinum-free regimen was non-inferior as a chemo-backbone. For heterogeneity of efficacy to immunotherapy, metastatic tumors in lymph nodes responded better to tislelizumab than primary tumor, suggesting that node-positive patients were potentially dominant population of neoadjuvant immunotherapy. Further results from the ongoing TREND trial and subsequent analysis of mechanism are urgently awaited. Clinical trial information: ChiCTR2000035262 .

A single-arm, multi-institutional, phase 2 study of a pembrolizumab-based organ preservation strategy for locally advanced larynx cancers: SMART-KEY (LACOG 0720) trial.

TPS6111 Background: Standard treatments for locally advanced larynx cancers include concurrent cisplatin/radiation therapy, or induction chemotherapy followed by radiation therapy alone, with the goal of organ preservation. Both strategies have been shown to achieve similar laryngectomy-free survival (LFS), but failed to improve overall survival (OS) compared with radiation therapy alone or surgery followed by radiation therapy. Although cisplatin given concurrently with radiation therapy is commonly used for organ preservation, there are concerns regarding long-term outcomes, such as late toxicities. Pembrolizumab with chemotherapy has been shown to improve OS in recurrent/metastatic head and neck squamous cell carcinomas (HNSCCs). Additionally, pembrolizumab combined with radiation therapy has been shown to be safe in locally advanced HNSCC. LACOG 0720 is designed to evaluate a pembrolizumab-based, cisplatin-free, and concurrent chemoradiation therapy-free regimen for larynx preservation, in an attempt to improve outcomes and avoid late toxicities. Methods: LACOG 0720 is a phase 2, single-arm, multicentric trial assessing patients with newly diagnosed squamous cell carcinoma of the larynx (glottic or supraglottic) and clinical stages III, IVA, or IVB (AJCC 8th Ed.). Patients with large volume T4 disease (invasion through the cartilage or extension > 1 cm to the base of the tongue) or T1 disease are excluded. Patients receive 3 cycles of induction chemo-immunotherapy (carboplatin AUC6, paclitaxel 175 mg/m², and pembrolizumab 200 mg, IV every 21 days [q21D]), followed by concurrent radioimmunotherapy (Intensity-modulated radiation therapy with pembrolizumab 200 mg IV q21D for 3 cycles), followed by consolidation immunotherapy (pembrolizumab 200 mg IV q21D for 11 cycles). The primary endpoint is two-year LFS rate. Secondary endpoints include two-year larynx dysfunction-free survival, OS, overall response rate, short-term and long-term toxicities, causes of death, patterns of failure, and quality of life. Predictive biomarkers of response and survival will be evaluated as exploratory analysis. The sample size was calculated based on the primary endpoint. Using the Chi-square Test for One Proportion and considering a one-sided 10% significance level, 39 patients are needed to achieve 80% power to detect the difference between the null hypothesis; that the true laryngectomy-free survival at two years is 59%, and the alternative hypothesis that the laryngectomy-free survival at two years is 75%. From Feb 2022 to Feb 2023, 24 patients were enrolled in 10 Brazilian centers. Results are expected in July 2024. NCT04943445. Clinical trial information: NCT04943445 .

Pathologic complete response after neoadjuvant systemic therapy for breast cancer in BRCA mutation carriers and noncarriers.

544 Background: Distinct pathological characteristics and mutational signatures in BRCA-associated breast cancers may result in differential response to chemotherapy but understanding of treatment response after neoadjuvant chemotherapy (NAC) is limited. We describe a single-institutional experience to compare rates of pathologic complete response (pCR) after NAC in BRCA carriers (g BRCA1/2) and noncarriers. Methods: From 11/2013 to 01/2022, 1426 consecutive women with clinical stage I-III breast cancer were treated with NAC followed by surgery. Baseline disease characteristics were compared between g BRCA1/2 and noncarriers using two-sample non-parametric tests. Conditional logistic regression was used to evaluate the association between BRCA status and pCR (i.e., ypT0/is pN0) adjusting for variables selected using backward elimination. Results: 92 (6.5%) and 73 (5.1%) had deleterious mutations in BRCA1 and BRCA2, respectively. Compared to noncarriers, g BRCA1/2 were younger (p<0.001) with clinical T1 (p=0.002) and triple negative disease (TN) (57% vs 25% noncarriers, p<0.001). Almost all patients received doxorubicin/cyclophosphamide/paclitaxel therapy (93%) with g BRCA1/2 more likely to receive carboplatin (p<0.001). pCR rate was 42% of g BRCA1, 21% of g BRCA2, and 26% of noncarriers (p=0.001). Among clinically node positive (cN+) patients, nodal pCR was higher in g BRCA1/2 compared to noncarriers (53/96 (55%) vs 371/856 (43%), p=0.012). This difference was seen in ER+/HER2- (36% gBRCA1/2 vs 20% noncarriers; p=0.027) and TN subtypes (79% g BRCA1/2 vs 45% noncarriers; p<0.001). Poorly differentiated tumors (p<0.001), cN+ (p=0.010), lower cT stage (p=0.028), ductal histology (p<0.001), TN and HER2+ receptor status (p<0.001), absence of lymphovascular invasion (p<0.001), carboplatin receipt (p=0.041), and BRCA1 status (p=0.001) were also associated with pCR on univariate analysis. After adjusting for differentiation and molecular subtype, BRCA1 status remained independently associated with pCR. Conclusions: g BRCA1 undergoing NAC have higher pCR rates relative to g BRCA2 and patients with sporadic disease. Across breast cancer subtypes, g BRCA1/2 more frequently converted to pN0. Defining biological mechanism for these findings would allow customization of treatment based on germline genetics. [Table: see text]

A CASE SERIES OF PATIENTS WITH CUTANEOUS T‐CELL LYMPHOMA TREATED WITH COMBINATION MOGAMULIZUMAB AND OTHER THERAPIES AFTER SINGLE AGENT MOGAMULIZUMAB

Introduction: Mogamulizumab (moga) is an anti-CCR4, monoclonal antibody approved as monotherapy for the treatment of relapsed/refractory mycosis fungoides (MF) and Sezary syndrome (SS). Combination therapies are frequently utilized in cutaneous T-cell lymphoma (CTCL), in part due to the variation in response across blood, nodal, and skin compartments. Little is known about moga in combination with other therapies. Methods: We conducted a single institution retrospective analysis of MF/SS patients who were treated with moga in combination with other systemic therapies, including peginterferon alpha-2a (IFNα), bexarotene, extracorporeal photopheresis (ECP), and oral methotrexate between March 2019 and March 2023. Baseline characteristics and clinical outcomes were recorded and summarized. Responses were assessed by Olsen staging criteria (Olsen et al., 2022). Results: We identified 9 patients treated with moga combination therapy at our institution (Table 1). Six of 7 patients transitioned from mono to combination therapy due to progressive disease or stable disease with uncontrolled symptom burden. Median time to next treatment was 157.5 days (range 42-330) for moga monotherapy. The best response observed in the 8 patients to single agent moga was classified as: 4 (50%) partial responses (PR), 3 (37.5%) stable disease (SD), and 1 (12.5%) progressive disease (PD). We identified a total of 7 different treatment combinations in our 9 patients (6 systemic therapies and 2 skin-directed), which included IFNα (n = 4), bexarotene (2), ECP (2), total skin electron beam radiation (TSEB) (2), narrow band ultraviolet-B therapy (NBUVB) (1), IFNα + ECP (2), and oral methotrexate (1). Multiple patients received more than one combination treatment. Among the combination therapies, the median time to next treatment was 137 days (range 24-224 days) with 2 out of 6 patients having ongoing responses to moga + IFNα +/- ECP. The patient with PR on moga + IFNα received 7 prior therapies. His skin involvement improved from T4 to T1 but significant disease in the blood persisted (B2). He continues moga + IFNα now 846 days later. Conclusions: Mogamulizumab has improved outcomes for MF/SS patients, but global complete responses are rare with the best responses seen in blood. In our series, the addition of IFNα provided clinical benefits to patients with SD or PD on single agent moga. One patient achieved a lengthy partial response despite persistent disease seen in peripheral blood samples. We speculate the combination of moga + IFNα may augment antibody-dependent cellular cytotoxicity thereby improving efficacy of moga. Additionally, combinatorial approaches may improve responses in skin, nodes, and viscera where lower responses are observed to single agent moga. Further investigations of moga combinations are needed. Keywords: Combination Therapies, Cutaneous non-Hodgkin lymphoma No conflicts of interests pertinent to the abstract.

Cell-free urinary tumor DNA to detect minimal residual disease prior to repeat-transurethral resection of bladder tumor in non-muscle invasive bladder cancer: A prospective study.

e16598 Background: Cell-free urinary tumor DNA (utDNA) generated from tumor genomic sequencing is an emerging biomarker showing tremendous potential for detecting minimal residual disease (MRD) in muscle-invasive and metastatic bladder cancer. We performed a prospective study to assess utDNA’s ability to measure MRD at the time of standard-of-care repeat transurethral resection of bladder tumor (rTURBT) in non-muscle invasive bladder cancer (NMIBC). Methods: Patients with high-risk NMIBC were enrolled prior to rTURBT. Index tumor and rTURBT mutational profile was performed via PredicineWES whole exome sequencing across 20,000 genes. Genes with non-synonymous (NS) mutations observed in index and rTURBT specimens identified in a minimum of two samples are reported. Urine samples were taken immediately prior to r-TURBT. utDNA detection was performed by ultra-deep sequencing of urinary cfDNA using a custom panel of up to 50-baseline mutations per patient together with a fixed core panel covering hotspot regions and actionable variants via PredicineBEACON Urinary tumor fraction was used to call utDNA positivity. The primary endpoint was the detection of utDNA to predict MRD at the time of repeat-TURBT. Results: Eleven patients underwent rTURBT for high risk NMIBC. Residual tumor was detected at rTURBT in 8/11 (73%) patients. Fifty genes with NS mutations found in at least two samples were identified including TP53, PIK3CA, RB1, MYC, CDKN1A and ARID1A. A median of 146 (range 39-418) and 91 NS (range 2-312) mutations were identified in the index and re-TUR specimens, respectively. Concordance rates were 83% on average between primary and rTURBT, highest for patients upstaged to T2 disease, and lowest for patients harboring CIS. Genomic alterations in urinary tumor DNA were detected in ten patients. The tumor fraction of utDNA was higher in patients with residual disease (mean 2.5% vs. 0.2%, p=0.10). Using tumor-fraction to predict MRD, the area under the receiver-operator curve (AUC) for this test was 0.85. Using an optimal threshold of ≥3.3% tumor-fraction to define utDNA positivity, the test had a sensitivity of 75% at 100% specificity. Conclusions: Urinary tumor DNA shows promise as a surrogate for minimal residual disease and may predict TURBT pathology for NMIBC. Genomic alterations between index and rTURBT tumors are highly concordant in papillary tumors even in the setting of upstaging, which may aid in targeted intravesical or systemic therapy selection. Larger cohorts and long-term follow up is needed to determine if utDNA can risk-stratify patients prior to rTURBT and predict long-term recurrence.

Phase 2 trial of intravesical cabazitaxel, gemcitabine, and cisplatin (CGC) for the treatment of non-muscle invasive BCG unresponsive urothelial carcinoma of the bladder.

TPS4616 Background: For patients with non-muscle invasive bladder cancer (NMIBC) unresponsive to Bacille Calmette-Guerin (BCG), multi-agent intravesical trials have been limited. The goal of this Phase 2 study is to investigate the efficacy of intravesical chemotherapy consisting of sequential cabazitaxel, gemcitabine, and cisplatin (CGC) in the salvage setting. Phase 1 results reporting on 18 subjects demonstrated adverse events limited to local Grade 1 and 2 toxicities. Partial funding support for the trial was provided by a pharmaceutical company. Methods: This is a Phase 2 trial (NCT02202772) presently enrolling patients with BCG unresponsive NMIBC as defined by the FDA who refuse or are ineligible for radical cystectomy. All patients undergo pre-treatment transurethral resection of bladder tumor (TURBT) and a 6-week regimen of intravesical cisplatin (100mg), gemcitabine (2gm), and cabazitaxel (5mg). Each drug is instilled weekly except for cisplatin, which is given every other week. Complete response is defined as having no evidence of cancer on post-induction biopsy and negative urine cytology at 3 months. Complete responders proceed with monthly and bimonthly maintenance therapy without cisplatin in the first and second years, respectively, for a total of 24 months. Results: To date thirty-one patients have been enrolled (with target accrual of 33), of whom seven are female. One patient withdrew consent before first evaluation cystoscopy. Mean age thus far is 72 years. All patients have previously received at least two prior induction cycles of BCG, and meet FDA criteria for BCG unresponsive disease. All patients have biopsy proven high grade disease at enrollment; 8 (27%) have high grade T1 disease; and 20 (67%) patients have CIS. Conclusions: Salvage options for BCG unresponsive NMIBC are limited. The CGC protocol has been demonstrated to be safe in a previous Phase 1 study, and accrual for this Phase 2 is near completion. Clinical trial information: NCT02202772 .

Association of ipsilateral radiation therapy with contralateral lymph node failure in patients with squamous cell carcinoma of the oral cavity: A systematic review and meta-analysis.

Ipsilateral neck radiotherapy (INRT) is controversial in some patients with oral cavity cancer due to concern for contralateral neck failure (CNF). A systematic review was performed and data were extracted following PRISMA guidelines. Outcomes were the rate of CNF following INRT and the rates of CNF by AJCC 7th ed. tumor and nodal staging. Fifteen studies consisting of 1825 patients were identified. Among the 805 patients treated with INRT, the rate of CNF was 5.7%. Patients with T4 tumors constituted 56% of all CNF cases. The rate of CNF increased by N stage (N0: 1.2%; N1: 3.8%; N2-N3: 17.4%) and was significantly higher for patients with N2-N3 than N0-N1 disease (p < 0.001). INRT is associated with an overall low risk of CNF in well-selected patients with N0-N1 disease. Patients with N2-3 and/or T4 disease should receive bilateral RT due to increased risk of CNF following INRT.

Can Definitive Radiation Therapy Substitute Surgical Resection in Locally Advanced T3 or T4 Sinonasal Squamous Cell Carcinoma?

This study aimed to compare oncologic outcomes between definitive radiation therapy (RT) and upfront surgical resection in patients with sinonasal squamous cell carcinoma (SCC). Between 2008 and 2021, 155 patients with T1-4b, N0-3 sinonasal SCC were analyzed. The 3-year overall survival (OS), local progression-free survival (LPFS), and overall progression-free survival (PFS) were evaluated using the Kaplan Meier method and compared using a log-rank test. A pattern of regional neck lymph node (LN) failure and treatment-related toxicity profiles were investigated. A total of 63 and 92 patients underwent upfront RT (RT group) and surgical resection (Surgery group), respectively. The RT group included significantly more patients with T3-4 disease than the Surgery group (90.5% vs 39.1%, P < .001). The rates of 3-year OS, LPFS, and PFS in the RT and Surgery groups were 68.6% versus 81.7% (P=.073), 62.3% versus 73.8% (P=.187), and 47.4% versus 66.1% (P=.005), respectively. However, the corresponding rates in patients with T3-4 disease were 65.1% versus 64.8% (P=.794), 57.4% versus 56.8% (P=.351), and 43.2% versus 46.5% (P=.638), respectively, demonstrating no statistically significant differences between the 2 treatment modalities. Among the 133 N0 patients, regional neck LN progression was observed in 17 patients, and the most common sites of regional neck LN failure were ipsilateral levels Ib (9 patients) and II (7 patients). The 3-year neck node recurrence-free rate in cT1-3N0 patients was 93.5%, while that in cT4N0 patients was 81.1% (P=.025). Upfront RT may be considered in selected patients with locally advanced sinonasal SCC, as we have demonstrated similar oncologic outcomes to those of surgery. Prophylactic neck treatment in T4 disease requires further investigation to evaluate its efficacy.

Impact of anatomic resection on long-term survival in patients with hepatocellular carcinoma with T1–T2 disease or microscopic vascular invasion

BackgroundThis study aimed to clarify potential candidates for anatomic resection (AR) among patients with pathological T1–T2 (pT1–T2) hepatocellular carcinoma (HCC) and to determine whether AR is effective for HCC with microscopic vascular invasion (MVI). MethodsWe retrospectively analyzed 288 patients with pT1a (n = 50), pT1b (n = 134) or pT2 (n = 104) HCC who underwent curative-intent resection between 1990 and 2010. Surgical outcomes were compared between patients who underwent AR (n = 189) and those who underwent nonanatomic resection (NAR; n = 99) according to pT category and MVI status. ResultsPatients who underwent AR were more likely to have good hepatic functional reserve and an aggressive primary tumor than those who underwent NAR. When patients were stratified according to pT category, AR had a more favorable impact on survival than NAR only in patients with pT2 HCC in univariate (5-year survival, 51.5% vs. 34.6%; p = 0.010) and multivariate analysis (hazard ratio 0.505; p = 0.014). However, AR had no impact on survival in patients with pT1a or pT1b HCC. In patients with MVI (n = 57), AR achieved better survival than NAR (5-year survival, 52.0% vs. 16.7%; p = 0.019) and was an independent prognostic factor (hazard ratio 0.335; p = 0.020). In patients without MVI (n = 231), there was no significant difference in survival between the two groups (p = 0.221). ConclusionAR was identified as an independent factor in improved survival in patients with pT2 HCC or HCC with MVI.

Intensity-Modulated Radiation Therapy for Early-Stage Squamous Cell Carcinoma of the Glottic Larynx: A Systematic Review and Meta-Analysis

Early-stage squamous cell carcinoma of the glottic larynx is commonly treated with 2-dimensional or 3-dimensional conventional radiation therapy (CRT). Despite its use in other head and neck cancers, intensity-modulated radiation therapy (IMRT) remains controversial in this patient population. A systematic review was performed by querying 3 databases (Pubmed, Embase, Web of Science) for articles published between December 1, 2000 and September 2, 2022. Included studies reported outcomes in at least 10 patients treated with IMRT for early-stage glottic cancer. Data were extracted and reported following PRISMA standards. Pooled outcomes were estimated using random-effects models. Primary outcome was the rate of local failure (LF) following IMRT. Secondary outcomes included rates of regional failure (RF) following IMRT and rates of LF and RF following CRT. A total of 15 studies (14 retrospective, 1 prospective) consisting of 2083 patients were identified. IMRT was used in 873 patients (64% T1, 28% T2). Multiple treatment (partial larynx, single vocal cord carotid sparing) and image-guided radiation therapy techniques were used. The pooled crude rate of LF was 7.6% (95% confidence inverval [CI], 3.6%-11.5%) and actuarial LF rates at 3 and 5 years were 6.3% (95% CI, 2.2%-10.3%) and 9.0% (95% CI, 4.4%-13.5%), respectively. The pooled crude rate of RF after IMRT was 1.5% (95% CI, 0.5%-2.5%). On metaregression analysis, increased rate of LF was significantly associated with T2 disease (P < .001) and grade 2 to 3 histology (P < .001). Treatment with CRT was reported in 738 patients (76% T1, 22% T2). Among the studies reporting outcomes of both modalities, there was no significant difference in LF (log odds ratio; P=.12) or RF (log odds ratio; P=.58) between IMRT or CRT. In patients with early-stage glottic cancer, retrospective data suggests local and regional control are similar for patients treated with IMRT and CRT. Additional prospective studies with uniform methods of volume delineation and image guidance are needed to confirm the efficacy of IMRT.

D160. HPV-associated Survival and Surgical Management of Advanced Squamous Cell Carcinoma of the Head And Neck

PURPOSE: The increasing incidence of human papillomavirus (HPV)-associated head and neck cancer (HNC) necessitates studies on patient outcomes and survival stratified by HPV status. Many studies have assessed HPV-associated survival across all HNC patients; we compare survival by HPV status for patients with advanced HNC to inform surgical management. METHODS: Adults with malignant squamous cell HNC diagnosed between 2011 and 2017 were identified from the Surveillance, Epidemiology and End Results (SEER) Head and Neck with HPV status database, which includes data from registries covering 47% of the United States population. Patients without HPV status, survival data or histopathologic confirmation of disease were excluded. “Invasive” carcinoma was defined as cancers with T4 staging, as this denotes bone involvement. Kaplan-Meier survival analyses were completed in R Studio (v1. 3.1). RESULTS: The analysis of survival by HPV status and tumor invasiveness included 13,493 patients; of these, 9,087 had HPV-associated disease and 1,564 had invasive disease. Survival analysis of all HNC patients revealed significantly higher 8-year survival for patients with HPV-associated disease than those without (p < 0.01). When analysis was narrowed to patients with T4 disease, no survival difference was found. CONCLUSION: HPV-associated HNC is often considered less severe than non-HPV-associated disease which may lead to more conservative management decisions. However, this first of its kind analysis of HNC subgroups demonstrates the absence of any HPV-associated survival benefit among patients with advanced disease involving the bone. These data suggest that such cancers should be managed with aggressive surgical resection and reconstruction, consistent with management of non-HPV-associated etiologies.

Comparison of Structural MRI Profiles Between Autopsy-Confirmed Chronic Traumatic Encephalopathy and Alzheimer’s Disease (P3-6.006)

Comparison of Structural MRI Profiles Between Autopsy-Confirmed Chronic Traumatic Encephalopathy and Alzheimer’s Disease (P3-6.006)

Impact of distance to treatment center on tumor stage of nasopharyngeal cancer at presentation.

Impact of distance to treatment center on tumor stage of nasopharyngeal cancer at presentation.

Assessing the Correlation of Rate of Pathological Complete Response and Outcome in Post Neoadjuvant Chemotherapy Setting and Molecular Subtypes of Breast Cancer.

Background Neoadjuvant chemotherapy (NAC) is being widely used in treating breast cancer (BC). This study aimed to analyze the correlation between clinicopathological features, immunohistochemistry (IHC)-based molecular subtypes, and the pathological response to NAC and its relationship with disease-free survival (DFS) and overall survival (OS). Materials and methods A retrospective analysis of 211 breast cancer patients who received NAC between 2008 and 2018 was performed. Tumors were classified by IHC into luminal A, luminal B, human epidermal growth factor receptor 2 (HER2)-enriched, and triple-negative subtypes. The chi-square test was used to assess the association between pathological response and clinicopathological parameters. Cox regression analysis was used to assess factors related to DFS and OS. Results Post NAC, 19.4% of patients achieved a pathologic complete response (pCR). Estrogen receptor (ER), progesterone receptor (PR), HER2 (p<0.001, 0.005, and 0.02), Ki67 (p=0.03), molecular subtypes (p<0.001), T stage (p=0.04), and N stage (p=0.01) were significantly associated with pathological response. The rate of pCR was highest among HER2-enriched and triple-negative tumors (45.2% and 28%, respectively) with OR=0.13 and p<0.001 for the HER2-enriched subtype. Patients with pCR were 61% less likely to develop metastasis (adjusted hazard ratio [aHR]=0.39, p=0.06, 95% CI=0.14-1.06) and were significantly associated with better OS (aHR=0.07, p=0.02, 95% CI=0.01-0.61). Patients who were ≤40 years old (aHR=2.1, p=0.01), with T4 (aHR=3.4, p=0.02), grade 3 (aHR=2.5, p=0.01), and node-positive disease (HR=2.24, p=0.02) were at an increased risk of developing metastasis. High Ki67 was found to be significantly associated with better DFS (p=0.006). Conclusion HER2-enriched and triple-negative BC were associated with a higher rate of pCR. Patients with pCR had significantly better DFS and OS. Younger age, advanced stage, higher grade, and lymph node involvement were risk factors for metastasis.

Multiple staging investigations may not change management in patients with high-grade dysplasia or early esophageal adenocarcinoma.

The clinical value of multiple staging investigations for high-grade dysplasia or early adenocarcinoma of the esophagus is unclear. A single-center prospective cohort of patients treated for early esophageal cancer between 2000 and 2019 was analyzed. This coincided with a transition period from esophagectomy to endoscopic mucosal resection (EMR) as the treatment of choice. Patients were staged with computed tomography (CT), endoscopic ultrasound (EUS) and 2-deoxy-2-[18F]fluoro-d-glucose (FDG) positron emission tomography(PET)/CT. The aim of this study was to assess their accuracy and impact on clinical management. 297 patients with high-grade dysplasia or early adenocarcinoma were included (endoscopic therapy/EMR n =184; esophagectomy n =113 [of which a 'combined' group had surgery preceded by endoscopic therapy n =23]). Staging accuracy was low (accurate staging EMR: CT 40.1%, EUS 29.6%, FDG-PET/CT 11.0%; Esophagectomy: CT 43.3%, EUS 59.7%, FDG-PET/CT 29.6%; Combined: CT 28.6%, EUS46.2%, FDG-PET/CT 30.0%). Staging inaccuracies across all groups that could have changed management by missing T2 disease were CT 12%, EUS 12% and FDG-PET/CT 1.6%. The sensitivity of all techniques for detecting nodal disease was low (CT 12.5%, EUS 12.5%, FDG-PET/CT0.0%). Overall, FDG-PET/CT and EUS changed decision-making in only 3.2% of patients with an early cancer on CT and low-risk histology. The accuracy of staging with EUS, CT and FDG-PET/CT in patients with high-grade dysplasia or early adenocarcinoma of the esophagus is low. EUS and FDG-PET/CT added relevant staging information over standard CT in very few cases, and therefore, these investigations should be used selectively. Factors predicting the need for esophagectomy are predominantly obtained from EMR histology rather than staging investigations.

MP41-15 DIFFERENCES IN SOMATIC AND GERMLINE VARIATIONS IN HISPANIC AND NON-HISPANIC PATIENTS WITH RENAL CELL CARCINOMA

You have accessJournal of UrologyCME1 Apr 2023MP41-15 DIFFERENCES IN SOMATIC AND GERMLINE VARIATIONS IN HISPANIC AND NON-HISPANIC PATIENTS WITH RENAL CELL CARCINOMA Peris Castaneda, Eric Lo, John Heard, Michael Nazmifar, Michael Kheshvadjian, and Michael Ahdoot Peris CastanedaPeris Castaneda More articles by this author , Eric LoEric Lo More articles by this author , John HeardJohn Heard More articles by this author , Michael NazmifarMichael Nazmifar More articles by this author , Michael KheshvadjianMichael Kheshvadjian More articles by this author , and Michael AhdootMichael Ahdoot More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003279.15AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Among patients with renal cell carcinoma (RCC), those of Hispanic ethnicity have worse disease burden. Hispanic patients (HP) are diagnosed at a younger age and have higher stage disease at diagnosis. Although some of the disparity is due to social factors, studies have shown differences in RCC histologic subtype between HP and non-Hispanic white patients. This suggests a potential molecular component conferring greater pre-treatment disease. HP have been underrepresented in molecular genomic studies of RCC and data on gene variation are lacking. Here, we aim to determine differences in germline and somatic alterations in HP and non-Hispanic patients (NHP) with RCC. METHODS: We queried a multi-institutional pan-cancer database of >5 million patients for patients aged ≥18 diagnosed with RCC. Demographic factors and disease-specific factors were compared between HP and NHP to assess for statistical significance (p<0.05). Frequency and type of germline and somatic alterations were compared. RESULTS: We identified 558 HP and 4829 NHP with RCC. No difference in gender distribution was observed. HP were younger at diagnosis (57.3 years vs 61.4 years in NHP) (p<0.001) and more likely to be diagnosed at or before age 46 (20% vs 11% in NHP) (p<0.001). Fifty-seven percent of HP reported being never smokers compared to 40% of NHP (p<0.001). A higher proportion of HP presented with T4 or T3 disease (75%, compared to 43% of NHP). Overall, somatic variant information was available for 166 HP and 667 NHP; germline variant information was available for 38 HP and 667 NHP. The most common somatic and germline variants in HP and NHW are shown in Figure 1. Overall, somatic alterations appeared commensurate with the general RCC population. HP showed higher rates of germline alterations in CHEK2, MSH6, FH, and FLCN compared to NHP. CONCLUSIONS: Differences in germline alterations are observed between HP and NHP with RCC. Further genomic studies that include HP are needed to better identify targetable genetic alterations and improve treatment decisions. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e561 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Peris Castaneda More articles by this author Eric Lo More articles by this author John Heard More articles by this author Michael Nazmifar More articles by this author Michael Kheshvadjian More articles by this author Michael Ahdoot More articles by this author Expand All Advertisement PDF downloadLoading ...

V08-03 INDIANA POUCH CONTINENT CUTANEOUS URINARY DIVERSION AFTER ROBOTIC-ASSISTED RADICAL CYSTECTOMY: A 16-YEAR EXPERIENCE

You have accessJournal of UrologyCME1 Apr 2023V08-03 INDIANA POUCH CONTINENT CUTANEOUS URINARY DIVERSION AFTER ROBOTIC-ASSISTED RADICAL CYSTECTOMY: A 16-YEAR EXPERIENCE Albert Kim and Kevin Chan Albert KimAlbert Kim More articles by this author and Kevin ChanKevin Chan More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003306.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Continent urinary diversion after radical cystectomy is an underutilized option even at high-volume centers with studies demonstrating socio-economic, geographical, and gender disparities. Efforts to optimize utilization of continent diversion must concentrate on changing perceptions regarding feasibility and accurate reporting of complications.The objective of this study is to report long-term clinical outcomes in bladder cancer patients receiving an Indiana pouch continent cutaneous urinary diversion (CCUD) after robot-assisted radical cystectomy. METHODS: After Institutional Review Board approval, a prospectively maintained bladder cancer database was queried for patients with T1-T4, N0-N1, M0 bladder cancer undergoing radical cystectomy with CCUD at a tertiary referral center from 2004 to 2020. Complications at 30- and 90-days were recorded according to the Clavien-Dindo classification. Continence rates were recorded by manual chart review. RESULTS: A total of 97 patients were included with a median follow-up of 93 months. Clinically, 91.8% had £T2 disease and 29.9 % received neoadjuvant chemotherapy. The median length of surgery was 8.0 hours, length of hospital stay was 8.3 days, and urinary continence rate was 99.0%. The overall complication rate was 73.2% and 76.5% at 30- and 90-days respectively. Most complications were low grade (Clavien I or II). Acute blood loss anemia and symptomatic urinary tract infection were the most common low grade complications. The major complication rate was 17.5% at 30-days and 22.7% at 90-days. The most common major complications were abdominal infection requiring percutaneous drain placement, Clavien Grade III, and uretero-colonic stricture requiring percutaneous nephrostomy tube placement and surgical revision, Clavien Grade III. The readmission rate was 21.4% and median overall survival was 108 months. CONCLUSIONS: CCUD provides exceptional functional outcomes with acceptable complication rates compared to other diversion types. Source of Funding: NONE Disclosures: NONE © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e749 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Albert Kim More articles by this author Kevin Chan More articles by this author Expand All Advertisement PDF downloadLoading ...