Clinical T1 Research Articles

Abstract GS5-01: Addition of platinum to sequential taxane-anthracycline neoadjuvant chemotherapy in patients with triple-negative breast cancer: A phase III randomized controlled trial

Abstract Background: Despite several studies, the impact of adding platinum on long-term outcomes in triple-negative breast cancer (TNBC) has not been definitively established. We conducted a single-centre randomized phase III trial to evaluate the efficacy and toxicity of adding platinum to standard neoadjuvant chemotherapy in these patients. Methods: Patients with histopathological diagnosis of TNBC without evidence of distant metastases who were planned to be treated with neoadjuvant chemotherapy (NACT) were randomized to experimental or control arms after stratification by menopausal status (premenopausal or perimenopausal, and postmenopausal) and stage [operable breast cancer (OBC, clinical T1-3, N0-1, M0), and locally advanced breast cancer (LABC, cT4 or N2-3, M0)]. NACT in control arm included paclitaxel 100 mg/m2 once per week for 8 weeks followed by doxorubicin (60 mg/m2) or epirubicin (90 mg/m2) plus cyclophosphamide (600 mg/m2) once every 21 days for 4 cycles while in experimental arm carboplatin (area-under-curve 2) was added once per week for 8 weeks with paclitaxel. After NACT patients received standard surgery for primary tumor and axillary lymph nodes (LN) followed by radiotherapy. The primary endpoint was disease-free survival (DFS) and the secondary endpoints were overall survival (OS), pathological complete response (pCR, absence of invasive cancer from breast and LN), and toxicity. Results: Between April 2010 and January 2020, 720 (355 control, 365 experimental) patients with a median age of 46 (25-69) years [< 50 years, 502 (69.7%), premenopausal 418 (58.2%)], were included in the study, of whom 285 (39.6%) had OBC and 435 (60.4%) had LABC, with a median clinical tumor size of 6.0 (1.2- 20.0) cm. At a median follow-up of 67.6 (18.9-142.2) months, in the experimental and control arms, the 5-year DFS were 70.6% (95% CI 65.7-75.5%) and 64.5% (95% CI 59.4-69.6%), respectively (HR 0.79, 95% CI 0.61-1.02, p=0.073), 5-year OS were 74.0 (95% CI 69.3-78.7%) and 66.7% (95% CI 61.6-71.8%), respectively (HR 0.75, 95% CI 0.57-0.98, p=0.034), and pCR were 55.2% (95% CI 49.7-69.5%) and 41.5% (95% CI 36.2-47.0%), respectively (p=0.0004). In subgroup analyses, the benefit of carboplatin was confined to patient’s < 50 years, with significant interaction between treatment and age. In women < 50 years of age, in experimental versus control arms, 5-year DFS and OS were 74.5% vs 62.3% (p=0.003, interaction p=0.003) and 76.8% vs 65.7% (p=0.003, interaction p=0.004), respectively. Addition of carboplatin had a significant beneficial impact on OS after adjusting for baseline clinical tumor size and age in a Cox model (HR 0.75, 95% CI 0.58-0.98, p=0.038). In experimental and control arms, numbers of patients with any grade >/=3 toxicity were 140 (38.5%) and 107/355 (30.14%), respectively, (p=0.02), grade >/=3 neutropenia were 2/364 (0.55%) and 1/355 (0.28%), respectively, grade >/=3 thrombocytopenia were 1/364 (0.27%) and 0 (0%), respectively, and febrile neutropenia were 26/364 (7.14%%) and 18/355 (5.07%), respectively (p=0.25). Conclusions: This study, to our knowledge the largest reported trial of neoadjuvant platinum in TNBC thus far, suggests that addition of carboplatin to sequential taxane-anthracycline neoadjuvant chemotherapy results in substantial and clinically meaningful improvement in disease-free and overall survival in young patients with TNBC and should be the standard of care in these patients. Citation Format: Sudeep Gupta, Nita S. Nair, Rohini Hawaldar, Vaibhav Vanmali, Vani Parmar, Seema Gulia, Jaya Ghosh, Shalaka Joshi, Rajiv Sarin, Tabassum Wadasadawala, Tejal Panhale, Sangeeta Desai, Tanuja Shet, Asawari Patil, Garvit Chitkara, Sushmita Rath, Jyoti Bajpai, Meenakshi Thakkur, Rajendra Badwe. Addition of platinum to sequential taxane-anthracycline neoadjuvant chemotherapy in patients with triple-negative breast cancer: A phase III randomized controlled trial [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 GS5-01.

Abstract P2-14-15: Comparison of recurrence-free survival according to axillary surgery extent for clinical N0, sentinel node(s) positive, primary breast cancer patients who underwent total mastectomy

Abstract Purpose We investigated the recurrence-free survival difference between limited axillary node surgery and axillary node dissection (ALND) in clinical N0 primary breast cancer patients with one to three sentinel node metastasis who underwent total mastectomy. Method We retrospectively analyzed clinical data of 579 primary breast cancer patients who underwent total mastectomy between 2014 and 2018 from Seoul National University Hospital and Asan Medical Center. All included patients had clinical T1-2, N0 disease at the time of diagnosis based on physical exam, radiologic evaluation, and pathologic assessment if needed. The patients had one to three metastatic sentinel node(s) at the time of surgery. The patients received sentinel lymph node biopsy (SLNB) with result of one to three metastatic node(s) and either proceeded to ALND or not. We performed propensity score matching between the SLNB and ALND group with baseline clinical factors including clinical T stage and number of metastatic sentinel node(s). Finally, 208 patients were matched 1:1 for each group respectively for further analysis. Also, we stratified the eligible patients based on radiation therapy for subgroup analysis. We examined disease-free survival, regional recurrence-free survival, distant metastasis-free survival and compared the results between the groups. Result The median follow-up period was 64.7 months. Among matched cohorts, mean number of metastatic nodes on final pathology result was 1.2 for SLNB group and 1.7 for ALND group. Also, mean number of total removed nodes was 8.3 for SLNB group and 17.4 for ALND group. The disease-free survival [DFS] at 7 years was 89.7% for SLNB group and 91.1% for ALND group with no statistically significant difference. (hazard ratio [HR] 1.43, 95% confidence interval [CI] 0.70 to 2.92, p=0.32) Among patients who were treated with radiation, the DFS was 94.1% in the SLNB group and 94.4% in the ALND group. (HR, 0.82, 95% CI 0.17 to 4.0, p=0.81) For the subgroup without radiation, the DFS was 87.7% in the SLNB group and 89.4% in the ALND group. (HR, 1.68, 95% CI 0.75 to 3.75, p=0.19) We observed no statistically significant differences in the regional recurrence-free survival at 7 years (95.8% in the SLNB vs. 95% in the ALND, HR 0.62, 95% CI 0.53-4.95, p=0.39), and in the distant metastasis-free survival at 7 years (95.8% in the SLNB vs. 95% in the ALND, HR 1.28, 95% CI 0.59 to 2.73, p=0.52) Conclusion Our results suggest that limited axillary surgery with sentinel node biopsy may be as effective as axillary node dissection in terms of recurrence-free survival, for clinically node negative, primary breast cancer patients with limited metastatic sentinel node(s) who are candidates for total mastectomy. Key words: Breast cancer, Total mastectomy, Axillary lymph node dissection, Sentinel lymph node biopsy. Citation Format: Jung Whan Chun, Hong-Kyu Kim, Han-Byoel Lee, Hyeong-Gon Moon, Jong Won Lee, Wonshik Han. Comparison of recurrence-free survival according to axillary surgery extent for clinical N0, sentinel node(s) positive, primary breast cancer patients who underwent total mastectomy. [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 P2-14-15.

Abstract P4-02-14: Gain of HER2 Amplification in Patients with HR+/HER2- and Triple Negative Early Breast Cancer Treated with Neoadjuvant Chemotherapy

Abstract Background: Neoadjuvant chemotherapy (NAC) is standard of care for the majority of patients with clinical stage II-III triple negative breast cancer (TNBC) and is considered in high-risk patients with hormone receptor positive (HR+)/human epidermal growth factor receptor 2 (HER2) negative (-) tumors, with expected pathological complete response (pCR) rates of 40-60% and 10-12%, respectively. In HER2- patients with residual disease (RD) after NAC, there is limited data on rates of gain of HER2 amplification. The biological and clinical significance of this phenomenon is unknown and determining the best adjuvant therapy for these patients remains a challenge. We sought to determine the rate of HER2 gain in a cohort of consecutive patients with HER2- breast cancer (BC) treated with NAC. Methods: From 01/2021 to 12/2021, we identified patients with HER2- breast cancer treated with NAC followed by surgery at our institution. Patients who received neoadjuvant endocrine therapy were excluded. The rates of pCR (ypT0/is ypN0) and HER2 status pre- and post-NAC were assessed. Estrogen receptor (ER), progesterone receptor (PR) and HER2 status on surgery specimens were internally determined for all patients using ASCO/CAP 2020 guidelines. ER-low was defined as ER expression by immunohistochemistry (IHC) 1-10%. Results: We included 256 patients, 130 (51%) HR+/HER2- [13/130(10%) ER-low] and 126 (49%) TNBC. Median age was 48 years (range 25-82) and the majority presented with clinical T2 (57%) and N1 (59%). Of 130 patients with HR+/HER2-tumors, 120 (92%) received dose-dense (dd) doxorubicin/cyclophosphamide-paclitaxel (AC-T). Of 126 TNBC patients, 46 (37%) received ddAC followed by carboplatin in combination with paclitaxel +/- pembrolizumab. Centralized HER2 status assessment on the core biopsy was performed in 22% of samples. Overall, pCR was achieved in 40% of TNBC and 11% of HR+/HER2-. Among the 192 patients with RD, the rate of HER2 gain was 8/192 (4%), including 3% (2/76) of TNBC and 5% (6/116) of HR+/HER2- patients. 7 of the 8 patients (88%) converted from IHC 1+ or 2+ fluorescence in situ hybridization (FISH) not amplified on core biopsy to IHC 2+ FISH amplified on the surgical specimen. In only 1 case, the HER2 status converted from IHC2+ FISH not amplified to IHC3+. 3/8 patients had multifocal disease. All 6 patients with HR+/HER2- BC and HER2 gain had high (>90%) ER expression (Table 1). All but one patient with HER2 gain received adjuvant anti-HER2 therapy. After a median follow-up of 10 months, no recurrence events occurred in this group.12 of the remaining 184 patients experienced a recurrence [11 distant recurrences (8 and 3, in the TNBC and HR+/HER2- groups, respectively), and there was 1 local event (localized chest wall recurrence) in the HR+/HER2- group]. Conclusions: At a single center, we found that in patients with HER2- BC treated with NAC, HER2 gain in patients with RD was uncommon and occurred more frequently in those with HR+ tumors. Analysis of a larger cohort is ongoing to corroborate these results. It is remains to be determined if this phenomenon represents a true HER2 status conversion or tumor heterogeneity. Table 1: Clinico-pathological characteristics of patients with HER2 gain on residual disease Citation Format: Emanuela Ferraro, Sonya Chew Minmin, Anton Safonov, Andrea V. Barrio, Shanu Modi, Andrew D Seidman, Hanna Y Wen, Edi Brogi, Mark E. Robson, Chau T Dang. Gain of HER2 Amplification in Patients with HR+/HER2- and Triple Negative Early Breast Cancer Treated with Neoadjuvant Chemotherapy [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 P4-02-14.

Factors associated with pathological tumor stage and T3a upstage in clinical T1-2 renal cell carcinoma.

Considering the oncological outcomes, understanding the preoperative factors associated with and predicting advanced stage and T3a upstage will help in risk assessment and selection of the right treatment. Patients with postoperative pathology of Renal Cell Carcinoma (RCC) and stage T1-2 N0M0 were included in the study. Demographic and pathological characteristics of the patients, Neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and De Ritis- the ratio of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were recorded. Patients were classified according to T stage (T1-2 vs T3-4) and T3a upstage (T3a upstaged vs non-T3a upstaged). A total of 289 patients participated in the study when inclusion and exclusion criteria were applied. No difference was found between the groups in terms of age, gender, body mass index, laterality, ABO blood group, Rh positivity and comorbidities. According to multivariate analysis, PLR, AST/ALT, Fuhrman grade, open radical nephrectomy (RN) and Clear Cell pathological subtype were found to be significant-independent factors in predicting advanced stage (T3-4) and T3a upstage (P<0.05). It was found that higher PLR and AST/ALT ratios were associated with more advanced stage and postoperative T3a upstage in RCC patients. In addition, these patients more frequently had open RN and had higher Fuhrman grades, while the clear cell subtype was less common.

Abstract GS4-02: Oncological Outcomes Following Omission of Axillary Lymph Node Dissection in Node Positive Patients Downstaging To Node Negative with Neoadjuvant Chemotherapy: the OPBC-04/EUBREAST-06/OMA study

Abstract Background: Data on the oncologic safety of omission of axillary lymph node dissection (ALND) in node positive (N+) patients who downstage to ypN0 with neoadjuvant chemotherapy (NAC) is sparse. Additionally, there is no consensus on which axillary staging procedure should be used in this setting, sentinel lymph node biopsy (SLNB) alone or in combination with localization and retrieval of the clipped positive node, also known as targeted axillary dissection (TAD). Whether the reduction in the false negative rate observed with TAD translates into a significant reduction in the rate of axillary recurrence is unknown. We sought to evaluate oncologic outcomes after omission of ALND in a large, real-world cohort of breast cancer (BC) patients and to compare rates of axillary recurrence after SLNB with dual tracer mapping vs. TAD. Methods: Data were collected from 19 centers in the Oncoplastic Breast Consortium (OPBC) and EUBREAST networks. Patients with T1-4 biopsy-proven N1-3 BC who underwent NAC followed by axillary staging with either SLNB with dual tracer mapping or TAD and who were pathologically node negative (ypN0) were included. ypN0 was defined as the absence of any tumor or isolated tumor cells. Competing risk analysis was performed to assess the cumulative incidence rates of axillary recurrence, locoregional recurrence, and any invasive (locoregional or distant) recurrence. Two-year cumulative incidence rates were compared between TAD and SLNB using the Gray’s test. Type I error rate was set to 0.05 (α). Results: We included 785 patients (565 treated with SLNB and 220 with TAD) treated with NAC followed by surgery from 01/2014-12/2020. Median patient age was 50 years. The majority (57%) of patients had clinical T2 tumors, and 95% had N1 disease. Most (55%) were HER2+, and 21% were triple negative. Most patients (81%) received anthracycline and taxane-based chemotherapy regimens, but NAC regimens differed between patients treated with TAD and those treated with SLNB (Table 1). All patients with HER2+ tumors received anti HER2 therapy. Nodal radiotherapy was administered to 76% of patients, and was more common in patients who underwent TAD (82% TAD vs 74% SLNB, p=0.017). Breast pathologic complete response (ypT0/is) was more frequent among those patients that had TAD (80% TAD vs. 66% SLNB, p&amp;lt; 0.001). TAD localization was with wire in 46%, radioactive seed in 40%, ultrasound in 5%, tattoo in 2%, and with a combination of these techniques in 7%. The clipped node was successfully retrieved in 94% of TAD cases. The median number of lymph nodes removed was lower in the TAD group compared to the SLNB group [3 (IQR 3-5) vs 4 IQR 3-5), p&amp;lt; 0.001], as was the median number of sentinel lymph nodes [3 (IQR 2-4) vs 4 IQR 3-5), p&amp;lt; 0.001] (Table 1). The 5-year rates of any axillary recurrence, locoregional recurrence, and any invasive recurrence in the entire cohort were 1.1% (95%CI 0.39-2.4%), 3.1% (95%CI 1.6-5.3%) and 10% (95%CI 7.6-13%), respectively. The two-year cumulative incidence of axillary recurrence did not differ between patients treated with TAD compared to SLNB (0% vs 0.9%, p=0.19). Conclusion: Early axillary recurrence after omission of ALND in patients who successfully downstage from N+ to ypN0 with NAC is a rare event following both SLNB or TAD, and was not significantly lower in TAD than SLNB. Although longer follow-up is needed to confirm these findings, the main advantage of TAD seems to be a reduction in the number of lymph nodes removed. Overall, these results support omission of ALND in patients who successfully downstage to node negative disease after NAC. Table 1: Clinicopathological Features of the Study Cohort, Stratified by Axillary Staging Technique Citation Format: Giacomo Montagna, Mary Mrdutt, Astrid Botty, Andrea V. Barrio, Varadan Sevilimedu, Judy C. Boughey, Tanya L. Hoskin, Laura H. Rosenberger, E Shelley Hwang, Abigail Ingham, Bärbel Papassotiropoulos, Bich Doan Nguyen-Sträuli, Christian Kurzeder, Danilo Diaz Aybar, Denise Vorburger, Dieter Michael Matlac, Edvin Ostapenko, Fabian Riedel, Florian Fitzal, Francesco Meani, Franziska Fick, Jacqueline Sagasser, Jörg Heil, Konstantin J. Dedes, Laszlo Romics, Maggie Banys-Paluchowski, Maria Del Rosario Cueva Perez, Marcelo Chavez Diaz, Martin Heidinger, Mathias K. Fehr, Mattea Reinisch, Nadia Maggi, Nicola Rocco, Nina Ditsch, Oreste Davide Gentilini, Regis Resende Paulinelli, Sebastian Sole Zarhi, Sherko Küemmel, Simona Bruzas, Simona Di Lascio, Tamara Parissenti, Uwe Güth, Valentina Ovalle, Christoph Tausch, Monica Morrow, Thorsten Kühn, Walter P. Weber. Oncological Outcomes Following Omission of Axillary Lymph Node Dissection in Node Positive Patients Downstaging To Node Negative with Neoadjuvant Chemotherapy: the OPBC-04/EUBREAST-06/OMA study [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 GS4-02.

A nomogram prediction model for lymph node metastasis risk after neoadjuvant chemoradiotherapy in rectal cancer patients based on SEER database.

Rectal cancer patients who received neoadjuvant chemoradiotherapy (CRT) may have a lower cancer stage and a better prognosis. Some patients may be able to avoid invasive surgery. It is critical to accurately assess lymph node metastases (LNM) after neoadjuvant chemoradiotherapy. The goal of this study is to identify clinical variables associated with LNM and to develop a nomogram for LNM prediction in rectal cancer patients following nCRT. From 2010 to 2015, patients were drawn from the Surveillance, Epidemiology, and End Results (SEER) database. To identify clinical factors associated with LNM, the least absolute shrinkage and selection operator (LASSO) aggression and multivariate logistic regression analyses were used. To predict the likelihood of LNM, a nomogram based on multivariate logistic regression was created using decision curve analyses. The total number of patients included in this study was 6,388. The proportion of patients with pCR was 17.50% (n=1118), and the proportion of patients with primary tumor pCR was 20.84% (n = 1,331). The primary tumor was pCR in 16.00% (n=213) of the patients. Age, clinical T stage, clinical N stage, and histology were found to be significant independent clinical predictors of LNM using LASSO and multivariate logistic regression analysis. The nomogram was developed based on four clinical factors. The 5-year overall survival rate was 78.9 percent for those with ypN- and 66.3 percent for those with ypN+, respectively (P<0.001). Patients over 60 years old, with clinical T1-2, clinical N0, and adenocarcinoma may be more likely to achieve ypN0. The watch-and-wait (WW) strategy may be considered. Patients who had ypN0 or pCR had a better prognosis.

Endoscopic therapy replaces surgery for clinical T1 oesophageal cancer in the Netherlands: a nationwide population-based study

BackgroundEndoscopic resection for early oesophageal cancer was introduced around 2000 in the Netherlands. The scientific question was how the treatment and survival of early oesophageal and gastro-oesophageal junction cancer has changed over time in the Netherlands.MethodsData were obtained from the nationwide population-based Netherlands Cancer Registry. All patients diagnosed with clinical in situ or T1 oesophageal or GOJ cancer without lymph node or distance metastasis during the study period (2000–2014) were extracted. Primary outcome parameters were the trends in treatment modalities over time and relative survival of each treatment regime.ResultsA total of 1020 patients were diagnosed with a clinical in situ or T1 oesophageal or gastro-oesophageal junction cancer without lymph node or distance metastasis. The proportion of patients who received endoscopic treatment increased from 2.5% in 2000 to 58.1% in 2014. During the same period the proportion of patients who received surgery decreased from 57.5 to 23.1%. Five-year relative survival of all patients was 69%. Five-year relative survival after endoscopic therapy was 83% and after surgery 80%. Relative excess risk analyses showed no significant difference in survival between patients in the endoscopic therapy group and patients in the surgery group after adjustment for age, sex, clinical TNM classification, morphology and tumour location (RER 1.15; CI 0.76–1.75; p 0.76).ConclusionOur results demonstrate an increase in endoscopic treatment and a decrease of surgical treatment for in situ and T1 oesophageal/GOJ cancer between 2000–2014 in the Netherlands. The relative 5-year survival after endoscopic treatment is high (83%) and comparable with surgery (80%).

Role of transoral robotic surgery in surgical treatment of early-stage supraglottic larynx carcinoma.

There are several options for primary surgical treatment of early-stage supraglottic squamous cell carcinoma (SCC), including transoral robotic surgery (TORS). The purpose of this study was to compare outcomes of TORS to open partial laryngectomy and transoral laser microsurgery (TLM). Patients with clinical classification T1-2 supraglottic SCC diagnosed 2010-2019, treated with TORS, open partial laryngectomy, or TLM in the National Cancer Database were selected. One thousand six hundred three patients were included: 17% TORS, 26.5% TLM, 56.5% open. TORS patients had the lowest rates of adjuvant treatment (28.4% vs. TLM: 45.0%, open: 38.5%, p < 0.001), and lower positive margin rates than TLM (16.9% vs. 30.5%, p < 0.001). Thirty-day and ninety-day post-operative mortality did not differ between the approaches. Five-year survival was higher following TORS compared to open surgery (77.8% vs. 66.1%, p=0.01); this difference persisted following matched-pair analysis. TORS may be a safe and effective surgical approach for early-stage supraglottic SCC in appropriate patients.

Consideration for reclassification of pathologically upstaged T3a renal cell carcinomas.

644 Background: Pathological upstaging to pT3a disease can occur after the surgical treatment of clinical T1 and T2 Renal Cell Carcinomas (RCCs), and this upstaging has been previously shown to be associated with poorer outcomes. With an intent to delve deeper into the disparateness in outcomes of pT3a disease, we investigated the survival of patients with an initial clinical stage of cT1, cT2 and cT3a. Methods: Using the National Cancer Database (NCDB), patients with RCC were categorized by pathological and clinical staging of RCC according to the American Joint Committee on Cancer Guidelines (AJCC). The primary outcome was measured as overall survival (OS) at the end of follow up. Five-year survival rates and Kaplan-Meier Analysis assessed the differences between cT1 → pT3a, cT2 → pT2, cT2 → pT3a, and cT3a → pT3a. Multivariable cox regression (MVA) assessed predictors OS with age, sex, ethnicity, Charlson Score, socioeconomic status, geography, tumor size histology and grade, lymph node metastasis, surgical margins, and surgery type (partial versus radical nephrectomy) as covariates. Results: 53908 patients were analyzed (10789 cT1 → pT3a, 22183 cT2 → pT2, 9676 cT2 → pT3a, 11260 cT3a → pT3a, mean follow up 62.3 months). Of all pT3a patients, 64.5% were upstaged from cT1-2. MVA for OS demonstrated Hispanic ethnicity to be protective (hazard ratio [HR]=0.88, P&lt;0.001) and revealed different histologic risks. MVA for OS demonstrated that cT2 → pT3a (HR=1.33, P&lt;0.001, cT1 → pT3a [ref]) and cT3a → pT3a (HR=1.35, P&lt;0.001, cT1 → pT3a [ref]) were associated with worsened OS, and that cT1 → pT3a and cT2 → pT2 (HR=0.96, P&lt;0.052, cT1 → pT3a [ref]) were associated with improved OS. Kaplan-Meier analysis revealed a difference in 5 year overall survival as well (cT1→pT3a 72%, cT2→pT2 77%, cT2→pT3a 61%, and cT3a→pT3a 59%, p &lt; 0.001). Conclusions: Patients with cT1 upstaged to pT3a have similar outcomes to cT2 staged to pT2 and better outcomes than cT2 upstaged with the latter’s outcomes being more like cT3a staged to pT3a. The TNM staging system from AJCC for RCCs should consider these outcomes and adjust the grouping for RCCs accordingly.

Adjuvant Radiation and Survival Following Surgical Resection of Sinonasal Adenocarcinoma.

This study aims to investigate the utility of adjuvant radiation in patients who undergo surgical resection for the management of node-negative sinonasal adenocarcinoma (SNAC). Retrospective database review. The 2004-2016 National Cancer Data Base (NCDB) was used to extract patients with surgically resected node-negative SNAC. Kaplan-Meier survival analysis and Cox-Proportional Hazards Modelling were used to analyze the impact of adjuvant radiation on overall survival (OS) following surgery. 349 patients with SNAC underwent surgical resection. Of these patients, 154 (44.1%) received adjuvant radiotherapy (RT). Although there was no significant difference in race, age, or sex of those receiving RT, those receiving RT have more advanced diseases and are more likely to have positive margins. Kaplan Meier analysis showed no significant difference in 5-year OS in patient who received adjuvant RT in comparison to those who underwent surgical resection alone (65.7% vs. 72.6%, respectively; p=0.378). In addition, when looking at only patients with positive margins, 5-year OS still did not have a significant difference (73.8% vs. 61.6%, respectively; p=0.101). Only patients with clinical AJCC T4 showed a statistically significant survival benefit with adjuvant RT (56.9% vs. 29.9%, respectively; p=0.009). Adjuvant RT does not appear to provide a significant survival benefit in patients with resected SNAC, with the exception of those with clinically AJCC T4 disease. 4 Laryngoscope, 133:2603-2612, 2023.

DeepSWI: Using Deep Learning to Enhance Susceptibility Contrast on T2*-Weighted MRI.

Although susceptibility-weighted imaging (SWI) is the gold standard for visualizing cerebral microbleeds (CMBs) in the brain, the required phase data are not always available clinically. Having a postprocessing tool for generating SWI contrast from T2*-weighted magnitude images is therefore advantageous. To create synthetic SWI images from clinical T2*-weighted magnitude images using deep learning and evaluate the resulting images in terms of similarity to conventional SWI images and ability to detect radiation-associated CMBs. Retrospective. A total of 145 adults (87 males/58 females; 43.9 years old) with radiation-associated CMBs were used to train (16,093 patches/121 patients), validate (484 patches/4 patients), and test (2420 patches/20 patients) our networks. 3D T2*-weighted, gradient-echo acquired at 3T. Structural similarity index (SSIM), peak signal-to-noise-ratio (PSNR), normalized mean-squared-error (nMSE), CMB counts, and line profiles were compared among magnitude, original SWI, and synthetic SWI images. Three blinded raters (J.E.V.M., M.A.M., B.B. with 8-, 6-, and 4-years of experience, respectively) independently rated and classified test-set images. Kruskall-Wallis and Wilcoxon signed-rank tests were used to compare SSIM, PSNR, nMSE, and CMB counts among magnitude, original SWI, and predicted synthetic SWI images. Intraclass correlation assessed interrater variability. P values <0.005 were considered statistically significant. SSIM values of the predicted vs. original SWI (0.972, 0.995, 0.9864) were statistically significantly higher than that of the magnitude vs. original SWI (0.970, 0.994, 0.9861) for whole brain, vascular structures, and brain tissue regions, respectively; 67% (19/28) CMBs detected on original SWI images were also detected on the predicted SWI, whereas only 10 (36%) were detected on magnitude images. Overall image quality was similar between the synthetic and original SWI images, with less artifacts on the former. This study demonstrated that deep learning can increase the susceptibility contrast present in neurovasculature and CMBs on T2*-weighted magnitude images, without residual susceptibility-induced artifacts. This may be useful for more accurately estimating CMB burden from magnitude images alone. 3. Stage 2.

Genomic Prostate Score: A New Tool to Assess Prognosis and Optimize Radiation Therapy Volumes and ADT in Intermediate-Risk Prostate Cancer.

Genomic classifiers such as the Genomic Prostate Score (GPS) could help to personalize treatment for men with intermediate-risk prostate cancer (I-PCa). In this study, we aimed to evaluate the ability of the GPS to change therapeutic decision making in I-PCa. Only patients in the intermediate NCCN risk group with Gleason score 3 + 4 were considered. The primary objective was to assess the impact of the GPS on risk stratification: NCCN clinical and genomic risk versus NCCN clinical risk stratification alone. We also analyzed the predictive role of the GPS for locally advanced disease (≥pT3+) and the potential change in treatment strategy. Thirty patients were tested for their GPS between November 2018 and March 2020, with the median age being 70 (45-79). Twenty-three patients had a clinical T1 stage. Eighteen patients were classified as favorable intermediate risk (FIR) based on the NCCN criteria. The median GPS score was 39 (17-70). Among the 23 patients who underwent a radical prostatectomy, Gleason score 3 + 4 was found in 18 patients. There was a significant correlation between the GPS and the percentage of a Gleason grade 4 or higher pattern in the surgical sample: correlation coefficient r = 0.56; 95% CI = 0.2-0.8; p = 0.005. In this study, the GPS combined with NCCN clinical risk factors resulted in significant changes in risk group.

Multiagent neoadjuvant chemotherapy compared to upfront surgery in pancreatic cancer of the body and tail using the National Cancer Database.

722 Background: While neoadjuvant chemotherapy is increasingly being using in pancreatic cancer treatment, it is unclear whether it is beneficial in treatment of body and tail tumors. Randomized controlled trials are lacking and previous observational studies have not demonstrated any benefit. We aimed to assess survival associations, trends over time and patient selection associations for multiagent neoadjuvant chemotherapy treated pancreatic cancer of the body and tail using data from the National Cancer Database (NCDB). Methods: We queried the NCDB for pancreatic adenocarcinoma in the body or tail diagnosed between 2010 – 2018 that received multiagent neoadjuvant chemotherapy and/or a distal pancreatectomy. Patients with clinical M1, clinical T4 and surgery other than partial pancreatectomy were excluded. Survival was compared with Kaplan-Meier estimates and multivariable Cox Proportional Hazard Estimates. Results: Between 2010 – 2018, the use of multiagent neoadjuvant chemotherapy increased from 5.7% to 31.8%. In total, 1951 patients were included with n = 384 receiving multiagent neoadjuvant chemotherapy (cases) and n = 1567 undergoing upfront surgery (controls). Neoadjuvant chemotherapy was associated with younger age, tumor in the pancreatic body, clinical N1-2 and with Ca 19-9 ≥98 U/mL. Neoadjuvant chemotherapy was associated with a decreased mortality rate in multivariable Cox regression models adjusting for preoperatively assessed variables (HR 0.65, 95% CI 0.53 – 0.81, p &lt; 0.001) and results were significant in both clinical T1-2 and T3 tumors. Patients treated with upfront surgery had higher rates of adjuvant chemotherapy receipt after resection (41.4% vs 70.6%) but there was no difference in R1 resection rates or 90-day postoperative mortality between the groups. The addition of neoadjuvant radiotherapy was not associated with improved survival in patients receiving neoadjuvant chemotherapy. Conclusions: Multiagent neoadjuvant chemotherapy is increasingly being used in the treatment of pancreatic cancer of the body and tail, especially in younger patients and patients with more aggressive tumor characteristics. Multiagent neoadjuvant chemotherapy is associated with improved survival but randomized trials are needed to establish causal relationships.

Docetaxel+Cisplatin+5-FU (DCF) Therapy as a Preoperative Chemotherapy to Advanced Esophageal Squamous Cell Carcinoma: A Single-center Retrospective Cohort Study.

Objective The aim of this study was to determine the safety and clinical efficacy of docetaxel+cisplatin+5-fluorouracil (DCF) as neoadjuvant chemotherapy (NAC). Methods In this single-center study, patient background and treatment outcomes (NAC efficacy assessment, NAC adverse events, short-term postoperative outcomes, and one-year postoperative outcomes) in patients treated with preoperative DCF and preoperative cisplatin+5-FU (CF) were compared retrospectively. Patients Seventeen patients diagnosed with esophageal squamous cell carcinoma (ESCC) and treated with preoperative DCF therapy and 50 patients treated with preoperative CF therapy between January 2013 and July 2019 were included in this study. Results There were significant differences in clinical T factor and clinical stage between the CF and DCF groups (p<0.05). All patients in the DCF therapy group were above clinical T3 and clinical stage III. The clinical response after NAC was partial response (PR) for 23 patients (46.0%) in the CF group and 13 patients (76.5%) in the DCF group (p=0.030). Regarding adverse events in NAC, neutropenia, febrile neutropenia (FN), diarrhea, and stomatitis were observed more frequently in the DCF group than in the CF group (p<0.05). The postoperative results [overall survival (OS), recurrence-free survival (RFS), one-year OS, one-year RFS] of the DCF group were comparable to those of the CF group. Conclusion DCF therapy has been recognized as an effective treatment option for advanced ESCC. However, the indication for DCF therapy should be chosen carefully because of the high incidence of adverse events.

Prediction Formula for Pathological Depth of Invasion From Clinical Depth of Invasion in Tongue Squamous Cell Carcinoma (SCC) Stage I/II Cases.

The depth of invasion (DOI) of tongue squamous cell carcinoma (SCC) is an important prognostic factor. The definition is clear for pathological DOI (pDOI), but the treatment strategy is determined by the preoperative clinical DOI (cDOI). Few studies have investigated the difference between these DOIs. The purpose of this study was to obtain the correlation equation between cDOI and pDOI for Stage I/II tongue SCC and to consider the points to be noted in actual clinical practice. In this retrospective study, 58 patients with clinical stage I/II tongue SCC were included. Correlations between cDOI and pDOI were obtained for all 58 cases, as well as for 39 cases which excluded superficial and exophytic lesions. The overall cDOI and pDOI median values were 8.0 and 5.5 mm, respectively; the 2.5 mm reduction was significant (p< 0.01). The correlation equation was pDOI = 0.81 × cDOI-0.23 (r = 0.73). Furthermore, re-analysis of the 39 cases revealed that pDOI = 0.84 × cDOI-0.37 (r = 0.62). Hence, a derived equation pDOI = 0.84 × (cDOI-0.44) was obtained to predict pDOI from cDOI. This study indicated that it is necessary to consider contraction due to specimen fixation by subtracting the thickness of the mucosal epithelium. Clinical T1 cases with a cDOI of 5 mm or less had a pDOI of 4 mm or less, and it would be expected to have low positive rate of neck lymph node metastasis.

Abstract 116: Cortical Thickness Estimation From Clinical T1 Weighted Magnetic Resonance Images To Predict Functional Outcomes After Mechanical Thrombectomy

Background: Endovascular treatment (EVT) is the standard of care for acute ischemic stroke caused by large vessel occlusion (LVO). However, successful EVT does not result in functional independence in many patients. This may be due to pre-existing cortical atrophy that might reduce compensatory plasticity and attenuate recovery. Identifying patients who will most benefit from EVT may be possible using baseline cortical thickness measures as a marker of brain health and providing additional prognostic utility for clinical T1-weighted (T1w) MRI. Objective: Estimate hemispheric and regional cortical thickness from clinical T1w-MRI and determine its influence on functional outcomes post successful EVT. Methods: We performed a retrospective analysis of a prospectively maintained Stroke Thrombectomy and Aneurysm Registry (n=602), collected between 2015 - 2021. We selected 213 patients (mean age 67.5 ± 14.6, 49.3% female) who had adequate quality MRI within 14 days of EVT and a record of the modified Rankin scale (mRS) at 90 days post EVT. Clinical T1w images were transformed into high-resolution images using the convolutional neural network SynthSR. Then, FreeSurfer was used to estimate hemispheric and regional mean cortical thickness from the side contralateral to the stroke, to avoid local lesion effects. In addition to hemispheric cortical thickness, we selected the insula, superior frontal gyrus (SFG), and superior temporal gyrus (STG) for the analysis due to their importance in sensorimotor processing, self-awareness, and social cognition respectively which are important during rehabilitation. Results: In an ordinal regression model adjusted for baseline mRS, the cortical thickness of the SFG and the STG was significantly predictive of 90-day mRS (p=0.005 and p=0.003 respectively), while hemispheric and insular cortical thickness were not. After adjusting for confounders and comorbidities, SFG and STG cortical thickness remained significant predictors of 90-day mRS (p&lt;0.001 for both). Conclusions: The correlation between decreased cortical thickness in specific regions and worse functional outcomes elucidates the effects of pre-existing cortical atrophy in key areas of the brain that may be more important than others during recovery.

Long-term results from NRG-GI002: A phase II clinical trial platform using total neoadjuvant therapy (TNT) in locally advanced rectal cancer (LARC).

7 Background: This NCTN multi-arm randomized phase II modular clinical trial platform utilizes TNT with parallel experimental arms (EAs) in LARC. EAs are not intended for direct comparison, but rather to concurrently randomized control arm (CA) patients. Primary endpoint (EP) and available secondary EPs (from EA1 using veliparib [V], PARPi; and EA2 using pembrolizumab [P], anti-PD-1) have been previously reported. We present long-term outcomes of all pts enrolled (NCT02921256). Methods: Stage II/III pts with MSS LARC (with any ONE of the following: distal location [cT3-4 ≤5cm from anal verge, any N]; bulky [any cT4 or tumor within 3mm of mesorectal fascia]; high risk for metastatic disease [cN2]; or not a sphincter-sparing surgery [SSS] candidate) were randomized to CA (neoadjuvant FOLFOX [x 4mo] → chemoRT [capecitabine with 50.4Gy] → surgery 8-12 wks later). EA1 added V (400mg PO BID) and EA2 added P (200mg IV Q3 wks x 6 doses) each concurrent with chemoRT. Primary EP: 4-point reduction in Neoadjuvant Rectal Cancer (NAR) score with a one-sided α=0.10, 80% power. NAR compared by linear model controlling for clinical T4 at entry (Y/N). Secondary EPs: OS, DFS. p-values are two-sided. Results: From 10/2016-2/2018, 178 pts were randomized (88 CA, 90 EA1). From 8/2018-5/2019, 185 pts were randomized (95 CA, 90 EA2). Baseline characteristics were previously reported. Median follow-up is 3.50 yrs for the 1st comparison. Median follow-up is 3.15 yrs for the 2nd comparison. Updated primary and long-term secondary outcomes are in the table. Conclusions: With longer follow-up, addition of V to TNT provided no significant differences in the NAR score or 3yr outcomes. The addition of P to TNT was associated with a statistically significant improvement in 3yr OS, but not DFS. Correlative molecular analyses are ongoing. Support: U10CA180868, -180822; UG1-189867; U24-196067; AbbVie; Merck. Clinical trial information: NCT02921256 . [Table: see text]

A novel nomogram to predict lymph node metastasis in cT1 non-small-cell lung cancer based on PET/CT and peripheral blood cell parameters

BackgroundAccurately evaluating the lymph node status preoperatively is critical in determining the appropriate treatment plan for non-small-cell lung cancer (NSCLC) patients. This study aimed to construct a novel nomogram to predict the probability of lymph node metastasis in clinical T1 stage patients based on non-invasive and easily accessible indicators.MethodsFrom October 2019 to June 2022, the data of 84 consecutive cT1 NSCLC patients who had undergone PET/CT examination within 30 days before surgery were retrospectively collected. Univariate and multivariate logistic regression analyses were performed to identify the risk factors of lymph node metastasis. A nomogram based on these predictors was constructed. The area under the receiver operating characteristic (ROC) curve and the calibration curve was used for assessment. Besides, the model was confirmed by bootstrap resampling.ResultsFour predictors (tumor SUVmax value, lymph node SUVmax value, consolidation tumor ratio and platelet to lymphocyte ratio) were identified and entered into the nomogram. The model indicated certain discrimination, with an area under ROC curve of 0.921(95%CI 0.866–0.977). The calibration curve showed good concordance between the predicted and actual possibility of lymph node metastasis.ConclusionsThis nomogram was practical and effective in predicting lymph node metastasis for patients with cT1 NSCLC. It could provide treatment recommendations to clinicians.

Comparative analysis of the effectiveness of neoadjuvant systemic therapy and primary surgical treatment of patients with &lt;i&gt;BRCA&lt;i/&gt;-associated triple-negative T1 breast cancer

BACKGROUND: BRCA-associated triple-negative breast cancer does not only have a better overall survival rate, but also a longer recurrence-free period in compatison to patients with sporadic breast cancer. BRCA-associated triple-negative breast cancer shows high sensitivity to chemotherapeutic agents, but the benefit of systemic neoadjuvant therapy for patients with tumor size T1 in triple-negative breast cancer is unclear.&#x0D; AIM: The aim of the study is to determine the recurrence rate in the patients with BRCA-associated triple-negative breast cancer and to determine the recurrence rate for the group of patients with tumor size T1, depending on the initial treatment.&#x0D; MATERIALS AND METHODS: The study includes the data of 129 patients diagnosed with BRCA-associated triple-negative breast cancer treated in the period from 2010 to 2022 at the Department of Breast Tumors of the N.N. Petrov National Medical Research Center of Oncology. All the patients have been divided into two groups depending on the initial treatment. Group I included 93 (72.1%) patients whose treatment was started with systemic neoadjuvant therapy, group II, whose initial treatment involved surgery, included 36 (27.9%) patients.&#x0D; RESULTS: In group I, the number of recurrences was 22 (23.6%), and in group II 6 (16.6%). Depending on the pathomorphological response to systemic neoadjuvant therapy, the patients of group I have been separated: in the group of patients with a complete pathomorphological response, the number of relapses was 6 (13.3%), and in the group of patients with a partial pathomorphological response 16 (33.3%). A comparative analysis of 2 groups with tumor size T1 has shown that in group I the number of patients with tumor size T1 was 11 (11.8%) cases, and in group II 16 (44.4%). Subgroup comparative analysis in group I, taking into account tumor size T1, has shown that recurrence has not been observed when a complete pathomorphological response was achieved in 8 (17.7%) patients, and in the group with partial pathomorphological response in 3 (6.25%) patients with tumor size T1. A relapse has been observed in 1 (2%) case. With clinical tumor size T1 (n = 16), there was no recurrence in group II.&#x0D; CONCLUSIONS: Patients diagnosed with BRCA-associated triple-negative breast cancer remain at a high risk of recurrence at a later stage of the disease, but this does not apply to patients with a tumor size T1 since the difference in relapse-free survival [AP1] between patients, whose treatment was started with neoadjuvant systemic therapy and patients, whose initial treatment involved surgery % with a clinical tumor size T1, is not confirmed.

Comparison between de novo and metachronous metastatic breast cancer: the presence of a primary tumour is not the only difference-a Dutch population-based study from 2008 to 2018.

The aim of this study was to compare characteristics and survival of patients with de novo and metachronous metastatic breast cancer. Data of patients with metastatic breast cancer were obtained from the Netherlands Cancer Registry. Patients were categorized as having de novo metastatic breast cancer (n = 8656) if they had distant metastases at initial presentation, or metachronous metastatic disease (n = 2374) in case they developed metastases within 5 or 10years after initial breast cancer diagnosis. Clinicopathological characteristics and treatments of these two groups were compared, after which multiple imputation was performed to account for missing data. Overall survival was compared for patients treated with systemic therapy in the metastatic setting, using Kaplan Meier curves and multivariable Cox proportional hazards models. The hazard ratio for overall survival of de novo versus metachronous metastases was assessed accounting for time-varying effects. Compared to metachronous patients, patients with de novo metastatic breast cancer were more likely to be ≥ 70years, to have invasive lobular carcinoma, clinical T3 or T4 tumours, loco-regional lymph node metastases, HER2 positivity, bone only disease and to have received systemic therapy in the metastatic setting. They were less likely to have triple negative tumours and liver or brain metastases. Patients with de novo metastases survived longer (median 34.7months) than patients with metachronous metastases (median 24.3months) and the hazard ratio (0.75) varied over time. Differences in clinicopathological characteristics and survival between de novo and metachronous metastatic breast cancer highlight that these are distinct patients groups.