T3N0 Disease Research Articles

Assessment of Optimal Treatment Strategies and Their Outcomes in T3N1 Rectal Cancers.

Background:This study compares the outcomes of a surgery first vs a neoadjuvant treatment strategy in T3N1M0 rectal cancers. Methods:This was a single-centre retrospective cohort study of patients admitted for curative treatment of T3N1 rectal cancer. Patients with pre-treatment T3N1 and pathological T3N1 disease were included in the study. Patients were divided into two groups depending on whether they had surgery or neoadjuvant therapy as their initial phase of treatment. Primary outcome measures were local recurrence and distant recurrence. Secondary outcomes were disease-free survival (DFS) and overall survival (OS). Tabulated results were analyzed with appropriate statistical tests. Results:One hundred and ten patients were initially selected. Fourty-eight were finally included after excluding patients who did not meet the staging criteria or were not eligible for curative treatment. Twenty-nine patients underwent surgery, and 19 patients with neoadjuvant therapy as their first treatment. No local recurrence was noted in either group, with a distant recurrence noted in group 2 (6.9%) and group 1 (5.26%) cases among the surgery-first and neoadjuvant-first groups, respectively. Disease-free survival and overall survival were 29.5 and 30 months for the surgery-first group and 22 and 22 months for the neo-adjuvant group, respectively. Conclusions:Outcomes in the surgery-first group were non-inferior to that of the neoadjuvant group. A threatened circumferential resection margin (CRM) on pretreatment staging warrants neoadjuvant therapy to ensure an R0 resection. Extramural vascular invasion (EMVI), being a negative prognostic factor, doesn't preclude a surgery-first approach.

Staging accuracy in patients with clinical T2N0 gastric cancer: Implications for treatment sequencing

BackgroundPatients with clinical T2N0 (cT2N0) gastric adenocarcinoma are recommended to undergo either perioperative chemotherapy or upfront resection. If T2N0 disease is pathologically confirmed, patients may be observed without chemotherapy. These guidelines create the possibility of both systemic therapy overuse and underuse depending on clinical staging accuracy. Our objectives were to define factors associated with upstaging after upfront resection and describe the association between postoperative chemotherapy and survival. MethodsPatients with cT2N0 gastric adenocarcinoma were identified using the National Cancer Database. Factors associated with upstaging were assessed by logistic regression. Survival was assessed using Kaplan-Meier and Cox proportional hazard analyses. ResultsOf 4,076 patients undergoing upfront resection for cT2N0 gastric cancer, 1,933 (47.4%) were pathologically upstaged. Patients were more likely to be upstaged if they had >3.0-cm (adjusted odds ratio [aOR] 2.31, 95% confidence interval [CI] 1.97–2.70; P < .001) or poorly differentiated tumors (aOR 2.22, 95% CI 1.89–2.60; P < .001). Patients were less likely to be upstaged if they had distal tumors (aOR 0.77, 95% CI 0.64–0.93; P = .006). Of those pathologically upstaged (n = 1,933), 1,111 (57.4%) received adjuvant chemotherapy that was associated with improved survival (HR 0.55, 95% CI 0.47–0.63; P < .001). Among those not upstaged (n = 2,143), 247 (11.5%) received adjuvant chemotherapy that was not associated with improved survival (HR 0.92, 95% CI 0.70–1.21; P = .54). ConclusionsPathologic upstaging after upfront resection in patients with cT2N0 gastric cancer is associated with patient and tumor characteristics. Adjuvant chemotherapy is associated with improved survival only in the patients upstaged at surgery. An upfront surgical approach may be preferred in select patients, especially if avoiding chemotherapy is desired.

A phase III randomized trial of radiotherapy optimization for low-risk HER2-positive breast cancer (HERO): NRG-BR008.

TPS613 Background: Breast radiotherapy (RT) is the standard of care for patients with early-stage breast cancer (BC) who undergo breast-conserving surgery (BCS). However, the magnitude of benefit of RT is less clear in BCS patients with low-risk disease who receive effective systemic therapy. Among patients with early-stage HER2-positive (HER2+) BC, 10-year locoregional recurrence has been reported as low as 1.5% following BCS, adjuvant chemotherapy and HER2-targeted therapy, and RT. Given these exceedingly favorable outcomes, with the addition of HER2-directed therapy, we seek to evaluate the feasibility of omitting RT among patients with early-stage HER2+ BC following BCS and appropriate systemic therapy. Methods: This is a phase III randomized trial for patients ≥40 years with early-stage, node-negative, HER2+ (IHC/FISH) BC treated with BCS with negative margins and sentinel lymph node biopsy or axillary dissection. Patients undergoing primary surgery must have pathologic T1 (≤2 cm) N0 disease, while patients receiving neoadjuvant therapy must have clinical T1-2 (with radiographically T≤3.0 cm) N0 disease and exhibit a pathologic complete response (ypT0N0) at surgery. All patients must receive cytotoxic chemotherapy and HER2-targeted therapy, either in the adjuvant or neoadjuvant setting. Stratification is by age (&lt;60; ≥60), tumor size (≤1 cm; &gt;1 cm), estrogen-receptor status (positive; negative), and systemic therapy sequencing (adjuvant vneoadjuvant). Patients will be randomized to standard breast RT in addition to continuation of trastuzumab to complete one year of treatment (Arm 1), or trastuzumab alone (Arm 2). Endocrine therapy will be recommended for patients with hormone-receptor positive tumors. The primary endpoint is the recurrence-free interval (RFI). Secondary endpoints include time to ipsilateral breast recurrence, locoregional recurrence, disease-free survival, and overall survival, in addition to the 7-year ipsilateral breast recurrence rate among those not receiving RT. A health-related quality of life sub-study will assess differences in patient-reported breast pain and worry. We estimate a 7-year RFI of 97.5% with RT and allow for a clinically acceptable decrement of 3.63% without RT (7-year RFI of 93.87%; HR 2.5) to establish omission of RT as non-inferior. NRG-BR008 aims to enroll 1,300 patients over 4.5 years, yielding 80% power to detect the non-inferiority of RT omission with a one-sided α=0.05. We expect to observe the required 38 RFI events within 6 years of additional follow-up. The NRG-BR008/HERO trial opened to accrual in March 2023. Accrual is 13/1,300 as of 02-05-2024. Clinical trial information: NCT05705401 .

Baseline (BL) characteristics and efficacy endpoints for patients (pts) with node-negative (N0) HR+/HER2− early breast cancer (EBC): NATALEE trial.

512 Background: NATALEE assessed ribociclib (RIB) + non-steroidal aromatase inhibitor (NSAI) vs NSAI alone in pts with HR+/HER2− EBC at increased risk of recurrence, including pts with N0 disease, and showed a statistically significant invasive disease-free survival (iDFS) benefit. We report BL characteristics, efficacy, and safety for the N0 subgroup. Methods: Pts with stage II/III HR+/HER2− EBC were randomized (R) 1:1 to RIB 400 mg/d (3 wk on/1 wk off for 36 mo) + NSAI (letrozole or anastrozole for ≥60 mo) or NSAI alone. Men and premenopausal women received goserelin. Pts could receive any standard (neo)adjuvant endocrine therapy (ET) ≤12 mo before randomization. In the intent-to-treat (ITT) population, 78% of pts completed 3y of RIB treatment (tx) or discontinued early with 21% still on tx at the time of this analysis (data cutoff: July 21, 2023; median follow up, 33 mo). The N0 subgroup included pts with T2N0 (stage IIA; with grade [G]3, or G2 disease and Ki-67 ≥20% or high genomic risk [HGR]), T3N0 (stage IIB), and T4N0 (stage IIIB); T1N0 was excluded. Results: Of 2549 pts R to RIB + NSAI and 2552 to NSAI alone, 285 (11%) and 328 (13%) had N0 disease, respectively. BL characteristics for the N0 subgroup were balanced across arms. Most pts were premenopausal (RIB + NSAI: 67% vs NSAI alone: 63%). Pts with N0 disease had anatomic stage IIA (RIB + NSAI: 74% vs NSAI alone: 73%), stage IIB (17% vs 13%), or stage IIIB (9% vs 12%) disease (Table). Most pts received prior chemotherapy (RIB + NSAI: 72% vs NSAI alone: 71%); prior ET was received by 59% vs 62% of pts with RIB + NSAI vs NSAI alone. For pts with T2N0 disease treated with RIB + NSAI vs NSAI alone, 49% vs 45% had G3 disease and 49% vs 53% had G2 disease (54% vs 56% with T2N0, G2 &amp; Ki-67 &gt; 20%; 13% vs 23% with T2N0, G2, Ki-67 ≤20%/missing &amp; HGR). Consistent with the ITT population, RIB + NSAI improved iDFS (HR, 0.72; 95% CI, 0.41-1.27; 3y rate with RIB + NSAI vs NSAI alone, 93.2% vs 90.6%), distant disease–free survival (DDFS; HR, 0.70; 95% CI, 0.38-1.29; 3y rate, 94.3% vs 91.5%), and distant recurrence–free survival (DRFS; HR, 0.58; 95% CI, 0.29-1.17; 3y rate, 96.3% vs 92.5%) in pts with high-risk N0 disease. The safety profile of RIB in the N0 subgroup was consistent with the ITT population. The rate of discontinuation due to all grade adverse events was 24% vs 8% with RIB + NSAI vs NSAI alone. Conclusions: This analysis showed a consistent efficacy benefit and manageable safety profile of RIB + NSAI vs NSAI alone in pts with N0 disease in NATALEE. The 3y iDFS, DDFS, and DRFS rates in the control arm at this early follow-up underscore the risk of recurrence for the N0 subgroup. These findings support the use of RIB in pts with HR+/HER2− EBC at increased risk of recurrence, including pts with N0 disease. Clinical trial information: NCT03701334 . [Table: see text]

Abstract PO2-08-07: Evaluating chemotherapy receipt and candidacy for PARP inhibitors in germline BRCA1/2 carriers with early and locally advanced breast cancer

Abstract Introduction: While enhanced breast screening of germline BRCA1/2 carriers results in earlier stage at diagnosis, the impact of tumour biology and BRCA mutation on chemotherapy receipt in early stage disease remains understudied. Methods: We retrospectively reviewed treatment administered following a first diagnosis of BRCA1/2-associated breast cancer between 2003-2023 at our institution. Chemotherapy receipt (neoadjuvant or adjuvant) was evaluated according to tumor size, biologic subtype, and BRCA mutation. Current guidelines for PARP inhibitor use were applied to estimate the proportion of affected BRCA1/2 carriers that would be deemed eligible for targeted therapy in the future. Results: Overall, 251 affected BRCA1/2 carriers were included; 137 (54.6%) BRCA1 (median age 40 years, range 19-72) and 114 (45.4%) BRCA2 (median age 43, range, 24-80 years). Chemotherapy was administered in 70.1% of index breast cancer cases and was significantly associated with clinical tumor size (36.7% T1a-T1b, 90.9% T1c, 95.2% T2, 95.3% T3-T4, p&amp;lt; 0.001), nodal status (71.8% cN0 vs. 100% cN1-2, p=0.004), and biologic subtype (90.0% TNBC vs. 75.0% ER+HER2-, p=0.02). BRCA1-associated breast cancers were less likely to present with DCIS or T1 tumours (%Tis/T1; 46.7% BRCA1 vs. 70.8% BRCA2, p&amp;lt; 0.001) and more likely to present with triple negative disease (71.4% BRCA1 vs. 24.6% BRCA2, p&amp;lt; 0.001). BRCA1 carriers were more likely to require chemotherapy for index breast cancer (81.8% BRCA1 vs. 56.1% BRCA2, p&amp;lt; 0.001). In subgroup analysis of early stage, T1N0 disease, chemotherapy was administered in 79.0% BRCA1 and 52.2% BRCA2 patients (p=0.03). If recent guidelines incorporating biologic subtype, nodal involvement, and response to neoadjuvant chemotherapy were retrospectively applied to the cohort, 33.6% would be deemed eligible for PARP inhibitors in the adjuvant setting, including 40.9% BRCA1 and 17.5% BRCA2 affected carriers (p &amp;lt; 0.001). Conclusion: Chemotherapy receipt is high in BRCA-associated breast cancers including in early stage, node-negative disease. Overall, one third of affected carriers are expected to be eligible for PARP inhibitors in the adjuvant setting. Future studies exploring how this information may impact decisions around risk-reducing mastectomy are warranted. Citation Format: Stephanie Wong, Carla Apostolova, Amina Ferroum, Basmah Alhassan, Ipshita Prakash, Mark Basik, Karyne Martel, Sarkis Meterissian, David Fleiszer, Nora Wong, Talia Malagon, William Foulkes, Jean-Francois Boileau. Evaluating chemotherapy receipt and candidacy for PARP inhibitors in germline BRCA1/2 carriers with early and locally advanced breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-08-07.

Abstract PO1-19-01: NRG-BR008: A Phase III Randomized Trial of Radiotherapy Optimization for Low-risk HER2-positive Breast Cancer (HERO)

Abstract Background: Breast radiotherapy (RT) is the standard of care for patients with early-stage breast cancer (BC) who undergo breast-conserving surgery (BCS). However, the magnitude of benefit of RT is less clear in BCS patients with low-risk disease who receive effective systemic therapy. Among patients with early-stage HER2-positive (HER2+) BC, 10-year locoregional recurrence has been reported as low as 1.5% following BCS, adjuvant chemotherapy and HER2-targeted therapy, and RT. Given these exceedingly favorable outcomes, with the addition of HER2-directed therapy, we seek to evaluate the feasibility of omitting RT among patients with early-stage HER2+ BC following BCS and appropriate systemic therapy. Methods: This is a phase III randomized trial for patients ≥40 years with early-stage, node-negative HER2+ (IHC/FISH) BC treated with BCS with negative margins and sentinel lymph node biopsy or axillary dissection. Patients undergoing primary surgery must have pathologic T1 (&amp;lt; 2 cm) N0 disease, while patients receiving neoadjuvant therapy must have clinical T1-2 (with radiographically T&amp;lt; 3.0 cm) N0 disease and exhibit a pathologic complete response (ypT0N0) at surgery. All patients must receive cytotoxic chemotherapy and HER2-targeted therapy, either in the adjuvant or neoadjuvant setting. Stratification is by age (&amp;lt; 60; ≥60), tumor size (≤1 cm; &amp;gt;1 cm), estrogen-receptor status (positive; negative), and systemic therapy sequencing (adjuvant vs neoadjuvant). Patients will be randomized to standard breast RT in addition to continuation of trastuzumab to complete a year of treatment (Arm 1), or trastuzumab alone (Arm 2). Endocrine therapy will be recommended for patients with hormone-receptor positive tumors. The primary endpoint is the recurrence-free interval (RFI). Secondary endpoints include the time to ipsilateral breast recurrence, locoregional recurrence, disease-free survival, and overall survival, in addition to the 7-year ipsilateral breast recurrence rate among those not receiving RT. A health-related quality of life sub-study will assess differences in patient-reported breast pain and worry. We estimate a 7-year RFI of 97.5% with RT and allow for a clinically acceptable decrement of 3.63% without RT (7-year RFI of 93.87%; HR 2.5) to establish omission of RT as non-inferior. NRG-BR008 aims to enroll 1,300 patients over 4.5 years, yielding 80% power to detect the non-inferiority of RT omission with a one-sided α=0.05. We expect to observe the required 38 RFI events within 6 years of additional follow-up. The NRG-BR008/HERO trial opened to accrual in March, 2023. NCT05705401. Support: U10CA180868, -180822, UG1CA189867, U24CA196067; Susan G. Komen Foundation (JR) Citation Format: Lior Braunstein, Melissa Mitchell, Hanna Bandos, William Sikov, Atif Khan, Peter Chen, Patricia Ganz, Reshma Jagsi, Julia White, Reena Cecchini, Hyejoo Kang, Shannon Puhalla, Kelly Bolton, Eileen Connolly, Erica Stringer-Reasor, Kimberly Gergelis, Thomas Julian, Eleftherios Mamounas, Norman Wolmark. NRG-BR008: A Phase III Randomized Trial of Radiotherapy Optimization for Low-risk HER2-positive Breast Cancer (HERO) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-19-01.

Hypofractionated Partial Breast Irradiation With Intensity-Modulated Radiotherapy in Early Breast Cancer or Carcinoma In Situ: An Investigational Short-Term Analysis.

This study aimed to analyze the treatment outcomes and adverse effects of moderately hypofractionated partial breast irradiation (PBI) in patients with early breast cancer. In total, 473 patients with early breast cancer or carcinoma in situ were diagnosed with Tis or T1N0 disease and underwent PBI following breast-conserving surgery. All histologic tumor types, close surgical margins within 1 mm of the tumor, and multifocal tumors were included in this study. A radiation dose of 50 Gy in 20 fractions was delivered over 4 weeks using intensity-modulated radiotherapy technique. Dosimetric data, recurrence patterns, survival outcomes, and adverse events were retrospectively analyzed. During a median follow-up of 28.9 months, seven patients (1.5%) experienced ipsilateral breast tumor recurrence (IBTR). Two patients had regional recurrence, four patients developed contralateral breast cancer, and no distant metastases were observed. The locoregional recurrence rate in the ipsilateral breast was 1.8%. Two deaths occurred during the follow-up period, but were not attributed to breast cancer. The 2-year disease-free survival and 2-year overall survival rates were was 94.0% and 99.8%, respectively. Acute adverse events occurred in 131 patients (27.1%), and were distributed among all grades, with only two patients (0.4%) experiencing grade 3 events. Late adverse events were noted in 16 patients (3.4%), and were distributed among all grades, including grade 3 events in four patients (0.8%). No grade 4 or 5 events were observed. Hypofractionated PBI demonstrated favorable IBTR rates in patients with early breast cancer, with low incidence of acute and late toxicities in the short-term analysis.

Patterns of Care for Patients with Locally Advanced Rectal Cancer Treated with Total Neoadjuvant Therapy between 2016-2020: An NCDB Analysis

Treatment for locally advanced rectal cancer (LARC), defined as T3/4 or any T with N+ disease, typically requires multi-modality management consisting of radiation (RT), chemotherapy (CHT), and surgery. Despite emerging evidence that total neoadjuvant therapy (TNT) is the preferred treatment of LARC, it remains unknown what proportion of patients are receiving TNT in the United States. Our objective was to (1) determine the proportion of patients with LARC receiving TNT over time, (2) determine the most common method in which TNT is being delivered, and (3) determine what factors are associated with a lower likelihood of receiving TNT in the United States. Retrospective data was obtained from the National Cancer Database (NCDB) for patients diagnosed with rectal cancer between 2016-2020. Patients were excluded if they had M1 disease, T1-2 N0 disease, incomplete staging information, non-adenocarcinoma histology, received RT to a non-rectum site, or received a non-definitive RT dose. Patients were determined to have received TNT if they (1) received RT and multi-agent (MA)-CHT prior to surgery, (2) had an interval of >180 days from the onset of neoadjuvant therapy to surgery if they received long course (LC)-chemoradiation (CRT) (based on 35 days for LC-CRT + 112 days for 8 cycles of MA-CHT + 30 days to surgery), or (3) had an interval of >150 days from the onset of neoadjuvant therapy to surgery if they received short course (SC)-RT (based on 5 days for SC-RT + 112 days for 8 cycles of MA-CHT + 30 days to surgery). Data were analyzed using linear regression, Chi-square test, and binary logistic regression. Of the 26,375 patients included, the median age was 60 (range 21-90) years, with the majority of patients being <65 years old (65.6%), male (62.1%), and non-Hispanic white (77.0%). A total of 5,003 (19.0%) patients received TNT, and 21,372 (81.0%) patients received classical combined modality therapy (CMT). The proportion of patients receiving TNT increased significantly over time, from 6.1% in 2016, 9.0% in 2017, 15.3% in 2018, 25.8% in 2019, to 34.6% in 2020 (slope = 7.36, 95% CI 4.58-10.15, R2 = 0.96, p = 0.040). The most common TNT regimen was MA-CHT followed by LC-CRT (73.2% of cases from 2016-2020). The proportion of patients receiving SC-RT as part of TNT significantly increased from 2.8% in 2016, 1.7% in 2017, 4.6% in 2018, 7.3% in 2019, to 13.7% in 2020 (slope = 2.74, 95% CI 0.37-5.11, R2 = 0.82, p = 0.035). On multivariate analysis, factors associated with a lower likelihood of TNT use included age >65 (OR 0.66, 95% CI 0.61-0.71, p<0.001), female gender (OR 0.92, 95% CI 0.86-0.98, p = 0.014), Black race (OR 0.87, 95% CI 0.77-0.98, p = 0.024), and T3 N0 disease (OR 0.60, 95% CI 0.52-0.70, p<0.001). TNT utilization rates have significantly increased in recent years, from 6.1% in 2016 to 34.6% in 2020. The observed trend appears to be in line with the recent National Comprehensive Cancer Network (NCCN) guidelines recommending TNT as the preferred approach.

427 Systemic Imaging for Early Laryngeal Cancer; a Single Centre Review of Guideline Application in Contemporary Clinical Practice

Abstract Aim Early-stage laryngeal cancer (T1 and T2) has low rate of locoregional and distant metastasis. Therefore, National Institute for Health and Care Excellence (NICE) guidelines were updated in 2016 and recommended to no longer offer systemic staging for early laryngeal cancer because systemic imaging was not deemed to be cost effective. Our study aims to evaluate (1) if NICE guidance on the role of systemic imaging in the assessment and management of early laryngeal cancer is being followed in our centre (2) assess the impact of this practice on our patients (3) perform a cost analysis relevant to our institution. Method We retrospectively reviewed all laryngeal cases at a major H&amp;N cancer centre between 01/01/2020 and 01/01/2022. The following information was collected for all the patients: neck/systemic imaging modalities performed on patients, demographics, site of original laryngeal tumour and any metastatic disease detected by systemic imaging. Next, we performed a cost analysis based on the cost analysis method undertaken by NICE. Results Our results showed n = 83 patients had laryngeal cancer between 01/01/2020 and 01/01/2022. Of which n = 30 had T1N0 and T2N0 disease. Systemic imaging found no metastatic disease, however n = 2 primary lung tumours and n = 1 lung infection was detected. The total cost for systemic imaging was £4,207.12 and total cost for neck imaging investigations it was £12,335.07. Conclusions Our study concludes NICE guidance is not being followed at our centre. Systemic imaging provides little benefit to patients and is an expensive practice.

Facial-submental island flap for reconstruction of hemitongue defects in young, middle-aged and elderly patients with early and middle stage oral tongue squamous cell carcinoma

BackgroundThis study evaluated the outcomes of facial-submental artery island flap (FSAIF) for reconstruction of the hemitongue following cancer ablation in patients with early and middle-stage oral tongue squamous cell carcinoma (OTSCC).MethodsIn total, 122 patients with early and middle-stage OTSCC were divided into young, middle-aged, and elderly groups. The Adult Comorbidity Evaluation-27 (ACE-27) index was used to determine the presence of comorbidities. The patients underwent surgical treatment with hemiglossectomy, neck dissection, and hemitongue reconstruction using FSAIF. In addition, stage I (n = 15) and II (n = 69) patients underwent ipsilateral selective neck dissection, whereas those with stage III (n = 38) underwent radical neck dissection. Six patients with T3N1 disease also underwent cobalt-60 adjuvant radiotherapy.ResultsYoung and elderly patients exhibited significant differences in comorbidities, as assessed by the ACE-27 (p < .05). The skin paddles in the young, middle-aged, and elderly patients were 3 × 9 to 4 × 12 cm, 3 × 11 to 4 × 12, and 3 × 10 to 5 × 13 cm in size, respectively. FSAIF failure occurred in four patients (success rate: 96.7%). No significant differences were observed in the skin paddle of the flap or rate of flap failure among the age groups (p > .05). Clavien-Dindo grades I, II, IIIa, IIIb, Iva, and IVb were assigned to 7.1, 36.1, 38.5, 9.8, 4.1, and 4.1% of the patients, respectively, with significant differences seen between the young and elderly patients (p < .05). In total, 52.5% of patients could eat normally, whereas 32.8% required a soft diet. Furthermore, 53.3 and 33.6% of patients achieved normal and intelligible speech, respectively. The aesthetic results were rated as excellent and good in 32.8 and 58.2% of patients, respectively. In total, 68.0% of the patients were alive and exhibited no evidence of disease, while 19.7% were alive with active disease. In addition, 12.3% of patients with stage III OTSCC died due to local recurrence or distant metastases. No differences in swallowing, speech, aesthetic, or survival outcomes were observed among the groups.ConclusionsFSAIF is a simple, safe, and reliable method for reconstructing hemitongue defects following cancer ablation in young, middle-aged, and elderly patients with early and middle-stage OTSCC.

Patterns of Failure in Resectable Stage I-IIIA NSCLC Treated with Neoadjuvant Immunotherapy Combinations, a Secondary Analysis of a Prospective Trial

<h3>Purpose/Objective(s)</h3> The impact of neoadjuvant immune checkpoint inhibitor (ICI)-based therapies on mediastinal recurrence patterns after resection for non-small cell lung cancer (NSCLC) is unknown. We describe patterns of mediastinal failure after receipt of neoadjuvant ICI and provide a descriptive analysis of patients who experienced a mediastinal recurrence. <h3>Materials/Methods</h3> Between August 2015 and August 2021, patients with stage I-IIIA NSCLC treated with nivolumab-based therapies prior to resection on the clinical trial NA_00092076 were identified. Patient, tumor, treatment, pathological, recurrences, and post-operative therapy data were obtained from the trial. Variables including central location, initial mediastinal node involvement were obtained via chart review. <h3>Results</h3> Of the 23 NSCLC patients identified: median age was 66 years (range: 48-78), 68% (n= 15) were male, and 39% (n=9) and 35% (n=8) had stage II and III NSCLC, respectively at initial diagnosis. Histological subtypes included adenocarcinoma (50%) and squamous (36%). ICI therapies included: nivolumab (48%, n=11), nivolumab/ipilimumab (17%, n=4), nivolumab with carboplatin/paclitaxel (4%, n=1). A majority of patients received a lobectomy (70%, n=16) and had a margin negative resection (95%, n=22). The median follow-up was 41 months (range: 1 – 74). A majority (70%, n=13) of patients had centrally located tumors. Nodal involvement included: 57% (n=13) N0, 35% (n=7) N1, and 13% (n=3) N2 disease. Two patients developed mediastinal recurrence, both with initial stage III disease. Of the 3 patients with cN2 disease, none received post-operative radiation (RT) after resection and 33% (n=1/3) developed mediastinal recurrence. Of the two patients who experience a mediastinal recurrence: Patient 1 (initial T1N2 disease) achieved major pathologic response (MPR) and overall tumor downstaging to ICI. Locoregional recurrence included the initially involved 4R node. The patient is without evidence of disease 4 years after salvage chemoRT. Patient 2 (initial T3N1 disease) had no MPR nor tumor down staging to ICI. This patient developed mediastinal and distant metastases after declining post-op RT after a R1 pneumonectomy. Both patients received neoadjuvant ICI alone and had initial tumor disease within 2 cm of central airways. <h3>Conclusion</h3> In this analysis, we provide the first report of patterns of mediastinal failure in patients with resectable stage I-IIIA NSCLC who have received neoadjuvant ICI-based therapies. Patients with MPR may still have risk of mediastinal recurrence. The patients who developed mediastinal failure in this cohort had initial N2 disease, lack of response to therapy, and R1 resection. These variables may be associated with mediastinal failure risk after neoadjuvant ICI-based therapies. Multi-institutional efforts are needed to better characterize the risk factors associated with mediastinal recurrence after neoadjuvant ICI.

21 Gene Recurrence Score to Select for Patients with T3N0 ER+HER2- Breast Cancer Likely to Benefit with Postmastectomy Radiation

<h3>Purpose/Objective(s)</h3> Postmastectomy radiation therapy (PMRT) is an option for patients with breast cancer who have T3N0 disease treated with mastectomy. Whether there is a benefit to PMRT in this subgroup of patients is a matter of debate. The 21 gene recurrence score (RS) can be used to select for patients likely to benefit from chemotherapy. Whether the use of the RS to select for patients likely to benefit from PMRT is currently not known. The purpose of the present study is to determine if the RS can select for patients with T3N0 ER+HER2- breast cancer likely to benefit from PMRT. The hypothesis is that patients with a low RS may not benefit from PMRT. <h3>Materials/Methods</h3> This study was conducted using patients from the National Cancer Data Base (NCDB). Patients included in this study were women diagnosed with ER+HER2- breast cancer with pT3N0 disease who were treated with mastectomy. The use of neoadjuvant chemotherapy was not allowed. Overall survival was compared between all patients using the Kaplan- Meier analysis and after stratifying patients by RS. Multivariable logistic regression ascertained factors associated with PMRT use. Cox proportional hazards modeling determined variables associated with OS. <h3>Results</h3> A total of 1,807 patients met the selection criteria, of whom 1,031 (57.1%) received PMRT, and 763 (42.2%) did not receive PMRT. Among all patients, use of PMRT was associated with improved OS (5-year OS 93.9% vs 89.5%, p=0.0079). After stratifying patients by RS, no OS difference was observed with the use of PMRT amongst patients with a low RS (5-year OS 95.0% vs 92.2%, p = 0.0941), whereas amongst patients with an intermediate/ high RS, improvement with the use of PMRT was observed (5-year OS 93.4% vs 88.5%, p = 0.0375). Factors predictive of PMRT use include use of chemotherapy and receipt of treatment at a nonacademic facility. On multivariate analysis, factors predictive of worse OS include increasing age, Charlson Deyo Comorbidity score ≥ 2, and omission of PMRT. <h3>Conclusion</h3> PMRT may have limited benefit in patients with ER+HER2- T3N0 breast cancer with a low RS. However, PMRT was associated with an OS benefit in these patients who had a high RS. Further research is required to confirm these findings and to determine the ability of the RS to select for patients most likely to benefit from PMRT.

Ultra-Hypofractionation for Whole-Breast Irradiation in Early Breast Cancer: Interim Analysis of a Prospective Study.

We report on the early clinical outcomes of a prospective series of early breast cancer (EBC) patients treated with ultra-hypofractionated post-operative whole-breast irradiation (WBI) after breast-conserving surgery (BCS) and axillary management. Primary endpoints were patient’s compliance and acute toxicity. Secondary endpoints included physician-rated cosmesis and ipsilateral breast tumour recurrence (IBTR). Acute toxicity was evaluated at the end of WBI, 3 weeks and 6 months thereafter, according to the Common Terminology Criteria for Adverse Events (v. 5.0). Patients were treated between September 2021 and May 2022. The treatment schedule for WBI consisted of either 26 Gy in 5 fractions over one week (standard approach) or 28.5 Gy in 5 fractions over 5 weeks (reserved to elders). Inverse planned intensity-modulated radiation therapy (IMRT) was used employing a static technique. A total of 70 patients were treated. Fifty-nine were treated with the 26 Gy/5 fr/1 w and 11 with the 28.5 Gy/5 fr/5 ws schedule. Median age was 67 and 70 in the two groups. Most of the patients had left-sided tumours (53.2%) in the 26 Gy/5 fr/1 w or right-sided lesions (63.6%) in the 28.5 Gy/5 fr/5 ws group. Most of the patients had a clinical T1N0 disease and a pathological pT1pN0(sn) after surgery. Ductal invasive carcinoma was the most frequent histology. Luminal A intrinsic subtyping was most frequent. Most of the patients underwent BCS and sentinel lymph node biopsy and adjuvant endocrine therapy. All patients completed the treatment program as planned. Maximum detected acute skin toxicities were grade 2 erythema (6.7%), grade 2 induration (4.4%), and grade 2 skin colour changes. No early IBTR was observed. Ultra-hypofractionated WBI provides favourable compliance and early clinical outcomes in EBC after BCS in a real-world setting.

Effect of postmastectomy radiotherapy on pT1-2N1 breast cancer patients with different molecular subtypes: A real-world study based on the inverse probability of treatment weighting method.

To investigate the significance of postmastectomy radiotherapy (PMRT) for different molecular subtypes of female breast cancer T1-2N1M0 based on inverse probability of treatment weighting (IPTW). The data of breast cancer patients diagnosed between 2010 and 2014 from the Surveillance, Epidemiology, and End Results (SEER) database were extracted. According to the status of hormone receptor (HR) and human epidermal growth factor receptor-2 (HER2), the patients were classified into luminal-A (HR+/HER2-), luminal-B (HR+/HER2+), HER2-enriched (HR-/HER2+), and TNBC (HR-/HER2-) subtypes. The association between radiation therapy and breast cancer-specific survival (BCSS) and Overall survival (OS) was retrospectively analyzed. Inverse probability of treatment weighting (IPTW) was applied to balance measurable confounders. Among the 16 894 patients, 6 055 (35.8%) were in the PMRT group and 10 839 (64.2%) were in the nonPMRT group, with a median follow-up of 48 months. There were 1003 deaths from breast cancer and 754 deaths from other causes. After IPTW, the covariates between groups reached complete equilibrium, the multifactorial Cox regression analysis showed that PMRT significantly prolonged OS and BCSS in Luminal-A and TNBC subtype breast cancer patients, yet it brought little significant survival advantage in Luminal-B and HER2-enriched subtype patients. Our study demonstrates a beneficial impact for PMRT on OS and BCSS among Luminal-A and TNBC subtype breast cancer patients with T1-2N1 disease.

Step-by-Step Guide to Surface Mold Applicator-Based Brachytherapy in a Case of Early Carcinoma Penis: An Organ-Preserving Approach

Purpose In this report we discuss an individually customized surface mold applicator technique to treat a case of early carcinoma penis. This case report is one of its kind which describes the brachytherapy treatment planning based on orthogonal X-ray technique. Material and methods T1N0 disease with squamous cell carcinoma histology involving the foreskin of penis and abutting the glans penis was treated by surface mold applicator technique. Impression of the organ was taken using alginate. Cast was prepared from the impression using Type 4 gypsum. The acrylic mold-based applicator was fabricated on the cast. The catheters were positioned and fixed on the acrylic mold. The organ is placed in the mold-based applicator and the catheters are reconstructed on two-dimensional imaging. The brachytherapy is delivered by the 18-channel high-dose rate Oncentra brachytherapy using Ir192 source. The dose given was 45 Gy in 15 fractions, twice daily more than 6 hours apart. Results Patient was reviewed after 6 weeks for follow-up and there was complete regression of the ulcer. At present, patient is on follow-up for the last 10 months and is now disease-free. Conclusion With judicious patient selection, surface mold brachytherapy is an attractive alternative to the interstitial brachytherapy. It is comfortable for the patient, is easily repeatable, and is time saving in high work load and limited resource settings. Early results with this technique are promising.

Assessment of Predictive Genomic Biomarkers for Response to Cisplatin-based Neoadjuvant Chemotherapy in Bladder Cancer

Cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy is recommended for patients with muscle-invasive bladder cancer (MIBC). It has been shown that somatic deleterious mutations in ERCC2, gain-of-function mutations in ERBB2, and alterations in ATM, RB1, and FANCC are correlated with pathological response to NAC in MIBC. The objective of this study was to validate these genomic biomarkers in pretreatment transurethral resection material from an independent retrospective cohort of 165 patients with MIBC who subsequently underwent NAC and radical surgery. Patients with ypT0/Tis/Ta/T1N0 disease after surgery were defined as responders. Somatic deleterious mutations in ERCC2 were found in nine of 68 (13%) evaluable responders and two of 95 (2%) evaluable nonresponders (p = 0.009; FDR = 0.03). No correlation was observed between response and alterations in ERBB2 or in ATM, RB1, or FANCC alone or in combination. In an exploratory analysis, no additional genomic alterations discriminated between responders and nonresponders to NAC. No further associations were identified between the aforementioned biomarkers and pathological complete response (ypT0N0) after surgery. In conclusion, we observed a positive association between deleterious mutations in ERCC2 and pathological response to NAC, but not overall survival or recurrence-free survival. Other previously reported genomic biomarkers were not validated. Patient summaryIt is currently unknown which patients will respond to chemotherapy before definitive surgery for bladder cancer. Previous studies described several gene mutations in bladder cancer that correlated with chemotherapy response. This study confirmed that patients with bladder cancer with a mutation in the ERCC2 gene often respond to chemotherapy.

Intraoperative radiation therapy for early-stage breast cancer: a single-institution experience.

BackgroundTo assess outcomes and toxicity after low-energy intraoperative radiotherapy (IORT) for early-stage breast cancer (ESBC).Materials and methodsWe reviewed patients with unilateral ESBC treated with breast-conserving surgery and 50-kV IORT at our institution. Patients were prescribed 20 Gy to the surface of the spherical applicator, fitted to the surgical cavity during surgery. Patients who did not meet institutional guidelines for IORT alone on final pathology were recommended adjuvant treatment, including additional surgery and/or external-beam radiation therapy (EBRT). We analyzed ipsilateral breast tumor recurrence, overall survival, recurrence-free survival and toxicity.ResultsAmong 201 patients (median follow-up, 5.1 years; median age, 67 years), 88% were Her2 negative and ER positive and/or PR positive, 98% had invasive ductal carcinoma, 87% had grade 1 or 2, and 95% had clinical T1 disease. Most had pathological stage T1 (93%) N0 (95%) disease. Mean IORT applicator dose at 1-cm depth was 6.3 Gy. Post-IORT treatment included additional surgery, 10%; EBRT, 11%; adjuvant chemotherapy, 9%; and adjuvant hormonal therapy, 74%. Median total EBRT dose was 42.4 (range, 40.05–63) Gy and median dose per fraction was 2.65 Gy. At 5 years, the cumulative incidence of ipsilateral breast tumor recurrence was 2.7%, the overall survival rate was 95% with no breast cancer-related deaths, and the recurrence-free survival rate was 96%. For patients who were deemed unsuitable for postoperative IORT alone and did not receive recommended risk-adapted EBRT, the IBTR rate was 4.7% versus 1.7% (p = 0.23) for patients who were either suitable for IORT alone or unsuitable and received adjuvant EBRT. Cosmetic toxicity data was available for 83%, with 7% experiencing grade 3 breast toxicity and no grade 4–5 toxicity.ConclusionsIORT for select patients with ESBC results in acceptable outcomes in regard to ipsilateral breast tumor recurrence and toxicity.

Abstract 5918: The comprehensive genomic profiling in early-stage (T1-2N0-1M0) breast cancer

Abstract Background: Breast cancer (BC) is one of the three most common cancers worldwide, which is a heterogeneous group of different disease subtypes, each with its own biology and clinical characteristics. Approximately 60% of patients with early-stage BC receive adjuvant treatment, however, only a small number derive a benefit. Recurrence remains a major obstacle. Comprehensive profiling analysis in early-stage (T1-2N0-1M0) BC with different disease subtypes might help understand the tumorigenesis mechanisms and pave the way to evaluate the recurrence risk in early-stage BC. Methods: A total of 418 patients diagnosed with early-stage BC were enrolled, including 82 patients with hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-positive (HER2+) BC, 49 HR-/HER2+ patients, 239 HR+/HER2- patients, and 48 HR-/HER2- patients. Capture-based targeted sequencing was performed on tumor tissue samples using a panel consisting of 520 cancer-related genes. The genomic profiling among different disease subtypes were investigated and tumor mutational burden (TMB) was calculated. Results: Besides HER2, TP53, CDK12, and PIK3CA were the most frequently mutated genes in both HR2-/HER2+ (75.5%, 65.3%, and 36.7%) and HR2+/HER2+ BC (67.1%, 57.3%, and 36.6%). PIK3CA and TP53 were also the most frequently mutated gene in both HR-/HER2- (22.9% and 81.3%) and HR+/HER2- (54% and 23.4%) BC. Moreover, alterations in KRAS (12.5%) and GATA3 (26.8%) were frequently occurred in HR-/HER2- and HR+/HER2- BC, respectively. Furthermore, a comparable TMB level was observed among four subtypes (median TMB: 3.0 mutations/Mb for HR+/HER2- BC; 3.7 mutations/Mb for other subtypes). Next, the genomic profiling was compared between T1-2N0 and T1-2N1 disease in four subtypes, respectively. No different mutation frequencies in cancer-related genes were observed between T1-2N0 and T1-2N1 disease in both HR+/HER2+ and HR-/HER2- BC. In HR+/HER2- BC, T1-2N1 disease had a higher mutation frequency of TRRAP (4% vs. 0%, p&amp;lt;0.05) and a lower mutation frequency in CHD4 (0% vs. 6%, p&amp;lt;0.01), ERBB3 (0% vs.5%, p&amp;lt;0.05), and CTCF (1% vs.6%, p&amp;lt;0.05) than T1-2N0 disease. In HR-/HER2+ BC, patients with T1-2N1 disease had more alterations occurring in HNF1B (23% vs. 0%, p&amp;lt;0.05) and CDK12 (77% vs.48%, p&amp;lt;0.05), and less alterations occurring in NCOR1 (0% vs. 13%, p=0.096) than those with T1-2N0 disease. Moreover, a higher mutation frequency in homologous recombination signaling pathway was associated with the presence of node metastases in HR-/HER2+ BC (52.2% vs. 76.9%, p=0.082). A comparable TMB level was observed between T1-2N0 and T1-2N1 in four subtypes, respectively. Conclusions: Our work reveals the molecular heterogeneity among four subtypes, and between T1-2N0 and T1-2N1 disease in a certain subtype. These findings suggest that molecular features may also need to be taken into consideration for recurrence risk assessment in early-stage BC. Citation Format: Bo Chen, Yingzi Li, Yuchen Zhang, Guochun Zhang, Haiwei Du, Dailin Sun, Junjun Li, Ning Liao. The comprehensive genomic profiling in early-stage (T1-2N0-1M0) breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5918.

Survival among subgroups of patients with stage II nasopharyngeal carcinoma

To assess survival between subgroups (T1N1, T2N0, and T2N1) of patients with stage II nasopharyngeal carcinoma (NPC). This retrospective cohort study evaluated pathologically confirmed stage II NPC patients from The Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2016. The included patients were divided into three subgroups: T1N1, T2N0, and T2N1. Overall survival (OS) and cancer-specific survival (CSS) were assessed using the Kaplan–Meier method among the three subgroups. This study investigated 836 patients: 383 (45.8%) patients were in the T1N1 subgroup, 175 (20.9%) patients were in the T2N0 subgroup, and 278 (33.3%) patients were in the T2N1 subgroup. The 5-year OS (75.7%, 68.6%, and 75.7%) and CSS (85.3%, 83.4%, and 84.5%) were similar among the T1N1, T2N0, and T2N1 subgroups. Univariate and multivariate regression analyses revealed that the subgroup (T1N1, T2N0, and T2N1) of stage II NPC was not an independent prognostic factor for OS or CSS. Survival was comparable among subgroups (T1N1, T2N0, and T2N1) of stage II NPC patients. However, patients with T1N1, T2N0, and T2N1 stage disease who receive different treatments might have different prognoses.

A National Assessment of T2 Staging for Intrahepatic Cholangiocarcinoma and the Poor Prognosis Associated with Multifocality.

T2 intrahepatic cholangiocarcinoma (ICC) isdefined as a solitary tumors with vascular invasion or multifocal tumors including satellite lesions, multiple lesions, and intrahepatic metastases. This study aimed to evaluate the prognosis associated with multifocal tumors. The National Cancer Database was queried from 2004 to 2017 for patients with non-metastatic ICC. The patients were grouped based on T2 staging, multifocality, and lymph node involvement. The study enrolled and classified 4887 patients into clinical (c) stage groups as follows: 15.2% with solitary T2N0 (sT2N0) tumors, 21.3% with multifocal T2N0 (mT2N0) tumors, and 63.5% with node-positive (TxN1) disease. Patients with (c)sT2N0 tumors had higher rates of surgical resection than those with (c)mT2N0 or (c)TxN1 disease (33.5% vs 19.7% vs 15.0%; p < 0.01). Median overall survival (OS) was better for the patients with (c)sT2N0 tumors than for those with multifocal and node-positive disease (15.4 vs 10.4 vs 10.4 months; p < 0.01). Onmultivariate analysis, (c)sT2N0 tumors were associated with better OS than (c)mT2N0 tumors [hazard ratio (HR), 1.31; 95% confidence interval (CI), 1.17-1.46; p < 0.01] or (c)TxN1 disease (HR,1.41; 95% CI 1.28-1.56; p < 0.01). In a subset analysis based on pathologic (p) staging of patients who underwent surgical resection with regional lymphadenectomy, multivariate analysis demonstrated that (p)sT2N0 tumors were associated with better OS than (p)mT2N0 tumors (HR,1.40; 95% CI 1.03-1.92; p = 0.03) or (p)TxN1 disease (HR, 2.05; 95% CI 1.62-2.58; p < 0.01). Multifocal T2N0 ICC is associated with poor OS and has a disparate prognosis compared with solitary T2N0 disease, even among patients who undergo resection. Future staging criteria should account for the poor outcomes associated with multifocal ICC.