5-year Locoregional Recurrence Research Articles

The impact of loco-regional treatment modality on the outcomes in breast cancer patients younger than forty years of age

PurposeTo determine the impact of the loco-regional treatment modality, on the loco-regional recurrence (LRR) rates and overall survival (OS) in breast cancer patients younger than 40 years.MethodsData of 623 breast cancer patients younger than 40 years of age were retrospectively reviewed. Patients were stratified according to the locoregional treatment approach into three groups: the mastectomy group (M), the mastectomy followed by radiation therapy group (MRX) and the breast conservative therapy group (BCT).ResultsMedian follow-up was 72 months (range, 6-180). Two hundred and nine patients were treated with BCT, 86 with MRM and 328 with MRX. The 10-year rate LRR rates according to treatment modality were: 13.4% for BCT, 15.1% for MRM and 8.5% for MRX (p 0.106). On univariate analysis, T stage (p 0.009), AJCC stage (p 0.047) and Her 2 status (p 0.001) were associated with LRR. Ten-year overall survival (OS) was 72.7% (78.5% in the BCT group, 69.8% in the MRM group and 69.8% in the MRX group, p 0.072).On Univariate analysis, age < 35 (p 0.032), grade III (p 0.001), N3 stage (p 0.001), AJCC stage III (p 0.005), ER negative status (0.04), Her 2-status positive (0.006) and lack of chemotherapy administration (p 0.02) were all predictors of increased mortality.ConclusionFor patients younger than 40 years of age, similar LRR and overall survival outcomes were achieved using BCT, M or MRX. Young age at diagnosis should not be used alone in recommending one loco-regional treatment approach over the others.

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.

Clinical outcomes in T4 and/or N2 rectal cancer treated with neoadjuvant chemoradiotherapy; A retrospective study

IntroductionTotal Neoadjuvant Therapy (TNT) in the management of locally advanced rectal cancer (LARC) did not show survival benefit over the standard long course chemoradiotherapy (CRT). Trials of TNT did not address the impact of each risk feature in isolation from other high-risk features. MethodologyIn this retrospective study, we describe the clinical outcomes of patients with T4 and/or N2 rectal adenocarcinoma who were treated with CRT followed by total mesorectal excision (TME). After obtaining the local regulatory approvals, demographic and clinical data were collected for those patients in Manitoba between January 2007 and December 2019. ResultsThe cohort included 331 patients. 61 patients had T4-only disease and 218 had N2-only disease. Mean age was 59.65 years. 74.3% received adjuvant chemotherapy (ACT), but only 56.5% completed the planned course. R0 resection was achieved in 93.4% of patients (78.7% and 97.2% in T4 and N2, respectively). Median follow up was 4.93 years. 3-year overall recurrence rate was 29%. 3-year locoregional recurrence (LRR) rate was 8% (16% and 6% in T4 and N2, respectively). 3-year overall survival (OS) rate was 84% in the whole cohort (72.6% and 87.1% in T4 and N2, respectively). Incomplete surgical resection was a poor prognostic factor for both OS and LRR. ACT was associated with a survival benefit in the whole cohort (p=0.001) and in the N2 sub-cohort (p=003) but there was no survival benefit observed in T4 sub-cohort. ACT did not have an impact on LRR. ConclusionsAchieving R0 resection in LARC with neoadjuvant therapy improves recurrence and survival rates. T4 disease carries a worse clinical outcome than N2 and consideration should be given to upstage T4 to stage III. Different high-risk features in LARC predict different clinical outcomes. In the era of TNT, personalization of treatment strategy based on these factors could potentially improve outcomes.

Clinicopathological characteristics and prognostic factors in invasive micropapillary carcinoma of the breast.

Invasive micropapillary carcinoma (IMPC) treatment only relies on the standard treatment of nonspecific invasive breast cancer (NSIBC), and it remains controversial whether the survival of patients improves. Therefore, this study aimed to analyze the clinicopathological features of IMPC and to investigate the factors affecting its prognosis. This retrospective cohort study included 104 IMPC patients who met the study's inclusion criteria out of a total of 4,532 patients with invasive breast cancer between January 2015 and December 2019. A contemporaneous cohort of 230 patients with non-specific invasive breast cancer (NSIBC) who underwent surgery was identified and matched using propensity scores. The survival rate for patients with IMPC ranged from 1.12% to 7.03%. Statistically significant differences were observed in the proportion of endocrine treatment, lymphatic invasion, estrogen receptor (ER)-positive rate, molecular subtypes, molecular typing, and 5-year loco-regional recurrence-free survival (LRRFS) between the two cohorts (p < 0.05). The univariate analysis showed that T stage, N stage, lymphatic invasion, vascular invasion, ER-positive rate, and progesterone receptor (PR)-negative rate were all prognosis risk factors (p < 0.05) for IMPC. Furthermore, the multivariate analysis indicated that lymphatic invasion and N stage were independent prognostic factors (p < 0.05). The incidence of micropapillary IMPC, among other pathological subtypes, is steadily increasing. ER-positive and PR-positive rates, as well as luminal subtypes, are frequent, with a concurrent increase in the 5-year locoregional recurrence rate. It would be interesting to compare the effect following these therapeutic modifications in larger cohorts in future studies.

Effect of laparoscopy-assisted vs open surgery on 3-year disease-free survival in patients with low rectal cancer: The LASRE randomized clinical trial.

8 Background: Laparoscopic surgery has been increasingly used for low rectal cancer due to short-term benefits versus open surgery, but the long-term oncologic outcomes have not been fully established. Methods: This is a multicenter, noninferiority trial. Surgeons who had completed ≥100 laparoscopic TME surgeries from 22 high-volume centers in China participated in this trial. A total of 1070 patients scheduled for curative-intent resection of low rectal cancer (lower margin &lt;5.0 cm dentate line) were randomized at a 2:1 ratio to undergo laparoscopic or open surgery from November 2013 to June 2018.The primary outcome was 3-year DFS; the noninferiority margin was 10% in the modified intent-to-treat population. Secondary outcomes included 3-year overall survival (OS) and locoregional recurrence. Results: The final analysis included 1039 patients (median age: 57 years, 620 men; 685 and 354 in laparoscopic and open groups, respectively). Clinical TNM stage was II/III in 659 patients, and I in the remaining 380 patients. The 3-year DFS rate was 81.4% in the laparoscopic group versus 79.8% in the open group (HR, 0.9 [95% CI, 0.7 to 1.2]; log-rank P = .558). The absolute difference was 1.6% (1-sided 97.5% CI, -3.34% to ∞), not exceeding the noninferiority . The 3-year OS rate was 91.7% in the laparoscopic group versus 93.7% in the open group (95% CI, -5.12% to1.54%, log-rank P = .243). The 3-year locoregional recurrence rate was 3.8% and 2.4%, respectively (95% CI, -1.07% to 3.45%, log-rank P = .209). Results of the per-protocol and as-treated analysis were consistent with the main analysis. Conclusions: Among patients with low rectal cancer, laparoscopic surgery performed by experienced surgeons is not inferior to open surgery concerning 3-year disease-free survival. These results support laparoscopic surgery as a safe, minimally invasive approach for low rectal cancer. Clinical trial information: NCT01899547 .

Treatment outcomes of early-stage endometrial cancer patients: A propensity score matching of vaginal brachytherapy versus pelvic radiotherapy.

This study aimed to report the treatment outcomes of radiation therapy for early-stage endometrial cancer patients. In addition, this study intended to identify high-risk factors that require pelvic radiotherapy (PRT) in addition to vaginal brachytherapy (VBT) for intermediate-risk endometrial cancer patients. Patients with early-stage endometrial cancer receiving postoperative VBT alone or with PRT were included. Propensity score matching was used to balance the two study groups. The primary endpoint was locoregional recurrence (LRR). Age-adjusted Charlson comorbidity index and substantial lymphovascular space invasion were selected for subgroup analyses to identify the benefits of PRT over VBT alone. From 2005 to 2017, a total of 288 patients underwent analysis following propensity score matching. Of these, 144 received VBT and 144 received PRT. There was no significant difference in 5-year LRR between VBT and PRT for both intermediate (0% vs. 0%) and high-intermediate risk patients (3.5% VBT vs. 5.4% PRT; HR 0.54: 0.05-6.00; p = 0.616). The subgroup analyses revealed no significant factors favoring PRT over VBT. Patients with high comorbidities may have higher risks of non-cancer death after receiving PRT. Postoperative VBT alone is sufficient for early-stage intermediate-risk endometrial cancer patients.

Methodological and Reporting Quality of Non-Inferiority or Equivalence Designs: A Systematic Review of Trial Characteristics, Design Consideration and Interpretation in Breast Cancer Radiotherapy Trials

To investigate the methodological and reporting quality of non-inferiority (NI)/equivalence trials of breast cancer radiotherapy and to provide suggestions for future NI/equivalence trials. Prospective phase III randomized controlled trials (RCTs) comparing different radiation modalities in patients with breast cancer and designed or interpreted as NI/equivalence were identified in PubMed, EMBASE and Cochrane library. Two reviewers independently extracted data on trial characteristics, statistical design assumptions and analysis considerations, primary end point results and conclusions. The relationship between the number of published trials and the year of publication was assessed by simple linear regression. Trials with pre-specified NI margins as absolute risk differences were reevaluated using margins as relative risk differences. A total of 1490 records were screened and 41 articles published between January 1, 2001 and May 9, 2022 were selected for full text review. A total of 21 trials were included (18 designed as NI and 3 as equivalence). Publication of these trials increased over time (p = 0.023). Trial interventions included dose fractionation (n = 10), partial/whole breast irradiation (n = 8) and tumor bed boost (n = 3). Eleven (52.4%) trials clearly described the non-efficacy benefits. The primary endpoints included 5-year local recurrence (LR) (n = 11), 5-year locoregional recurrence (n = 3), acute/late toxicities (n = 5), 2-year LR and cosmetic outcome (n = 1), and 10-year LR (n = 1). Only seven (33.3%) trials provided justification of the margins. The absolute and relative risk margins were both mentioned in nine (42.9%) trials' methods and reported in six (28.6%) trials' results. The analyzed populations were intention-to-treat (ITT) in 10, both ITT and per-protocol in 9 trials. Seventeen (81%) trials reported confidence interval (CI), with twelve reporting CI that agreed with the type I error used in sample size calculation, but only eight (38.1%) reported p value for NI/equivalence test. Fifteen (71.4%) trials concluded NI/equivalence. Five (23.8%) trials had misleading conclusions (four for not mentioning small sample size insufficient to confirm NI/equivalence and one for inconsistent with the published results). Thirteen (61.9%) trials reported that the protocol's initial accrual target was not met, with ten (47.6%) owing to overestimation of event rates. For trials that met NI only based on absolute margin, three of eight (37.5%) trials were classified as inconclusive with the assumed relative margins. The use of NI/equivalence trials of breast cancer radiotherapy has dramatically increased recently, but there is substantial room for improvement in the methodological and reporting quality of NI/equivalence trials.

Oncotype Recurrence Score (RS) at the Extremes of Tumor Size: Which Drives Clinical Outcomes?

Tumor size is an established and independent risk factor for local-regional recurrence (LRR) and distant recurrence (DM). More recently, the recurrence score calculated from a 21-gene expression assay (Oncotype DXTM, Exact Sciences) has also been correlated with LRR and DM. We sought to determine the impact of the interaction between tumor size and Oncotype RS, particularly when the variables are in discrepancy with each other. More specifically, we evaluated clinical outcomes in patients with small tumors (≤1 cm) and high RS (≥26) and, separately, in patients with large tumors (>5 cm) with low RS. Between 2008 and 2020, 310 patients were identified retrospectively as having been treated for early-stage, hormone-receptor positive, Her2-negative breast cancers with tumor size ≤1 cm that were node-negative and had RS ≥ 26 at our institution. In addition, 64 patients were identified with tumor size >5 cm and RS < 26 (irrespective of nodal status). Locoregional recurrence rates (LRR) and invasive recurrence rates (composite of LRR and distant recurrence) were estimated using the Kaplan-Meier method. Patient characteristics are shown in Table 1. In the group of patients with small tumors and high RS, the 5- and 10-year invasive recurrence rates with 95% CI were 8% (4.2-12) and 17% (8.2-26). The 5- and 10-year locoregional recurrence rates with 95% CI were 5.8% (2.7-8.8) and 15% (6.2-23). In the group of patients with large tumors and low RS, 10-year rates could not be estimated with the available data. The 5- and 8-year invasive recurrence rates with 95% CI were 3.2% (0-7.5) and 3.2% (0-7.5). The 5- and 8-year locoregional recurrence rates with 95% CI were 1.6% (0-4.7) and 1.6% (0-4.7). Our findings suggest that patients with small tumors and high RS are at a higher risk for LRR compared to the average ≤1 cm node-negative breast cancer based on published data on the effect of tumor size on LRR and DM. Similarly, tumors larger than 5 cm with low RS appear to behave indolently and in a manner consistent with more favorable risk (despite their large size). These findings may have important implications for the tailoring of local-regional treatment strategies.

Breast-conserving surgery versus mastectomy for treatment of breast cancer after neoadjuvant chemotherapy.

To compare recurrence and survival outcomes between breast-conserving surgery (BCS) and mastectomy after neoadjuvant chemotherapy (NACT). The data of 730 patients who underwent NACT between 2000 and 2014 were retrospectively reviewed. A total of 104 (14.2%) patients received BCS and 626 (85.8%) received mastectomy. Locoregional recurrence (LRR), distant metastases (DM), disease-free survival (DFS), breast cancer-specific survival (BCSS), and overall survival (OS) were analyzed using the Kaplan-Meier method. The impact of BCS versus mastectomy on outcomes was assessed by multivariate Cox models. Inverse probability of treatment weighting (IPTW) was used to balance covariates between the two groups. The median follow-up of BCS and mastectomy groups were 86.5 and 87.4 months, respectively. There were significant differences in distribution of most baseline characteristics between two groups. Compared with those who underwent mastectomy, the patients with BCS had similar 5-year LRR, DM, and DFS rates, but had significantly higher 5-year BCSS (98.9% vs. 90.4%, P = 0.005) and OS (98.9% vs. 90.1%, P = 0.003) rates. Multivariate analysis also showed that BCS significantly improved BCSS (HR = 0.27, 95% CI: 0.08-0.85, P = 0.025) and OS (HR = 0.25, 95% CI: 0.08-0.79, P = 0.018). After IPTW adjustment, the LRR, DM, DFS, BCSS and OS between two groups had no significant differences. The recurrence and survival outcomes are comparable with BCS and mastectomy. Thus, BCS is a safe treatment option for selected breast cancer patients after NACT.

Prognostic Value of Lymphovascular Invasion in Patients With Pyriform Sinus Carcinoma Treated With Surgery Plus Adjuvant Chemo-/Radiotherapy.

We aimed to determine the prognostic value of lymphovascular invasion (LVI) in pyriform sinus carcinoma (PSC) after primary surgery with adjuvant radiotherapy (RT) or concurrent chemoradiotherapy (CCRT). Patients who underwent primary surgery at our institution between 2000 and 2018 were included in this study and retrospectively analyzed. The endpoints were locoregional recurrence (LRR), distant metastasis (DM), and disease-specific survival (DSS). We reviewed 117 patients with PSC. LVI was identified in 29 patients (24.8%). The 5-year LRR rate, DM rate, and DSS rate were 29.4%, 31.7%, and 45.9%, respectively. Tumors with LVI were associated with a significantly higher LRR (P = 0.002, HR 3.678, 95% CI 1.646-8.218) and DM (P = 0.003, HR 3.666, 95% CI 1.543-8.709) and a lower DSS (P = 0.001, HR 2.814, 95% CI 1.519-5.213) in multivariate analysis. LVI is a significant predictor of poor prognosis in patients with PSC treated with surgery plus adjuvant RT/CCRT.

Population-based Long-term Outcomes for Squamous Cell Carcinoma of the Nasal Cavity.

This study evaluates population-based outcomes of patients with squamous cell carcinoma (SCC) of the nasal cavity treated in British Columbia. A retrospective review of nasal cavity SCC treated from 1984 to 2014 was performed (n = 159). Locoregional recurrence (LRR) and overall survival (OS) were evaluated. The 3-year OS was 74.2% for radiation alone, 75.8% for surgery alone, and 78.4% for surgery and radiation ( P = 0.16). The 3-year LRR was 28.4% for radiation alone, 28.2% for surgery alone, and 22.6% for surgery and radiation ( P = 0.21). On multivariable analysis, surgery and postoperative radiation relative to surgery alone was associated with a lower risk of LRR (hazard ratio: 0.36, P = 0.03). Poor Eastern Cooperative Oncology Group status, node-positive, orbital invasion, smoking, and advanced age were associated with worse OS (all P <0.05). In this population-based analysis, multimodality treatment with surgery and adjuvant radiation were associated with improved locoregional control for SCC of the nasal cavity.

Abstract P4-02-12: Validation of Profile for the Omission of Local Adjuvant Radiotherapy (POLAR) in early-stage invasive breast cancer patients of the Scottish Conservation Trial

Abstract Background: Adjuvant whole breast radiotherapy (RT) is provided to almost all women with early-stage invasive breast cancer after breast conserving surgery and appropriate systemic therapy. While there is increasing interest to personalize the use of RT based on molecular profiling, to date, there is no molecular signature available to reliably assess the benefit of radiotherapy after surgical resection. Here we assess the ability of a 16-gene signature named Profile for the Omission of Local Adjuvant Radiotherapy (POLAR) to identify who may be suitable candidates for radiotherapy omission in patients of the Scottish Conservation Trial. Methods: The POLAR signature was applied to archival tissue from the Scottish Conservation Trial, which randomized 585 patients with stage I-II breast cancer, tumor size &amp;lt; 4 cm, and age ≤70 years old to receive RT or not. The archival tissue was measured for ER (ER+ &amp;gt;10%), PgR (PgR+ ≥20%), Ki67 (Ki67 high ≥14%), and HER2 (HER2+ defined as HER2 over-expressed or amplified). 26% received adjuvant chemotherapy, the remainder received tamoxifen 20 mg/daily for 5 years. Cox models for the locoregional recurrence (LRR) endpoint tested the association between treatment arms separately for patients with a low and high POLAR score using a pre-specified cut point. Cumulative incidences were computed, with distant metastasis and death without recurrence considered competing events. Results: 224 patients had tissue available and complete clinical data for analysis, 40 (18%) were node-positive. The distribution of clinicopathologic variables between the RT and no RT arms remained balanced. 43% were ER+/PgR+/Ki67 low/HER2-, 31% were ER+/HER2-/Ki67 high or PgR-, 5% were HER2+, and 13% were triple negative. The continuous standardized POLAR score was prognostic for LRR in the no RT arm after adjusting for relevant covariates (HR=1.78 [1.20-2.64], p=0.003). For patients with a POLAR-high score, the 10-year LRR rate was 31% [21%-42%] for patients not receiving RT and 8% [3%-15%] for patients receiving RT (HR 0.36 [0.19-0.69], p=0.0022). For patients with a POLAR low score, the 10-year LRR rates were 20% [10%-33%] for patients not receiving RT and 6% [1%-18%] for patients receiving RT; HR=0.28 [0.08-0.98], p=0.046). In the subgroup of node-negative patients with ER+/HER2-negative tumors (N=137), there was a statistically significant RT benefit for patients with a POLAR high score (HR=0.31 [0.11-0.88], p=0.028) but not for patients with a POLAR low score (HR=0.5 [0.1-2.4], p=0.39). Conclusions: For patients with early-stage invasive breast cancer treated with breast-conserving surgery without RT, POLAR is prognostic for LRR and may refine the selection of “low risk” for omission of RT. Citation Format: Karen J. Taylor, John MS Bartlett, John Bennett, S. Laura Chang, Bradley Arrick, Frederick Baehner, Joseph F. Loane, Tammy Piper, Elizabeth Mallon, Joanna Dunlop, Wilma J. Jack, Jacqueline Caldwell, Ian Kunkler, Linda J. Williams, Corey W. Speers, Felix Y. Feng, Lori Pierce, David A. Cameron. Validation of Profile for the Omission of Local Adjuvant Radiotherapy (POLAR) in early-stage invasive breast cancer patients of the Scottish Conservation 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 P4-02-12.

Abstract OT1-12-02: Preliminary report of the PRECISION Trial (Profiling Early Breast Cancer for Radiotherapy Omission): A Phase II Study of Breast-Conserving Surgery Without Adjuvant Radiotherapy for Favorable-Risk Breast Cancer

Abstract Background: Breast conserving surgery (BCS) is typically followed by adjuvant radiotherapy (RT) based on several landmark trials demonstrating improvements in disease control and survival. Since completion of these historical trials, the advent of molecular subtyping has revealed that breast cancer is not a single disease entity, but rather a class of cancers with differential risk profiles. We evaluated whether RT could be safely omitted following BCS for patients with the most favorable subtype as defined by the Prosigna PAM50 assay. Methods: We conducted a multicenter prospective single-arm cohort study with IRB approval and an FDA investigational device exemption (IDE). Eligible patients were women 50 to 75 years of age (inclusive) who had undergone BCS revealing tumors ≤2cm in size, that were estrogen or progesterone receptor positive (HR+), HER2 negative, grade 1-2, node negative (N0), with negative excision margins (no ink on tumor). Intent to take endocrine therapy was required. Upon registration, tumors were submitted for central Prosigna testing and those with Risk of Recurrence (ROR) score ≤40 were deemed eligible for the investigational omission of RT. The primary endpoint was the 5-year locoregional recurrence rate (LRR). Anticipating a total of 345 RT-omitting patients to enroll over 3.5 years, the study was designed with 90% power to exclude a 5-year LRR of 5% using a one-sample exponential test with one-sided type I error of 0.025. Results: From 2016 to 2020, 671 patients were registered from 13 centers, inclusive of affiliated regional network sites. Of these, 382 patients had a ROR Score ≤40 and opted to forego RT, comprising the main intention-to-treat (ITT) study population. Median age was 65 years (range 50 to 75), and median tumor size was 0.9 cm (range 0.1 to 2.0 cm). At a median follow-up of 26.9 months, 12 events were observed: 4 patients had ipsilateral in-breast recurrences, 7 had contralateral breast cancers, and 1 developed an unrelated melanoma. There were no regional-nodal or distant recurrences. The 2-year cumulative rate of LRR was 0.3% (95% CI: 0 – 1.0%). Of the 4 ipsilateral breast recurrences, 2 were in the same quadrant as the original primary tumor. Conclusion: In this preliminary report of the PRECISION trial, patients 50-75 years of age undergoing BCS and endocrine therapy for pT1N0 HR+ HER2-negative breast cancer with ROR score ≤40 had exceedingly low rates of LRR in the absence of adjuvant RT at a median follow-up of 26.9 months. Additional follow-up is required to determine whether these favorable results are durable. Citation Format: Lior Z. Braunstein, Julia Wong, Deborah A. Dillon, Yu-Hui Chen, Paul Catalano, Oren Cahlon, Mahmoud B. El-Tamer, Rachel Jimenez, Atif Khan, Carmen Perez, Rinaa Punglia, Ron Shiloh, Laura Warren, David Wazer, Jean Wright, Elizabeth Buckley, Tari King, Simon Powell, Eric Winer, Jennifer Bellon. Preliminary report of the PRECISION Trial (Profiling Early Breast Cancer for Radiotherapy Omission): A Phase II Study of Breast-Conserving Surgery Without Adjuvant Radiotherapy for Favorable-Risk Breast Cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT1-12-02.

Abstract P2-11-31: FAVORABLE LOCOREGIONAL CONTROL IN CLINICALLY NODE-NEGATIVE HORMONE-RECEPTOR POSITIVE BREAST CANCER WITH LOW 21-GENE RECURRENCE SCORES: A SINGLE INSTITUTIONAL STUDY WITH 10-YEAR FOLLOW-UP

Abstract Background: Recent studies have shown a lower likelihood of locoregional recurrences in patients with low 21-gene recurrence score (RS). In this single institutional study, we investigated any associations between different cut-off values of 21-gene RS and histopathological factors and outcome in patients with long-term follow-up. Methods: Between February 2010 to February 2013, 61 patients with early stage clinically node-negative hormone receptor-positive and HER2-negative breast cancer tested for the 21-gene RS assay, were included into the study. The clinicopathological, treatment and outcome characteristics were analyzed. Results: Median age was 48 (range, 29-72). Of those, 53 patients were diagnosed with Stage 1 (86.9%) and 8 patients were Stage 2 (13.1%) following surgery. Patients with high histologic grade (HG), or with Ki-67&amp;gt;=25% were significantly more likely to have intermediate/high RS based on RS &amp;gt;11 and &amp;gt;18 (Table 1). Based on the 21-gene RS assay, only 19 patients (31%) received adjuvant chemotherapy. At a median follow-up of 112 months, 3 patients developed local recurrences (4.9%) treated with endocrine therapy alone. Among patients treated with endocrine treatment alone (n=42), the clinicopathological characteristics including age &amp;lt; 40, age &amp;lt; 50, high histologic or nuclear grade, high Ki67-scores (&amp;gt;=20%, &amp;gt;=25%, &amp;gt;=30%), presence of lymphovascular invasion, luminal-A type tumor, multifocality, lymph node positivity, tumor size more than 2 cm, RS&amp;gt;=18 or RS&amp;gt;11 were not significantly found to be associated with 10-year locoregional recurrence free survival (LRRFS). However, patients with a RS &amp;gt;=16 have significantly shown a poorer 10-year LRRFS cpmpared to those with RS &amp;lt; 16 (RS &amp;lt; 16; 100% vs RS&amp;gt;=16; 75%, p=0.039, Table 2). Conclusions: These results suggest that Oncotype DX assay may be of little value in patients with high histologic grade or high Ki67 scores (&amp;gt;= 25%) as treatment decision criteria to determine any benefit from chemotherapy. Furthermore, patients with a RS &amp;gt;=16 are more likely to benefit from adjuvant chemotherapies, whereas those with a RS &amp;lt; 16 have an excellent outcome and local control on long term follow-up with endocrine treatment alone. Further prospective studies should be performed to validate these findings in future. Table 1. Correlation of 21-gene Recurrence Score (RS) including different cut-off values with Ki-67 scores and histopathological factors Table 2. Clinicopathologic factors and 21-gene Recurrence Score (=RS) associated with disease free survival (DFS) and locoregional recurrence free survival free survival (=LRRFS). (DFS is equal to LRRFS since none of the patients developed distant metastases) Citation Format: Cihan Uras, Neslihan Cabıoğlu, Fatma Tokat, Halil Kara, Ozlem ER, Taner Korkmaz, Nuran Bese, Umit Ince. FAVORABLE LOCOREGIONAL CONTROL IN CLINICALLY NODE-NEGATIVE HORMONE-RECEPTOR POSITIVE BREAST CANCER WITH LOW 21-GENE RECURRENCE SCORES: A SINGLE INSTITUTIONAL STUDY WITH 10-YEAR FOLLOW-UP [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 P2-11-31.

Comparison of stereotactic body radiation therapy versus surgery for multiple primary lung cancers after prior radical resection: A multicenter retrospective study

BackgroundPatients who previously underwent surgical resection of initial primary lung cancer are at a high risk of developing multiple primary lung cancers (MPLCs). The purpose of this study was to compare the efficacy and safety between stereotactic body radiation therapy (SBRT) and surgery for MPLCs patients after prior radical resection for the first lung cancers. MethodsIn this multicenter retrospective study, eligible MPLC patients with tumor diameter of 5.0 cm or less at N0M0 who underwent SBRT or reoperation between January 2013 and August 2020 were enrolled. The primary endpoint was the 3-year locoregional recurrence and treatment-related toxicity. Kaplan-Meier method was used to calculate survival rates. The χ2 test was adapted to assess the difference of categorical variables between the two subgroup patients. ResultsA total of 203 (73 in the SBRT group and 130 in the surgery group) patients from three academic cancer centers were evaluated with a median follow-up of 38.3 months. The cumulative 1-, 2-, and 3-year incidences of locoregional recurrence were 5.6 %, 7.0 % and 13.1 % in the SBRT group versus 3.2 %, 4.8 % and 7.4 % in the surgery group, respectively [hazard ratio (HR), 1.97; 95 % confidence interval (CI), 0.74–5.24; P = 0.14]. The cancer-specific survival rates were 95.9 %, 94.5 % and 88.1 % versus 96.9 %, 94.6 % and 93.8 % in the SBRT and surgery groups respectively (HR, 1.72; 95 % CI, 0.67–4.44; P = 0.23). In the SBRT group, two patients (2.7 %) suffered from grade 3 radiation pneumonitis, while in the surgery group, grade 3 complications occurred in four (3.1 %) patients, and four cases were expired due to pneumonia or pulmonary heart disease within 90 days after surgery. ConclusionsSBRT is an effective therapeutic option with limited toxicity compared to surgery for patients with MPLCs after prior radical surgical resection, and it could be considered as an alternative treatment for those patients.

Development and Validation of a Genomic Profile for the Omission of Local Adjuvant Radiation in Breast Cancer.

Adjuvant radiotherapy (RT) is used for women with early-stage invasive breast cancer treated with breast-conserving surgery. However, some women with low risk of recurrence may safely be spared RT. This study aimed to identify these women using a molecular-based approach. We analyzed two randomized trials of women with node-negative invasive breast cancer to ± RT following breast-conserving surgery: SweBCG91-RT (stage I-II, no adjuvant systemic therapy) and Princess Margaret (age 50 years or older, T1-T2, adjuvant tamoxifen). Transcriptome-wide profiling was performed (Affymetrix Human Exon 1.0 ST microarray). Patients with estrogen receptor-positive/human epidermal growth factor receptor 2-negative tumors and with gene expression data were included. The SweBCG91-RT cohort was divided into training (N = 243) and validation (N = 354) cohorts. A 16-gene signature named Profile for the Omission of Local Adjuvant Radiation (POLAR) was trained to predict locoregional recurrence (LRR) using elastic net regression. POLAR was then validated in the SweBCG91-RT validation cohort and the Princess Margaret cohort (N = 132). Patients categorized as POLAR low-risk without RT had a 10-year LRR of 6% (95% CI, 2 to 16) and 7% (0 to 27) in SweBCG91-RT and Princess Margaret cohorts, respectively. There was no significant benefit from RT in POLAR low-risk patients (hazard ratio [HR], 1.1 [0.39 to 3.4], P = .81, and HR, 1.5 [0.14 to 16], P = .74, respectively). Patients categorized as POLAR high-risk had a significant decreased risk of LRR with RT (HR, 0.43 [0.24 to 0.78], P = .0055, and HR, 0.25 [0.07 to 0.92], P = .038, respectively). An exploratory analysis testing for interaction between RT and POLAR in the combined validation cohort was performed (P = .066). The novel POLAR genomic signature on the basis of LRR biology may identify patients with a low risk of LRR despite not receiving RT, and thus may be candidates for RT omission.

Evaluation of Her-2 protein in histologically tumor-free margins of oral squamous cell carcinoma: An immunohistochemical study.

The status of the 5-year survival rate and loco-regional recurrence in oral squamous cell carcinoma (OSCC) has remained unchanged over the decades. Recent advances in oral cancer research have revealed that the presence of molecular alterations in histologically tumor-free margins of OSCC has a prognostic significance and can aid in designing therapeutic strategies. However, the literature on molecular studies on histologically tumor-free margins is scant, especially in the Indian population. Considering the prognostic implications of Her-2 in malignancies of the breast, ovary, and OSCC, we aimed to assess the expression of Her-2 protein in histologically tumor-free margins of OSCC and to establish correlation with clinico-pathological parameters. 4 μ m thick sections from formalin-fixed paraffin-embedded tissue blocks of 40 histologically tumor-free margins of OSCC affecting the buccal mucosa and/or lower gingiva-buccal sulcus and 40 normal oral mucosa samples were subjected to immunohistochemical analysis for the Her-2 antibody. The obtained data were analyzed statistically. The mean ages in study and control groups were 49.83 years (SD ± 10.43) and 37.28 years (SD ± 8.61), respectively, with male predominance. Local recurrence was seen in 52.5% of patients. Follow-up data revealed that a total of 71.4% of patients succumbed to mortality and all of them had reported local recurrence. Overall, the presence of local recurrence and the status of survival showed a statistically significant association (p = 0.0001). All the samples in the study and control groups were negative for Her-2 immuno-expression. The study indicated the lack of Her-2 immuno-expression in histologically tumor-free margins of OSCC with several speculated explanations. As it is a preliminary study, further studies employing both immunohistochemistry (IHC) and gene amplification in histologically tumor-free margins of OSCC affecting different anatomical sites are warranted. This will aid in identifying the subset of patients that may benefit from targeted therapy.

Effect of postoperative radiotherapy for patients with differentiated thyroid cancer.

We evaluated the efficacy and safety of postoperative radiotherapy (PORT) for differentiated thyroid cancer (DTC) with high risk features. This retrospective study analyzed 187 patients treated for DTC from 1985 to 2019. DTC referred to nonanaplastic thyroid cancer originating from follicular cells. PORT was defined as the administration of external beam radiation to the thyroid and regional lymph nodes following surgery for initially diagnosed DTC. The patients were included in the analysis if they received PORT or exhibited any of the following features: (a) pT4 or pN1b according to the 8th American Joint Committee on Cancer, (b) poorly differentiated thyroid cancer (PDTC), or (c) unfavourable variants such as anaplastic foci and etc. After 1:1 propensity matching, a total of 108 patients were analyzed according to PORT receipt. The median follow-up duration of the matched group was 10.4 years. After matching, most of the variables became balanced, but the PORT group still had more PDTC and DTC with anaplastic foci. Radioactive iodine (RAI) was less frequently administered in the PORT group. PORT yielded a significantly higher 5-year locoregional recurrence free survival (LRFS) than the No PORT group (5-year LRFS 86.1% vs. 72.7%, p = 0.022), but the 10-year cancer specific survival (CSS) was similar between them (97.8% vs. 85.9%, p = 0.122). The multivariable analysis indicated that PORT was a favourable prognostic factor (Hazard ratio 0.3, 95% Confidence interval 0.1-0.8, p = 0.02) for LRFS, but not for CSS. Among 133 patients without PORT for initial disease, 39 of them received salvage surgery followed by salvage PORT. No severe toxicity after PORT was reported. PORT reduced locoregional recurrence in DTC patients without severe toxicity. PORT can be an effective and safe treatment to improve locoregional control in DTC with high risk features. However, further study is warranted to identify those who can benefit from PORT.

Risk factors to identify the indication for regional nodal irradiation in T1-2N1M0 breast cancer: A joint analysis of 4,243 real-world cases from two institutions.

The aim of this study is to evaluate the role of regional nodal irradiation (RNI) in patients with T1-2N1M0 breast cancer and to identify the subgroup that could benefit from RNI. A total of 4,243 women with pT1-2N1M0 breast cancer treated at two institutions in China were retrospectively reviewed. Survival rates were calculated by the Kaplan-Meier method and compared by the log-rank test. The association of risk factors with survival outcomes was evaluated using multivariable proportional hazards regression. A total of 932 patients (22.0%) received RNI. At a median follow-up of 5.9 years, the 5-year locoregional recurrence (LRR), distant metastasis (DM), disease-free survival (DFS), and overall survival (OS) rates were 4.0% and 7.2% (P = 0.001), 13.2% and 10.6% (P = 0.465), 85.0% and 84.7% (P = 0.131), and 93.9% and 92.8% (P = 0.004) in the RNI and non-RNI groups, respectively. Multivariate analysis revealed that RNI was an independent prognostic factor for lower LRR (P = 0.001) and longer DFS (P = 0.013). Patients were stratified into low-, intermediate-, and high-risk groups based on the eight non-therapeutic risk factors. RNI significantly decreased the 5-year LRR (2.2% vs. 7.0%, P = 0.001) and improved the 5-year DFS (88.8% vs. 84.9%, P = 0.015) and OS (95.8% vs. 93.9%, P = 0.010) in the intermediate-risk group. However, neither the low-risk group nor the high-risk group had survival benefit from RNI. T1-2N1M0 breast cancer is a heterogeneous disease. We found that RNI only improved survival in the intermediate-risk group. It might be omitted in low-risk patients, and the role of RNI in high-risk patients needs further study.

Favorable locoregional control in clinically node-negative hormone-receptor positive breast cancer with low 21-gene recurrence scores: a single-institution study with 10-year follow-up

BackgroundRecent studies have shown a lower likelihood of locoregional recurrences in patients with a low 21-gene recurrence score (RS). In this single-institution study, we investigated whether there are any associations between different cutoff values of 21-gene RS, histopathological factors, and outcome in patients with long-term follow-up.MethodsThe study included 61 patients who had early-stage (I-II) clinically node-negative hormone receptor-positive and HER2-negative breast cancer and were tested with the 21-gene RS assay between February 2010 and February 2013. Demographic, clinicopathological, treatment, and outcome characteristics were analyzed.ResultsThe median age was 48 years (range, 29–72 years). Patients with high histologic grade (HG), Ki-67 ≥ 25%, or Ki-67 ≥ 30% were more likely to have intermediate/high RS (≥ 18). Based on the 21-gene RS assay, only 19 patients (31%) received adjuvant chemotherapy. At a median follow-up of 112 months, 3 patients developed locoregional recurrences (4.9%), which were treated with endocrine therapy alone. Among patients treated with endocrine treatment alone (n = 42), the following clinicopathological characteristics were not found to be significantly associated with 10-year locoregional recurrence free survival (LRRFS): age < 40 years, age < 50 years, high histological or nuclear grade, high Ki-67-scores (≥ 15%, ≥ 20%, ≥ 25%, ≥ 30%), presence of lymphovascular invasion, luminal-A type, multifocality, lymph node positivity, tumor size more than 2 cm, RS ≥ 18, and RS > 11. However, patients with RS ≥ 16 had significantly poorer 10-year LRRFS compared to those with RS < 16 (75% vs. 100%, respectively; p = 0.039).ConclusionsThe results suggest that patients with clinically node-negative disease and RS ≥ 16 are more likely to benefit from adjuvant chemotherapies. However, those with RS < 16 have an excellent outcome and local control in long-term follow-up with endocrine treatment alone.