Omission Of Radiotherapy Research Articles

Omission of Adjuvant Radiotherapy in Low-Risk Elderly Males with Breast Cancer

Randomized clinical trials demonstrate that lumpectomy + hormone therapy (HT) without radiation therapy (RT) yields equivalent survival and acceptable local-regional outcomes in elderly women with early-stage, node-negative (T1-2N0) hormone-receptor positive (HR+) breast cancer. Whether these data apply to men with the same inclusion criteria remains unknown. We hypothesized that outcomes in males would be comparable to those seen in females, with RT not conferring an overall survival (OS) benefit over HT alone. We conducted a retrospective matched-cohort study using the National Cancer Database for males ≥65 years with pathologic T1-2N0 (≤3 cm) HR+ breast cancer treated with breast conserving surgery with negative margins from 2004-2019. Patients who received chemotherapy, had nodal or distant metastases, or unknown follow-up were excluded. Adjuvant treatment was classified as HT alone, RT alone, or HT+RT. Due to limitations of survival analysis on retrospective data, male patients were matched with female patients to determine comparable outcomes based on age (± 3 years), Charlson Deyo comorbidity score, T-stage, and adjuvant treatment. Survival analysis was performed using Cox regression and Kaplan-Meier analysis. To adjust for confounding, inverse probability of treatment weighting (IPTW) was used. A total of 523 patients met inclusion criteria, with 24.4% receiving HT, 16.3% receiving RT, and 59.2% receiving HT+RT. Median follow-up was 6.9 years (IQR: 5.0-9.4 years). Unadjusted 5-yr OS rates in the HT, RT, and HT+RT cohorts were 79.2% (95% CI 70.7-85.5%), 80.9% (95% CI 70.3-88.0%), and 93.3% (95% CI 89.7-95.7%), respectively. Adjusted 10-yr OS rates in the HT, RT, and HT+RT cohorts were 82.3% (95% CI 78.6-85.5%), 83.6% (95% CI 80.0-86.7%), and 92.8% (95% CI 90.1-94.8%), respectively. On unadjusted multivariable Cox regression analysis (MVA), relative to HT, receipt of HT+RT was associated with improvements in OS (HR: 0.603; 95% CI: 0.410-0.888; p = 0.01). RT alone was not associated with improved OS (HR: 1.116; 95% CI: 0.710-1.755; p = 0.633). On adjusted MVA, relative to HT, receipt of HT+RT was associated with improvements in OS (HR: 0.551; 95% CI: 0.370-0.820; p = 0.003). Again, RT alone was not associated with improved OS (HR: 0.991; 95% CI: 0.613-1.604; p = 0.972). Other factors associated with OS included age, Charlson Deyo score, T stage, and grade. Overall, in the matched women, the same trends were found as in the men, the best survival was in HT+RT, but no difference in OS between HT vs. RT. Among men ≥65 years old with T1-2N0 HR+ breast cancer, RT alone did not confer an OS benefit over HT alone. Combined RT+HT did yield improvements in OS, though there are likely significant unmeasured confounders contributing to these outcomes in patients treated with the most aggressive approach. Our findings support that RT omission may be a reasonable option in elderly men with T1-2N0 HR+ breast cancer treated with lumpectomy + HT.

Standardizing Breast Adjuvant Radiation Therapy Practices in a Diverse Health System through Development of a Delphi Consensus Supported Clinical Algorithm

Adjuvant radiation therapy (RT) for early breast cancer is a highly effective treatment option. However, the multitude of available techniques backed by strong clinical evidence can result in a lack of consistency in treatment approaches, even within a single healthcare organization. This presents challenges for both providers and patients in making informed decisions. To address this issue, our radiation department, which serves a large and diverse health system, developed a clinical algorithm for adjuvant RT for breast cancer. This algorithm was created to enhance the quality and standardization of care delivered across our network. A modified Delphi technique was used. A panel of eight experienced breast radiation oncologists from our institution was assembled. The panel first identified the common clinical scenarios encountered in treating patients with adjuvant breast RT, and then made recommendations for the primary and alternative approaches for each scenario. NCCN guidelines, ASTRO executive summaries, and published national and international randomized trials were used for reference. In case of disagreements, the final recommendation was reached through a majority vote. The draft algorithm was also shared with medical oncologists, surgeons, and patient advocates to gather their input prior to final approval by the expert panel. Consensus was reached for three broad clinical scenarios for patients who have undergone lumpectomy or mastectomy: Ductal Carcinoma in Situ (DCIS), Invasive Cancer Node Negative (ICN0), and Invasive Cancer Node Positive (ICN+). The panel agreed subdivision of the scenarios into three risk groups (low, intermediate, and high) and three age groups, based on guidelines and consensus statements. For DCIS patients, size, grade, margin status, hormone receptor status, and tumor focality were used for further stratification. For ICN0 patients, HER2 receptor status and lymphovascular space invasion were also included. For ICN+ patients, nodal status (negative versus 1-3 positive nodes versus more than 3 positive nodes) was used for stratification. Additionally, DCIS and ICN0 patients were further divided into age groups. The panel reached consensus recommendations for RT, including whole breast RT, partial breast RT, chest wall RT, regional nodal irradiation, or omission of RT for each sub-group. Clinical trial enrollment was also recommended where appropriate. A breast cancer adjuvant RT algorithm was developed with the aim of standardizing care for patients with breast cancer. Implementation is expected to standardize treatment recommendations in our health system and to streamline the shared decision-making process with patients.

Response-Adapted Omission of Radiotherapy in Pediatric Patients with Intermediate- and High-Risk Hodgkin Lymphoma Treated per EuroNet-PHL-C1: A Single Institution Analysis of Outcomes and Patterns of Failure

EuroNet-PHL-C1 demonstrated that 40% of intermediate- and high-risk pediatric Hodgkin lymphoma (HL) patients treated with OEPA-COPDAC chemotherapy achieved adequate response (AR) at early response assessment (ERA), and thus were able to omit radiotherapy (RT). However, patterns of failure with this treatment paradigm, and specifically, whether or not all initial sites of disease require RT for those with inadequate response (IR) at ERA is unknown. The purpose of our study is to examine outcomes and patterns of failure for those treated per EuroNet-PHL-C1 at our institution. Our hypothesis is that limiting RT to only sites of IR at ERA does not result in increased failures. An IRB-approved retrospective review of all intermediate- and high-risk classical HL pediatric patients treated at our institution per EuroNet-PHL-C1 between 2015 and 2021 was performed. Patients were treated per protocol with radiation omitted for those with AR (Deauville 1-2 and >75% tumor shrinkage) at ERA (PET/CDT after 2 cycles of chemo). For those with IR who required RT, only sites of IR (Deauville 3-5) at ERA were treated using involved site radiation treatment (ISRT), instead of all initial sites of disease as on EuroNet-PHL-C1. Outcomes including overall survival (OS) and progression free survival (PFS) were calculated using Kaplan-Meier curves and patterns of failure were classified as either initial site only, new site only, or initial and new sites. A total of 35 patients were identified, of which 33 had evaluable follow up with median follow up of 33 months. The median age at diagnosis was 14 (range, 4-18) and 48% were female. Of the 33, 7 (21%) had IR at ERA and thus required RT, while 26 (79%) were spared RT. In the group who received RT, 4/7 (57%) had initial B-symptoms and 4/7 (57%) had initial bulky disease, compared to 9/26 (35%) and 20/26 (77%), respectively, in those who did not receive RT. For our entire cohort, 2-year PFS and OS were 91% and 100%, respectively. For those who had RT, 2-year PFS was 83% compared to 92% in those who did not need RT. There was a total of 3 relapses (9%) at last follow up with 1/7 (14%) in those who had RT vs. 2/26 (8%) in those without RT. For the patient who relapsed after RT, relapse occurred both at initial and new sites. For the 2 who relapsed who did not receive RT, 1 was both in initial and new sites, while the other was initial site only. At our institution, the majority of patients treated per EuroNet-PHL-C1 avoided RT with excellent outcomes. For those requiring RT, limiting RT to only sites of IR at ERA does not appear to adversely affect outcomes, though analysis is limited by the low number of failures.

De-Implementation of Low-Value Care for Women 70 Years of Age or Older with Low-Risk Breast Cancer During the COVID-19 Pandemic

BackgroundOlder women with early-stage estrogen receptor-positive (ER+) invasive breast cancer (IBC) are at risk for overtreatment. Guidelines allow for sentinel lymph node biopsy (SLNB) and radiotherapy omission after breast-conserving surgery (BCS) for women 70 years of age or older with T1, clinical node negativity (cN0), and ER+ IBC. The study objective was to evaluate radiotherapy and SLNB de-implementation in older women with low-risk IBC after the resource limitations of the COVID-19 pandemic.MethodsAn institutional database was analyzed to identify women 70 years of age or older who received BCS for IBC from 2012 to 2022. The patients were divided into two cohorts: (1) patients with low-risk IBC (pT1, cN0, and ER+/HER2–) who were eligible for radiotherapy and SLNB omission and (2) patients with high-risk IBC (pT2-T4, cN+, ER–, or HER2+) who were ineligible for therapy omission. Clinicopathologic variables in both cohorts were analyzed.ResultsThe study enrolled 881 patients. For the patients with low-risk IBC, the annual rates of radiotherapy were stable from 2012 to 2019. However, radiotherapy utilization decreased significantly from 2020 to 2022 (58% in 2012 vs 36% in 2022; p = 0.04). In contrast, radiotherapy usage among the patients with high-risk IBC was stable from 2012 to 2022 (79% in 2012 vs 79% in 2022; p = 0.95). Among the patients with low-risk IBC, SLNB rates decreased from 86% in 2012 to 56% in 2022, but this trend predated those in 2020. The factors significantly associated with SLNB and receipt of radiotherapy among the patients with low-risk IBC were younger age, larger tumors, grade 3 disease, and involved nodal status (p < 0.01).ConclusionThis study demonstrated appropriate and sustained de-escalation of radiotherapy in older women with low-risk IBC after the COVID-19 pandemic.

Ki67 assessment protocol as an integral biomarker for avoiding radiotherapy in the LUMINA breast cancer trial.

The LUMINA trial demonstrated a very low local recurrence rate in women ≥55 years with low-risk luminal A breast cancer (defined as grade I-II, T1N0, hormone receptor positive, HER2 negative and Ki67 index ≤13.25%) treated with breast-conserving surgery and endocrine therapy (but no other systemic therapy), supporting the safe omission of radiation in these women. Here we describe the protocol for Ki67 assessment, the companion diagnostic used to guide omission of adjuvant radiotherapy. Ki67 immunohistochemistry was performed on full-face sections at one of three regional labs. Pathologists trained in the International Ki67 in Breast Cancer Working Group (IKWG) method demarcated tumour areas on scanned slides and scored 100 nuclei from each of at least five randomly selected 1-mm fields. For cases with high Ki67 heterogeneity, further virtual cores were selected and scored in order to confidently assign a case as luminal A (≤13.25%) or B (>13.25%). Interlaboratory variability was assessed through an annual quality assurance programme during the study period. From the quality assurance programme, the mean Ki67 index across all cases/labs was 13%. The observed intraclass correlation coefficient (ICC) and kappa statistics were ≥0.9 and ≥0.7, respectively, indicating a substantial level of agreement. Median scoring time was 4 min per case. The IKWG-recommended scoring method, performed directly from slides, requiring up to four scored fields, is concordant with the LUMINA scoring method (ICC ≥ 0.9). Ki67 is a practical, reproducible, and inexpensive biomarker that can identify low-risk luminal A breast cancers as potential candidates for radiation de-escalation. ClinicalTrials.gov number, NCT01791829.

Omitting Radiotherapy after Breast-Conserving Surgery in Luminal A Breast Cancer

BackgroundAdjuvant radiotherapy is prescribed after breast-conserving surgery to reduce the risk of local recurrence. However, radiotherapy is inconvenient, costly, and associated with both short-term and long-term side effects. Clinicopathologic factors alone are of limited use in the identification of women at low risk for local recurrence in whom radiotherapy can be omitted. Molecularly defined intrinsic subtypes of breast cancer can provide additional prognostic information.MethodsWe performed a prospective cohort study involving women who were at least 55 years of age, had undergone breast-conserving surgery for T1N0 (tumor size <2 cm and node negative), grade 1 or 2, luminal A–subtype breast cancer (defined as estrogen receptor positivity of ≥1%, progesterone receptor positivity of >20%, negative human epidermal growth factor receptor 2, and Ki67 index of ≤13.25%), and had received adjuvant endocrine therapy. Patients who met the clinical eligibility criteria were registered, and Ki67 immunohistochemical analysis was performed centrally. Patients with a Ki67 index of 13.25% or less were enrolled and did not receive radiotherapy. The primary outcome was local recurrence in the ipsilateral breast. In consultation with radiation oncologists and patients with breast cancer, we determined that if the upper boundary of the two-sided 90% confidence interval for the cumulative incidence at 5 years was less than 5%, this would represent an acceptable risk of local recurrence at 5 years.ResultsOf 740 registered patients, 500 eligible patients were enrolled. At 5 years after enrollment, recurrence was reported in 2.3% of the patients (90% confidence interval [CI], 1.3 to 3.8; 95% CI, 1.2 to 4.1), a result that met the prespecified boundary. Breast cancer occurred in the contralateral breast in 1.9% of the patients (90% CI, 1.1 to 3.2), and recurrence of any type was observed in 2.7% (90% CI, 1.6 to 4.1).ConclusionsAmong women who were at least 55 years of age and had T1N0, grade 1 or 2, luminal A breast cancer that were treated with breast-conserving surgery and endocrine therapy alone, the incidence of local recurrence at 5 years was low with the omission of radiotherapy. (Funded by the Canadian Cancer Society and the Canadian Breast Cancer Foundation; LUMINA ClinicalTrials.gov number, NCT01791829.)

Is de-escalation of treatment by omission of radiotherapy associated with fear of cancer recurrence in women with early breast cancer? An exploratory study

PurposeSafe de-intensification of adjuvant radiotherapy (RT) for early breast cancer (BC) is currently under evaluation. Little is known about the patient experience of de-escalation or its association with fear of cancer recurrence (FCR), a key issue in survivorship. We conducted a cross-sectional study to explore this association.MethodsPsychometrically validated measures including the Fear of Cancer Recurrence Inventory-Short Form were completed by three groups of women with early BC: Women in the PROSPECT clinical trial who underwent pre-surgical MRI and omitted RT (A), women who underwent pre-surgical MRI and received RT (B); and women who received usual care (no MRI, received RT; C). Between group differences were analysed with non-parametric tests. A subset from each group participated in a semi-structured interview. These data (n = 44) were analysed with directed content analysis.ResultsQuestionnaires from 400 women were analysed. Significantly lower FCR was observed in Group A (n = 125) than in Group B (n = 102; p = .002) or Group C (n = 173; p = .001), and when participants were categorized by RT status (omitted RT vs received RT; p < .001). The proportion of women with normal FCR was significantly (p < .05) larger in Group A (62%) than in Group B (35%) or Group C (40%). Two qualitative themes emerged: ‘What I had was best’ and ‘Coping with FCR’.ConclusionsOmitting RT in the setting of the PROSPECT trial was not associated with higher FCR than receiving RT. Positive perceptions about tailored care, lower treatment burden, and trust in clinicians appear to be protective against FCR.

Predictors of Early Versus Late Recurrence in Invasive Lobular Carcinoma of the Breast: Impact of Local and Systemic Therapy

BackgroundInvasive lobular carcinoma (ILC) of the breast is known for high risk of late recurrence, yet some patients still recur within 5 years of diagnosis. Determining factors associated with early/late recurrence could help tailor treatment and surveillance strategies.MethodsUsing an institutional database, we evaluated patients with ILC and ≥ 5 years of follow-up or recurrence within 5 years. We used multivariate logistic regression and the Kaplan-Meier method to evaluate which clinicopathologic features and treatment strategies were associated with recurrence < 5 years since diagnosis versus recurrence ≥ 5 years since diagnosis. Additionally, we explored the association between Clinical Treatment Score 5 (CTS5) with early versus late recurrence.ResultsAmong 513 cases of stage I–III ILC, there were 75 early and 54 late recurrences during a median follow-up period of 9.4 years. Early recurrence was associated with larger tumors (mean 4.2 cm vs. 2.9 cm, p < 0.0001), higher incidence of > 3 positive nodes (32.4% vs. 9.11%, p > 0.0001), and more aggressive tumor biology (low/negative progesterone receptor expression, higher grade, and higher Ki67). Late recurrence was associated with younger age (mean 55.6 vs. 59.2 years, p = 0.037) and elevated body mass index (BMI > 25 kg/m2 in 60.1.0% vs. 45.4%, p = 0.021). Omission of adjuvant endocrine therapy or radiotherapy after lumpectomy conferred increased risk of early rather than late recurrence.ConclusionFactors related to tumor aggressiveness and treatment were associated with early recurrence, whereas patient related factors were related to late recurrence. These data may help guide treatment strategies and surveillance approaches for patients with ILC.

Observation vs. radiotherapy in primary mediastinal B-cell lymphoma patients with complete response to standard immunochemotherapy: The IELSG37 randomized trial.

LBA7505 Background: Primary mediastinal B-cell lymphoma (PMBCL) has a good prognosis if remission is rapidly achieved with dose‐intensive immunochemotherapy. In these patients mediastinal radiotherapy (RT) may consolidate responses; however, it increases the risk of second malignancies and coronary or valvular heart disease. The IELSG37 trial was planned with a non-inferiority design to test whether RT can be omitted in patients who achieve a complete metabolic response (CMR) after immunochemotherapy. Methods: Patients with newly diagnosed PMBCL were eligible. Initial rituximab and anthracycline-based therapy was chosen according to local practice. CMR was defined, upon central review of positron emission computed tomography (PET/CT) scans, as Deauville score 1 to 3, according to the Lugano classification. Responding patients were randomized to observation (OBS) or consolidation RT (30 Gy). Randomization was stratified on gender, chemotherapy regimen, country, and PET/CT score. The primary endpoint was progression-free survival (PFS) after randomization. The sample size (540 patients to enrol, and 376 to randomize) was calculated assuming a 30-month PFS probability of 0.85 in both arms, with alpha at 0.05, 80% power and a hazard ratio (HR) of 1.77 as non-inferiority margin. Results: At a median follow-up of 30 months, the number of observed events was considerably lower than expected, hence, the Independent Data Monitoring Committee (IDMC) of the trial recommended to complete the planned total accrual without increasing the study size or duration. The primary endpoint analysis was performed, according to the IDMC recommendation, with ≥80% of patients having a minimum follow-up of 30 months. 545 patients (209 men, 336 women) were enrolled. Induction immunochemotherapy was completed and response assessed in 530 patients, 268 of them (50.6%) achieved a CMR and were randomly allocated to OBS (n = 132) or RT (n = 136). The PFS at 30 months was 98.5% (95%CI, 94.3 – 99.6) in the RT arm and 96.2% (95%CI, 91.1-98.4) in the OBS arm (P = 0.278). The estimated relative effect of radiotherapy vs observation in terms of hazard ratio (HR) was 0.47 (0.12-1.89) without adjustments and 0.79 (0.19-3.31) after stratification for the variables used for randomization. At 30 months the absolute risk reduction from RT was 2.3% (-1.5 to 6.2) unadjusted, and 0.8% (-3.0 to 8.3) with stratified HR. The number needed to treat is high (43 patients, unadjusted, and 126 after stratification). The 5-year overall survival was 99% in both arms. Longer follow-up is needed to examine late toxicity. Conclusions: This study is the largest prospective study of PMBCL ever conducted and although the event rate did not reach the assumed level, its evidence supports the omission of RT in patients achieving a CMR after immunochemotherapy.

Interim PET-guided treatment for early-stage NLPHL: a subgroup analysis of the randomized GHSG HD16 and HD17 studies

AbstractThe optimal first-line treatment for nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) diagnosed in early stages is largely undefined. We, therefore, analyzed 100 NLPHL patients treated in the randomized HD16 (early-stage favorable; n = 85) and HD17 (early-stage unfavorable; n = 15) studies. These studies investigated the omission of consolidation radiotherapy (RT) in patients with a negative interim positron emission tomography (iPET) (ie, Deauville score <3) after chemotherapy (HD16: 2× doxorubicin, bleomycin, vinblastine, and dacarbazine [ABVD]; HD17: 2× escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone [BEACOPP] plus 2× ABVD). Patients with NLPHL treated in the HD16 and HD17 studies had 5-year progression-free survival (PFS) rates of 90.3% and 92.9%, respectively. Thus, the 5-year PFS did not differ significantly from that of patients with classical Hodgkin lymphoma treated within the same studies (HD16: P = .88; HD17: P = .50). Patients with early-stage favorable NLPHL who had a negative iPET after 2× ABVD and did not undergo consolidation RT tended to have a worse 5-year PFS than patients with a negative iPET who received consolidation RT (83% vs 100%; P = .05). There were 10 cases of NLPHL recurrence. However, no NLPHL patient died during follow-up. Hence, the 5-year overall survival rate was 100%. Taken together, contemporary Hodgkin lymphoma-directed treatment approaches result in excellent outcomes for patients with newly diagnosed early-stage NLPHL and, thus, represent valid treatment options. In early-stage favorable NLPHL, consolidation RT appears necessary after 2× ABVD to achieve the optimal disease control irrespective of the iPET result.

Neoadjuvant cemiplimab with platinum-doublet chemotherapy and cetuximab to de-escalate surgery and omit adjuvant radiation in locoregionally advanced head &amp; neck squamous cell carcinoma (HNSCC).

6019 Background: Locoregionally advanced (LA) HNSCC treated with surgery can carry significant functional morbidity, further intensified by adjuvant (adj) radiation (RT) often with concurrent chemotherapy. Although the pathologic response rate of anti-PD1 therapy is modest, combination approaches may provide enhanced clinical benefit. This pilot study evaluates whether the combination of neoadjuvant cemiplimab + platinum-doublet chemotherapy + cetuximab is safe, feasible, and effective in pathologic down-staging to reduce the extent of surgery and justify omission of adj RT. Methods: 10 patients (pts) with resectable LA HNSCC who would warrant adj RT per clinical stage were enrolled. Neoadjuvant treatment consisted of cetuximab loading dose with cemiplimab followed by 3 cycles of chemotherapy (cisplatin or carboplatin + docetaxel) with cetuximab and cemiplimab prior to definitive surgical resection. Standard of care adj RT+/- chemotherapy was administered based on pathologic staging. Pts with ypT0-2N0 tumors without adverse features or ypT0-1N1 tumors with minimal residual disease ( &lt; 10% viable tumor) were offered 6 months of adj cemiplimab in lieu of RT. Primary endpoint was safety (defined by dose limiting toxicity (DLT) related to the addition of cemiplimab to this combination regimen). Secondary endpoints included feasibility (defined as no surgical delay &gt; 20 weeks from start of neoadjuvant therapy due to treatment toxicity) and pathologic down-staging allowing for omission of adj RT. Results: 10 pts completed treatment with no DLTs and surgical delays. 8/10 (80%) pts were clinically staged as T3/T4 and 5/10 (50%) were N2b/c (AJCC 7th Ed). Pathologic down-staging was observed in 9/10 (90%) pts after neoadjuvant therapy. 60% had a major pathologic response and 40% had a complete pathologic response. 6/8 pts and 7/10 pts who would have required a mandibulectomy and free flap, respectively, did not require it following neoadjuvant treatment. Of the 5/10 (50%) pts who were eligible for omission of adj RT, 4 did not undergo RT and 3 received adj cemiplimab. All pts remain disease-free at a median follow-up of 16 months. The most common adverse events (AEs) of any grade (G) were rash (80%), nausea (70%), fatigue (50%), and diarrhea (50%). 2/10 (20%) pts experienced a G3 or G4 immune-related AE attributed to the addition of cemiplimab. One pt developed G3 transaminase elevation prior to surgery and 1 pt experienced G3 myasthenia gravis and G4 myocarditis (resolved) outside the DLT window. Conclusions: Neoadjuvant cemiplimab with platinum-doublet chemotherapy and cetuximab has an acceptable toxicity profile, is feasible in pts with LA HNSCC, and led to notable pathologic down-staging allowing for reduction in extent of surgery and omission of adj RT. Further evaluation of this regimen is clearly warranted. Clinical trial information: NCT04722523 .

Re-referral for post-op radiation in elderly breast cancer patients who initially omit RT but are unable to tolerate endocrine therapy.

e12507 Background: Omission of Radiation in the setting of Elderly patients 70 yo and above with ER+, cN0, pT1 tumors who receive adjuvant endocrine therapy (HT) is standard of care per NCCN. However, the average adherence rate of HT ranges from 41% to 72%, which is not optimal for patient outcomes. In our institution, we evaluated the treatments of all patients who qualified for omission of radiation upfront and the number of re-referrals for adjuvant radiation in Elderly Breast cancer patients who were unable to tolerate HT past 6 months. Methods: Data was obtained through the National Cancer Registry at our institution for 2021 and reviewed mid 2022. Inclusion criteria included patients diagnosed with Pathologically Invasive Breast Cancer AJCC Stage I-IIB age 70 and above. A total of 176 patients were eligible for review. 86 patients did not qualify for inclusion into study due to 7 receiving surgical treatment outside our system. Furthermore, 81 patients did not qualify due to the following reasons or combination: Mastectomy (19), Triple Negative, Greater than 2 cm, N+, AI only. A total of 90 patients qualified for omission and review. Six month HT therapy cut off was extrapolated by Barbieri et al who determined a 6 month delay of RT after surgery was not associated with an increased risk of relapse. Results: From the 90 patients who qualified for omission of radiation, 67 % (n = 60) of patients chose radiation omission, 30% (n = 27) of patients chose upfront radiation, and 3% (n = 3) of patients declined all therapy. Of the 60 patients who chose omission, 87% of patients had continued HT, however 2 patients passed away within 1 year of surgery. A total of 13% of patients (n = 8) who omitted radiation did not go past 6 months of HT, and only 2 out of 8 patients (25%) were referred back to radiation oncology and moved forward with treatment. For the 27 patients who chose radiation upfront even though they qualified for omission, the most common reason per records was the patient was unsure after initial multidisciplinary clinic that they would be able to tolerate HT. Interestingly, 27% of these patients ended up stopping HT within 9 months due to side effects. Conclusions: Omission of radiation is an option for Elderly Early stage breast cancer patients in the setting of HT. However, HT compliance is variable due to side effects. In our one year single institution study, only 25% of patients who omitted RT and did not get past 6 months of HT were sent back for radiation. We encourage an increased awareness and communication between Radiation Oncology and Medical Oncology regarding the option of radiation for patients who do not pass 6 months of HT. Our institution has implemented an Epic message system and Breast Navigation to aid in re-referral. It is also imperative at the time of Radiation Oncology consultation to discuss the possibility of intolerance to HT in the setting of omission may indicate radiation therapy at a later date.

NRG-BR007: A phase III trial evaluating de-escalation of breast radiation (DEBRA) following breast-conserving surgery (BCS) of stage 1, HR+, HER2-, RS ≤18 breast cancer.

TPS623 Background: Approximately 50% of newly diagnosed invasive breast cancers are stage 1, with the majority being ER/PR-positive, HER2-negative. Genomic assays such as the Oncotype DX have identified patients (pts) with reduced risk of distant metastasis and without benefit from chemotherapy added to endocrine therapy, freeing them from excess toxicity. Genomic assays are also recognized as prognostic for in-breast recurrence (IBR) after BCS and could similarly allow de-escalation of adjuvant radiotherapy (RT). Reducing overtreatment is of interest to pts, providers, and payers. Methods: We hypothesize that BCS alone is non-inferior to BCS plus RT for in-breast recurrence and breast preservation in women intending endocrine therapy (ET) for stage 1 invasive breast cancer (ER &amp;/or PR positive, HER2-negative with an Oncotype DX Recurrence Score [RS] of ≤18). Stratification is by age (&lt;60; ≥60), tumor size (≤1 cm; &gt;1-2cm), and RS (&lt;11, 11-18). Pts are randomized post-BCS to Arm 1 with breast RT using standard methods (hypo- or conventional-fractionated whole breast RT with/without boost, or APBI) with ≥5 yrs of ET (tamoxifen or AI) or Arm 2 with ≥5 yrs of ET (tamoxifen or AI) alone. The specific regimen of ET in both arms is at the treating physician’s discretion. Eligible pts are stage 1: pT1 (≤2 cm), pN0, age ≥50 to &lt;70 yrs, s/p BCS with negative margins (no ink on tumor), s/p axillary nodal staging (SNB or ALND), ER &amp;/or PR positive (ASCO/CAP), HER2-negative (ASCO/CAP), and Oncotype DX RS of ≤18 (diagnostic core biopsy or resected specimen). Primary endpoint is in-breast recurrence (invasive breast cancer or DCIS). Secondary endpoints are breast conservation rate, invasive in-breast recurrence, relapse-free interval, distant disease-free survival, overall survival, patient-reported breast pain, patient-reported worry about recurrence, and adherence to ET. We assume a clinically acceptable difference in IBR of 4% at 10 yrs to judge omission of RT as non-inferior (10-yr event-free survival for RT group is 95.6% vs 91.6% for the omission of RT group). BR007 is powered to detect non-inferiority with 80% power and a one-sided α=0.025, assuming that there would be a ramp-up in accrual in the first two years (leveling off in Yrs 3-5); 1,670 pts (835 per arm) are required for randomization. Conservative loss to follow-up is 1% per yr. Some of the T1a pts screened may have Oncotype DX scores &gt;18, making them ineligible for the study. In the accrual process, 1,714 pts will be required to register to ensure that our final randomized cohort is 1,670 pts. Current accrual (02-08-2023) is 370 screened and 323 randomized (~87% of predicted accrual). Clinical trial information: NCT04852887 .

Assessing the marginal costs of radiation therapy and antiestrogen therapy for post-lumpectomy, early-stage breast cancer across Medicaid and Medicare plans.

529 Background: With recent Level I evidence (FAST FORWARD) supporting radiation therapy (RT) duration as short as one week and Level I evidence (CALGB9343) supporting RT omission in favor of antiestrogen endocrine therapy (ET) alone in select patients, the necessity of both RT and ET, adjuvantly, in early-stage breast cancer (BC) has been questioned. Evidence providing granular details on the role of insurance in the aggregate cost of RT and ET is lacking. This project disaggregates costs by insurance plan to increase transparency of out-of-pocket (OOP) cost estimates. Methods: National Comprehensive Cancer Network guidelines were utilized to determine the proper treatments, with FAST FORWARD radiation dose/fractionation (26 Gy in 5 fractions) representing RT. Treatments were identified using Current Procedural Terminology and Healthcare Common Procedure Coding System codes. OOP costs, deductibles, and copay/coinsurance were calculated for Medicaid, Original Medicare, Medigap Plan G, and Medicare Part D Rx. The medicare.gov, medicaid.oh.gov, aarpmedicareplans.com, and cms.gov were used to determine pricing. Price estimates reflect actual costs per insurance plan rather than costs estimated from claims data. All procedures were considered to be performed in an Ohio hospital setting, insurance coverages were based on the zip code 44106, and total expenses were based on all treatments plus a 5-year follow-up (not adjusted for inflation). Results: Treatment charges for ET include medical oncology initial consultation, biannual medical oncology follow-up, baseline bone density study, and Anastrozole cost (5-years). Treatment charges for RT include initial consultation, treatment planning, dosimetry calculations, treatment device, simulation and verification, RT delivery, on-treatment visits, and medical physics consultation. Original Medicare beneficiaries face an OOP cost of 20% for Medicare Part B claims with no cost cap for approved procedures after the deductible. Medications are covered under Medicare Part D with copays. This results in a marginal OOP treatment charge (after 5-year follow-up) of $767.54 for ET alone and $1,416.78 for ET + RT. Medigap Plan G beneficiaries face a marginal OOP charge of $1,225 for both ET alone and ET + RT, assuming the $226 Medicare Plan B deductible is met by the cost of lumpectomy during the year of RT. For Medicaid beneficiaries (assuming all treatments are approved by Medicaid), all expenses are covered without limit, resulting in no OOP expense for either treatment plan. Conclusions: Discussions of adding RT to ET for post-lumpectomy early-stage BC often involves considerations of treatment costs. This model (based on actual cost estimates per insurance plan rather than claims data) can help to enhance cost transparency by comparing expenses between Medicare and Medicaid plans.

Not Too Little, Not Too Much: Optimizing More Versus Less Locoregional Treatment for Older Patients With Breast Cancer.

Although undertreatment of older women with aggressive breast cancers has been a concern for years, there is increasing recognition that some older women are overtreated, receiving therapies unlikely to improve survival or reduce morbidity. De-escalation of surgery may include breast-conserving surgery over mastectomy for appropriate candidates and omitting or reducing extent of axillary surgery. Appropriate patients to de-escalate surgery are those with early-stage breast cancer, favorable tumor characteristics, are clinically node-negative, and who may have other major health issues. De-escalation of radiation includes reducing treatment course length through hypofractionation and ultrahypofractionation regimens, reducing treatment volumes through partial breast irradiation, omission of radiation for select patients, and reducing radiation dose to normal tissues. Shared decision making, which aims to facilitate patients making decisions concordant with their values, can guide health care providers and patients through complicated decisions optimizing breast cancer care.

EE269 Cost-Effectiveness of Profile Omission of Local Adjuvant Radiotherapy (POLAR), A Novel Genomic Signature, after Breast Conserving Surgery for Women with Invasive Early-Stage Breast Cancer (ESBC)

Adjuvant radiotherapy (RT), the standard of care for women diagnosed with invasive ESBC after breast-conserving surgery (BCS), is shown to reduce the risk of recurrence for most women; however, it can be associated with major adverse effects including lung/cardiac/breast toxicity. Recently, the POLAR signature was reported to successfully identify women who would or would not benefit from RT after BCS. This study evaluated the cost-effectiveness of the POLAR signature for guiding RT omission compared to RT for all women with hormone receptor-positive (HR+), HER2-negative stage I/IIA breast cancer.

¿Se puede optimizar el tratamiento adyuvante en cáncer de mama de bajo riesgo?

In Oncology, we increasingly looking for the personalization of breast cancer treatment under the premise of “less is more”, there is currently a growing interest in identifying a subset of patients with early-stage breast cancer in whom the low risk of recurrence allows us to optimize adjuvant treatment. Radiotherapy in breast cancer has shown benefits at all stages and in all age groups, with minimal morbidity and excellent tolerance. Radiotherapy treatment has evolved, the volume of treatment has been reduced in low-risk subgroups (partial breast irradiation) and hypofractionated treatments, standard today, have demostrated disease control rates comparable to previous ones with a clear improvement in the quality of life of the patients. Endocrine therapy (ET) in breast cancer impacts local and distant recurrence, breast cancer-specific mortality and overall survival, but it associates significant side effects in the short, medium and long term and there are many women who have difficulty to tolerating this treatment. In this review, we try to answer questions such as: Is the omission of radiotherapy an option? And the omission of ET? In which patient profile can we consider optimizing adjuvant treatment?

Adjuvant Therapy for Elderly Breast Cancer Patients after Breast-Conserving Surgery: Outcomes in Real World Practice.

We aimed to evaluate the standard of care of adjuvant radiotherapy (RT) after breast-conserving surgery (BCS) in elderly female patients (≥65 years) treated outside of clinical trials and to identify potential factors related to the omission of RT and the interaction with endocrine therapy (ET). All women treated with BCS at two major breast centers between 1998 and 2014 were evaluated. Data were provided by the Tumor Registry Munich. Survival analyses were conducted using the Kaplan-Meier method. Prognostic factors were identified using multivariate Cox regression analysis. The median follow-up was 88.4 months. Adjuvant RT was performed in 82% (2599/3171) of patients. Irradiated patients were younger (70.9 vs. 76.5 years, p < 0.001) and were more likely to receive additional chemotherapy (p < 0.001) and ET (p = 0.014). Non-irradiated patients more often had non-invasive DCIS tumors (pTis: 20.3% vs. 6.8%, p < 0.001) and did not undergo axillary surgery (no axillary surgery: 50.5% vs. 9.5%, p < 0.001). Adjuvant RT was associated with improved locoregional tumor control after BCS in invasive tumors (10-year local recurrence-free survival (LRFS): 94.0% vs. 75.1%, p < 0.001, 10-year lymph node recurrence-free survival (LNRFS): 98.1% vs. 93.1%, p < 0.001). Multivariate analysis confirmed significant benefits for local control with postoperative RT. Furthermore, RT led to increased locoregional control even in patients who received ET (10-year LRFS 94.8% with ET + RT vs. 78.1% with ET alone, p < 0.001 and 10-year LNRFS: 98.2% vs. 95.0%, p = 0.003). Similarly, RT alone had significantly better locoregional control rates compared to ET alone (10-year LRFS 92.6% with RT alone vs. 78.1% with ET alone, p < 0.001 and 10-year LNRFS: 98.0% vs. 95.0%, p = 0.014). The present work confirms the efficacy of postoperative RT for breast carcinoma in elderly patients (≥65 years) treated in a modern clinical setting outside of clinical trials, even in patients who receive ET.

De-Implementation of Axillary Staging and Radiotherapy in Low-Risk Breast Cancer Patients Aged 70-79 Years from Six Italian Cancer Institutes.

In women aged ≥70 with low-risk breast cancer (BrC), some major international guidelines recommend against sentinel lymph node biopsy (for example, those from the Society of Surgical Oncology, U.S.) and post-lumpectomy radiotherapy (for example, those from the National Comprehensive Cancer Network, U.S.). We assessed the frequency of both procedures in six National Cancer Institutes (IRCCSs) in the North, the Centre, and the South of Italy. Data on tumour characteristics and treatment were obtained from each centre. Patients aged 70-79 years diagnosed with a pT1-pT2, clinically axillary lymph node-negative, oestrogen and/or progesterone receptor-positive, and human epidermal growth factor receptor 2-negative BrC between 2015 and 2020 were eligible for the study. Factors associated with the omission of the two procedures were evaluated using binary penalised logistic regression models. Axillary staging was omitted in 33/1000 (3.3%) women. After simultaneous adjustment for the centre of treatment and all other key variables, axillary staging was omitted more often in 2015-2016 vs. 2017-2020 (odds ratio (OR): 2.7; 95% CI: 1.0-7.5), in women aged 75-79 vs. 70-74 years (OR: 2.3; 95% CI: 1.1-4.9), and in those who had mastectomy vs. breast-conserving surgery (OR: 3.3; 95% CI: 1.2-9.0). The higher the histological grade was, the less frequent were the omissions (OR for grade 3 vs. grade 1: 0.2; 95% CI: 0.0-0.7). Post-lumpectomy radiotherapy was omitted in 56/651 (8.6%) women with no significant association with age, period, tumour stage, and tumour grade. In conclusion, the omission of axillary staging and post-lumpectomy radiotherapy in low-risk older BrC patients was rare in the Italian IRCCSs. Although women included in the study cannot be considered a nationally representative sample of BrC patients in Italy, our findings can serve as a baseline to monitor the impact of future guidelines. To do that, the recording and storage of hospital-based information should be improved.

Can adjuvant radiotherapy be omitted for oral cavity cancer patients who received neoadjuvant therapy and surgery? A retrospective cohort study.

Surgery and postoperative adjuvant therapy comprise the standard treatment for locally advanced resectable oral squamous cell carcinoma (LAROSCC), while preoperative neoadjuvant therapy is being explored without sufficient confirmation of improved survival. De-escalation regimens after neoadjuvant therapy, such as those omitting adjuvant radiotherapy, may provide comparable or better outcomes, suggesting rigorous assessment of adjuvant therapy outcomes is needed in LAROSCC patients. The authors thus performed this retrospective study in LAROSCC patients who received neoadjuvant therapy and surgery, to compare the outcomes for overall survival (OS) and locoregional recurrence-free survival (LRFS) between the adjuvant radiotherapy (radio) and nonradiotherapy (nonradio) cohorts. Patients diagnosed with LAROSCC who received neoadjuvant therapy and surgery were enrolled and divided into radio and nonradio cohorts to determine whether adjuvant radiotherapy could be omitted after neoadjuvant therapy and surgery. From 2008 to 2021, 192 patients were enrolled. No significant differences were found in OS or LRFS between the radio and nonradio patient cohorts. The 10-year estimated OS rates were 58.9 versus 44.1% in radio versus nonradio cohorts, while 10-year estimated LRFS rates were 55.4 versus 48.2%, respectively. For clinical stage III patients, 10-year OS rates were 62.3 versus 62.6% (radio vs. nonradio), and estimated 10-year LRFS rates were 56.5 versus 60.7% (radio vs. nonradio). Multivariate Cox regression modeling of postoperative variables showed pathologic response of primary tumor and pathologic regional lymph nodes staging were associated with survival, while the adjuvant radiotherapy exposure was not included in the model due to nonsignificance. These findings support further prospective evaluation of adjuvant radiotherapy omission, and suggest that de-escalation trials are warranted for LAROSCC surgery patients who received neoadjuvant therapy.