Risk Factors For Local-regional Recurrence Research Articles

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.

American Radium Society Appropriate Use Criteria Postmastectomy Radiation Therapy: Executive Summary of Clinical Topics

To conduct an appropriate use criteria expert panel update on clinical topics relevant to current clinical practice regarding postmastectomy radiation therapy (PMRT). An analysis of the medical literature from peer-reviewed journals was conducted from May 4, 2010 to May 4, 2022 using the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines to search the PubMed database to retrieve a comprehensive set of relevant articles. A well-established methodology (modified Delphi) was used by the expert panel to rate the appropriate use of procedures. Evidence for key questions in PMRT regarding benefit in special populations and technical considerations for delivery was examined and described. Risk factors for local-regional recurrence in patients with intermediate-risk disease that indicate benefit of PMRT include molecular subtype, age, clinical stage, and pathologic response to neoadjuvant chemotherapy. Use of hypofractionated radiation in PMRT has been examined in several recent randomized trials and is under investigation for patients with breast reconstruction. The use of bolus varies significantly by practice region and has limited evidence for routine use. Adverse effects occurred with both PMRT preimplant and postimplant exchange in 2-staged breast reconstruction. Most patients with even limited nodal involvement will likely benefit from PMRT with significant reduction in local-regional recurrence and potential survival. Patients with initial clinical stage III disease and/or any residual disease after neoadjuvant chemotherapy should be strongly considered for PMRT. Growing evidence supports the use of hypofractionated radiation for PMRT with equivalent efficacy and decreased acute side effects, but additional evidence is needed for special populations. There is limited evidence to support routine use of bolus in all patients. Timing of PMRT regarding completion of 2-staged breast reconstruction requires a discussion of increased risks with radiation postimplant exchange compared with increased risk of failure of reconstruction or surgical complications with radiation preimplant exchange.

Predictors of relapse and evaluation of the role of postoperative radiation therapy in a modern series of patients with surgically resected stage III (N2) non–small cell lung cancer

PurposeFor patients with stage III (N2) non–small cell lung cancer (NSCLC) treated with surgical resection, postoperative chemotherapy improves overall survival (OS), but the role of postoperative radiation therapy (PORT) is controversial. The purpose of this study was to evaluate risk factors for local-regional recurrence and to evaluate the impact of PORT on local-regional control (LRC) and OS in a modern series of patients with surgically resected stage III (N2) NSCLC. Methods and materialsA retrospective review was performed of patients with Stage III (N2) NSCLC who underwent curative intent resection at our institution between February 1999 and January 2012. OS, LRC, and metastasis-free survival were estimated from the date of surgery using the Kaplan Meier method. ResultsA total of 71 patients were included in the study. Patient median age was 63 years. Histology was adenocarcinoma in 69% of patients. Pretreatment positron emission tomography/computed tomography staging was performed for 90% of patients, and preoperative chemotherapy was administered in 23%. The rate of R0 resection was 96%. Forty-one patients (58%) received PORT and the median PORT dose was 50 Gy (range, 41.4-60 Gy). The median follow-up time for living patients was 5.0 years. Five-year OS for all patients was 66%. OS at 5 years for patients who received PORT compared with patients who did not receive PORT was 71% versus 60%, respectively (hazard ratio [HR], 0.61; 95% CI, 0.30-1.44; P = .28). LRC at 5 years for patients who received PORT compared with patients who did not receive PORT was 89% versus 76%, respectively (HR, 0.44; 95% CI, 0.13-1.45; P = .17). Factors associated with decreased LRC were male sex (P = .011) and primary tumor (pT) stage (pT3/4 vs. pT1/2, P = .006). Metastasis-free survival at 5 years for patients who received PORT compared with those who did not receive PORT was 62% versus 63%, respectively (HR, 1.07; 95% CI, 0.51-2.40; P = .86). ConclusionsIn this modern series of patients with resected stage III (N2) NSCLC, patients who received PORT had higher rates of OS and LRC, but these differences were not statistically significant.

Treatment choices for patients with invasive lobular breast cancer: a doctor survey.

Invasive lobular breast cancer (ILC) has distinct features that present challenges for management. We surveyed doctors regarding management approaches, opinions on quality of evidence supporting their practice, and future research needs. An online questionnaire was developed and circulated to breast cancer surgical, radiation and medical oncologists. The questionnaire was completed by 88/428 doctors (20.6%); 22/56 (39.3%) surgeons, 21/64 (32.8%) radiation oncologists and 45/308 (14.6%) medical oncologists. The majority (65%) of surgeons were comfortable treating ILC patients using the same surgical management as patients with invasive ductal cancers (IDC). Furthermore, 25% would perform a similar surgery but would obtain larger gross margins. There was equipoise for radiation oncologists regarding whether or not ILC was an independent risk factor for local-regional recurrence after either breast-conserving surgery or mastectomy. Of those radiation oncologists who believe ILC is an independent risk factor for recurrence after mastectomy, 44.4% would offer radiation in the absence of usual indications. Medical oncologists approached systemic therapy for ILC patients similarly to those with comparable IDCs. Areas identified as most controversial and requiring future research were preoperative magnetic resonance imaging, radiotherapy post-mastectomy and the responsiveness of ILC to adjuvant chemotherapy compared with endocrine therapy. There is a variation in doctors' beliefs, management and opinions regarding the quality of evidence for the management of ILC. Clinical trials specifically assessing the management of ILC are required to guide clinical practice.

Abstract P5-21-09: Oncologist treatment choices in patients with early stage invasive lobular breast carcinoma - a survey

Abstract Introduction: Invasive lobular carcinoma (ILC) is common and accounts for 5-15% of all breast cancers. ILC has distinct clinical and histological features that separate it from invasive ductal carcinoma (IDC) with regards to its breast imaging characteristics, patterns of recurrence and sensitivity to systemic therapy. ILC presents challenges to the physician in many aspects of local-regional and systemic therapy choices. We surveyed breast cancer physicians on their beliefs and practice patterns on issues around the management of ILC. Methods: A questionnaire was developed and circulated electronically using a modified Dillman technique to surgical, radiation, and medical oncologists across Canada and Ireland. Results: The questionnaire was completed by 91 of 429 physicians (21% response rate). Response rate by specialty was 25/69 (36%), 21/54 (41%) and 45/306 (13%) for surgical, radiation and medical oncologists respectively. Most surgeon responders (77%) would feel "uncomfortable making treatment decisions for ILC with a mammogram alone" and 100% would be "more comfortable with an MRI". Although 55% reported treating ILC as they would IDC, 22% of surgeons will purposefully obtain larger gross margins intra-operatively. Some radiation oncologists believe ILC is an independent risk factor for local-regional recurrence after breast conserving surgery (49%), and after mastectomy (29%). 33% of radiation oncologists would offer radiation therapy after mastectomy specifically because of the ILC subtype even in the absence of usual indications for radiotherapy. Most medical oncologists treat ILC comparably to IDC with the factors having the largest influence on systemic treatment decisions being tumour stage, hormone receptor status and HER-2 status. 51% of medical oncologists treat ILC with adjuvant chemotherapy as they do for IDC at least ‘most of the time’, while 40% use neoadjuvant chemotherapy as frequently as they do for IDC at least ‘most of the time’. 75% of medical oncologists manage the hormonal treatment of ILC as they do IDC ‘most of the time’ or ‘always’. Conclusions: There remains significant clinical equipoise in the local-regional and systemic management of ILC. This survey has demonstrated wide variations in both beliefs and practices of management for ILC. Clinical guidance, developed on clinical trials specifically assessing the management of ILC, is required. Citation Format: Carmel Jacobs, Mark Clemons, Mohamed FK Ibrahim, Christina Addison, Jean-Michel Caudrelier, Ian D Graham, Brain Hutton, Angel Arnaout. Oncologist treatment choices in patients with early stage invasive lobular breast carcinoma - a survey [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-21-09.

Abstract P3-14-12: Risk factors for local regional recurrence in patients undergoing breast conserving surgery following neoadjuvant chemotherapy and validation of the MD Anderson prognostic index

Abstract Background: Breast conserving surgery (BCS) is a primary goal of neoadjuvant chemotherapy (NAC) in patients with locally advanced breast cancer, especially with recent improvements in tumor response. Patient selection for BCS following NAC may be different than classic local regional recurrence (LRR) risk factors. Here we investigate risk factors for LRR and attempt to validate the MD Anderson Prognostic Index (MDAPI) for LRR in a single institution series. Methods: Data were analyzed for 178 consecutive patients treated at one institution who underwent NAC followed by BCS and whole breast radiotherapy between the years 1999 and 2011. Using univariate and multivariate analysis, multiple clinicopathologic factors were investigated, as well as the subgroups of the MDAPI. Chi-square tests were used to compare the LRR-free survival rates between subgroups. Results: The median follow-up was 70.33 months and the 5-year LRR-free survival was 93.18%. Multivariate analysis demonstrated that clinical stage and pathologic stage were both statistically significant for LRR-free survival, while pattern of residual disease was of borderline statistical significance. The MDAPI was not significantly associated with LRR-free survival (MDAPI low 93.80%, Intermediate 88.23%, High 88.89%). Five-Year Local Regional Recurrence -Free Survival According to Clinicopathologic Factors # Patients5yr LRR-Free SurvivalPathologic Stage p = 0.03301580.0%14292.5%27692.5%3994.6%pCR38100%Clinical Stage p = 0.0291580.0%213796.3%33883.8%MDAPI Score P = 0.506Low (0 or 1)12993.80%Int (2)3488.23%High (3)988.89%*MDAPI Score Factors cN Stage P = 0.305cN0-N116593.3%cN2-N31070%LVI P = 0.453No-LVI15793.5%Yes-LVI2390.9%pT&amp;gt;2cm P = 0.158Residual Tumor Morphology P = 0.055Multifocal Resid Tumor5996.5%Solitary Mass6690.6%No Resid Tumor5394.3%*These factors make up the MDA Prognostic Index Conclusion: Overall the 5-year LRR-free survival was high at 93.18%, which compares favorably to similar neoadjuvant patient cohorts who receive mastectomy instead of BCS. Our analysis indicates clinical stage and pathologic stage are significant in predicting LRR. Of the four predictive factors utilized by the MDAPI, only multifocal residual disease showed weak predictive power (p = 0.055) in our population; however, it correlated with higher LRR-free survival, the opposite of its indication in the MDAPI. The MDAPI was not useful in our patient population; the risk groups did not significantly correlate with LRR-free survival. This may be secondary to low total number of recurrence events and also the small number of patients in the MDAPI-high group (9 patients had an MDAPI score of 3, and none had a score of 4). As further data emerge regarding biology of tumors and recurrence, it may be a combination of molecular profiling and residual cancer burden that is a better predictor for LRR. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-14-12.

Cavity Margin Status Is an Independent Risk Factor for Local-Regional Recurrence in Breast Cancer Patients Treated with Neoadjuvant Chemotherapy Before Breast-Conserving Surgery

The objection of this study is to investigate whether the cavity margin (CM) status has different predictive efficacy for local-regional recurrence (LRR) in patients who have received or have not received neoadjuvant chemotherapy (NAC) before breast-conserving surgery. We identified 61 patients who received NAC before breast-conserving surgery. A nonrandomized unmatched cohort of 295 patients without history of receiving NAC were also included in this study. Clinicopathological features and follow-up data were abstracted and analyzed. Patients in the NAC-treated group had more advanced diseases when compared with patients in the nonNAC-treated group. With a median follow-up of 42 months, the LRR-free survival rate of patients with positive CMs was significantly lower than that of patients with negative CMs in the NAC-treated group. This distinction was not observed in the nonNAC-treated group. Univariate and multivariate analysis revealed that positive CM was the only independent predictive factor for LRR in the NAC-treated group but not in nonNAC-treated patients. CM status had different predictive efficacy for LRR in different settings. Association between CM status and LRR was observed in NAC-treated patients rather than nonNAC-treated patients. More extensive surgical treatment might be needed in NAC-treated patients when their CMs are positive.

Postmastectomy Radiotherapy In Breast Cancer With High Risk of Relapse: Current and Future Approaches

Postmastectomy radiotherapy in patients with breast cancer remains controversial in oncology . The major risk factor for local-regional recurrence is the tumor size and the number of lymph node metastases. The common sites of postmastectomy recurrence are the chest wall and the supraclavicle fossa. Postmastectomy radiotherapy decreases local-regional recurrence and improves survival in selected patients . This article presents a short overview of this issue based on the author's professional medical experience and reviews the literature.

Risk factors for local-regional recurrence following preoperative radiation therapy and surgery for head and neck cancer (stage II-IVB).

To discover possible risk factors for local-regional recurrence (LRR) following preoperative radiation therapy and curative surgery for head and neck squamous cell carcinoma (SCC) (stage II-IVB). Clinical records from 1987 to 1999 of 161 patients with head and neck SCC (oral cavity, 80 patients; larynx, 50; hypopharynx, 19; oropharynx, 12) who underwent preoperative radiation therapy and surgery were retrospectively reviewed. One hundred thirty-two (82%) of the patients had stage III or IV cancer. The median radiation dose was 38 Gy. The 5-year overall survival rate and LRR rate were 58% and 35%, respectively. At multivariate analysis, oral cavity cancer (P =.020), clinical T stage (P =.016), clinical N stage (P =.017), and status of surgical margins (P =.008) emerged as variables that were significantly associated with LRR. The analysis of only those patients with lymph node involvement showed that oral cavity cancer (P =.008), advanced N-stage cancer (P =.045), and long interval between the start of preoperative radiation therapy and surgery (> or =7 weeks) (P =.019) emerged as variables that were significantly associated with LRR. Oral cavity cancer, advanced T or N stage of disease, and unsatisfactory margins were risk factors for LRR. A long interval (> or =7 weeks) was a risk factor for LRR in patients with lymph node involvement.

Non-Small Cell Lung Cancer: Prognostic Factors in Patients Treated with Surgery and Postoperative Radiation Therapy

To determine survival outcomes, to identify adverse prognostic factors for relapse, and to compare American Joint Commission on Cancer (AJCC) staging systems in patients with non-small cell lung cancer (NSCLC) treated with surgery and postoperative radiation therapy. Between 1980 and 1995, 211 patients with NSCLC underwent surgery and postoperative radiation therapy. Surgery consisted of wedge resection (12.5%), lobectomy (67.8%), or pneumonectomy (19.7%). Pathologic stages (1992 AJCC) included I (n = 22), II (n = 70), IIIA (n = 104), and IIIB (n = 12). Indications for radiation therapy included compromised margins (n = 81) and/or positive mediastinal nodes (n = 55). Prognostic factors were identified by using univariate and multivariate models. Overall 3-year survival for patients with stage I, II, and IIIA cancer was 58.9%, 44.1%, and 43.2%, respectively. Older age (P = .008), male sex (P = .021), large primary tumor (P = .004), and multiple positive mediastinal nodes (P = .046) were associated with worse rates of survival. Actuarial risk of local-regional relapse (36 patients) was 21.4% at 3 years. In a multivariate model, use of wedge resection (P = .001), positive margins (P = .010), and larger pathologic tumor (P = .059) were risk factors for local-regional recurrence. Actuarial rate of distant failure was 55.2% at 3 years. Local-regional control can be achieved with surgery and radiation therapy in approximately 80% of patients; however, the rate of distant metastasis remains unacceptably high. Other variables, such as multiple positive nodes, may serve to identify patients at higher risk for relapse and poorer survival. Methods for improving treatment outcomes in these patients should be pursued.

Long-term follow-up of axillary node-positive breast cancer patients receiving adjuvant tamoxifen alone: patterns of recurrence

Purpose: To determine the patterns, incidence and risk factors for local-regional recurrence in patients with Stage II and III breast cancer treated with adjuvant tamoxifen alone, without adjuvant radiation. Material and Methods: The records of patients referred to the London Regional Cancer Centre with a diagnosis of breast cancer between 1980–1989 were reviewed. During this time period, it was the policy of the institution to omit local-regional radiation to patients receiving adjuvant systemic therapy. One hundred and fifty axillary node-positive Stage II and III breast cancer patients received adjuvant tamoxifen alone without postoperative local-regional radiation; these patients form the basis of this report. Results: Median follow-up was 67 months for the entire patient group and 85 months for the living patients. During this time, 42% of patients developed a recurrence, 22% first recurred in local-regional sites. The total incidence of local-regional recurrence (including those patients who first relapsed with systemic metastases) was 30%. Of the segmental mastectomy patients, 13% had recurrences in the intact breast. Of the modified radical mastectomy patients, 10% developed chest wall recurrences. Five percent of recurrences were first in the axilla and 6% in the supraclavicular nodes. Five-year actuarial survival for the entire patient group was 79% and disease-free survival was 60%, with a median disease-free survival time of 87 months. Five-year local-regional relapse-free survival was 76%. Five-year local-regional relapse-free survival was < 76% for those patients with 4 or more positive axillary nodes, regardless of tumor size. On univariable analysis, positive resection margins, number of positive axillary nodes, menopausal status, and negative estrogen and progesterone receptors were significant for isolated local-regional recurrence. On multivariable analysis, only positive resection margins and negative receptors remained significant. In terms of regional recurrence specifically, negative estrogen and progesterone-receptor status and positive resection margins were, again, prognostically significant. Conclusions: Postmenopausal women receiving adjuvant tamoxifen who have positive resection margins, ≥ 4 positive axillary nodes and/or negative estrogen and progesterone receptors, are at higher risk of local and regional recurrence and should, therefore, receive local-regional radiation.

Local-regional failure in patients treated with adjuvant chemotherapy for breast cancer.

Risk factors for local-regional recurrence of breast cancer were analyzed in a retrospective review of 117 patients treated with adjuvant CMF (Cytoxan [Mead Johnson & Co, Evansville, Ind], methotrexate, 5-fluorouracil) after radical or modified radical mastectomy at the Vincent T. Lombardi Comprehensive Cancer Center (Washington, DC). The median follow-up time was 50 months after mastectomy. The median time to recurrence was 23 months. The actuarial local-regional failure rate was 19% at five years. Risk of local failure correlated with size of primary (27% for T3 v 15% for T1) and axillary node status (36% for four or more positive nodes v 9% for three or fewer positive nodes). These findings suggest a rationale for the addition of postoperative radiation therapy in high-risk patients treated with adjuvant chemotherapy.