Risk Factors For Local Failure Research Articles

OC-0059 Clinical characteristics and risk factors for local failure in cervix cancer patients after MR IGABT

OC-0059 Clinical characteristics and risk factors for local failure in cervix cancer patients after MR IGABT

RADT-19. EFFECTS OF RADIATION DOSE-RATE AND TUMOR CHARACTERISTICS ON LOCAL CONTROL AND TOXICITY AFTER RADIOSURGERY FOR ACOUSTIC NEUROMAS

Abstract INTRODUCTION The effect of stereotactic radiosurgery (SRS) dose-rate on tumor control for acoustic neuroma (AN, or vestibular schwannoma) is unclear. METHODS This was a retrospective study of all patients treated for AN with frame-based cobalt-60 SRS at the Toronto Western Hospital between 2005-2019. Dose rates on the day of SRS were calculated from the calibration dose-rate while accounting for the cobalt-60 half-life of 5.2713 years. Local failure was defined as continued tumor growth >36 months post-SRS, tumor resection for LF, or use of any repeat SRS for LF. Cumulative incidence of LF was reported after accounting for competing risks of death, on a per-lesion basis. Comparisons of actuarial LF were made using Gray’s test. Multivariable analysis of LF was performed using a proportional hazards model. RESULTS A total of 607 patients were treated for 617 acoustic neuromas. Median follow-up was 5.0 years. 158 tumors (26%) were cystic. 71 tumors (12%) had previous resection. Nine patients received 10-11 Gy due to large tumor size; all remaining patients received 12 Gy to approximately the 50% isodose line. Median dose rate was 2.4 Gy/min (range, 1.3-3.7). There was no association between dose rate and LF (≥ 2.4 Gy/min vs. < 2.4 Gy/min, 6.07% vs. 6.12% at 5-year follow-up, p = 0.75). The adjusted local failure-specific hazard ratio (HR) for dose rate (per Gy/min) was 1.2 (95% CI 0.69-2.1, p = 0.52). Patients with previous surgery had higher LF, with a HR of 3.6 (95% CI 1.7-7.8, p = 0.0012), after adjusting for presence of cysts (HR 0.27, p = 0.034) and maximum tumor diameter (HR 1.055 per cm, p = 0.071). CONCLUSIONS In a large cohort of patients with acoustic neuromas, radiosurgery dose-rate was not associated with tumor control. Previous resection was a strong risk factor for local failure after SRS.

Incomplete resection increases the risk of local recurrence and negatively affects functional outcome in patients with tenosynovial giant cell tumor of the hindfoot

BackgroundDiffuse tenosynovial giant cell tumors (TGCT) are more likely to occur in the hindfoot and tend to recur after surgical excision. We performed a pooled analysis of hindfoot TGCT cases to identify factors associated with local recurrence and functional outcomes. MethodsWe retrospectively reviewed medical records of 33 patients diagnosed with TGCT (15, localized cases; 18 diffused cases) of the hindfoot between 1998 and 2017. Median follow-up was 32 months. Multivariable Cox proportional hazards regression analysis was conducted to estimate the hazard ratios for risk factors for local failure. Generalized linear regression models were used to assess whether resection status, tumor size, tumor type or bone involvement correlated with the Musculoskeletal Tumor Society (MSTS) score. ResultsLocal failure was reported in 30% (10/33) patients. Multivariable analysis showed that macroscopically incomplete resection was the only independent prognostic factor for poor local failure-free survival (P=.001). Incomplete resection significantly decreased MSTS score and negatively affected functional outcome (P=.047). ConclusionsIncomplete resection increases the risk of local recurrence and negatively affects functional outcome in patients with TGCT of the hindfoot.

Analysis of Minimum GTV/ITV to 100 Gy BED Isodose Distance as a Risk Factor for Local Failure after SBRT for NSCLC

Analysis of Minimum GTV/ITV to 100 Gy BED Isodose Distance as a Risk Factor for Local Failure after SBRT for NSCLC

Image-Guided Robotic Radiosurgery for Treatment of Recurrent Grade II and III Meningiomas. A Single-Center Study

Stereotactic radiosurgery (SRS) has been increasingly applied for malignant meningiomas as an alternative to conventionally fractioned radiation therapy. We performed a retrospective analysis of an institutional patient cohort with malignant meningiomas treated by image-guided SRS. All patients with atypical or anaplastic meningiomas who were treated by SRS using CyberKnife (CK) were identified. Local failure and regional and/or distant recurrences were evaluated together with toxicity and overall survival. We identified 127 treated lesions (105 atypical and 22 anaplastic) in 35 patients. The mean time interval between the last surgery and subsequent CK-SRS was 30.8 ± 24.5 months. Most lesions (83.5%) were treated using single-fraction CK-SRS. The median planning target volume of all 127 lesions was 1.71 cm3 (range, 0.06-22.5 cm3). The median follow-up period was 23 months (range, 2.1-60.3 months). The estimated local control rates were 97%, 77%, and 67% at 12, 36, and 60 months, respectively, in atypical meningiomas and 66% each at 12 and 24 months in anaplastic meningiomas. The regional progression-free survival was 93%, 73%, and 59% at 12, 36, and 60 months, respectively, in atypical lesions and 93% and 46% at 12 and 24 months in anaplastic lesions. The estimated distant tumor progression-free interval in atypical lesions was 80%, 44%, and 44% at 12, 36, and 60 months, respectively, and 49% and 24% at 12 and 24 months, respectively, in anaplastic lesions. Age was identified as a risk factor for local failure. Although the real boundaries of efficacy of SRS have to be further evaluated in a prospective trial, it seems that aggressive treatment by high-dose single or multisession SRS of recurring malignant meningiomas provides satisfactory local control rates.

Clinical Features of High-Grade Extremity and Trunk Sarcomas in Patients Aged 80 Years and Older: Why Are Outcomes Inferior?

Background: The population of many countries is aging and a significant number of elderly patients with soft-tissue sarcoma are being seen at cancer centers. The unique therapeutic and prognostic implications of treating soft-tissue sarcoma in geriatric patients warrant further consideration in order to optimize outcomes.Patients and Methods: This is a single-institution retrospective study of consecutive non-metastatic primary extremity and trunk high-grade sarcomas surgically treated between 1996 and 2012, with at least 2 years of follow-up for survivors. Patient characteristics and oncological outcomes were compared between age groups (≥80 vs. <80 years), using Chi-square or Fisher-exact test and Log-Rank or Wilcoxon test, respectively. Deaths from other causes were censored for disease-specific survival estimation. A p< 0.05 was regarded as statistically significant.Results: A total of 333 cases were eligible for this study. Thirty-six patients (11%) were aged ≥80 years. Unplanned surgery incidence and surgical margin status were comparable between the age groups. Five-year local-recurrence-free, metastasis-free and disease-specific survivals were 72% (≥80 years) vs. 90% (<80 years) (p = 0.004), 59 vs. 70% (p = 0.07) and 55 vs. 80% (p < 0.001), respectively. A significantly earlier first metastasis after surgery (8.3 months vs. 20.5 months, mean) and poorer survival after first metastasis (p = 0.03) were observed. Cox analysis revealed “age ≥80 years” as an independent risk factor for local failure and disease-specific mortality, with hazard ratios of 2.41 (95% CI: 1.09–5.32) and 2.52 (1.33–4.13), respectively. A competing risks analysis also showed that “age ≥80 years” was significantly associated with the disease-specific mortality.Conclusions: Oncological outcomes were significantly worse in high-grade sarcoma patients aged ≥80 years. The findings of more frequent local failure regardless of a consistent primary treatment strategy, an earlier time to first metastasis after surgery, and poorer prognosis after first metastasis suggest that more aggressive tumor biology, in addition to multiple co-morbidity, may explain the inferiority.

Patterns of recurrence after stereotactic radiosurgery for treatment of meningiomas

The purpose of this study was to evaluate patterns of failure after stereotactic radiosurgery (SRS) for meningiomas and factors that may influence these outcomes. Based on a retrospective chart review, 279 patients were treated with SRS for meningiomas between January 1999 and March 2011 at Wake Forest Baptist Health. Disease progression was determined using serial imaging, with a minimum follow-up of 6 months (median 34.2 months). The median margin dose was 12.0 Gy (range 8.8-20 Gy). Local control rates for WHO Grade I tumors were 96.6%, 84.4%, and 75.7% at 1, 3, and 5 years, respectively. WHO Grade II and III tumors had local control rates of 72.3%, 57.7%, and 52.9% at 1, 3, and 5 years, respectively. Tumors without pathological grading had local control rates of 98.7%, 97.6%, and 94.2% at 1, 3, and 5 years, respectively. Of the local recurrences, 63.1% were classified as marginal (within 2 cm of treatment field). The 1-, 3-, and 5-year rates of distant failure were 6.5%, 10.3%, and 16.6%, respectively, for Grade I tumors and 11.4%, 17.2%, and 22.4%, respectively, for Grade II/III tumors. Tumors without pathological grading had distant failure rates of 0.7%, 3.2%, and 6.5% at 1, 3, and 5 years, respectively. Wilcoxon analysis revealed that multifocal disease (p < 0.001) and high-grade histology (WHO Grade II or III; p < 0.001) were significant predictors of local recurrence. Additionally, male sex was a significant predictor of distant recurrence (p = 0.04). Multivariate analysis also showed that doses greater than or equal to 12 Gy were associated with improved local control (p = 0.015). In this patient series, 12 Gy was the minimum sufficient margin dose for the treatment of meningiomas. Male sex is a risk factor for distant failure, whereas high-grade histology and multifocal disease are risk factors for local failure.

Correlation of Local Failure With Measures of Dose Insufficiency in the High-dose Single-fraction Treatment of Bony Metastases

Correlation of Local Failure With Measures of Dose Insufficiency in the High-dose Single-fraction Treatment of Bony Metastases

Factors Predicting for Local Control in Patients With Desmoplastic Melanoma

Desmoplastic melanoma (DM) is a rare variant of melanoma that may be locally aggressive. The purpose of this review was to elucidate risk factors for local failure after wide local excision of DM. Two hundred ninety patients who were diagnosed with DM between 1989 and 2010 were retrospectively identified after approval by the IRB. Histopathologic variables, including perineural invasion (PNI), patient demographics, and details regarding surgery and radiation therapy were recorded. All available cases were reviewed internally and classified pure versus mixed DM per the Memorial Sloan Kettering Cancer Center system. The incidence of local recurrence as first site of recurrence was recorded. Median age (range) was 68 (16-96) years and 213/290 (73%) were men. Median Breslow depth (range) was 3.9 (0.5-35.0) mm. Radiation therapy (RT) was delivered to 115 patients (40%), among which 100 cases (87%) were to the primary site alone. RT was given with electrons alone in 83/115 (72%) patients. Hypofractionation (n = 55, 48%) (6 Gy times 5 fractions every 72 hrs) and conventional fractionation (n = 47, 41%) were both utilized. RT was more likely to be delivered in thicker (>4 mm), head and neck location, Clark's level V, ulcerated primaries, and with positive margins (all p < 0.05). Overall 37/290 (13%) patients developed local failure as the first site of failure. 17% (24/144) patients with PNI developed local failure versus ≤9% for those without PNI, although p = 0.14. Seventeen percent of patients (28/168) who did not receive radiation recurred versus 7% (8/115) for those who received RT (p = 0.02, OR = 2.7, 95% CI: 1.2-6.1). On multivariable analysis (MVA) with age and Breslow's thickness dichotomized using their medians, location (OR = 3.08, 95% CI: 1.15-8.30 for head and neck versus trunk and extremities), RT (OR = 8.08, 95% CI: 2.62-24.96 for no RT vs. RT) and Clark's level (OR = 4.0, 95% CI: 1.47-10.87 for V vs. others) were significant for local recurrence. On MVA, RT was one of the factors significant for relapse-free survival with a hazards ratio of 3.1 for no RT versus RT (p < 0.0001). DM may be a locally recurrent and aggressive variant of malignant melanoma. Adjuvant radiation therapy may be useful in selected cases in order to improve local control after surgical excision.

Proton‐based radiotherapy for unresectable or incompletely resected osteosarcoma

A study was undertaken to assess clinical outcome and the role of proton therapy for local control of osteosarcoma (OSA). All patients who received proton therapy or mixed photon-proton radiotherapy from 1983 to 2009 at the Massachusetts General Hospital were reviewed. Criteria for proton therapy were the need for high dose in the context of highly conformal radiotherapy of unresected or partially resected OSA, positive postoperative margins, postoperative imaging studies with macroscopic disease, or incomplete resection as defined by the surgeon. The primary endpoint was local control of the site treated; secondary endpoints were disease-free survival (DFS), overall survival (OS), long-term toxicity, and prognostic factors associated with clinical outcome. Fifty-five patients with a median age of 29 years (range, 2-76 years) were offered proton therapy. The mean dose was 68.4 gray (Gy; standard deviation, 5.4 Gy). Of the total dose, 58.2% (range, 11%-100%) was delivered with protons. Local control after 3 and 5 years was 82% and 72%, respectively. The distant failure rate was 26% after 3 and 5 years. The 5-year DFS was 65%, and the 5-year OS was 67%. The extent of surgical resection did not correlate with outcome. Risk factors for local failure were ≥ 2 grade disease (P < .0001) and total treatment length (P = .008). Grade 3 to 4 late toxicity was seen in 30.1 % of patients. One patient died from treatment-associated acute lymphocytic leukemia, and 1 from secondary carcinoma of the maxilla. Proton therapy to deliver high radiotherapy doses allows locally curative treatment for some patients with unresectable or incompletely resected OSA.

Correlation of Local Failure With Measures of Dose Insufficiency in the High-Dose Single-Fraction Treatment of Bony Metastases

In the setting of high-dose single-fraction image-guided radiotherapy of spine metastases, the delivered dose is hypothesized to be a significant factor in local control. We investigated the dependence of local control on measures of dose insufficiency. The minimum doses received by the hottest 100%, 98%, and 95% (D(min), D(98), and D(95)) of the gross target volume (GTV) were computed for 91 consecutively treated lesions observed in 79 patients. Prescribed doses of 18-24 Gy were delivered in a single fraction. The spinal cord and cauda equina were constrained to a maximum dose of 12-14 Gy and 16 Gy, respectively. A rank-sum test was used to assess the differences between radiographic local failure and local control. With a median follow-up of 18 months, seven local failures have occurred. The distributions of GTV D(min), D(98), and D(95) for treatments resulting in local failure were found to be statistically different from the corresponding distributions of the patient group as a whole. Taking no account of histology, p values calculated for D(min), D(98), and D(95) were 0.004, 0.012, and 0.031, respectively. No correlations between local failure and target volume or between local failure and anatomic location were found. The results indicate that D(min), D(98), and D(95) may be important risk factors for local failure. No local failures in any histology were observed when D(min) was >15 Gy, suggesting that this metric may be an important predictor of local control.

Factors Influencing Local Failure in Rectal Cancer: Analysis of 2315 Patients From a Population-Based Series

This study aimed to identify risk factors for local failure in an effort to optimize treatment for rectal cancer. A total of 154 patients with local failure after abdominal resection were identified from a population-based consecutive series of 2315 patients who underwent operations for rectal cancer in the Stockholm region between January 1995 and December 2004. Surgeons trained in total mesorectal excision performed the surgery, and preoperative radiotherapy was given according to defined protocols. Data from the 9 hospitals in the region, prospectively registered in a database, were reviewed with regard to tumor location and stage, radiation therapy, surgical treatment, and follow-up. In a multivariable analysis, independent risk factors for local failure were distal tumor location and advanced tumor and nodal stage, omission of preoperative radiation, residual disease, and hospitals with lower caseload. Low anterior resection and total mesorectal excision were deployed more often in centers with low failure rates. Discriminators for radiation therapy were patients with male gender, less advanced age, and tumors situated <6 cm from the anal verge. The variability of patient outcome according to local failure depends on tumor stage, nodal stage, and location. Omission of radiation therapy and surgical performance are important additional risk factors to consider when optimizing treatment for rectal cancer.

Die Rolle der Magnetresonanztomographie für die Indikationsstellung zur präoperativen Therapie beim Rektumkarzinom

Traditionally, the decision to apply preoperative treatment for rectal cancer patients has been based on the T- and N-category. Recently, the radial distance of the tumor to the circumferential resection margin (CRM) has been identified as an important risk factor for local failure. By magnetic resonance imaging (MRI) this distance can be measured preoperatively with high reliability. Thus, selected groups have started to limit the indication for preoperative therapy to tumors extending to - or growing within 1 mm from - the mesorectal fascia (CRM+). Pros and cons of this selected approach for preoperative treatment and first clinical results are presented. Prerequisites are the availability of modern high-resolution thin-section MRI technology as well as strict quality control of MRI and surgical quality of total mesorectal excision (TME). By selecting patients with CRM-positive tumors on MRI for preoperative therapy, only approximately 35% patients will require preoperative radiotherapy (RT) or radiochemotherapy (RCT). However, with histopathologic work-up of the resected specimen after primary surgery, the indication for postoperative RCT is given for a rather large percentage of patients, i.e., for pCRM+ (5-10%), intramesorectal or intramural excision (30-40%), pN+ (30-40%). Postoperative RCT, however, is significantly less effective and more toxic than preoperative RCT. A further point of concern is the assertion that patients, in whom a CRM-negative status is achieved by surgery alone, do not benefit from additional RT. Data of the Dutch TME trial and the British MRC (Medical Research Council) CR07 trial, however, suggest the reverse. To omit preoperative RT/RCT for CRM-negative tumors on MRI needs to be further investigated in prospective clinical trials. The German guidelines for the treatment of colorectal cancer 2008 continue to indicate preoperative RT/RCT based on the T- and N-category.

Proton Beam Radiotherapy of Uveal Melanoma: Italian Patients Treated in Nice, France

To evaluate the results of 15 years of experience with proton beam radiotherapy in the treatment of intraocular melanoma, and to determine univariate and multivariate risk factors for local failure, eye retention, and survival. A total of 368 cases of intraocular melanoma were treated with proton beam radiotherapy at Centre Lacassagne Cyclotron Biomedical of Nice, France, between 1991 and 2006. Actuarial methods were used to evaluate rate of local tumor control, eye retention, and survival after proton beam radiotherapy. Cox regression models were extracted to evaluate univariate risk factors, while regularized least squares algorithm was used to have a multivariate classification model to better discriminate risk factors. Tumor relapse occurred in 8.4% of the eyes, with a median recurrence time of 46 months. Enucleation was performed on 11.7% of the eyes after a median time of 49 months following proton beam; out of these, 29 eyes were enucleated due to relapse and 16 due to other causes. The univariate regression analysis identified tumor height and diameter as primary risk factors for enucleation. Regularized least squares analysis demonstrated the higher effectiveness of a multivariate model of five risk factors (macula distance, optic disc distance, tumor height, maximum diameter, and age) in discriminating relapsed vs nonrelapsed patients. This data set, which is the largest in Italy with relatively long-term follow-up, demonstrates that a high rate of tumor control, survival, and eye retention were achieved after proton beam irradiation, as in other series.

1–35 Is Lobular Carcinoma In Situ as a Component of Breast Carcinoma a Risk Factor for Local Failure After Breast-Conserving Therapy? Results of a Matched Pair Analysis

1–35 Is Lobular Carcinoma In Situ as a Component of Breast Carcinoma a Risk Factor for Local Failure After Breast-Conserving Therapy? Results of a Matched Pair Analysis

Low local recurrence rate without postmastectomy radiation in node-negative breast cancer patients with tumors 5 cm and larger

To assess the need for adjuvant radiotherapy following mastectomy for patients with node-negative breast tumors 5 cm or larger. Between 1981 and 2002, a total of 70 patients with node-negative breast cancer and tumors 5 cm or larger were treated with mastectomy and adjuvant systemic therapies but without radiotherapy at three institutions. We retrospectively assessed rates and risk factors for locoregional failure (LRF), overall survival (OS), and disease-free survival (DFS) in these patients. With a median follow-up of 85 months, the 5-year actuarial LRF rate was 7.6% (95% confidence interval, 3%-16%). LRF was primarily in the chest wall (4/5 local failures), and lymphatic-vascular invasion (LVI) was statistically significantly associated with LRF risk by the log-rank test (p=0.017) and in Cox proportional hazards analysis (p=0.038). The 5-year OS and DFS rates were 83% and 86% respectively. LVI was also significantly associated with OS and DFS in both univariate and multivariate analysis. This series demonstrates a low LRF rate of 7.6% among breast cancer patients with node-negative tumors 5 cm and larger after mastectomy and adjuvant systemic therapy. Our data indicate that further adjuvant radiation therapy to increase local control may not be indicated by tumor size alone in the absence of positive lymph nodes. LVI was significantly associated with LRF in our series, indicating that patients with this risk factor require careful consideration with regard to further local therapy.

Is lobular carcinoma in situ as a component of breast carcinoma a risk factor for local failure after breast‐conserving therapy?

The goals of the current study were to compare the clinicopathologic presentations of patients with lobular carcinoma in situ (LCIS) as a component of breast carcinoma who were treated with breast conserving surgery (BCS) and radiation therapy (RT) with those of patients without LCIS as part of their primary tumor and to report rates of local control by overall cohort and specifically in patients with positive margins for LCIS and multifocal LCIS. Sixty-four patients with Stages 0-II breast carcinoma with LCIS (LCIS-containing tumor group, LCTG) that had received BCS+RT treatment at the University of Michigan between 1989 and 2003 were identified. These patients were matched to 121 patients without LCIS (control group) in a 1:2 ratio. The median follow-up time was 3.9 years (range, 0.3-18.9 yrs). There were no significant differences between the two groups with regard to clinical, pathologic, or treatment-related variables or in mammographic presentation, with the exception of a higher proportion of the LCTG patients who received adjuvant hormonal therapy (P = 0.01). The rates of local control at 5 years were 100% in the LCTG group and 99.1% in the control group (P = 0.86). The presence of LCIS at the margins and the size and presence of multifocal LCIS did not alter the rate of local control. The extent of LCIS and its presence at the margins did not reduce the excellent rates of local control after BCS+RT. The data suggest that LCIS in the tumor specimen, even when multifocal, should not affect selection of patients for BCS and whole-breast RT.

Placing the Boost in Breast-conservation Radiotherapy: A Review of the Role, Indications and Techniques for Breast-boost Radiotherapy

Randomised trials have established that the addition of a boost dose of radiotherapy to the lumpectomy site after whole-breast adjuvant radiotherapy further improves local control achieved by whole-breast radiotherapy alone. The absolute size of this benefit varies according to the baseline risk of local recurrence. Age is the strongest predictor of benefit. Below the age of 40 years, the absolute benefit of a boost seems to be substantial, and there are no clearly identified groups unlikely to benefit. Above the age of 50 years, the benefit is small, and several additional risk factors for local failure would need to be present to merit boost treatment. These may include tumour size, high grade, high mitotic rate, lymphovascular invasion, extensive and high grade associated with intraduct carcinoma, receptor-positive tumours when avoidance of anti-oestrogen therapy is desired or receptor-negative tumours. Other independent reasonable indications for the use of a boost would be positive margins where further surgery is not indicated. If a boost is indicated, a variety of techniques may be used and toxicity and cosmetic results remain highly acceptable. Overall, there seems to be no substantial differences in boost technique results; however, interstitial techniques may have advantages for deeper targets compared with electrons. Irrespective of technique, accurate localisation will maximise the benefit of a boost. Surgical clips are strongly recommended to facilitate localisation.

Factors increasing local recurrence in breast-conserving surgery

From 20-year follow-up results of two pioneering randomized controlled trials demonstrating equal survival after mastectomy and breast-conservation therapy, recent high-quality, evidence-based clinical practice recommendations have been made. Breast-conservation therapy undoubtedly represents substantial progress for a better quality of life for women with early-stage breast cancer. However, lumpectomy is associated with a substantial proportion, approximately 10–20%, of local recurrence in long-term follow-up studies even after accounting for postoperative radiotherapy. Risk factors for local failure include margin status, young age and an extensive intraductal component. Young age and family history strongly suggest the need for genetic testing before initiation of treatment. Women with BRCA1 or BRCA2 mutations should be informed about the increased risk of contralateral breast cancer and ipsilateral failure after breast-conservation therapy. Bilateral mastectomy should also be offered as a treatment option. There is controversy over whether current effective adjuvant treatment, including chemotherapy and endocrine therapy, beyond appropriate local treatment as surgery and radiotherapy, can improve local control. Instead of debate over whether an ipsilateral tumor after breast-conservation therapy is local recurrence or a new primary cancer by analyzing conflicting data lacking strong evidence, efforts should be focused on reducing this risk irrespective of origin. Selecting women for breast-conservation therapy and achieving margin control can reduce ipsilateral failures.

LCIS as a component of breast cancer: Is it a risk factor for local failure

The incidence of lobular carcinoma in situ (LCIS) has steadily increased in the last two decades, particularly among post-menopausal women. While LCIS has historically been considered a marker for the development of breast cancer (BC), recent molecular studies suggest that it may be a precursor for invasive disease, with the potential for malignant progression similar to that observed with ductal carcinoma in situ (DCIS). In this case, the extent of LCIS and its presence at the surgical margins of lumpectomy specimens could impact the risk of subsequent in-breast tumor recurrence (IBTR) following breast-conserving surgery (BCS) and radiotherapy (RT). Therefore, the aims of this study were to compare the clinico-pathologic presentations of patients with LCIS as a component of BC treated with BCS and RT vs. patients without LCIS as part of their primary cancer (control group-CG) and to report rates of local control by overall cohort, and specifically in patient subsets with positive margins for LCIS and multifocal LCIS. Following IRB approval, the charts of 65 patients diagnosed with DCIS or invasive BC (stage I/II) with LCIS as a component, who had BCS+RT between 1/1989–12/2003 were identified. The CG consisted of 126 patients matched by age and date of diagnosis in a 2:1 ratio. All pathology slides were reviewed for the presence or absence of LCIS, and the slides of the LCIS-containing tumors group (LCTG) were re-reviewed by a single pathologist to assess the extent of LCIS in the specimen and its presence at the surgical margins. All patient characteristics, staging, treatment and outcome variables by group were analyzed and compared. ≤Median follow-up times for the LCTG and the CG were comparable at 4.1 and 4.4 years, respectively (range 0.1–18.9 years). There were no significant differences between the two groups in clinical, pathologic, or treatment-related variables with the exception of a higher proportion of the LCTG who received adjuvant hormonal therapy (p = 0.05). Median age at diagnosis was 58 years in both groups (range: 39–85 years) and more then 70% were postmenopausal. Eight (12.3%) patients in the LCTG and 11 (8.0%) in the CG had contralateral BC prior to, concurrent, or after the current diagnosis (p = 0.33). For the LCTG: LCIS was associated with infiltrating lobular carcinoma (ILC) in 38.5% of cases, infiltrating ductal carcinoma (IDC) in 17%, IDC+ILC in 21.5%, DCIS in 21.5%, and other in 1.5%. In the CG, the distribution was ILC 23%, IDC 39%, both 14%, DCIS 20%, and other 3% (p = 0.0001). For patients with mammographic findings, results were similar in both cohorts. Presentations in the LCTG included a mass-only in 40%, calcifications-only in 38% and both in 22% vs. a mass in 58%, calcifications only in 24%, and both in 18% in the CG (p = 0.11). The LCIS component was unifocal in 59% and multifocal in 41% with a median of 4 foci (range 3–9) per tumor in the multifocal group. The median size of the LCIS component was 0.2 mm, (range 0.05–10). The margins were positive or close (≤2mm) for LCIS in 41% of the LCTG. Conversely, margins were positive/close for DCIS or invasive disease in 15% of the CG vs. 0% in the LCTG (P < 0.0001). The rates of local control at 5- and 10-years were 100% and 100% in the LCTG and 99.1% and 96.9% in the CG (p = 0.8690). The presence of LCIS at the margins and multifocal LCIS did not alter the rate of local control. The presence of LCIS as a histologic component of BC had no influence on the rate of IBTR, and the extent in the surgical specimen and its presence at the margins did not reduce the excellent rates of local control following BCS and RT.