Search

Introduction: Axillary response to neoadjuvant endocrine therapy (NET) for the treatment of hormone receptor-positive breast cancer (HR+ BC) is not well-described. This study was designed to characterize nodal response after NET., Methods: Patients receiving NET followed by curative intent surgery at a comprehensive cancer center from 1998 to 2022 in a prospectively collected registry were included. Patients with distant metastasis were excluded. Primary outcome was nodal pathologic complete response (pCR). Downstaging was defined as post-NET decrease in category., Results: We included 123 patients; the majority were cT2 (n = 59) or cT3 (n = 35), and cN0 (n = 81). Median age was 70.0 years (interquartile range 62.1-76.0). Forty-two patients (34.1%) were clinically node-positive. After NET, 73 (59.8%) underwent breast-conserving surgery. All patients underwent sentinel lymph node biopsy, and 12 (9.8%) underwent completion axillary lymph node dissection. In-breast downstaging was achieved in 51 (41.5%) patients, 1 (0.8%) had breast pCR, and 14 (11.4%) had breast upstaging. Axillary downstaging was achieved in 10 (23.8%), 6 patients (14.3%) had nodal pCR, and 14 (33.3%) had axillary upstaging. At 10-year follow-up, local recurrence was 1% and distant recurrence was 14%, while disease-free survival was 82%. After adjusting for demographic and clinical factors, age was the only characteristic associated with mortality (hazard ratio 1.07, 95% confidence interval 1.01-1.13)., Conclusions: In HR+ BC treated with NET, long-term disease-free survival is good, although nodal pCR is uncommon for cN+ patients. Future studies are needed to elucidate optimal neoadjuvant systemic therapy and to delineate oncologically safe strategies to deescalate axillary management for residual microscopic disease., (© 2024. Society of Surgical Oncology.)

Background: Breast-conserving surgery (BCS) is a mainstay for breast cancer management, and obtaining negative margins is critical. Some have advocated for the use of preoperative magnetic resonance imaging (MRI) in reducing positive margins after BCS. We sought to determine whether preoperative MRI was associated with reduced positive margins., Patients and Methods: The SHAVE/SHAVE2 trials were multicenter trials in ten US centers with patients with stage 0-3 breast cancer undergoing BCS. Use of preoperative MRI was at the discretion of the surgeon. We evaluated whether or not preoperative MRI was associated with margin status prior to randomization regarding resection of cavity with shave margins., Results: A total of 631 patients participated. Median age was 64 (range 29-94) years, with a median tumor size of 1.3 cm (range 0.1-9.3 cm). Patient factors included 26.1% of patients (165) had palpable tumors, and 6.5% (41) received neoadjuvant chemotherapy. Tumor factors were notable for invasive lobular histology in 7.0% (44) and extensive intraductal component (EIC) in 32.8% (207). A preoperative MRI was performed in 193 (30.6%) patients. Those who underwent preoperative MRI were less likely to have a positive margin (31.1% versus 38.8%), although this difference was not statistically significant (p = 0.073). On multivariate analysis, controlling for patient and tumor factors, utilization of preoperative MRI was not a significant factor in predicting margin status (p = 0.110). Rather, age (p = 0.032) and tumor size (p = 0.040) were the only factors associated with margin status., Conclusion: These data suggest that preoperative MRI is not associated margin status; rather, patient age and tumor size are the associated factors., (© 2023. Society of Surgical Oncology.)

Background: The optimal treatment strategy for small node-negative human epidermal growth factor receptor 2-positive (HER2+) breast cancer remains controversial. Neoadjuvant chemotherapy may risk overtreatment, whereas surgery first fails to identify patients with residual disease in need of escalated adjuvant systemic therapy. We investigated patient characteristics associated with receipt of neoadjuvant chemotherapy., Methods: Adult women with cT1-T2/N0, HER2+ breast cancer between 2013 and 2017 in the National Cancer Database who underwent surgery within 8 months of diagnosis were included. Patients were classified as receiving neoadjuvant chemotherapy versus a surgery-first approach. We assessed the sociodemographic and clinical predictors of neoadjuvant chemotherapy versus surgery first and associations between neoadjuvant chemotherapy and breast cancer treatments using multivariable regression models., Results: We identified 56,784 women, of whom 12,758 (22%) received neoadjuvant chemotherapy, 29,139 (53%) received adjuvant chemotherapy, 12,907 (24%) received no chemotherapy, and 1980 were missing chemotherapy information. After adjustment, cT2 stage was the strongest predictor of neoadjuvant chemotherapy compared with surgery first. Younger age and later diagnosis year were positively associated with receipt of neoadjuvant chemotherapy. In contrast, hormone receptor positivity, Black race, rural county, and government-funded or no health insurance were inversely associated with neoadjuvant chemotherapy. In multivariable analyses, patients who received neoadjuvant chemotherapy were more likely to have a mastectomy (vs. lumpectomy) and sentinel lymph node biopsy or no nodal surgery (vs. axillary lymph node dissection). Patients who received neoadjuvant chemotherapy were more likely to receive multi-agent (vs. single-agent) chemotherapy than those who received adjuvant chemotherapy., Conclusions: Substantial differences in the utilization of neoadjuvant chemotherapy exist in women with HER2+ breast cancer, which reflect both clinical parameters and disparities. Optimal treatment strategies should be implemented equitably across sociodemographic groups., (© 2021. Society of Surgical Oncology.)

Background: Talimogene laherparepvec (T-VEC) is an oncolytic virus approved for the treatment of unresectable, recurrent melanoma. The role of T-VEC after progression on systemic immunotherapy (IO) remains undefined. The goal of this study was to characterize the efficacy of T-VEC after failure of IO in patients with unresectable metastatic melanoma., Methods: An international, multi-institutional review of AJCC version 8 stage IIIB-IV melanoma patients treated with T-VEC after failure of IO was performed at six centers from October 2015-December 2020. Primary outcome was in-field response; secondary outcomes included analyses of in-field and overall progression-free survival (PFS) and in-field and overall disease-free survival (DFS) after a complete response. Subset analysis of T-VEC initiation sequentially after or concurrently with IO was performed., Results: Of 112 patients, median age at T-VEC initiation was 69 years (range 21-93); 65 (58%) were male. Before T-VEC, 57% patients received one IO regimen, 42% received two or more, with most patients (n = 74, 66%) receiving T-VEC sequential to IO. Most were stage 3C (n = 51, 46%) at T-VEC initiation, 29 (26%) received injections to nodal disease. Over median follow-up of 14 months, in-field response at final T-VEC injection was 37% complete (CR), 14% partial (PR). T-VEC initiation sequentially or concurrently did not significantly affect in-field response (p = 0.26). Median in-field PFS was 15 months (95% confidence interval 4.6-NE). Median overall DFS after CR was 32 months (95% confidence interval 17-NE)., Conclusions: T-VEC after failure of IO is effective in unresectable, metastatic stage IIIB-IV melanoma. T-VEC initiation sequentially or concurrently did not significantly affect in-field response., (© 2021. Society of Surgical Oncology.)

Background: De-escalation of axillary surgery after neoadjuvant chemotherapy (NAC) requires careful patient selection. We seek to determine predictors of nodal pathologic complete response (ypN0) among patients treated on CALGB 40601 or 40603, which tested NAC regimens in HER2+ and triple-negative breast cancer (TNBC), respectively., Patients and Methods: A total of 760 patients with stage II-III HER2+ or TNBC were analyzed. Those who had axillary surgery before NAC (N = 122), or who had missing pretreatment clinical nodal status (cN) (N = 58) or ypN status (N = 41) were excluded. The proportion of patients with ypN0 disease was estimated for those with and without breast pathologic complete response (pCR) according to pretreatment nodal status., Results: In 539 patients, the overall ypN0 rate was 76.3% (411/539) to 93.2% (245/263) in patients with breast pCR and 60.1% (166/276) with residual breast disease (RD) (P < 0.0001). For patients who were cN0 pretreatment, the ypN0 rate was 88.8% (214/241), 96.3% (104/108) with breast pCR, and 82.7% (110/133) with RD. For patients who were cN1, 66.2% (157/237) converted to ypN0, 91.7% (111/121) with breast pCR and 39.7% (46/116) with RD. For patients who were cN2/3, 65.6% (40/61) converted to ypN0, 88.2% (30/34) with breast pCR and 37.0% (10/27) with RD. On multivariable analysis, only pretreatment clinical nodal status and breast pCR/RD were associated with ypN0 status (both P < 0.0001)., Conclusions: Breast pCR and pretreatment nodal status are predictive of ypN0 axillary nodal involvement, with < 5% residual nodal disease among cN0 patients who experience breast pCR. These findings support the incorporation of axillary surgery de-escalation strategies into NAC trials., (© 2021. Society of Surgical Oncology.)

Background: The utility of sentinel lymph node biopsy (SLNB) for non-ulcerated T1b melanoma is debated and associated costs are poorly characterized. Prior work using institutional registries may overestimate the incidence of nodal positivity in this population., Objective: The aim of this study was to estimate the use of SLNB, positivity prevalence, and procedural costs in patients with non-ulcerated T1b melanoma using a population-based registry., Methods: We identified patients with clinically node-negative, non-ulcerated melanoma 0.8-1.0 mm thick (T1b according to the 8th edition standard of the American Joint Committee on Cancer) in the Surveillance, Epidemiology, and End Results database from 2010 to 2016. The prevalence of SLNB procedures and positive sentinel nodes were calculated. Factors associated with SLNB and sentinel node positivity were assessed using logistic regression. Medicare reimbursement costs and patient out-of-pocket expenses for SLNB and wide local excision (WLE) versus WLE alone were estimated., Results: Among 7245 included patients, 3835(53%) underwent SLNB, 156 (4.1%, 95% confidence interval 3.5-4.7) of whom had a positive SLNB. Younger age, >1 mitosis per mm 2 , female sex, and truncal tumor location were associated with higher odds of positivity. The estimated SLNB cost to identify one patient with stage III disease was $71,700 (range $54,648-$83,172). Out-of-pocket expenses for a Medicare patient were estimated to be $652 for a WLE and SLNB and $79 for a WLE alone., Conclusions: In this population-based study, only 4% of selected non-ulcerated T1b patients had a positive SLNB, which is lower than prior reports. At the population level, SLNB is associated with high costs per prognostic information gained.

Background: Although sentinel lymph node (SLN) biopsy is a standard procedure used to identify patients at risk for melanoma recurrence, it fails to risk-stratify certain patients accurately. Because processes in SLNs regulate anti-tumor immune responses, the authors hypothesized that SLN gene expression may be used for risk stratification., Methods: The Nanostring nCounter PanCancer Immune Profiling Panel was used to quantify expression of 730 immune-related genes in 60 SLN specimens (31 positive [pSLNs], 29 negative [nSLNs]) from a retrospective melanoma cohort. A multivariate prediction model for recurrence-free survival (RFS) was created by applying stepwise variable selection to Cox regression models. Risk scores calculated on the basis of the model were used to stratify patients into low- and high-risk groups. The predictive power of the model was assessed using the Kaplan-Meier and log-rank tests., Results: During a median follow-up period of 6.3 years, 20 patients (33.3%) experienced recurrence (pSLN, 45.2% [14/31] vs nSLN, 20.7% [6/29]; p = 0.0445). A fitted Cox regression model incorporating 12 genes accurately predicted RFS (C-index, 0.9919). Improved RFS was associated with increased expression of TIGIT (p = 0.0326), an immune checkpoint, and decreased expression of CXCL16 (p = 0.0273), a cytokine important in promoting dendritic and T cell interactions. Independent of SLN status, the model in this study was able to stratify patients into cohorts at high and low risk for recurrence (p < 0.001, log-rank)., Conclusions: Expression profiles of the SLN gene are associated with melanoma recurrence and may be able to identify patients as high or low risk regardless of SLN status, potentially enhancing patient selection for adjuvant therapy.

Background: Inflammatory breast cancer (IBC) has historically been characterized by high rates of recurrence and poor survival; however, there have been significant improvements in systemic therapy. We sought to investigate modern treatment of IBC and define the yield and prognostic significance of axillary lymph nodes after neoadjuvant chemotherapy (NAC)., Methods: Women with clinical stage T4d, N0-N3, M0 IBC from 2012 to 2016 in the National Cancer Database were included. Kaplan-Meier survival curves and Cox regression were used to assess mortality by receptor subtype and nodal status., Results: We identified 5265 patients; 37% hormone receptor (HR) +/HER2 - , 19% HR +/HER2 + , 18% HR -/HER2 + , and 26% triple-negative, and 5-year overall survival was 51.6%. Only 34% were treated according to guidelines with NAC, modified radical mastectomy, and adjuvant radiation. Pathologically positive lymph nodes (ypN +) after NAC varied by subtype and clinical nodal status (cN) ranging from 82% in cN + HR +/HER2 - patients to 19% in cN0 HR -/HER2 + patients. ypN + strongly correlated with survival in all subtypes with the most pronounced impact in HR +/HER2 + patients, with 90% 5-year overall survival in ypN0 versus 66% for ypN + (HR 4.29, 95% CI 1.58-11.70, p = 0.03)., Conclusions: Five-year survival in M0 IBC is 51.6%. Positive nodes after NAC varied by subtype and clinical N status but is sufficiently high and provided meaningful prognostication in all subtypes to support continued routine pathologic assessment. Future study is warranted to identify reliable, less morbid, methods of staging the axilla in IBC patients appropriate for deescalation of axillary surgery.

Background: In the era of coronavirus disease 2019 (COVID-19), many Complex General Surgical Oncology (CGSO) fellowship programs implemented virtual interviews (VI) during the 2020 interview season. At our institution, we had the unique opportunity to conduct an in-person interview (IPI) prior to the pandemic-related travel restrictions, and a VI after the restrictions were in place., Objective: The goal of this study was to understand how the VI model compares with the traditional IPI approach., Methods: Online surveys were distributed to both groups, collecting feedback on their interview experience. Responses were evaluated using a two-sample t test assuming equal variances., Results: Twenty-three of 26 (88%) applicants completed the survey. Most applicants reported that the interview gave them a satisfactory understanding of the CGSO fellowship (100% IPI, 92% VI) and the majority in both groups felt that the interview experience allowed them to accurately represent themselves (92% and 82%, respectively). All participants in the IPI group felt they were able to get an adequate understanding of the culture of the program, while only 64% in the VI group agreed with that statement (p = 0.02). IPI applicants were more likely to agree that the interview experience was sufficient to allow them to make a ranking decision (92% vs. 54%; p = 0.04)., Conclusions: While the VI modality offers several advantages over the IPI, it still falls short in conveying some of the more subjective aspects of the programs, including program culture. Strategies to provide applicants with better insight into these areas during the VI will be important moving forward.

Introduction: In the past two decades, three prospective randomized trials demonstrated that elderly women with early stage hormone positive breast cancer had equivalent disease-specific mortality regardless of axillary surgery. In 2016, the Choosing Wisely campaign encouraged patients and providers to reconsider the role of axillary surgery in this population. We sought to identify factors that contribute to adopting non-operative management of the axilla in these patients., Materials and Methods: We performed a retrospective analysis of women ≥ 70 years old with cT1/T2, hormone positive invasive ductal carcinoma who underwent partial or total mastectomy, with/without axillary surgery, and did not receive adjuvant chemotherapy from the National Cancer Database from 2004 to 2015. We used multivariable log-binomial regression to model the risk of undergoing axillary surgery across region, care setting, and Charlson-Deyo scores, and analyzed temporal trends using Poisson regression. From 2004 to 2015, 87,342 of 99,940 women who met inclusion criteria (83%) had axillary surgery. Over time, axillary surgery increased from 78% to 88% (p < 0.001). This rise was consistent across region (p = 0.81) and care setting (p = 0.09), but flattened as age increased (p < 0.001). Omitting axillary surgery was more likely in patients treated in New England (RR 0.88, 95% CI 0.86, 0.89) and patients ≥ 85 (RR 0.66, 95% CI 0.65, 0.67)., Conclusions: Axillary surgery continues to be the preferred option of axillary management in elderly women with early stage, clinically node negative, hormone-positive, invasive breast cancer despite no survival benefit. Identifying factors to improve patient selection and dissemination of current recommendations can improve adoption of current evidence on axillary surgery in the elderly.

Historically, through the conduct of prospective clinical trials, breast cancer surgeons have performed less radical breast and axillary surgeries with no survival decrement to our patients. Currently, other opportunities exist for the treating breast surgeon to do less. Possibilities include active surveillance for ductal carcinoma in situ, ablative therapy for small primary breast cancers, selective omission of a sentinel node biopsy, and selective elimination of breast surgery after neoadjuvant systemic therapy. Breast surgeons must be leaders in the development and testing of effective therapy with the least intervention possible.

Background: Oncolytic viruses are genetically engineered or naturally occurring viruses that selectively replicate in cancer cells without harming normal cells. Talimogene laherparepvec (Imlygic ® ), the first oncolytic viral therapy approved for treatment of cancer, was approved for treatment of locally advanced melanoma in October 2015., Purpose: As a biologic product, use of T. laherparepvec in the clinical setting requires pretreatment planning and a unique systematic approach to deliver the therapy. The processes we describe herein could be adopted by other centers that choose to prescribe T. laherparepvec., Methods: We studied our clinical trial experience with T. laherparepvec before we embarked on using commercially available T. laherparepvec. We created a standard operating procedure (SOP) with multidisciplinary buy-in and oversight from leadership in Infection Control at our institution. We reflected on clinical cases and the actual procedures of administering T. laherparepvec to create the SOP., Results: The preimplementation planning, patient selection, identification of lesions to treat, the actual procedure, and ongoing assessment of patients are described. Tumoral-related factors that lead to unique challenges are described., Conclusions: A process to ensure safe and responsible implementation of a program to administer T. laherparepvec for treatment of melanoma may improve the quality of treatment for patients who suffer from advanced melanoma.

Although breast-conserving therapy is considered the preferred treatment for the majority of women with early-stage breast cancer, mastectomy rates in this group remain high. The patient, physician, and systems factors contributing to a decision for mastectomy are complicated. Understanding the individual patient's values and goals when making this decision is paramount to providing a shared decision-making process that will yield the desired outcome. The cornerstones of this discussion include education of the patient, access to decision-aid tools, and time to make an informed decision. However, it is also paramount for the physician to understand that a significant majority of women with an informed and complete understanding of their surgical choices will still prefer mastectomy. The rates of breast conservation versus mastectomy should not be considered a quality measure alone. Rather, the extent by which patients are informed, involved in decision-making, and undergoing treatments that reflect their goals is the true test of quality. Here we explore some of the factors that impact the patient preference for breast conservation versus mastectomy and how shared decision-making can be maximized for patient satisfaction.

Background: Increasingly, women with stage 2 and 3 breast cancers receive neoadjuvant therapy, after which many are eligible for breast-conserving surgery (BCS). The question often arises as to whether BCS, if achievable, provides adequate local control. We report the results of local recurrence (LR) from the I-SPY 1 Trial in the setting of maximal multidisciplinary treatment where approximately 50 % of patients were treated with BCS., Methods: We analyzed data from the I-SPY 1 Trial. Women with tumors ≥3 cm from nine clinical breast centers received neoadjuvant doxorubicin, cyclophosphamide and paclitaxel followed by definitive surgical therapy, and radiation at physician discretion. LR following mastectomy and BCS were analyzed in relation to clinical characteristics and response to therapy as measured by residual cancer burden., Results: Of the 237 patients enrolled in the I-SPY 1 Trial, 206 were available for analysis. Median tumor size was 6.0 cm, and median follow-up was 3.9 years. Fourteen patients (7 %) had LR and 45 (22 %) had distant recurrence (DR). Of the 14 patients with LR, nine had synchronous DR; one had DR > 2 years later. Only four (2 % of evaluable patients) had LR alone. The rate of LR was low after mastectomy and after BCS, even in the setting of significant residual disease., Conclusions: Overall, these patients at high risk for early recurrence, treated with maximal multidisciplinary treatment, had low LR. Recurrence was associated with aggressive biological features such as more advanced stage at presentation, where LR occurs most frequently in the setting of DR.

Background: Gene expression studies have identified distinct breast cancer subtypes, including luminal A, luminal B, Her2-enriched, and Basal-like, which differ in survival. The impact of subtypes on locoregional recurrence (LRR) after neoadjuvant chemotherapy for locally advanced breast cancer is unknown., Methods: A total of 149 patients with stage II and III breast cancer with known ER, PR, and HER2 who underwent neoadjuvant chemotherapy from 1991 to 2005 were analyzed. We used clinical assays to distinguish luminal A (ER or PR+/HER2-, n = 55), luminal B (ER or PR+/HER2+, n = 25), HER2 (ER and PR-/HER2+, n = 20), and Basal-like (ER, PR, and HER2-, n = 49) subtypes. Covariates associated with LRR were evaluated by logistic regression and differences between subtypes tested using Wald χ(2)., Results: Median follow-up was 55 months. Forty-nine (33%) patients had breast conservation (BCT) with radiation, 82 (55%) had a mastectomy with radiation, and 18 (12%) had a mastectomy alone. Eighty-eight (59%) were clinically node positive. A pathologic complete response was seen in 39 (26%) patients. LRR was identified in 11 (7%) patients: 2 after BCT (4%) and 9 after mastectomy (9%). LRR rates by subtype are as follows: luminal A 2 of 55 (4%), luminal B 1 of 25 (4%), Her2 1 of 20 (5%), and basal-like 7 of 49 (14%). Compared with all other subtypes, basal-like patients were more likely to have a LRR (7/49 (14%) vs. 4/100 (4%), p = 0.03)., Conclusions: Molecular subtype predicts LRR with basal-like patients more likely to develop LRR. These patients may be candidates for investigation with novel chemotherapy regimens and radiation sensitizing agents, which may offer improvement in local control.

Background: Multiple partial breast radiotherapy techniques are available. We have previously presented the technical details of our procedure of delivering partial breast irradiation with a single fraction of intraoperative radiotherapy (IORT) targeting the tumor in situ prior to partial mastectomy. This study details our completed, single-institution trial., Materials and Methods: An IRB-approved, DSMB-monitored phase II trial was performed with the following inclusion criteria: women age ≥48, ultrasound-visible invasive ductal cancers <3 cm, clinically negative axillary nodes. IORT was delivered using mobile electron irradiator, at least a 1.5-cm radial and 1-cm deep margin; patients received 15 Gy and immediately underwent partial mastectomy. Ipsilateral breast recurrence was classified as true/marginal, elsewhere in the breast or nodal basin. Kaplan-Meier methods were used to estimate survival functions and exact 95% confidence intervals are reported., Results: Between 2003 and 2007, 71 women underwent IORT (median follow-up: 3.5 years). For patients with tumor-involved or close margins, additional therapy was required: 7 patients, total mastectomy; 11, whole breast radiation. Four women experienced invasive ipsilateral breast failures (1 new primary, 3 margin recurrences) for a 3-year local control rate of 49 of 53 (94.8%; 95% confidence interval 92.4% [95% CI] 84.2–98.3%), actuarial three-year in breast recurrence was 8% (95% CI 2–18%), and breast cancer-specific survival was 100%., Conclusions: Intraoperative radiotherapy delivered to an in situ tumor is feasible, but our local control rate at 3.5 years is concerning. Possible changes to this technique to improve local control rates include better preoperative imaging (MRI), routine intraoperative ultrasound, and improved IORT delivery (larger cone, increased dose).

Background: The follow-up of patients with cutaneous melanoma is controversial. Current recommendations suggest routine history and physical examination every 3 to 6 months for the first 3 years and correlate studies including laboratory tests and radiographic imaging. However, the utility of these recommendations are unclear. The purpose of this study was to determine the impact of routine imaging on the method of detection of first recurrence in patients with stage II and sentinel lymph node-positive stage III melanoma., Methods: We analyzed a prospective database of all cutaneous melanoma patients treated at our institution from 1997 to 2005 who had at least 2 years of follow-up. The method of detection of initial recurrence was analyzed., Results: One hundred eighteen patients with stage II (n = 83) or III (n = 35) melanoma who were followed for at least 2 years were identified. Forty-three of these patients developed recurrence (median time to recurrence, 14 months). Site of first recurrence was as follows: 4 local, 17 in transit, 7 regional lymph node, and 15 distant. Twenty-nine recurrences (67%) were either patient detected or symptomatic. Eleven (26%) were detected by the physician at routine follow-up. Only three (7%) were identified by imaging (two chest X-ray and one brain magnetic resonance imaging) in an otherwise asymptomatic patient., Conclusions: Two-thirds of all initial recurrences of cutaneous melanoma were either detected by a patient or were symptomatic, with most of the remainder detected during routine physical examination. Routine imaging added little value in the detection of initial recurrence.

Introduction: Intraoperative radiotherapy (IORT) has the potential to eliminate the access problems associated with standard 6-week post-operative external beam radiotherapy for patients with breast cancer. However, accurate delivery of the IORT dose for breast cancer has been problematic due to difficulty estimating the tumor bed after tumor removal and tissue re-approximation. We are investigating the feasibility of partial breast irradiation using a single fraction of IORT delivered to the tumor in vivo prior to surgical resection., Methods: In a trial, approved by the University of North Carolina School of Medicine Institutional Review Board, patients > or =55 years old with infiltrating ductal carcinoma without an extensive intraductal component with an overall tumor size < or =3.0 cm receive a single dose of IORT in place of standard post-operative radiotherapy., Results: All patients undergo preoperative ultrasonography to define the target volume. In a standard operating room, the tumor is exposed through a standard partial mastectomy incision. IORT is then delivered using a mobile, self-shielded, magnetron-driven X-band linear accelerator (Intraop Corp, Santa Clara, CA, USA). 15 Gy is delivered to the 90% isodose line covering the tumor with a 1 cm margin anterior-posterior and 2 cm margins laterally. After IORT, partial mastectomy is performed in the usual manner., Conclusions: IORT for breast cancer, delivered to the exposed tumor in vivo, is feasible and allows accurate estimation of the tumor bed. Further follow-up is ongoing to determine the efficacy of this approach.

Background: Accelerated partial breast irradiation (APBI) has gained widespread interest as a means of improving the convenience and availability of breast conserving radiotherapy. Intraoperative radiation therapy (IORT) is an APBI technique that delivers breast radiotherapy as a single dose at the time of partial mastectomy. We adapted the technique of Veronesi to deliver IORT prior to tumor excision to improve delivery to the region at risk and reduce the volume of normal tissue irradiated., Methods: Patients age >or=55 with ultrasonographically defined tumors

The diagnosis of breast cancer or melanoma in a pregnant patient presents some unique and difficult challenges for both patients and providers. Lymphatic mapping and sentinel lymph node (SLN) biopsy has become an attractive alternative to elective lymphadenectomy procedures for patients with breast cancer and melanoma. However, there is no data on the safety or utility of sentinel node mapping in pregnant patients. Therefore, we reviewed our experience with mapping in gravid patients. Academic institutions throughout North Carolina were asked to contribute cases of mapping performed during pregnancy. A total of nine women underwent sentinel node mapping during pregnancy. All nine were Caucasian with an average age of 32. SLN were found in all cases and mapping procedures were for breast cancer (three), and melanoma (six). There were no adverse reactions to the SLN procedures and one patient developed a seroma at a biopsy site. All went on to have term deliveries without known adverse effects. This limited experience shows that SLN mapping procedures are feasible in pregnant patients. However, this is not a general endorsement of such procedures in pregnant patients. We suggest that potential risks of vital dye or radioactive tracers be clearly explained to the parents when the mother is a candidate for a mapping procedure, and be balanced against the risk of delaying therapy or omitting nodal staging.

Background: The prognostic significance of micrometastasis after neoadjuvant chemotherapy for locally advanced breast cancer is unknown. We examined the residual lymph node metastasis size in patients after treatment with neoadjuvant chemotherapy to determine the relevance of metastasis size on outcome., Methods: Stage II/III breast cancer patients treated with neoadjuvant chemotherapy at our institution from 1991 to 2002 were included. We examined the relationship of postneoadjuvant chemotherapy lymph node metastasis size and number with distant disease-free survival (DDFS) and overall survival (OS)., Results: In 122 patients with a median follow-up of 5.4 years, we found not only that patients with an increasing number of residual positive nodes had progressively worse DDFS and OS (P < .0001 for both) compared with patients with negative nodes, but also that the size of the largest lymph node metastasis was associated with worse DDFS and OS (P < .0001 for both) in both univariate and multivariate analysis. Compared with negative nodes, even lymph node micrometastasis (<2 mm) was associated with worsened DDFS and OS (adjusted P = .02 and P = .005, respectively)., Conclusions: Residual micrometastatic disease in the axillary lymph nodes after neoadjuvant chemotherapy is predictive of worse prognosis than negative nodes. In this study, the lymph node metastasis size and the number of involved lymph nodes were independent powerful predictors of DDFS and OS.

Background: Patients with thin (Breslow thickness < or =1.0 mm) melanoma have a good prognosis (5-year survival >90%). Consequently, the added benefit of lymphatic mapping and sentinel lymphadenectomy (LM/SL) in these patients is controversial. We hypothesize that LM/SL with a focused examination of the sentinel node (SN) will detect a significant number of SN metastases in patients with thin melanoma and that certain clinical or histopathologic factors may serve as predictors of SN tumor involvement., Methods: Over 6 years, 349 patients with melanoma underwent LM/SL and were prospectively entered into an institutional review board (IRB)-approved database. LM/SL was performed with a combined radiotracer and blue dye technique. SNs were serially sectioned, and each section was examined by a dermatopathologist at multiple levels with hematoxylin and eosin as well as immunohistochemical stains., Results: One hundred forty-six patients (42%) had a melanoma with Breslow thickness < or =1.0 mm; six (4%) of these 146 patients had a tumor-involved SN. On multivariate analysis, none of the clinical or histopathologic factors examined were significantly associated with SN tumor involvement in patients with thin melanoma. Completion lymphadenectomy was performed on all patients with a tumor-involved SN. None of the patients had non-SN tumor involvement., Conclusions: The incidence of SN tumor involvement in patients with thin melanoma is considerable. Although we were unable to identify predictors of SN tumor involvement in patients with thin melanoma, efforts to identify predictors of SN tumor involvement should continue. Until better predictors are identified, we continue to advocate offering LM/SL to patients with thin melanomas who demonstrate clinical or histopathologic characteristics that have historically been associated with an increased risk of recurrence and mortality.

Background: Routine elective superficial parotidectomy for patients with primary cutaneous melanomas of the scalp, auricle, or face has been questioned. We evaluated an alternative, i.e., lymphatic mapping and sentinel lymphadenectomy, for patients with primary cutaneous melanomas draining to the region of the parotid gland., Patients: Retrospective review of our large (>8000 patients) melanoma database identified 39 patients with primary melanomas (American Joint Committee on Cancer stage I or II) of the scalp (n = 19), auricle (n = 11), or face (n = 9) who underwent intraoperative lymphatic mapping to identify a sentinel node (SN) in the region of the parotid gland, between June 1985 and July 1997., Results: A SN was identified in the parotid region of 37 patients (94.9%), four of whom had SN metastases. The mean number of SN obtained was 2.3/patient (range, 1-4/patient). The two patients (5.1%) for whom a parotid-region SN could not be identified underwent superficial parotidectomy during the same operation. Among the 33 patients with tumor-free SN, with a median follow-up period of 33.2 months (range, 1-121 months), there was one (3.1%) intraparotid recurrence; thus, the false-negative rate was 3.1%. The procedure-related surgical morbidity rate was only 2.6% (one case of temporary facial nerve paresis)., Conclusions: For patients with primary melanomas of the scalp, auricle, or face, sentinel lymphadenectomy can be performed accurately in the parotid region and offers a low-morbidity alternative to routine elective superficial parotidectomy.

Background: Invasive lobular carcinoma (ILC) accounts for 5% to 10% of all invasive breast cancers. Although breast conservation therapy using local excision and postoperative irradiation is a standard therapy for early invasive ductal breast cancer, the result of this strategy in ILC is not well documented. We sought to determine the rate of locoregional recurrence after breast conservation therapy in patients with ILC., Methods: A retrospective review of 74 patients with ILC treated with breast conservation therapy at The University of Texas M. D. Anderson Cancer Center (n = 43) or The John Wayne Cancer Institute (n = 31) between 1977 and 1993 was performed., Results: The median age of patients was 60 years, and median follow-up was 56 months (range 1 to 207 months). Thirty-nine patients had American Joint Committee on Cancer stage I disease, 30 had stage IIa disease, and five had stage IIb disease. All patients underwent surgical resection and postoperative radiation therapy. Twelve patients received postoperative adjuvant chemotherapy, and 27 patients were treated with adjuvant hormonal therapy. The 5-year actuarial locoregional recurrence rate was 9.8%, and the median time to recurrence was 77 months (range 41 to 113 months). Patients with positive or close (< or = 1 mm) surgical margins were at increased risk for local recurrence on univariate analysis (p = 0.034). Of the nine patients with breast recurrence, six underwent salvage therapy with total mastectomy and are disease free at the time of this writing, two patients died of distant disease, and one is alive with local disease at the time of this report. The 5-year disease-specific survival rate was 93.7%., Conclusions: Breast conservation therapy for ILC achieves locoregional control in the majority of patients. However, long-term follow-up of patients is important because many local recurrences following breast conservation therapy are late events.