Objective: To assess the efficiency of Simplified Lymphatic Microsurgical Preventing Healing Appr... more Objective: To assess the efficiency of Simplified Lymphatic Microsurgical Preventing Healing Approach (S-LYMPHA) in preventing lymphedema (LE) in a prospective cohort of patients. Background: LE is a serious complication of axillary lymph node dissection (ALND) with an incidence rate of 25%. LYMPHA has been proposed as an effective adjunct to ALND for the prevention of LE. This procedure, however, requires microsurgical techniques and significant coordination between services. Methods: All patients, undergoing ALND with or without S-LYMPHA between January 2014 and December 2016 were included in the study. During follow-up visits, tape-measuring limb circumference method was used to detect LE. The incidence of LE was compared between ALND with and without S-LYMPHA. Results: A total of 380 patients were included in the analysis. Median followup time was 15 (1-32) months. Patients, who underwent S-LYMPHA, had a significantly lower rate of LE both in univariate and multivariate analysis [3% vs 19%; P ¼ 0.001; odds ratio 0.12 (0.03-0.5)]. Excising more than 22 lymph nodes and a co-diagnosis of diabetes mellitus were also correlated with higher clinical LE rates on univariate analysis, but only excising more than 22 lymph nodes remained to be significant on multivariate analysis. Conclusions: S-LYMPHA is a simple method, which decreases incidence of LE dramatically. It should be considered as an adjunct procedure to ALND for all patients during initial surgery.
112 Background: Triple-negative (basal) and HER2+ subtypes have been associated with increased ri... more 112 Background: Triple-negative (basal) and HER2+ subtypes have been associated with increased risk of locoregional recurrence (LRR) in earlier studies of breast-conserving therapy (BCT), in which fewer patients received systemic therapy compared with recent standards, including HER2-targeted therapy. We analyzed whether basal and HER2+ subtypes are independent prognostic factors for LRR in BCT patients treated with modern systemic therapy. Methods: We retrospectively studied 415 patients with invasive breast cancer who received BCT from 1992 to 2009. Axillary surgery was done in 404 patients (97%). Forty eight percent of patients received chemotherapy (anthracycline/taxane 34%, trastuzumab-containing 4%, other 10%). Hormone therapy was given in 67%. Progression-free survival (PFS) and OS were estimated by the Kaplan-Meier method. Rate of LRR was estimated by the method of cumulative incidence allowing for competing risks. The effect of prognostic factors was examined by Fine and Gray’s test. Results: Median follow-up was 60 months. Median age was 54 (26–86). Stage: T1 70%, T2 26.3%, T3 8%; N0 75%, N1 23.5%, N2 1.7%. Receptor status was available in 301 patients to approximate subtypes: 66% Luminal A, 9% Luminal B, and 5% HER2+, and 20% Basal. Overall, there were 11 LRR, 15 distant metastasis, and 20 deaths. The 10-year PFS and OS were 85.4% and 90.5%, respectively. The 5 and 10-year cumulative incidence of LRR were 2.8% (95%CI: 1.4–5.2) and 4.5% (95%CI: 2.2–8.2) respectively. On univariate analysis, Basal vs. Luminal A (HR: 9.12, p<0.001) and tumor size >2cm vs. ≤2cm (HR: 4.00, p=0.022) were significant prognostic factors for LRR as first failure. On multivariate analysis, only basal subtype (HR: 6.29, p=0.011) retained significance; others effects, including luminal B/HER2 combined subtypes, were not significant. Conclusions: Long-term clinical outcomes were excellent in this cohort of breast cancer patients treated with BCT and modern systemic therapy, with 10-year LRR 4.5% and OS 90.5%. Basal subtype was an independent predictor for LRR. Conversely, HER2+ subtype was not associated with increase in LRR, in this cohort treated with BCT and trastuzumab.
International Journal of Radiation Oncology Biology Physics, Nov 1, 2018
defined as patients receiving RT 1-3 months before CPI (10%), within 1 month of CPI (9%), and >1 ... more defined as patients receiving RT 1-3 months before CPI (10%), within 1 month of CPI (9%), and >1 month after CPI (18%). None of these variables were associated with older age (Fisher's Exact Test, p>0.05). Complete/partial response, stable disease or progressive disease was achieved in 30.4%, 28.8% and 40.8%, respectively; response was independent of age (pZ0.21). On KM analysis, older age was associated with improved PFS (HRZ0.74, 95% CIZ0.554-0.997), and RT to a Non-CNS site at the time of CPI was associated with improved PFS [HRZ0.59 (0.34-1.01)). On multivariate Cox analysis, older age (Adjusted HR 'AHR'Z0.68, p<0.021) and RT to a Non-CNS site (AHRZ0.46, p<0.009) were prognostic for PFS. Similar trends were observed for TTF. Older age and RT (irrespective of timing or site) were not associated with OS (p>0.1). Conclusion: Among patients receiving CPIs for the treatment of advanced lung cancer, older age is not associated with a worse OS or higher rates of SAEs, but may be associated with improved PFS and TTF. Prospective data is needed to better examine the impact of RT on OS in the setting of CPIs for older patients.
International Journal of Radiation Oncology Biology Physics, Nov 1, 2009
Purpose/Objective(s): Locally advanced breast cancer (BC) comprises 10-20% of new cases and is a ... more Purpose/Objective(s): Locally advanced breast cancer (BC) comprises 10-20% of new cases and is a common presentation of BC in South Florida. There is little data concerning capecitabine and radiation therapy for the treatment of locally advanced disease. Only one phase II trial (Gaui, 2007) studied the combination of these modalities and it showed safe and effective control of inoperable disease. However, no study has examined low dose capecitabine as a radiation sensitizing agent. Our goal was to retrospectively assess locoregional control (LRC) outcomes in patients with locally advanced BC treated with concurrent RT and low dose capecitabine. Materials/Methods: We retrospectively reviewed records of 20 consecutive patients with stage II-IV BC that received concurrent capecitabine and radiation between 1/2003 and 2/2008. Patients were treated with this regimen for inflammatory carcinoma, disease recurrence, or poor response to treatment. Results: Median age at diagnosis was 50 (range 34-74). Race was Caucasian (n=4), Asian (n = 1), African Descent (n = 4), and Hispanic (n = 11). Clinical stages were IIA (n = 1 with recurrent disease), IIB (n = 1, T3N0), IIIA (n = 6), IIIB (n = 5), IIIC (n = 5), and IV (n = 2). Eight patients had inflammatory carcinoma. Three patients presented with locally recurrent disease prior to radiation. Average clinical tumor size at initial presentation was 6.7 cm. All patients had either neoadjuvant and/or adjuvant chemotherapy. All patients went on to definitive surgery (MRM =19, BCT = 1). One (5%) patient had a pCR. All others had \pCR. One patient had positive surgical margins. Patients were treated with a mean dose of 60 Gy to the chest wall (including boost) and 45 Gy to the supraclavicular fossa. Seven patients had axillary boost with a mean dose of 45.5 Gy. All patients received concurrent capecitabine and RT. The dose of capecitabine was 500mg daily starting with the first day of radiation and ending at completion of RT. Median follow-up time was 21 months from time of diagnosis and 12 months from completion of RT. Fifteen patients were alive with no clinical evidence of disease. Five patients had metastases (two of these at the start of radiation). One of the patients with metastatic disease died. No patients had local regional recurrence (LRR). By the last week of treatment the RTOG ARMSC skin criteria was as follows: Score 2 (n = 9), Score 3(n = 8), Score 4 (n = 3, all with chest wall involvement). At six weeks post RT, all patients had minimal skin toxicity. Conclusions: Despite short follow up, small patient numbers, and increased acute toxicity, capecitabine appears to be a safe and effective radiosensitizer. Concurrent capecitabine and RT provided effective LRC with acceptable toxicity in this group of BC patients at very high risk of LRR. These results encourage a future prospective trial.
International Journal of Radiation Oncology Biology Physics, Nov 1, 2009
from first day of treatment) toxicities were assessed retrospectively using the RTOG acute toxici... more from first day of treatment) toxicities were assessed retrospectively using the RTOG acute toxicity criteria and CTCAE version 3, respectively. Results: Median age was 61.6 years (range 38.4-84.7 years). Median follow-up was 22.0 months (mean 27.83, range 6.5-60.4 months). Median tumor size was 1.1 cm (range 0.4-2.9 cm). Stage was 0 in 11, I in 38, IIA in 1, and IIB in 1. Treatment was delivered using photons only in 40 and mixed photon/electron beams in 11 patients. Prescribed dose/fractionation was 38.5 Gy in 3.85 Gy fractions bid over 5 days for all patients. Deep inspiration breath hold gating and image-guided radiotherapy using implanted fiducial markers have been used since July 2007 and January 2008, respectively. Locoregional control was 100%. Distant metastasis-free and overall survival was 98%, with one stage IIB patient developing distant metastases 22 months after radiotherapy and dying 49 months after radiotherapy. There were no grade 2 or higher acute toxicities. There were 2 grade 2 late skin toxicities consisting of persistent moderate breast edema. No pulmonary or cardiac toxicity was seen. Musculoskeletal toxicity included 3 grade 1 (mild chest wall pain without radiographic evidence of fracture) and 1 grade 2 (symptomatic non-displaced rib fractures). Conclusions: In appropriately selected patients, 3DCRT-APBI can be executed safely and effectively in the community setting. Both local control and short-term toxicity appear at least comparable to that of whole breast radiotherapy; however, long-term results of a prospective clinical trial are needed to firmly establish the appropriateness of APBI.
Introduction: The increase in survival after childhood radiation therapy for some blood malignanc... more Introduction: The increase in survival after childhood radiation therapy for some blood malignancies has led to increase in the diagnosis of radiation induced secondary solid malignancies (SSM). Diagnostic and therapeutic radiation is a known risk factor for malignancy. Although rare, it has been demonstrated in the literature that diagnostic and therapeutic radiation is associated with breast cancer in women. Male breast cancer (MBC) is a rare condition, accounting for approximately 1% of all breast cancers. Not surprisingly, there is a paucity of case reports in the literature describing radiation as a risk factor for cancer in men. Case Report: Herein we report a young man presenting with invasive breast cancer 19 years after receiving radiation therapy and bone marrow transplant (BMT) for acute lymphocytic leukemia (ALL) in childhood. After standard diagnostic and metastatic workup, treatment included neoadjuvant chemotherapy, surgery and adjuvant radiation therapy and adjuvant hormonal therapy. Outcome and follow up data are reported in the paper as well. Discussion: Only two similar cases were reported earlier, for two patients who developed breast cancer 13 and 15 years after exposure to radiation therapy. Our case report extends the latency period to 19 years. The most important prognostic indicators were stage at diagnosis and lymph node status. Conclusion: Radiation induced MBC should be considered in the differential diagnosis of breast related symptoms, even with a very remote history of exposure. The younger the age of exposure, the more years the patient has at risk of breast cancer. It is important to attempt early detection in these patients before the disease progresses to an advanced stage. Survivors of radiation treated primary cancer should be closely monitored for SSM, including breast cancer, for the rest of their lives. Yearly clinical breast exams and selective imaging studies should probably be offered to the subgroup of male patients at higher risk, including those with early age at exposure (younger than 10 years), and those getting TBI for the treatment of ALL.
Background: Lymphedema (LE) is a serious complication of axillary lymph node dissection (ALND) wi... more Background: Lymphedema (LE) is a serious complication of axillary lymph node dissection (ALND) with an incidence rate of 16%. Lymphatic Microsurgical Preventing Healing Approach (LYMPHA) has been proposed as an effective adjunct to ALND for the prevention of LE. This procedure however requires microsurgical techniques. The aim of this study was to assess the efficiency of Simplified-LYMPHA (SLYMPHA) in preventing LE in a prospective cohort of patients. Methods: All patients, undergoing ALND with or without SLYMPHA between January 2014 and December 2016 were included in the study. SLYMPHA is a slightly modified and simplified version of LYMPHA. It is performed by the operating surgeon performing the ALND. One or more lymphatic channels identified by reverse arm mapping are inserted using a sleeve technique into the cut end of a neighboring vein. During follow-up visits, tape-measuring limb circumference method was used to detect clinical LE. Demographic, clinical, surgical and pathol...
Objective: Therapeutic management of ductal carcinoma in situ (DCIS) is heterogeneous among count... more Objective: Therapeutic management of ductal carcinoma in situ (DCIS) is heterogeneous among countries worldwide, and some treatment indications are still controversial. To investigate DCIS management in different countries; identify both consensual practices and controversial topics; and survey opinions about the future management of DCIS. Materials and Methods: The Senologic International Society network members participated to an online survey using a questionnaire, between November 2021 and February 2022. Results: Twenty-two responses from 20 different countries showed that organized breast cancer screening programs were present for 87% participants, and DCIS cases represented 13.7% of all breast cancers. Most participants used the grade classification (100%), the morphological classification (78%) and performed immunohistochemistry assays (73%). In case of conservative treatment, the mean re-excision rate was 10.3% and clear margins of mean 2.5 mm were considered healthy. Radical mastectomy rate was 35.5% with a breast reconstruction rate of 53%. Tumor bed boost indications were heterogeneous, and 73% of participants indicated hormone therapy for hormone-positive DCIS. Surgery and radiotherapy omission for some low-risk DCIS were considered by 73% of participants. Multigene assays were used by 43% of participants. Concerning future changes in DCIS management, participants mostly answered surgical de-escalation (48%), radiotherapy de-escalation (35) and/or active surveillance for some cases (22%). Conclusion: This survey provided an overview of the current practices of DCIS management worldwide. It showed that some areas are rather consensual: incidence increases over time, treatment in young women, pathological classifications, definition of healthy margins, the skin-sparing mastectomy and
Purpose Accumulating evidence supports usage of sentinel lymph node biopsy (SLNB) for clinically ... more Purpose Accumulating evidence supports usage of sentinel lymph node biopsy (SLNB) for clinically node positive (cN+) breast cancer (BC) patients, who become clinically node negative (ycN-) after neoadjuvant chemotherapy (NAC). How to reassess the axilla after NAC is a challenging issue. In our institution, Systematic Sonographic Axillary Staging (SSAS) is currently being tested in this group of patients. The aim of this study is to analyze the early results of this approach. Method During initial presentation, systematic sonographic axillary staging is done preferentially by the surgeon. Needle biopsy is then performed of suspicious node(s). At completion of NAC, the axilla is again systematically staged sonographically, taking into account the pre-treatment disease locations. Any residual morphologically suspicious node undergoes a repeat needle biopsy. According to the evidence of residual disease, the patient is either scheduled for axillary dissection (AD) or for SLNB. We analyz...
Objective Positive margins remain a significant psychological and economic burden after breast co... more Objective Positive margins remain a significant psychological and economic burden after breast conserving surgery. The aim of this study was to test the hypothesis that advanced oncoplastic techniques as well as intraoperative integrative imaging with intraoperative ultrasound and mobile digital specimen radiography decreases positive margin rate in breast conserving surgery. Methods A single-institution retrospective review of a prospectively collected database was performed. Patients with breast neoplasms who underwent lumpectomy with or without using intraoperative integrative imaging approaches and oncoplastic techniques were included. The primary outcome was positive margin rate for each technique. Results A total of 392 patients were included in the study. The median age of the cohort was 59 years. Overall positive margin rate was 15%. Ductal carcinoma in situ (DCIS) histology and larger tumor size were associated with higher positive margin rate. Intraoperative integrative im...
Antiestrogen mediated cell cycle arrest requires the CDK inhibitor, p27. Src kinase mediates p27 ... more Antiestrogen mediated cell cycle arrest requires the CDK inhibitor, p27. Src kinase mediates p27 loss and antiestrogen resistance in ER+ breast cancer lines in vitro. In ER+ xenografts, the Src inhibitor, saracatinib, restored antiestrogen responses in resistant tumors. This led to a Phase I/randomized double-blind Phase II trial to test effects of saracatinib with anastrozole for ER+ and/or PR+ postmenopausal breast cancer. Phase I accrued 12 subjects and showed 175 mg po saracatinib is safely given with 1 mg po daily anastrozole with good PK . In Phase II, postmenopausal women with new ER+ and/or PR+, HER2- breast cancers ≥ 2 cm were randomized 2:1 to either neoadjuvant anastrozole with saracatinib or anastrozole/placebo over 6 months. Response was assayed by clinical 2D measurements each cycle and by MRI pre-study, at 10 weeks and prior to surgery. The Phase II primary endpoint was to test if tumor volume decrease (from 2D clinical measures) with dual therapy (dual) exceeded that...
Background: Women with locally advanced breast cancer (LABC) are often treated with neo-adjuvant ... more Background: Women with locally advanced breast cancer (LABC) are often treated with neo-adjuvant chemotherapy to reduce the size of the tumor prior to surgery, to enable breast conserving surgery and to observe the clinical effect of therapy in real time. Studies have shown that the 25–27% of individuals who have a pathologic complete response (pCR) to neoadjuvant therapy have a survival advantage of 80% in 5 years, which is double the expected survival of the remaining patients without pCR. If patients who are likely to show a pCR could be identified prior to initiation of therapy, it would enable more informed treatment decisions – patients likely to respond would be served well by current neoadjuvant chemotherapy protocols, while those unlikely to respond may be better suited to innovative new strategies for drug discovery [von Minckwitz et al. JCO 2006]. Genomic assays, which are widely used to provide prognostic and predictive information in early breast cancer, have the potent...
PurposeIndications for sentinel lymph node biopsy (SLNB) for thin melanoma are continually evolvi... more PurposeIndications for sentinel lymph node biopsy (SLNB) for thin melanoma are continually evolving. We present a large multi-institutional study to determine factors predictive of sentinel lymph node (SLN) metastasis in thin melanoma.Patients and MethodsRetrospective review of the Sentinel Lymph Node Working Group database from 1994 to 2012 identified 1,250 patients who had an SLNB and thin melanomas (≤ 1 mm). Clinicopathologic characteristics were correlated with SLN status and outcome.ResultsSLN metastases were detected in 65 (5.2%) of 1,250 patients. On univariable analysis, rates of Breslow thickness ≥ 0.75 mm, Clark level ≥ IV, ulceration, and absence of regression differed significantly between positive and negative SLN groups (all P < .05). These four variables and mitotic rate were used in multivariable analysis, which demonstrated that Breslow thickness ≥ 0.75 mm (P = .03), Clark level ≥ IV (P = .05), and ulceration (P = .01) significantly predicted SLN metastasis with ...
Background: We have previously shown that the neutrophil/lymphocyte ratio (NLR) is a predictor of... more Background: We have previously shown that the neutrophil/lymphocyte ratio (NLR) is a predictor of survival among breast cancer patients. The aim of this study was to determine the predictive value of NLR among different nodal and chemotherapy subgroups of triple negative breast cancer (TNBC). Methods: Patients with stage 1–3 TNBC who underwent treatment from 2007 to 2014 and had blood counts prior to treatments were included. Patients were categorized into high (≥2) and low (<2) NLR groups. Primary outcomes were overall survival (OS) and disease-free survival (DFS). Results: The average follow-up time was 54 months. The high NLR group had worse OS (HR 2.8, CI 1.3–5.9, p < 0.001) and DFS (HR 2.3, CI 1.2–4.2, p < 0.001) than the low NLR group. After adjusting for confounding variables, high NLR was an independent prognostic factor for both OS (HR 5.5, CI 2.2–13.7, p < 0.0001) and DFS (HR 5.2, CI 2.3–11.6, p < 0.0001). Categorization of TNBC patients by NLR (high vs. low...
Objective: To assess the efficiency of Simplified Lymphatic Microsurgical Preventing Healing Appr... more Objective: To assess the efficiency of Simplified Lymphatic Microsurgical Preventing Healing Approach (S-LYMPHA) in preventing lymphedema (LE) in a prospective cohort of patients. Background: LE is a serious complication of axillary lymph node dissection (ALND) with an incidence rate of 25%. LYMPHA has been proposed as an effective adjunct to ALND for the prevention of LE. This procedure, however, requires microsurgical techniques and significant coordination between services. Methods: All patients, undergoing ALND with or without S-LYMPHA between January 2014 and December 2016 were included in the study. During follow-up visits, tape-measuring limb circumference method was used to detect LE. The incidence of LE was compared between ALND with and without S-LYMPHA. Results: A total of 380 patients were included in the analysis. Median followup time was 15 (1-32) months. Patients, who underwent S-LYMPHA, had a significantly lower rate of LE both in univariate and multivariate analysis [3% vs 19%; P ¼ 0.001; odds ratio 0.12 (0.03-0.5)]. Excising more than 22 lymph nodes and a co-diagnosis of diabetes mellitus were also correlated with higher clinical LE rates on univariate analysis, but only excising more than 22 lymph nodes remained to be significant on multivariate analysis. Conclusions: S-LYMPHA is a simple method, which decreases incidence of LE dramatically. It should be considered as an adjunct procedure to ALND for all patients during initial surgery.
112 Background: Triple-negative (basal) and HER2+ subtypes have been associated with increased ri... more 112 Background: Triple-negative (basal) and HER2+ subtypes have been associated with increased risk of locoregional recurrence (LRR) in earlier studies of breast-conserving therapy (BCT), in which fewer patients received systemic therapy compared with recent standards, including HER2-targeted therapy. We analyzed whether basal and HER2+ subtypes are independent prognostic factors for LRR in BCT patients treated with modern systemic therapy. Methods: We retrospectively studied 415 patients with invasive breast cancer who received BCT from 1992 to 2009. Axillary surgery was done in 404 patients (97%). Forty eight percent of patients received chemotherapy (anthracycline/taxane 34%, trastuzumab-containing 4%, other 10%). Hormone therapy was given in 67%. Progression-free survival (PFS) and OS were estimated by the Kaplan-Meier method. Rate of LRR was estimated by the method of cumulative incidence allowing for competing risks. The effect of prognostic factors was examined by Fine and Gray’s test. Results: Median follow-up was 60 months. Median age was 54 (26–86). Stage: T1 70%, T2 26.3%, T3 8%; N0 75%, N1 23.5%, N2 1.7%. Receptor status was available in 301 patients to approximate subtypes: 66% Luminal A, 9% Luminal B, and 5% HER2+, and 20% Basal. Overall, there were 11 LRR, 15 distant metastasis, and 20 deaths. The 10-year PFS and OS were 85.4% and 90.5%, respectively. The 5 and 10-year cumulative incidence of LRR were 2.8% (95%CI: 1.4–5.2) and 4.5% (95%CI: 2.2–8.2) respectively. On univariate analysis, Basal vs. Luminal A (HR: 9.12, p&amp;amp;lt;0.001) and tumor size &amp;amp;gt;2cm vs. ≤2cm (HR: 4.00, p=0.022) were significant prognostic factors for LRR as first failure. On multivariate analysis, only basal subtype (HR: 6.29, p=0.011) retained significance; others effects, including luminal B/HER2 combined subtypes, were not significant. Conclusions: Long-term clinical outcomes were excellent in this cohort of breast cancer patients treated with BCT and modern systemic therapy, with 10-year LRR 4.5% and OS 90.5%. Basal subtype was an independent predictor for LRR. Conversely, HER2+ subtype was not associated with increase in LRR, in this cohort treated with BCT and trastuzumab.
International Journal of Radiation Oncology Biology Physics, Nov 1, 2018
defined as patients receiving RT 1-3 months before CPI (10%), within 1 month of CPI (9%), and >1 ... more defined as patients receiving RT 1-3 months before CPI (10%), within 1 month of CPI (9%), and >1 month after CPI (18%). None of these variables were associated with older age (Fisher's Exact Test, p>0.05). Complete/partial response, stable disease or progressive disease was achieved in 30.4%, 28.8% and 40.8%, respectively; response was independent of age (pZ0.21). On KM analysis, older age was associated with improved PFS (HRZ0.74, 95% CIZ0.554-0.997), and RT to a Non-CNS site at the time of CPI was associated with improved PFS [HRZ0.59 (0.34-1.01)). On multivariate Cox analysis, older age (Adjusted HR 'AHR'Z0.68, p<0.021) and RT to a Non-CNS site (AHRZ0.46, p<0.009) were prognostic for PFS. Similar trends were observed for TTF. Older age and RT (irrespective of timing or site) were not associated with OS (p>0.1). Conclusion: Among patients receiving CPIs for the treatment of advanced lung cancer, older age is not associated with a worse OS or higher rates of SAEs, but may be associated with improved PFS and TTF. Prospective data is needed to better examine the impact of RT on OS in the setting of CPIs for older patients.
International Journal of Radiation Oncology Biology Physics, Nov 1, 2009
Purpose/Objective(s): Locally advanced breast cancer (BC) comprises 10-20% of new cases and is a ... more Purpose/Objective(s): Locally advanced breast cancer (BC) comprises 10-20% of new cases and is a common presentation of BC in South Florida. There is little data concerning capecitabine and radiation therapy for the treatment of locally advanced disease. Only one phase II trial (Gaui, 2007) studied the combination of these modalities and it showed safe and effective control of inoperable disease. However, no study has examined low dose capecitabine as a radiation sensitizing agent. Our goal was to retrospectively assess locoregional control (LRC) outcomes in patients with locally advanced BC treated with concurrent RT and low dose capecitabine. Materials/Methods: We retrospectively reviewed records of 20 consecutive patients with stage II-IV BC that received concurrent capecitabine and radiation between 1/2003 and 2/2008. Patients were treated with this regimen for inflammatory carcinoma, disease recurrence, or poor response to treatment. Results: Median age at diagnosis was 50 (range 34-74). Race was Caucasian (n=4), Asian (n = 1), African Descent (n = 4), and Hispanic (n = 11). Clinical stages were IIA (n = 1 with recurrent disease), IIB (n = 1, T3N0), IIIA (n = 6), IIIB (n = 5), IIIC (n = 5), and IV (n = 2). Eight patients had inflammatory carcinoma. Three patients presented with locally recurrent disease prior to radiation. Average clinical tumor size at initial presentation was 6.7 cm. All patients had either neoadjuvant and/or adjuvant chemotherapy. All patients went on to definitive surgery (MRM =19, BCT = 1). One (5%) patient had a pCR. All others had \pCR. One patient had positive surgical margins. Patients were treated with a mean dose of 60 Gy to the chest wall (including boost) and 45 Gy to the supraclavicular fossa. Seven patients had axillary boost with a mean dose of 45.5 Gy. All patients received concurrent capecitabine and RT. The dose of capecitabine was 500mg daily starting with the first day of radiation and ending at completion of RT. Median follow-up time was 21 months from time of diagnosis and 12 months from completion of RT. Fifteen patients were alive with no clinical evidence of disease. Five patients had metastases (two of these at the start of radiation). One of the patients with metastatic disease died. No patients had local regional recurrence (LRR). By the last week of treatment the RTOG ARMSC skin criteria was as follows: Score 2 (n = 9), Score 3(n = 8), Score 4 (n = 3, all with chest wall involvement). At six weeks post RT, all patients had minimal skin toxicity. Conclusions: Despite short follow up, small patient numbers, and increased acute toxicity, capecitabine appears to be a safe and effective radiosensitizer. Concurrent capecitabine and RT provided effective LRC with acceptable toxicity in this group of BC patients at very high risk of LRR. These results encourage a future prospective trial.
International Journal of Radiation Oncology Biology Physics, Nov 1, 2009
from first day of treatment) toxicities were assessed retrospectively using the RTOG acute toxici... more from first day of treatment) toxicities were assessed retrospectively using the RTOG acute toxicity criteria and CTCAE version 3, respectively. Results: Median age was 61.6 years (range 38.4-84.7 years). Median follow-up was 22.0 months (mean 27.83, range 6.5-60.4 months). Median tumor size was 1.1 cm (range 0.4-2.9 cm). Stage was 0 in 11, I in 38, IIA in 1, and IIB in 1. Treatment was delivered using photons only in 40 and mixed photon/electron beams in 11 patients. Prescribed dose/fractionation was 38.5 Gy in 3.85 Gy fractions bid over 5 days for all patients. Deep inspiration breath hold gating and image-guided radiotherapy using implanted fiducial markers have been used since July 2007 and January 2008, respectively. Locoregional control was 100%. Distant metastasis-free and overall survival was 98%, with one stage IIB patient developing distant metastases 22 months after radiotherapy and dying 49 months after radiotherapy. There were no grade 2 or higher acute toxicities. There were 2 grade 2 late skin toxicities consisting of persistent moderate breast edema. No pulmonary or cardiac toxicity was seen. Musculoskeletal toxicity included 3 grade 1 (mild chest wall pain without radiographic evidence of fracture) and 1 grade 2 (symptomatic non-displaced rib fractures). Conclusions: In appropriately selected patients, 3DCRT-APBI can be executed safely and effectively in the community setting. Both local control and short-term toxicity appear at least comparable to that of whole breast radiotherapy; however, long-term results of a prospective clinical trial are needed to firmly establish the appropriateness of APBI.
Introduction: The increase in survival after childhood radiation therapy for some blood malignanc... more Introduction: The increase in survival after childhood radiation therapy for some blood malignancies has led to increase in the diagnosis of radiation induced secondary solid malignancies (SSM). Diagnostic and therapeutic radiation is a known risk factor for malignancy. Although rare, it has been demonstrated in the literature that diagnostic and therapeutic radiation is associated with breast cancer in women. Male breast cancer (MBC) is a rare condition, accounting for approximately 1% of all breast cancers. Not surprisingly, there is a paucity of case reports in the literature describing radiation as a risk factor for cancer in men. Case Report: Herein we report a young man presenting with invasive breast cancer 19 years after receiving radiation therapy and bone marrow transplant (BMT) for acute lymphocytic leukemia (ALL) in childhood. After standard diagnostic and metastatic workup, treatment included neoadjuvant chemotherapy, surgery and adjuvant radiation therapy and adjuvant hormonal therapy. Outcome and follow up data are reported in the paper as well. Discussion: Only two similar cases were reported earlier, for two patients who developed breast cancer 13 and 15 years after exposure to radiation therapy. Our case report extends the latency period to 19 years. The most important prognostic indicators were stage at diagnosis and lymph node status. Conclusion: Radiation induced MBC should be considered in the differential diagnosis of breast related symptoms, even with a very remote history of exposure. The younger the age of exposure, the more years the patient has at risk of breast cancer. It is important to attempt early detection in these patients before the disease progresses to an advanced stage. Survivors of radiation treated primary cancer should be closely monitored for SSM, including breast cancer, for the rest of their lives. Yearly clinical breast exams and selective imaging studies should probably be offered to the subgroup of male patients at higher risk, including those with early age at exposure (younger than 10 years), and those getting TBI for the treatment of ALL.
Background: Lymphedema (LE) is a serious complication of axillary lymph node dissection (ALND) wi... more Background: Lymphedema (LE) is a serious complication of axillary lymph node dissection (ALND) with an incidence rate of 16%. Lymphatic Microsurgical Preventing Healing Approach (LYMPHA) has been proposed as an effective adjunct to ALND for the prevention of LE. This procedure however requires microsurgical techniques. The aim of this study was to assess the efficiency of Simplified-LYMPHA (SLYMPHA) in preventing LE in a prospective cohort of patients. Methods: All patients, undergoing ALND with or without SLYMPHA between January 2014 and December 2016 were included in the study. SLYMPHA is a slightly modified and simplified version of LYMPHA. It is performed by the operating surgeon performing the ALND. One or more lymphatic channels identified by reverse arm mapping are inserted using a sleeve technique into the cut end of a neighboring vein. During follow-up visits, tape-measuring limb circumference method was used to detect clinical LE. Demographic, clinical, surgical and pathol...
Objective: Therapeutic management of ductal carcinoma in situ (DCIS) is heterogeneous among count... more Objective: Therapeutic management of ductal carcinoma in situ (DCIS) is heterogeneous among countries worldwide, and some treatment indications are still controversial. To investigate DCIS management in different countries; identify both consensual practices and controversial topics; and survey opinions about the future management of DCIS. Materials and Methods: The Senologic International Society network members participated to an online survey using a questionnaire, between November 2021 and February 2022. Results: Twenty-two responses from 20 different countries showed that organized breast cancer screening programs were present for 87% participants, and DCIS cases represented 13.7% of all breast cancers. Most participants used the grade classification (100%), the morphological classification (78%) and performed immunohistochemistry assays (73%). In case of conservative treatment, the mean re-excision rate was 10.3% and clear margins of mean 2.5 mm were considered healthy. Radical mastectomy rate was 35.5% with a breast reconstruction rate of 53%. Tumor bed boost indications were heterogeneous, and 73% of participants indicated hormone therapy for hormone-positive DCIS. Surgery and radiotherapy omission for some low-risk DCIS were considered by 73% of participants. Multigene assays were used by 43% of participants. Concerning future changes in DCIS management, participants mostly answered surgical de-escalation (48%), radiotherapy de-escalation (35) and/or active surveillance for some cases (22%). Conclusion: This survey provided an overview of the current practices of DCIS management worldwide. It showed that some areas are rather consensual: incidence increases over time, treatment in young women, pathological classifications, definition of healthy margins, the skin-sparing mastectomy and
Purpose Accumulating evidence supports usage of sentinel lymph node biopsy (SLNB) for clinically ... more Purpose Accumulating evidence supports usage of sentinel lymph node biopsy (SLNB) for clinically node positive (cN+) breast cancer (BC) patients, who become clinically node negative (ycN-) after neoadjuvant chemotherapy (NAC). How to reassess the axilla after NAC is a challenging issue. In our institution, Systematic Sonographic Axillary Staging (SSAS) is currently being tested in this group of patients. The aim of this study is to analyze the early results of this approach. Method During initial presentation, systematic sonographic axillary staging is done preferentially by the surgeon. Needle biopsy is then performed of suspicious node(s). At completion of NAC, the axilla is again systematically staged sonographically, taking into account the pre-treatment disease locations. Any residual morphologically suspicious node undergoes a repeat needle biopsy. According to the evidence of residual disease, the patient is either scheduled for axillary dissection (AD) or for SLNB. We analyz...
Objective Positive margins remain a significant psychological and economic burden after breast co... more Objective Positive margins remain a significant psychological and economic burden after breast conserving surgery. The aim of this study was to test the hypothesis that advanced oncoplastic techniques as well as intraoperative integrative imaging with intraoperative ultrasound and mobile digital specimen radiography decreases positive margin rate in breast conserving surgery. Methods A single-institution retrospective review of a prospectively collected database was performed. Patients with breast neoplasms who underwent lumpectomy with or without using intraoperative integrative imaging approaches and oncoplastic techniques were included. The primary outcome was positive margin rate for each technique. Results A total of 392 patients were included in the study. The median age of the cohort was 59 years. Overall positive margin rate was 15%. Ductal carcinoma in situ (DCIS) histology and larger tumor size were associated with higher positive margin rate. Intraoperative integrative im...
Antiestrogen mediated cell cycle arrest requires the CDK inhibitor, p27. Src kinase mediates p27 ... more Antiestrogen mediated cell cycle arrest requires the CDK inhibitor, p27. Src kinase mediates p27 loss and antiestrogen resistance in ER+ breast cancer lines in vitro. In ER+ xenografts, the Src inhibitor, saracatinib, restored antiestrogen responses in resistant tumors. This led to a Phase I/randomized double-blind Phase II trial to test effects of saracatinib with anastrozole for ER+ and/or PR+ postmenopausal breast cancer. Phase I accrued 12 subjects and showed 175 mg po saracatinib is safely given with 1 mg po daily anastrozole with good PK . In Phase II, postmenopausal women with new ER+ and/or PR+, HER2- breast cancers ≥ 2 cm were randomized 2:1 to either neoadjuvant anastrozole with saracatinib or anastrozole/placebo over 6 months. Response was assayed by clinical 2D measurements each cycle and by MRI pre-study, at 10 weeks and prior to surgery. The Phase II primary endpoint was to test if tumor volume decrease (from 2D clinical measures) with dual therapy (dual) exceeded that...
Background: Women with locally advanced breast cancer (LABC) are often treated with neo-adjuvant ... more Background: Women with locally advanced breast cancer (LABC) are often treated with neo-adjuvant chemotherapy to reduce the size of the tumor prior to surgery, to enable breast conserving surgery and to observe the clinical effect of therapy in real time. Studies have shown that the 25–27% of individuals who have a pathologic complete response (pCR) to neoadjuvant therapy have a survival advantage of 80% in 5 years, which is double the expected survival of the remaining patients without pCR. If patients who are likely to show a pCR could be identified prior to initiation of therapy, it would enable more informed treatment decisions – patients likely to respond would be served well by current neoadjuvant chemotherapy protocols, while those unlikely to respond may be better suited to innovative new strategies for drug discovery [von Minckwitz et al. JCO 2006]. Genomic assays, which are widely used to provide prognostic and predictive information in early breast cancer, have the potent...
PurposeIndications for sentinel lymph node biopsy (SLNB) for thin melanoma are continually evolvi... more PurposeIndications for sentinel lymph node biopsy (SLNB) for thin melanoma are continually evolving. We present a large multi-institutional study to determine factors predictive of sentinel lymph node (SLN) metastasis in thin melanoma.Patients and MethodsRetrospective review of the Sentinel Lymph Node Working Group database from 1994 to 2012 identified 1,250 patients who had an SLNB and thin melanomas (≤ 1 mm). Clinicopathologic characteristics were correlated with SLN status and outcome.ResultsSLN metastases were detected in 65 (5.2%) of 1,250 patients. On univariable analysis, rates of Breslow thickness ≥ 0.75 mm, Clark level ≥ IV, ulceration, and absence of regression differed significantly between positive and negative SLN groups (all P < .05). These four variables and mitotic rate were used in multivariable analysis, which demonstrated that Breslow thickness ≥ 0.75 mm (P = .03), Clark level ≥ IV (P = .05), and ulceration (P = .01) significantly predicted SLN metastasis with ...
Background: We have previously shown that the neutrophil/lymphocyte ratio (NLR) is a predictor of... more Background: We have previously shown that the neutrophil/lymphocyte ratio (NLR) is a predictor of survival among breast cancer patients. The aim of this study was to determine the predictive value of NLR among different nodal and chemotherapy subgroups of triple negative breast cancer (TNBC). Methods: Patients with stage 1–3 TNBC who underwent treatment from 2007 to 2014 and had blood counts prior to treatments were included. Patients were categorized into high (≥2) and low (<2) NLR groups. Primary outcomes were overall survival (OS) and disease-free survival (DFS). Results: The average follow-up time was 54 months. The high NLR group had worse OS (HR 2.8, CI 1.3–5.9, p < 0.001) and DFS (HR 2.3, CI 1.2–4.2, p < 0.001) than the low NLR group. After adjusting for confounding variables, high NLR was an independent prognostic factor for both OS (HR 5.5, CI 2.2–13.7, p < 0.0001) and DFS (HR 5.2, CI 2.3–11.6, p < 0.0001). Categorization of TNBC patients by NLR (high vs. low...
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Papers by Eli Avisar