Positive Lymph Research Articles

Abstract P1-01-14: Axillary assessment by Systemic Axillary Sonography (SAS) for axillary disease treated with neoadjuvant chemotherapy

Abstract Objective. For patients with breast cancer related lymph node metastases, neoadjuvant chemotherapy (NAC) can de-escalate axillary surgery. A radiologic marker (RM) is commonly placed at the time of the initial biopsy to ensure removal of that node at final surgery, but the utility of this marker is largely debated. Systematic Axillary Sonography (SAS) consists of a thorough sonographic axillary staging before and after NAC with possible post NAC node biopsy and has been previously suggested as an alternative. The primary aim of this study was to assess the effectiveness of SAS in axillary evaluation after NAC. The secondary aim was to compare the effectiveness of SAS to RM. Methods. A retrospective analysis of prospectively collected data from 95 patients from 2010 to 2020 at University of Miami Hospital and Jackson Memorial Hospital. Study inclusion criteria were positive axillary lymph node (LN) biopsy, NAC, performance of SAS and axillary surgery. Results. 89 patients were analyzable. The median age was 49±12. All patients had clinical axillary exam and axillary US with positive LN biopsy. 62 patients had additional breast MRI before treatment. All patients had clinical axillary exam and axillary US after chemotherapy. 58 patients had post-treatment MRI and 49 repeated axillary LN biopsy. Pre-treatment clinical exam of the axilla had a sensitivity of 73%. When MRI was added the sensitivity rose to 95%. Since axillary US and positive axillary node biopsy were a prerequisite, the sensitivity of pre-NAC US cannot be assessed. After chemotherapy, all patient underwent axillary examination and US assessment. Repeated axillary clinical exam had low sensitivity of 31% and high specificity of 85%. Repeat MRI exam showed low sensitivity and specificity of 53% and 49% respectively. Post-NAC US without subsequent LN biopsy had a sensitivity of 55% with specificity of 67%. The addition of repeat axillary LN biopsy increased the sensitivity of SAS to 100%. 59 patients in our group had RM placed during pre-NAC axillary LN biopsy. 24 underwent axillary dissection without sentinel lymph node biopsy (SLNB) and 35 patients had a SLNB. The RM was retrieved in 32/35 patients. The “clipped” node was also sentinel node in 66% (12/35). The final pathology revealed benign results in all “clipped” non-sentinel nodes. 18% (6/33) of patients with “clipped” node were diagnosed with axillary metastases in “non-clipped” lymph nodes. Conclusion. SAS is a cheap, quick and reliable method facilitating pre and post-treatment assessment and restaging of the axilla after NAC. Post-NAC biopsy, when indicated, better defines eligibility for axillary surgery decreasing morbidity and cost. In this study, placement of a RM was of no significant benefit. Patient characteristicsRaceTumor gradeWhite, non-hispanic19Gr 13White-hispanic46Gr 240Black, non-hispanic18Gr 346Asian3Receptor statusUnknown3HR+/HER2-42Age49+/-12HR+/HER2+19BMI29+/-5.7HR-/HER2+7Menopausal statusHR-/HER2-21Premenopausal49Tumor sizePostmenopausal40T19T238T328T414LN statusN158N221N310 Citation Format: Siarhei Melnikau, Christina Layton, Tolga Ozmen, Megan Allen, Eli Avisar. Axillary assessment by Systemic Axillary Sonography (SAS) for axillary disease treated with neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-01-14.

Abstract P3-19-17: Radiation of the low axilla in the prone position

Abstract Background: Whole breast irradiation (WBI) after a positive sentinel lymph node biopsy (SNB) is recommended to be treated in the supine position to facilitate inclusion of the low axilla with “high tangents” when regional nodal irradiation is not planned. Treatment in the prone position has several advantages over supine positioning including minimizing heart and lung doses for many and decreased skin toxicity for larger breasted women. We hypothesized that, using three dimensional conformal radiation therapy (3DCRT), the low axilla can be safely and adequately treated in the prone position with minimal toxicity and good outcomes. Methods: We identified patients who underwent post lumpectomy whole breast and low axilla irradiation in the prone position using 3DCRT from 2014 to 2020. Standard 3DCRT treatment planning included delineation of surgical cavity, breast and low axillary clinical target volumes (CTV) with 5 mm expansion to planning target volumes (PTV). The “low axilla” CTV was generally defined as the level I axilla according to the RTOG Breast Cancer Atlas. Dosimetric data for both targets and organs at risk (OARs) was extracted from approved treatment plans’ dose-volume histograms (DVHs). Toxicity and cancer outcomes were collected from the electronic medical records. Descriptive statistical analysis was performed. Results: Seventy patients were identified. Median age was 61 years (range 34-87), median body mass index (BMI) was 30.4 kg/m2 (range 22.1-49.1), and 88.6% (N=62) had hormone sensitive, HER2 negative breast cancer. The median tumor size was 1.35 cm (range 0.07-4.5cm). For 56 patients (80.0%), a SNB was done with median of 2 (range 1-7) sentinel nodes removed - 19 (34%) with macro-metastasis (median size 4 mm, range 2.2-13mm), 21 (37.5%) with micrometastasis, and 16 (28.6%) with isolated tumor cells. Three patients had an additional node with isolated tumor cells. Thirteen (18.6%) were Nx (no nodal evaluation) and 1 had an unsuccessful SLNB with no lymph nodes obtained. Hypofractionation was used in 97.1% (N=68): 4256 cGy in 16 fractions (N=44, 62.8%) or 4000 cGy in 15 fractions (N=24, 34.3%). All targets were covered adequately. The median V95/V90 of the PTVbreast_eval, PTVlump_eval, and PTVAx were 96%/98.3% (range 76.2/91.9% - 99.6/101.4%), 100.1%/101.2% (range 87.6/94.9%-102.8/103.3%), and 95.3%/97.5% (range 82.4/91.6%-100.4/101.7%) respectively. The mean heart dose for all patients was 83.5 cGy; 82.7 cGy for right-sided tumors and 83.8 cGy for left-sided tumors. The median V16 of the ipsilateral lung was 4.25% (range 0.2 - 11.3%). Overall, toxicity was low with no grade 3 or higher events. For acute toxicity, most patients (N=54, 77.1%) reported grade 1 fatigue and had either grade 1 (N=52, 74.2%) or grade 2 (N=15, 21.4%) dermatitis. For late toxicity, 14 patients (20%) were referred to physical therapy after radiation, 7 (10%) for range of motion, 5 (7%) for arm lymphedema evaluation and 4 (6%) for other reasons. With a median follow-up of 18.5 months (range 0-63 months), 1 patient recurred both locally and regionally (1.4%) and one other patient recurred distantly. Conclusions: Patients with a positive SNB or are Nx who are recommended to have post-lumpectomy whole breast and low axilla irradiation can be safely and adequately treated in the prone position using 3DCRT with minimal toxicity and good outcomes. Citation Format: Victoria Doss, Erin Healy, Sasha Beyer, Sachin R. Jhawar, Jose G. Bazan, Julia White. Radiation of the low axilla in the prone position [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-19-17.

Abstract P3-20-02: The association of clinicopathological variables and patient´s preference with surgical decision-making for early breast cancer

Abstract Background: Mastectomy (Mx) and breast conserving surgery (BCS) when combined with adjuvant whole breast radiotherapy (RT) have been shown to give equivalent outcome in randomized trials . In recent years, a number of retrospective population-based studies suggest that BCS offers superior survival compared to Mx. In these studies, treatment has not been randomized, but selected based on patient and tumour characteristics or patient´s own choice. The aim of this study was to compare clinicopathological variables in women with tumours less than 30mm in size treated with either BCS or Mx, where both surgical methods would have been feasible based on postoperatively recorded tumour characteristics. Our second aim was to explore the underlying reason for choosing Mx as surgical approach. Method: The study is a population-based retrospective analysis of prospectively collected data from the Swedish National Breast Cancer Register (NBCR). The source population are women registered with primary invasive breast cancer with a tumour size up to 30 mm and no more than four positive axillary lymph nodes, treated between 2013-2016 in the northern health care region in Sweden. During this time period, the reason for selecting Mx was registered in this region with five optional alternatives: 1.Age < 40 years, 2.Large tumour size/extent relative breast volume, 3.Multifocality/multicentricity, 4.RT contraindicated due to comorbidity and 5.Patient´s own choice. All cases with male breast cancer and patients treated with neoadjuvant therapy were excluded.Logistic regression analyses were performed to assess the association of tumour and patient characteristics with receiving a mastectomy shown as odds ratios with 95% confidence intervals (CI). Results: A total of 1860 women met our inclusion criteria, 1346 of which had undergone BCS (mean age 63) and 514 Mx (mean age 66). For 1309 women (97.1%) in the BCS group and 146 (27.6%) in the Mx group adjuvant RT was added to the breast, chest wall and/or ipsilateral regional lymph nodes after surgery. Clinical detection, OR 3.35 (95%CI 3.32-5.14), higher T stage OR 2.66 (2.00-3.54), N stage OR 1.84 (1.46-2.32) and multifocality, OR 4.59 (3.56-5.92) were associated with a higher likelihood of receiving Mx. Women treated with Mx had more lobular tumours, OR 1.42 (1.05-1.92), higher grade, OR 2.27 (1.65-3.13), more hormone receptor negative, 1.47 (1.09-1.98) and HER2 positive tumours, OR 1.61 (1.19-2.17) compared to women treated with BCS.The most common reason for choosing Mx was large tumour size and/or multifocality (52.8%). The second most common reason was the woman´s own preference (36.6%). In 9 % of the cases RT was considered contraindicated, hence Mx was recommended by the treating surgeon or tumour board. Conclusion: Women with invasive breast cancer up to 30mm selected for treatment with Mx have less favourable prognostic characteristics than those treated with BCS. Selection bias may largely explain the survival benefits of BCS compared to Mx demonstrated in observational studies. Table 1: Distribution of factors listed as reason of mastectomy as surgical treatment. Table based on a a total of 431 mastectomy cases where reason for Mx were listed. RT = Radiotherapy No. of patients%Age < 40 years61.4large tumour size/extent relative breast volume13531.3Multifocality/multicentricity9321.5RT contraindicated due to comorbidity399.0Patients own choice15836.6 Citation Format: Emma Söderberg, Malin Sund, Fredrik Wärnberg, Lars Holmberg, Greger Nilsson, Hans Garmo, Carl Blomqvist, Charlotta Wadsten. The association of clinicopathological variables and patient´s preference with surgical decision-making for early breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-20-02.

Abstract P1-01-07: Factors predicting a lower likelihood of residual nodal disease in clinically-node positive patients undergoing sentinel node surgery after neoadjuvant chemotherapy for breast cancer

Abstract Background: Residual nodal disease at the completion axillary lymph node dissection (ALND) has been reported in over 60% in patients with a positive sentinel lymph node biopsy (SLNB) after neoadjuvant chemotherapy (NAC). This study aimed to explore whether any clinical or histopathological characteristics of patients may be associated with a lower likelihood of having non-SLN metastasis at ALND. Methods: Between January 2004 to January 2021, 459 patients with cT1-4/N1-3 underwent ALND due to a positive SLNB after NAC. Demographic, clinical and histopathological characteristics of patients were analyzed to predict the non-SLN metastasis at ALND. Sentinel lymph node ratio was defined as the ratio of the number of positive SLN to the total excised SLNs. Results: Median age was 47 (21-84). Of those, the majority of the patients had cT1-2 (67.8%) and cN1 disease (78.1%), whereas 76.5% of tumors were invasive ductal carcinoma. The frequency of non-SLN metastases according to the tumor subtypes were 59.5% in luminal A, 73.8% in HER2(-) luminal B, 60.3% in HER2(+) luminal B, 66.7% in non-luminal HER2(+), and 66.7% in triple negative breast carcinoma. Of those with removal more than 2 SLNs, having 1 positive SLN, or breast pathologic complete response, or cT1-2 disease , or a SLN ratio <50% or low volume metastatic disease including isolated tumor cell (ITC)/micrometastasis were statistically less likely found to have a non-SLN metastasis (p<0.05). Factors associated with a non-SLN involvement less than 40% were a SLN ratio <50% (39.2%) and low volume metastatic disease (36.4%). Multivariate logistic regression analysis revealed a decreased likelihood for non-SLN metastasis at ALND for patients with cT1-2 (OR= 0.45; 95% CI: 0.25-0.82; p=0.009), ITC and micrometastasis (OR=0.24; 95% CI: 0.09-0.65; p=0.006), and a SLN-ratio <50% ((OR=0.15; 95% CI: 0.08-0.26; p<0.001). A subgroup of patients with cT1-2/N1 having a SLN ratio <50% or ITC/micrometastasis were found to have 25.9% and 28.6% non-SLN positivity at ALND, respectively. Conclusions: In patients with a positive SLN after NAC, the likelihood of having residual disease at ALND was high across all tumor subtypes and clinical patient and tumor characteristics. However, the residual nodal disease rate was found to be lower than 30% in carefully selected patient subgroups with cT1-2/N1 along with ITC/micrometastasis or a SLN ratio <50% (Table 1) . These results suggest omission of ALND could be considered in meticulously selected patients with cT1-2 and low volume metastatic disease as long as axillary radiation and effective systemic treatment provided Table 1. Factors associated with non-SLN metastasis at ALND FactorsOR(95%CI)p-valuecT0.009*1&20.45(0.25-0.82)3&4Reference (1)SLN Status0.006*ITC and micrometastasis0.24(0.09-0.65)MacrometastasisReference (1)SLN-Ratio (%)<0.001*<50%Reference(1)≥50%0.15(0.08-0.26)*:p<0.05, Logistic regression(enter method), OR:Odds Ratio; Dependent variable:Non-SLN positivity Citation Format: Neslihan Cabioglu, Hasan Karanlık, Abdullah Igci, Mahmut Muslumanoglu, Mustafa Tukenmez, Selman Emiroglu, Enver Ozkurt, Semen Onder, Pinar Saip, Yesim Eralp, Adnan Aydiner, Ekrem Yavuz, Vahit Ozmen. Factors predicting a lower likelihood of residual nodal disease in clinically-node positive patients undergoing sentinel node surgery after neoadjuvant chemotherapy for breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-01-07.

Abstract P3-19-03: Preliminary results of a feasibility study assessing radiation response with MRI/CT directed preoperative accelerated partial breast irradiation in the prone position for hormone responsive early stage breast cancer

Abstract BACKGROUND: Accelerated partial breast irradiation (APBI) has emerged as an alternative to whole breast irradiation (WBI) following lumpectomy for select patients. However, the challenges to post-operative APBI include targeting inaccuracy and the inability to measure tumor response to radiation. We hypothesized that preoperative APBI (pAPBI) could reliably target the tumor using MRI-guidance that is acquired prone in combination with our established prone breast radiation delivery. We developed methodology for prone CT simulation to establish radiation position, MRI acquisition in treatment position, registration of MRI-CT data for treatment planning, and treatment delivery with daily cone-beam CT using the same immobilization platform. This study aimed to assess the reproducibility, toxicity and local control associated with MRI/CT-directed prone pAPBI. METHODS: This was a prospective, single arm study enrolling patients >50 yo with clinical (c) Stage IA ER+/PR+/HER2- breast cancer intending lumpectomy. Axillary US and MRI imaging to confirm clinical node negative disease was required. A planning CT in the prone position was followed by MRI using the same prone immobilization platform. Rigid registration of MRI-CT data was used for radiation planning. pAPBI of 3850 cGy was delivered in 10 fractions BID with the same prone immobilization technique. Another MRI was obtained 4 weeks post-APBI to assess tumor response. The intensity, kinetics and volume of the lesion on MRI was quantitatively assessed and an experienced reader evaluated MRI volume and kinetic changes in the tumor post-APBI. Lumpectomy was performed 4-6 weeks after APBI. Simon 2 stage design required assessment after accrual of 19 patients for assessment of feasibility. RESULTS: Nineteen cStage IA ER+/PR+/HER2- breast cancer patients with a median age of 65 (range 51-78) were enrolled on the study, completed APBI, lumpectomy, and adjuvant AI. Median follow up was 3.4 years. Mean clinical tumor size was 1.1 cm ± 0.4 and mean path tumor size was 0.94 cm ± 0.6. There was complete pathologic response in 10.5% (n=2) and an additional 36.8% (n=7) were downstaged from clinical stage (measured by mammogram/US) to pathologic stage, resulting in a total response of 47.4% (n=9). Six (31.6%) patients had stable disease after APBI. Four (21.0%) were upstaged from clinical stage to pathological stage. Tumor response detected by MRI significantly correlated with tumor response based on clinical to pathologic stage (p=0.03). Cosmesis was rated as excellent/good in 89.5% (n=17) patients post-APBI. Cosmesis worsened to fair in 2 patients post-APBI, one of which required adjuvant WBI after focal triple negative breast cancer was detected on pathology. Three patients had positive macrometastatic lymph nodes on final pathology despite clinically negative nodes on imaging. One in-breast recurrence outside the RT field was detected by MRI at 14 months, resulting in a locoregional recurrence rate of 5.4% at 3.4 years. Another patient developed metastases at 20 months. CONCLUSIONS: Using the same prone platform, all patients successfully underwent CT simulation, MRI acquisition, and completed pAPBI. Nearly half of enrolled patients had a measurable tumor response to pAPBI based on MRI and pathologic response, confirming the accuracy and reproducibility of defining tumor targets with our MRI/CT-directed pAPBI approach. While this methodology for prone pAPBI resulted in good cosmesis and local control and remains a promising approach for select patients, the challenge of excluding patients with subclinical lymph node positive disease remains. Correlative studies will determine whether Ki-67 and OncotypeDx pre- and post-APBI can help predict response to pAPBI. Citation Format: Sasha Beyer, Tamara Smith, Ashley Sekhon, Jose Bazan, Sachin Jhawar, Erin Healy, Lai Wei, Vedat Yildiz, Mohamed Mohamed, Michael Knopp, Julia White. Preliminary results of a feasibility study assessing radiation response with MRI/CT directed preoperative accelerated partial breast irradiation in the prone position for hormone responsive early stage breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-19-03.

Diagnostic accuracy of axillary nodal ultrasound after neoadjuvant chemotherapy in node-positive breast cancer patients: A validation study.

To determine the accuracy and false negative rate of axillary ultrasound compared to sentinel node biopsy. The retrospective study was conducted at the Aga Khan University Hospital, Karachi, from February 1 to March 31, 2021, and comprised data of breast cancer patients who had undergone neo-adjuvant chemotherapy followed by axillary lymph node dissection or axillary disease diagnosed using lymph node biopsy or sentinel lymph node biopsy between January 1, 2016, and December 30, 2020. After receiving neoadjuvant chemotherapy, axillary ultrasound findings were compared with histopathology of lymph nodes. Data was analysed using SPSS 22. Of the 155 patients evaluated, 104(67.1%) were diagnosed with negative axillary lymph nodes and 51(32.9%) were diagnosed with positive axillary lymph nodes post-chemotherapy. The overall mean age was 51.13±1.3 years. When histopathology results were compared with those of axillary ultrasound, 36(23.2%) cases turned out to be true positive, while 23(14,8%) were false negative, yielding a positive predictive value of 75% and negative predictive value of 65%. Axillary ultrasound had 75% accuracy, false negative rate 30%, sensitivity 61% and specificity 84.4%. Axillary ultrasound was found to be fairly useful, but not completely reliable, in identifying positive lymph nodes.

Target Axillary Dissection with Preoperative Tattooing Positive Axillary Lymph Nodes in Breast Cancer

Target Axillary Dissection with Preoperative Tattooing Positive Axillary Lymph Nodes in Breast Cancer

Impact of the viability assessment of lateral lymph node metastasis in rectal cancer after neoadjuvant chemoradiotherapy

Preoperative chemoradiotherapy (CRT) followed by total mesorectal excision (TME) without lateral lymph node (LLN) dissection is widely performed for lower advanced rectal cancer. However, it is unclear whether residual cancer cells in the LLNs undergo apoptosis, disappear, or regrow if unresected. Overall, 293 consecutive patients with T3/4 rectal cancer who underwent CRT followed by radical surgery between September 2003 and December 2018 were retrospectively reviewed. We assessed apoptosis of the residual primary tumor, mesorectum lymph nodes (MLN), and LLN using M30 cytoDEATH immunostaining and evaluated the degree of apoptosis. The difference in the prognosis of the lateral lymph node metastasis positive (LLNM +) and lateral lymph node metastasis negative (LLNM-) groups was assessed. There were 31 patients (10.6%) who were diagnosed with a complete response by hematoxylin and eosin (HE) staining. The residual cancer cells showed complete apoptosis in the primary lesion in 28 patients, in the metastatic MLN in only two patients, and in the metastatic LLN in one patient. The LLNM + group had a significantly poorer distant recurrence, recurrence-free survival, and overall survival than the LLNM- group. The majority of the residual cancer tissue in LNs observed by HE staining was found to be non-apoptotic. If LLN metastasis is suspected on pretreatment imaging, performing LLN dissection together with TME should be considered.

Can We Successfully De-Escalate Axillary Surgery in Women Aged ≥ 70 Years with Ductal Carcinoma in Situ or Early-Stage Breast Cancer Undergoing Mastectomy?

Omission of sentinel lymph node biopsy (SLNB) in older women with clinically node-negative, hormone receptor-positive (HR+) early-stage breast cancer undergoing lumpectomy is accepted, given established low rates of regional recurrence. The safety of omitting SLNB in women undergoing mastectomy is unknown and may differ depending on extent of breast disease and variation in radiotherapy use. From 2006 to 2018, 123 cTis and 328 cT1-2 HR+/HER2- tumors from 410 women aged ≥ 70 years who underwent mastectomy and SLNB were included (41 bilateral cases). The rate of nodal positivity and effect of nodal positivity on adjuvant therapy use were examined. Median age was 74 years; 21% of patients had positive sentinel lymph nodes, 7% had micrometastases, and 14% had macrometastases. Of cases of cTis tumors, 31% were upstaged to invasive carcinoma; 1% had macrometastases. Fewer cases of cT1 than cT2 tumors had macrometastases [13% (26/200) versus 29% (37/128); p < 0.001]. Eight percent of patients with pT1 tumors (18/228) and 27% of patients with pT2 tumors (30/113) received chemotherapy. Most patients with pT1, pN1 disease (78%; 25/32) did not receive chemotherapy. Rates of locoregional recurrence were similar between patients with cT1 or cT2 tumors with and without nodal metastases (median follow-up, 4.5 years). Women aged ≥ 70 years with cTis and cT1N0 HR+/HER2- tumors who underwent mastectomy had low rates of nodal positivity, similar to rates reported for lumpectomy. Given this and the RxPONDER results, omission of SLNB may be considered, as findings are unlikely to alter adjuvant therapy recommendations.

Elucidating the clinical-pathological factors and prognosis in breast cancer young surviving women who had a subsequent pregnant

Objective. To elucidate the impact of clinical-pathological factors on overall survival (OS) in patients who got pregnant after breast cancer treatment. Methods. Retrospective cohort of women age younger than 40 years with breast cancer history without active disease at diagnosis of postcancer pregnancy. Clinical-pathological factors were analized by age group and recent birth. Overall survival (OS) was evaluated from Kaplan-Meier method. The association between clinical-pathological factors and OS was examined using Cox proportional hazards method to estimate hazard ratio (HR) with 95% confidence intervals (CI). Results: A total of 14 patients were selected. Median age was 28.5 years (interquartile range, 26-35). Locally advanced stage (IIB-IIIB) was diagnosed in 64.3%. Patients lower than 35 years experienced more positive clinical lymph nodes (72.7%), grade 2 (63.6%) and ER/PgR-negative tumors (54.5% and 72.7%, respectively). The patients with ER-positive tumors showed an improvement non-significant at 5-year OS (87%; p = 0.097). In the bivariate analysis, patients with a higher number of pathological lymph nodes (pNs) had a 12% increase in the risk of death than those with lower number (HR = 1.12; 95% CI: 1.02 to 1.2). The multivariate model (after adjustment for number of pNs, age and tumor size) ascertained that the nodal status was the only independent predictor associated to a worse OS (HR = 1.15; 95% CI: 1.01 to 1.3). Conclusion. Pregnancy after cancer did not have a detrimental effect on survival. The patients &lt; 35 years old group showed more unfavorable tumor features at diagnosis, which can largely explain a poorer prognosis. Nodal status was the most important prognostic factor that predicted the poor prognosis.

The efficacy of lapatinib in patients with metastatic HER2 positive breast cancer who received prior therapy with monoclonal antibodies and antibody-drug conjugate: a single institutional experience

The choice of the anti-HER2 agent depends on country-specific availability, the specific, previously administered anti-HER2 therapy and the relapse-free interval, although there is not much published data on the use of lapatinib after progression on pertuzumab and/or T-DM1. The aim of this research is to determine efficacy of lapatinib in this setting. This research included 111 patients with metastatic HER2 positive breast cancer who received lapatinib with capecitabine at The Oncology Institute of Vojvodina. Lapatinib was given to 83 patients after trastuzumab without prior exposure to pertuzumab or T-DM1 while 28 patients received lapatinib after prior exposure to trastuzumab, pertuzumab and/or T-DM1. In order to determine efficacy of lapatinib in both groups, we measured progression free survival (PFS) and overall survival (OS), as well as by subsets: hormonal status (ER-positive and/or PR-positive tumours versus ER-negative and PR-negative tumours), the number of positive axillary lymph nodes (four or more positive axillary lymph nodes versus less than four positive axillary lymph nodes), marker of proliferation (Ki-67 ≥ 30 versus Ki-67 < 30), disease free interval (metastatic recurrence ≤ 1 year after initial diagnosis versus metastatic recurrence > 1 year after initial diagnosis or de novo metastatic disease. Median PFS was 5.6 months (95% CI 4.6–6.6) in the group of patients who received lapatinib after prior exposure to trastuzumab, pertuzumab and/or T-DM 1 and 7.4 months (95% CI 6.1–10.2) in the group of patients who received lapatinib after trastuzumab (HR, 0.79; 95% CI 0.61–0.98; P = 0.09). The patients with negative prognostic factors such as hormone receptor negativity, more than four positive axillary lymph nodes, marker of proliferation Ki 67 ≥ 30 and metastatic recurrence ≤ 1 year after initial diagnosis, had a similar PFS, regardless of receiving lapatinib after prior exposure to trastuzumab, pertuzumab and/or T-DM1 or without prior exposure. Median OS was 10.1 months (95% CI 8.6-NR) in the group that received lapatinib after exposure to trastuzumab, pertuzumab and/or T-DM1 and 16.3 months (95% CI 14.4–20.2) in the group of patients who received lapatinib after trastuzumab (HR, 0.76; 95% CI, 0.59–0.94; P = 0.04). Patients with negative prognostic factors such as hormone receptor negativity, more than four positive axillary lymph nodes and marker of proliferation Ki 67 ≥ 30, had no distinctly worse OS, regardless of receiving lapatinib after prior exposure to trastuzumab, pertuzumab and/or T-DM1 or without prior exposure. Lapatinib with capecitabine is an effective therapeutic option, especially in patients with negative prognostic factors, who have received prior chemotherapy, trastuzumab, pertuzumab, T-DM1 and remains an acceptable option for HER2 positive metastatic breast cancer until the novel drugs are approved in developing countries.

A Novel Predictive Nomogram including Serum Lipoprotein a Level for Nonsentinel Lymph Node Metastases in Chinese Breast Cancer Patients with Positive Sentinel Lymph Node Metastases.

Background We developed a new nomogram combining serum biomarkers with clinicopathological features to improve the accuracy of prediction of nonsentinel lymph node (SLN) metastases in Chinese breast cancer patients. Methods We enrolled 209 patients with breast cancer who underwent SLN biopsy and axillary lymph node dissection. We evaluated the relationships between non-SLN metastases and clinicopathologic features, as well as preoperative routine tests of blood indexes, tumor markers, and serum lipids, including lipoprotein a (Lp(a)). Risk factors for non-SLN metastases were identified by logistic regression analysis. The nomogram was created using the R program to predict the risk of non-SLN metastases in the training set. Receiver operating characteristic (ROC) analysis was applied to assess the predictive value of the nomogram model in the validation set. Results Lp(a) was significantly associated with non-SLN metastasis status. Compared with the MSKCC model, the predictive ability of our new nomogram that combined Lp(a) level and clinical variables (pathologic tumor size, lymphovascular invasion, multifocality, and positive/negative SLN numbers) was significantly greater (AUC: 0.732, 95% CI: 0.643–0.821) (C-index: 0.703, 95% CI: 0.656–0.791) in the training cohorts and also performed well in the validation cohorts (C-index: 0.773, 95% CI: 0.681–0.865). Moreover, the new nomogram with Lp(a) improved the accuracy (12.10%) of identification of patients with non-SLN metastases (NRI: 0.121; 95% CI: 0.081–0.202; P = 0.011). Conclusions This novel nomogram based on preoperative serum indexes combined with clinicopathologic features facilitates accurate prediction of risk of non-SLN metastases in Chinese patients with breast cancer.

Tumor cell invasion in blood vessels assessed by immunohistochemistry is related to decreased survival in patients with bladder cancer treated with radical cystectomy

BackgroundLymphovascular invasion (VI) is an established prognostic marker for many cancers including bladder cancer. There is a paucity of data regarding whether the prognostic significance of lymphatic invasion (LVI) differs from blood vessel invasion (BVI). The aim was to examine LVI and BVI separately using immunohistochemistry (IHC), and investigate their associations with clinicopathological characteristics and prognosis. A secondary aim was to compare the use of IHC with assessing VI on standard HAS (hematoxylin-azophloxine-saffron) sections without IHC.MethodsA retrospective, population –based series of 292 invasive bladder cancers treated with radical cystectomy (RC) with curative intent at Vestfold Hospital Trust, Norway were reviewed. Traditional histopathological markers and VI based on HAS sections were recorded. Dual staining using D2–40/CD31 antibodies was performed on one selected tumor block for each case.ResultsThe frequency of LVI and BVI was 32 and 28%, respectively. BVI was associated with features such as higher pathological stages, positive regional lymph nodes, bladder neck involvement and metastatic disease whereas LVI showed weaker or no associations. Both BVI and LVI independently predicted regional lymph node metastases, LVI being the slightly stronger factor. BVI, not LVI predicted higher pathological stages. BVI showed reduced recurrence free (RFS) and disease specific (DSS) survival in uni-and multivariable analyses, whereas LVI did not. On HAS sections, VI was found in 31% of the cases. By IHC, 51% were positive, corresponding to a 64% increased sensitivity in detecting VI. VI assessed without IHC was significantly associated with RFS and DSS in univariable but not multivariable analysis.ConclusionsOur findings indicate that BVI is strongly associated with more aggressive tumor features. BVI was an independent prognostic factor in contrast to LVI. Furthermore, IHC increases VI sensitivity compared to HAS.

The log odds of positive neck lymph nodes is a superior lymph node predictor for overall survival in head and neck cancer: a population-based analysis in Germany

BackgroundThis population-based study investigated the influence of different lymph node (LN) classifications on overall survival (OS) in head and neck cancer (HNC).Methods401 patients (median age: 57 years; 47% stage IV) of the Thuringian cancer registries with diagnosis of a primary HNC receiving a neck dissection (ND) in 2009 and 2010 were included. OS was assessed in relation to total number of LN removed, number of positive LN, LN ratio, and log odds of positive LN (LODDS).ResultsMean number of LODDS was 0–0.96 ± 0.57. When limiting the multivariate analysis to TNM stage, only the UICC staging (stage IV: HR 9.218; 95% CI 2.721–31.224; p < 0.001) and LODDS > – 1.0 (HR 2.120; 95% CI 1.129–3.982; p = 0.019) were independently associated with lower OS.ConclusionLODDS was an independent and superior predictor for OS in HNC in a population-based setting with representative real-life data.

Patterns of Completion Axillary Dissection for Patients with Clinical T1-2N0 Breast Cancer Undergoing Total Mastectomy with Positive Sentinel Lymph Nodes

Patterns of Completion Axillary Dissection for Patients with Clinical T1-2N0 Breast Cancer Undergoing Total Mastectomy with Positive Sentinel Lymph Nodes

Sentinel Lymph Node Staging with Indocyanine Green for Patients with Cervical Cancer: The Safety and Feasibility of Open Approach Using SPY-PHI Technique.

(1) Background: Sentinel lymph node staging (SLN) with indocyanine green (ICG) in cervical cancer is the standard of care in most national and international guidelines. However, the vast majority of relevant studies about the safety and feasibility of this method are conducted on minimally invasive surgery; (2) Methods: This study is a retrospective analysis of a retrospective collected database of 76 consecutive patients with cervical cancers, who were operated laparoscopically (50%), or laparotomy (50%). Sentinel nodes were defined as the ICG-positive pelvic nodes in the first and second echelons. False negative cases were defined as positive non-sentinel lymph nodes despite successful sentinel mapping or failed mapping bilaterally by per-patient assessment or unilaterally by pelvic sidewall assessment; (3) Results: Regardless of the approach (open or laparoscopic), the SLN technique achieved a total sensitivity, specificity, and negative predictive value (NPV) of 94.7%, 98.6%, and 94.7%, respectively in the entire sample. The bilateral detection rate was as high as 93.4% with identical results in both approaches. The sensitivity and NPV for SNL in open surgery was found to be similar to minimal access surgery; (4) Conclusions: ICG and SPY-PHI technique is a reliable tool to detect sentinel lymph nodes in cervical cancer during laparotomy.

Development of a prediction model based on LASSO regression to evaluate the risk of non-sentinel lymph node metastasis in Chinese breast cancer patients with 1\u20132 positive sentinel lymph nodes

This study aimed to develop an intraoperative prediction model to evaluate the risk of non-sentinel lymph node (NSLN) metastasis in Chinese breast cancer patients with 1–2 positive sentinel lymph nodes (SLNs). The clinicopathologic data of 714 patients with 1–2 positive SLNs were investigated. Univariate and multivariate analyses were performed to identify the risk factors of NSLN metastasis. A new mathematical prediction model was developed based on LASSO and validated in an independent cohort of 131 patients. The area under the receiver operating characteristic curve (AUC) was used to quantify performance of the model. Patients with NSLN metastasis accounted for 37.3% (266/714) and 34.3% (45/131) of the training and validation cohorts, respectively. A LASSO regression-based prediction model was developed and included the 13 most powerful factors (age group, clinical tumour stage, histologic type, number of positive SLNs, number of negative SLNs, number of SLNs dissected, SLN metastasis ratio, ER status, PR status, HER2 status, Ki67 staining percentage, molecular subtype and P53 status). The AUCs of training and validation cohorts were 0.764 (95% CI 0.729–0.798) and 0.777 (95% CI 0.692–0.862), respectively. We presented a new prediction model with excellent clinical applicability and diagnostic performance for use by clinicians as an intraoperative clinical tool to predict risk of NSLN metastasis in Chinese breast cancer patients with 1–2 positive SLNs and make the final decisions regarding axillary lymph node dissection.

Impact of clinical-pathological factors on locoregional recurrence in mastectomy patients with T1-2N1 breast cancer: who can omit adjuvant radiotherapy?

PurposePostmastectomy radiation therapy (PMRT) in T1–T2 tumors with 1–3 positive axillary lymph nodes (ALNs) is controversial. This study was to identify prognostic factors of locoregional control (LRC) following mastectomy with or without PMRT for patients with T1-2N1 breast cancer and to discuss the selection of patients who might omit PMRT.Materials and methodsBetween January 2006 and December 2012, the data of 1474 postmastectomy patients staged pT1-2N1 were analyzed. PMRT was applied in 663 patients. LRC and disease-free survival (DFS) were calculated using the Kaplan–Meier method. Cox regression model was applied in the univariate and multivariate analyses to recognize the recurrence risk factors.ResultsWith the median follow-up duration of 93 months (range, 5–168 months), 78 patients (5.3%) failed to secure LRC and 220 patients (14.9%) experienced any recurrence. The 7.7-year LRC and DFS was 94.9% and 85.4% respectively in the entire cohort. PMRT significantly improved 7.7-year LRC from 93.4% to 96.6% (p = 0.005), but not the DFS (p = 0.335). Multivariate analysis revealed that PMRT was an independent prognostic factor of LRC (p < 0.001), meanwhile, age ≤ 40 years (p = 0.012), histological grade 3 (p = 0.004), 2–3 positive nodes (p < 0.001) and tumor size of 3–5 cm (p = 0.045) were significantly associated with decreased LRC. The 7.7-year LRC for patients with 0, 1, and 2–4 risk factors was 97.7% / 98.9% (p = 0.233), 95.3% / 98.0% (p = 0.092), and 80.3% / 94.8% (p < 0.001) in the non-PMRT and PMRT group, respectively.ConclusionsIn patients with T1-2N1 breast cancer, clinical-pathological factors including young age, histological grade 3, 2–3 positive nodes, and tumor size of 3–5 cm were identified to be predictors of a poorer LRC following mastectomy. Patients with 0–1 risk factor might consider the omission of PMRT.

Clinical Impact of Unexpected Para-Aortic Lymph Node Metastasis in Surgery for Resectable Pancreatic Cancer.

Simple SummaryPara-aortic lymph node (PALN) metastasis in pancreatic cancer (PC) is regarded as a contraindication to surgical resection. Nevertheless, the prognostic impact of unexpected intraoperative PALN metastasis is not firmly established. This retrospective study aims to analyze the prognostic impact of unexpected PALN metastasis and give insight on what surgeons should consider for patients with unexpected intraoperative PALN metastasis.Radiologically identified para-aortic lymph node (PALN) metastasis is contraindicated for pancreatic cancer (PC) surgery. There is no clinical consensus for unexpected intraoperative PALN enlargement. To analyze the prognostic role of unexpected PALN enlargement in resectable PC, we retrospectively reviewed data of 1953 PC patients in a single tertiary center. Patients with unexpected intraoperative PALN enlargement (group A1, negative pathology, n = 59; group A2, positive pathology, n = 13) showed median overall survival (OS) of 24.6 (95% CI: 15.2–33.2) and 13.0 (95% CI: 4.9–19.7) months, respectively. Patients with radiological PALN metastasis without other metastases (group B, n = 91) showed median OS of 8.6 months (95% CI: 7.4–11.6). Compared with group A1, groups A2 and B had hazard ratios (HRs) of 2.79 (95% CI, 1.4–5.7) and 2.67 (95% CI: 1.8–4.0), respectively. Compared with group A2, group B had HR of 0.96 (95% CI: 0.5–1.9). Multivariable analysis also showed positive PALN as a negative prognostic factor (HR 2.57, 95% CI: 1.2–5.3), whereas positive regional lymph node did not (HR 1.32 95% CI: 0.8–2.3). Thus, unexpected malignant PALN has a negative prognostic impact comparable to radiological PALN metastasis. This results suggests prompt pathologic evaluation for unexpected PALN enlargements is needed and on-site modification of surgical strategy would be considered.

Dantrolene Prevents the Lymphostasis Caused by Doxorubicin in the Rat Mesenteric Circulation.

Background and Purpose: Doxorubicin (DOX) is a risk factor for arm lymphedema in breast cancer patients. We reported that DOX opens ryanodine receptors (RYRs) to enact “calcium leak,” which disrupts the rhythmic contractions of lymph vessels (LVs) to attenuate lymph flow. Here, we evaluated whether dantrolene, a clinically available RYR1 subtype antagonist, prevents the detrimental effects of DOX on lymphatic function.Experimental Approach: Isolated rat mesenteric LVs were cannulated, pressurized (4–5 mm Hg) and equilibrated in physiological salt solution and Fura-2AM. Video microscopy recorded changes in diameter and Fura-2AM fluorescence tracked cytosolic free calcium ([Ca2+ i]). High-speed in vivo microscopy assessed mesenteric lymph flow in anesthetized rats. Flow cytometry evaluated RYR1 expression in freshly isolated mesenteric lymphatic muscle cells (LMCs).Key Results: DOX (10 μmol/L) increased resting [Ca2+ i] by 17.5 ± 3.7% in isolated LVs (n = 11). The rise in [Ca2+ i] was prevented by dantrolene (3 μmol/L; n = 10). A single rapid infusion of DOX (10 mg/kg i.v.) reduced positive volumetric lymph flow to 29.7 ± 10.8% (n = 7) of baseline in mesenteric LVs in vivo. In contrast, flow in LVs superfused with dantrolene (10 μmol/L) only decreased to 76.3 ± 14.0% (n = 7) of baseline in response to DOX infusion. Subsequently, expression of the RYR1 subtype protein as the presumed dantrolene binding site was confirm in isolated mesenteric LMCs by flow cytometry.Conclusion and Implications: We conclude that dantrolene attenuates the acute impairment of lymph flow by DOX and suggest that its prophylactic use in patients subjected to DOX chemotherapy may lower lymphedema risk.