Node-positive Patients Research Articles

Selective Neck Dissection for Node-Positive Oral Cavity Squamous Cell Carcinoma: A Retrospective Cohort Study

Introduction Selective neck dissection in clinically node-negative neck is considered the standard of care for oral squamous cell carcinomas (SCCs). Controversy still prevails in node-positive disease regarding the extent of neck dissection. In our part of the world, comprehensive neck dissection is mostly considered to be the minimal optimal treatment for palpable neck disease. Objective To compare regional control and disease-specific survival between clinically node-positive and node-negative patients undergoing selective neck dissection for oral SCC. Methods This was a retrospective cohort study conducted in the department of ENT, Head and Neck surgery at a tertiary care hospital. All patients with biopsy-proven oral and lip SCC, with or without nodal disease, who underwent selective neck dissection between April 2006 and July 2015 were included in the study. Results During the study period, 111 patients with oral SCC underwent selective neck dissection, of whom 71 (62%) were clinically node-negative and 40 (38%) patients had clinically positive nodes in the neck. The mean follow-up was 16.62 months (standard deviation [SD]: 17.03). The overall regional control rates were 95 versus 96% for clinical negative versus positive nodes, respectively ( p = 0.589). The disease-specific survival was 84.5% in the node negative group versus 82.5% in the node-positive group ( p = 0.703). Conclusion Selective neck dissection in node-positive neck oral SCC has similar regional control rates when compared with node-negative neck SCC. The difference in disease-specific survival between the two groups is also not significant.

Importance of Nodal Metastases Location in Pancreatoduodenectomy for Pancreatic Ductal Adenocarcinoma: Results from a Prospective, Lymphadenectomy Protocol.

BackgroundImplementing a prospective lymphadenectomy protocol, we investigated the nodal yields and metastases per anatomical stations and nodal echelon following upfront pancreatoduodenectomy (PD) for cancer. Next, the relationship between the extension of nodal dissection, the number of examined and positive nodes (ELN/PLN), disease staging and prognosis was assessed.MethodsLymphadenectomy included stations 5, 6, 8a-p, 12a-b-p, 13, 14a-b, 17, and jejunal mesentery nodes. Data were stratified by N-status, anatomical stations, and nodal echelons. First echelon was defined as stations embedded in the main specimen and second echelon as stations sampled as separate specimens. Recurrence and survival analyses were performed by using standard statistics.ResultsOverall, 424 patients were enrolled from June 2013 through December 2018. The median number of ELN and PLN was 42 (interquartile range [IQR] 34-50) and 4 (IQR 2-8). Node-positive patients were 88.2%. The commonest metastatic sites were stations 13 (77.8%) and 14 (57.5%). The median number of ELN and PLN in the first echelon was 28 (IQR 23-34) and 4 (IQR 1-7). While first-echelon dissection provided enough ELN for optimal nodal staging, the aggregate rate of second-echelon metastases approached 30%. Nodal-related factors associated with recurrence and survival were N-status, multiple metastatic stations, metastases to station 14, and jejunal mesentery nodes.ConclusionsFirst-echelon dissection provides adequate number of ELN for optimal staging. Nodal metastases occur mostly at stations 13/14, although second-echelon involvement is frequent. Only station 14 and jejunal mesentery nodes involvement was prognostically relevant. This latter station should be included in the standard nodal map and analyzed pathologically.Supplementary InformationThe online version contains supplementary material available at 10.1245/s10434-022-11417-3.

Abstract OT1-04-04: AXSANA - EUBREAST 3 (axillary surgery after neoadjuvant treatment): An international prospective multicenter cohort study of the EUBREAST study group to evaluate different surgical methods of axillary staging (sentinel lymph node biopsy, targeted axillary dissection, axillary dissection) in clinically node-positive breast cancer patients treated with neoadjuvant chemotherapy (NCT04373655)

Abstract Background The optimal surgical staging procedure of the axilla in patients who convert from a clinically positive (cN+) to a clinically negative node status (ycN0) through neoadjuvant chemotherapy is still controversial. Widely diverse techniques such as full Axillary Lymph Node Dissection (ALND), Targeted Axillary Dissection (TAD), Targeted Lymph Node Biopsy (TLNB) and Sentinel Lymph Node Biopsy alone (SLNB) are given preference in different international guidelines. So far, no comparative data on the oncological outcome or the morbidity of the different procedures are available. Further research is needed to safely de-escalate the extent of axillary surgery in this patient group. Trial design The AXSANA study is an international prospective cohort study including cN+ patients converting to ycN0 status and treated with different axillary staging techniques according to the standard at their treating institution. The study is initiated by the EUBREAST network. The trial includes patients with cT1-4c tumors, who present initially with axillary lymph node metastasis and are scheduled for neoadjuvant chemotherapy. According to an amendment in 2020 the inclusion of patients with highly suspicious nodes without minimally invasive biopsy is allowed. All patients converting to ycN0 status undergo follow-up for 5 years irrespectively of the ypN status. Primary endpoints: Invasive disease-free survival, axillary recurrence rate and health-related quality of life (HRQoL). HRQoL are evaluated using four standardized questionnaires (EORTC QLQ-C 30, EORTC QLQ BR 23, Lymph ICF and SOC-13) at baseline and after 1, 3 and 5 years after surgery. Secondary endpoints are the feasibility and performance of different axillary staging techniques (detection rate, number of removed lymph nodes and association with complications, arm morbidity and quality of life, operating time and use of clinical and economic resources); impact of learning curve, and the detailed mapping of surgical and oncological treatment standards in different countries. The impact on different regional treatment strategies (radiotherapy, ALND) in patients with ypN0(i+), ypN1(mi) and ypN1 is assessed. Current status of the study: On June 30th 157 study sites from 15 countries are open for recruitment (Austria 2, Czech Republic 1, Finland 1, Germany 112, Greece 3, Italy 1, Norway 1, Poland 3, Portugal 5, Romania 2, Russia 1, Sweden 4, Switzerland 4, Spain 6, Turkey 11). 620 patients have been included in the study. Among patients who converted to ycN0 status, 144 have been scheduled for ALND, 157 for TAD and 49 for SLNB. The study is still open for further international study sites. Funding: AGO-B, Claudia-von Schilling Foundation, Ehmann Foundation, AWOgyn, Merit Medical, Endomagnetics, Mammotome Target accrual: 3000 patients worldwide Citation Format: Thorsten Kühn, Steffi Hartmann, Elmar Stickeler, Jana de Boniface, Oreste Gentilini, Sarah Fröhlich, Franziska Ruf, Marc Thill, Michael Hauptmann, Guldeniz Karadeniz Cakmak, Isabel Rubio, Maria Luisa Gasparri, Michaelis Kontos, Eduard-Alexandru Bonci, Laura Niinikoski, Rosa Di Micco, Dawid Murawa, David Pinto, Florentia Peintinger, Christine Solbach, Matilda Appelgren, Jens-Uwe Blohmer, Michael Weigel, Gabriele Kaltenecker, Michael Schrauder, Janine Simons, Marjolein Smidt, Ellen Schlichting, Lukas Dostalek, Alexander Sergeevich Emelyanov, Elisabeth Thiemann, Semra Gunay, Sybille Loibl, Maggie Banys-Paluchowski. AXSANA - EUBREAST 3 (axillary surgery after neoadjuvant treatment): An international prospective multicenter cohort study of the EUBREAST study group to evaluate different surgical methods of axillary staging (sentinel lymph node biopsy, targeted axillary dissection, axillary dissection) in clinically node-positive breast cancer patients treated with neoadjuvant chemotherapy (NCT04373655) [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 OT1-04-04.

Abstract P3-19-15: Prognostic impact of radiation therapy in mucinous carcinoma of the breast

Abstract Purpose/Objectives Mucinous carcinoma (MC) of the breast is an uncommon variant of breast cancer which has a favorable prognosis. Current guidelines for ER/PR-positive, HER2-negative pure-MC state that endocrine therapy (ET) is only required for tumors ≥3cm and node-positive patients while chemotherapy (CTX) is not required but can be considered for node positive-patients. While radiation therapy (RT) currently remains a part of breast-conserving therapy (BCT) for this histology, the prognostic impact of RT in pure MC remains unclear. Materials/Methods The National Cancer Database (NCDB) was queried (2004-2017) for patients with non-metastatic, histologically confirmed MC who received breast-conserving surgery. Kaplan-Meier analysis was used to evaluate overall survival (OS). Univariate (UVA) and multivariate (MVA) analyses were conducted using Cox proportional hazard models to determine which clinical and treatment factors were prognostic for overall survival. Results A total of 24,837 patients with median age 70 (IQR 61-78) were included in this study. A total of 66% of carcinomas were grade 1 and 34% were grade 2. A total of 79% were pT1, 20% were pT2, and 1% were pT3-4. A total of 96% were pN0 and 4% were pN1-3. A total of 99% were ER+, 92% were PR+, and 96% were HER2-. A total of 61% received RT, 70% received ET, and 8% received CTX. The 10-year OS was 73% for those who received RT and 41% for those who did not. On UVA, RT (HR 0.31, p< 0.0001; CI 0.29-0.33), ET (HR 0.52, p< 0.0001; CI 0.49-0.55), CTX (HR 0.40, p< 0.0001; CI 0.35-0.46), and black race (HR 0.87, p= 0.006; CI 0.79- 0.96) were positive prognostic factors for OS while older age (HR 1.10, p< 0.0001; CI 1.09-1.10), CDCC comorbidity score (HR 1.93, p< 0.0001; CI 1.81- 2.06), and tumor size (HR 1.01, p< 0.0001; CI 1.01-1.02) were negative prognostic factors. On MVA, RT (HR 0.64, p< 0.0001; CI 0.59-0.69) and ET (HR 0.85, p< 0.0001; CI 0.78- 0.91) remained positive prognostic factors while older age (HR 1.08, p< 0.0001; CI 1.08-1.09), CDCC comorbidity score (HR 1.61, p< 0.0001; CI 1.50- 1.73), and tumor size (HR 1.02, p< 0.0001; CI 1.01- 1.02) remained negative prognostic factors; chemotherapy (HR 1.19, p= 0.039; CI 1.01- 1.39) became a negative prognostic factor and black race (HR 0.99, p= 0.92; CI 0.89- 1.12) was no longer prognostic. Conclusion This is the largest study to date on mucinous carcinoma of the breast and the role of RT after breast-conserving surgery. Use of postoperative RT after lumpectomy is associated with improved OS in patients with breast MC, suggesting that post-lumpectomy RT should remain standard of care. Citation Format: Neil Chevli, Kaidi Wang, Waqar Haque, Mary R. Schwartz, Julie Nangia, Jennifer Sasaki, Andrew M. Farach, Sandra S. Hatch, E. Brian Butler, Bin S. Teh. Prognostic impact of radiation therapy in mucinous carcinoma of the breast [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 P3-19-15.

Abstract P2-13-29: Analysis of GP2 immune response and relationship to recurrence in a prospective, randomized, placebo-controlled, single-blinded, multicenter, phase IIb study evaluating the reduction of recurrences using HER2/neu peptide GP2 (GLSI-100) vs. GM-CSF alone after adjuvant trastuzumab in HER2 positive women with operable breast cancer

Abstract Background: Delayed type hypersensitivity (DTH) skin tests in the randomized, active-controlled, single-blinded, multicenter Phase IIb trial investigating GLSI-100 (GP2+GM-CSF) administered in the adjuvant setting to node-positive and high-risk node-negative breast cancer patients with tumors expressing any degree of HER2 (immuno-histochemistry [IHC] 1-3+) (NCT00524277) have been analyzed. The trial enrolled HLA-A*02 patients randomized to receive GLSI-100 versus GM-CSF alone. The trial's primary objective was to determine if treatment with GLSI-100, a HER2-derived peptide, reduces recurrence rates. Analyses for this trial showing GLSI-100 to be efficacious, safe and immunogenic have been previously reported by Patel et al. and Mittendorf et al.. Methods: Consented patients were randomized and scheduled to receive GLSI-100 (500 mcg GP2: 125 mcg GM-CSF) or control (GM-CSF only) via 6 intradermal injections every 3-4 weeks as part of the Primary Immunization Series (PIS) for the first 6 months and 4 booster intradermal injections every 6 months thereafter. Boosters were introduced during the trial, thus some patients did not receive all 4 boosters. DTH skin tests were assessed at baseline and after the 6th dose with the orthogonal mean of each skin reaction measured 48-72 hours after injection using the sensitive ballpoint-pen method.. Results: The study enrolled 180 patients across 16 clinical sites with both HER2 3+ positive and low HER2 expressors (1-2+). After 5 years of follow-up, the Kaplan-Meier estimated 5-year DFS rate in the 46 HER2 3+ patients treated with GLSI-100, if the patient completed the PIS, was 100% versus 89.4% (95% CI:76.2, 95.5%) in the 50 placebo patients treated with GM-CSF (p = 0.0338). GLSI-100 was shown to be well tolerated with no SAEs deemed related to study medication and elicited a potent immune response measured by local skin tests and immunological assays. Injection site reactions were common, occurring in almost 100% of patients treated with either GLSI-100 or GM-CSF alone. Previous publications have reported the increase in DTH response reported among patients after treatment with GLSI-100. However, it was of interest to understand the positive DTH responses to GP2 noted at baseline. 22.8% of patients reacted to GP2 at baseline with induration of 5mm or greater. In the subgroup of patients who later experienced a breast cancer recurrence, 36.4% (8/22) had such a baseline response. Analysis of the time to recurrence among those recurring found that the median time to recurrence was 0.6 years for those with a baseline response while those that did not have a positive baseline DTH response to GP2 took 1.2 years to recur.. Conclusions: This study demonstrated that GLSI-100 safely elicited a potent immune response as evidenced by increased DTH skin responses with treatment paired with improved disease-free survival. It is theorized that a positive baseline DTH skin test to GP2 may be evidence of an existing immune response to GP2 associated with residual disease, impending recurrence, or prior treatments. Further studies assessing if GP2 immune response is an important prognosticator of cancer disease state or recurrence are planned. Citation Format: Snehal S Patel, David B McWilliams, Mira S Patel, Christine T Fischette, Jaye Thompson, F. Joseph Daugherty. Analysis of GP2 immune response and relationship to recurrence in a prospective, randomized, placebo-controlled, single-blinded, multicenter, phase IIb study evaluating the reduction of recurrences using HER2/neu peptide GP2 (GLSI-100) vs. GM-CSF alone after adjuvant trastuzumab in HER2 positive women with operable 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 P2-13-29.

Abstract P3-20-05: Trends of axillary treatment in sentinel node-positive breast cancer patients undergoing amputation

Abstract Objectives: To evaluate patterns of care in axillary treatment of Dutch patients - who were diagnosed with stage I-IV primary invasive breast cancer, underwent amputation and were found positive by sentinel lymph node biopsy (SLNB) - in the years following the publication of the American College for Surgeons Oncology Group (ACOSOG)-Z0011 and After Mapping of the Axilla: Radiotherapy Or Surgery (AMAROS) trials. Methods: Data from females diagnosed between January 1st 2009 and December 31st 2018 were obtained from the Netherlands Cancer Registry (NKR). Trends in completion axillary lymph node dissection (cALND), administration of adjunctive radiotherapy and, inversely, of omission of any kind of axillary treatment, were revealed by descriptive analyses on SNL positive patients. Results: Of 28,070 cT1-4 breast cancer patients undergoing amputation with SLNB from 2009 up until 2018, 10,706 were diagnosed as SLN positive. In the latter, the frequency of subsequent cALND went down significantly from 78% in 2009 to 10% in 2018 (P < 0.001), while adjunctive radiotherapy increased from 4% to 49% (P < 0.001). Omission of any additional local treatment increased from 18% to 41% (P < 0.001). In N1 patients cALND decreased from 57% to 13% (P < 0.001) and was mostly replaced by radiotherapy, increasing from 2% to 70% (P < 0.001). In N1mi and N0i+ patients, cALND decreased to less than 1% of cases in 2018, while radiotherapy increased from 4% to 40% and 8% to 13% (P < 0.001), respectively. Conclusion: In SLN positive breast cancer patients undergoing breast amputation, cALND had become rare 10 years following the AMAROS and Z0011 trial results. While radiotherapy mostly replaced cALND in the vast majority of N1 patients, less than half of N1mi and only a tenth of N0i+ patients received radiotherapy as the only adjunctive axillary treatment by the end of 2018. Citation Format: Eline EF Verreck, Julia van Steenhoven, Anne Kuijer, Marissa van Maaren, Sabine Siesling, Thijs van Dalen. Trends of axillary treatment in sentinel node-positive breast cancer patients undergoing amputation [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 P3-20-05.

Abstract ES8-4: Axillary management in upfront surgery - staging, local control or both?

Abstract Axillary management in women undergoing upfront surgery for operable breast cancer has changed dramatically over the last several decades. Axillary lymph node dissection (ALND), a procedure that was historically used in both clinically node negative and node positive patients to stage the axilla and optimize locoregional control, is associated with the potential for significant long-term morbidity in the form of upper extremity lymphedema, paresthesia, and shoulder dysfunction. Efforts to minimize the morbidity associated with ALND, as well as the recognition that only a minority of patients with clinically node negative disease are found to have nodal metastases at the time of axillary surgery, prompted the development and validation of sentinel lymph node biopsy (SLNB). In women who are clinically node negative, SLNB has been shown to accurately stage the axilla without compromising oncologic outcomes, identifying nodal disease in up to 30% of cases. The application of clinical trial data from Z0011 and AMAROS in T1-T2 breast cancer with 1-2 positive lymph nodes undergoing breast conservation allow for omission of completion ALND with no impact on locoregional control or survival. The ongoing POSNOC trial (NCT02401685) will further determine whether women with T1-T2 disease undergoing breast conservation or mastectomy require directed axillary treatment in the form of ALND or axillary radiation to minimize the risk of axillary failure. An altogether omission of axillary staging in clinically node negative breast cancer remains an area of evolving interest, with CALGB 9343 trial data supporting this approach in older women with stage I estrogen-receptor positive (ER+) HER2- breast cancer. Trials examining the omission of SLNB in other select patient populations with negative axillary imaging are the subject of ongoing investigation. At present, prognostic information derived from SLNB for clinically node negative women undergoing upfront surgery for early-stage triple negative and HER2+ breast cancer, premenopausal ER+HER2- breast cancer, and BRCA1/2-associated breast cancer remain important for adjuvant systemic therapy decision-making. Citation Format: S Wong. Axillary management in upfront surgery - staging, local control or both? [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 ES8-4.

Abstract P4-06-06: Role of lymphatic SEC62 expression in prediction of treatment response in patients undergoing neoadjuvant chemotherapy for primary breast cancer

Abstract Background Chromosome 3q26 amplifications have been shown to represent a frequent alteration in various cancer entities including breast cancer. SEC62 - a 3q26 encoded gene - was identified as a potential onco- and tumor-driver gene for the pathogenesis of breast cancer. Sec62 seems to induce an increased stress tolerance, enhanced cell migration and proliferation in SEC62 overexpressing cells. Patients with SEC62 overexpressing breast cancer have been shown to have a higher rate of lymph node metastasis and poorer overall prognosis. Hence, we aspired to further evaluate the function of lymphatic SEC62 expression and its predictive role on the response to neoadjuvant chemotherapy. Objectives We aimed to assess the role of lymph node SEC62 expression as a predictive biomarker for response to neoadjuvant chemotherapy, besides we sought to evaluate potential differences in SEC62 expression levels in metastatic lymph node core biopsies and final pathology specimen according to breast cancer subtype. Material & Methods All nodal positive patients treated for primary breast cancer with neoadjuvant chemotherapy at the Department of Gynaecology and Obstetricts, Saarland University Hospital, Homburg, Germany between 01/2009 and 12/2019 were enrolled in this retrospective study. We analyzed SEC62 expression in tissue samples by immunohistochemistry (IHC). Sec62 immunoreactivity was evaluated using the immunoreactive score (IRS) according to Remmele and Stegner (0-12). For the assessment of the Sec62 protein content of the tumor cells, we rated Sec62 “low” for a score of 0-8, and “high” for 9-12 as described in previous publications. IHC was performed on initial lymph node core biopsy (CB) tissue (pre-treatment) or sentinel node biopsy specimen and on definite pathology specimen (PS) obtained during axillary dissection after completion of neoadjuvant chemotherapy.SEC62 expressions in both samples were compared and correlated with response to neoadjuvant chemotherapy, evaluated pathologically using the semi-quantitative response to neoadjuvant chemotherapy scoring system by Sinn et al. ranging from 0 (no effect) to 4 (no tumor detectable). Results 103 patients were assessed for eligibility. 15 cases were excluded, due to incomplete clinical information or insufficient slide quality, leaving 88 patients for final analysis. Median patient age was 55 (32-78) years and median response to neoadjuvant chemotherapy score of 2 (0-4). 11 (12.5%) patients had luminal A, 31 (35.2%) luminal B, 21 (23.9%) Her2/neu positive and 25 (28.4%) triple negative breast cancer. Median SEC62 expression in lymph node core biopsies was significantly higher compared to expression in final specimen (p<0.01). While no differences in basic expression of SEC62 in CB and the response to neoadjuvant chemotherapy were detected, patients with an IRS score ≤ 8 in PS and patients with a difference of IRS score ≥6 between CB and PS showed a significantly higher median response to neoadjuvant chemotherapy score compared to other patients (p< 0.01). Analyzing median Sec62 IHC expression in final pathology specimen, we observed significantly lower Sec62 scores for Her2/neu positive and triple negative patients compared to other subtypes (p<0.01). Median SEC62 expression showed the highest decrease between CB and PS in Her2/neu positive and triple negative patients. Regarding response to neoadjuvant chemotherapy, the effects described above could be observed in all breast cancer subtypes, but were strongest in triple negative patients. Conclusion We identified lymph node SEC62 expression as a promising biomarker for prediction of response to neoadjuvant chemotherapy in breast cancer patients. This effect seems to be strongest in patients with triple negative breast cancer. Citation Format: Julia Zimmermann, Anna Jung, Merle Doerk, Mariz Kasoha, Barbara Linxweiler, Maximilian Linxweiler, Mathias Wagner, Rainer Bohle, Marc Radosa, Erich Solomayer, Julia C Radosa. Role of lymphatic SEC62 expression in prediction of treatment response in patients undergoing neoadjuvant chemotherapy for primary 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 P4-06-06.

Sentinel lymph node melanoma metastases: Assessment of tumor burden for clinical prediction of outcome in the first Multicenter Selective Lymphadenectomy Trial (MSLT-I)

PurposeAs clinical management decisions in patients with Stage III melanoma have become more complex, precise pathologic characterization of sentinel lymph node (SLN) metastases has become critical to guide management. The extent of SLN involvement correlates with risk of adverse outcomes, but reported methods of disease quantification vary. We examined SLN metastases from patients participating in an international clinical trial and compared several methods of tumor burden quantification. MethodsSLNs from 146 node-positive patients in the first Multicenter Selective Lymphadenectomy Trial (MSLT-I) were centrally-reviewed and characterized by number of tumor-positive nodes, percent nodal area tumor replacement, maximum dimension of largest metastasis, tumor penetrative depth, number of tumor foci, metastasis microanatomic location, and extracapsular extension. These data were analyzed for correlation with non-SLN metastasis and melanoma-specific survival (MSS). ResultsThe median number of tumor-involved SLNs was 1. The median maximum metastasis dimension was 1.11 mm. Median SLN area involvement was 1.5%. Tumor burden measures were highly correlated with each other. Factors associated with non-SLN metastasis by univariable analysis were primary tumor ulceration and extent of metastases. Tumor thickness, ulceration, non-SLN metastasis and multiple measures of SLN tumor burden were significantly related to MSS on univariable analysis. After multivariable adjustment, number of involved SLNs (p = 0.05) and percent nodal area tumor replacement (p = 0.02) were independent predictors of MSS. ConclusionCentral review of MSLT-I pathology indicates that primary tumor and SLN tumor characteristics predict non-SLN metastasis and MSS. Percent nodal involvement was more powerfully prognostic than the more commonly used maximum dimension of largest metastasis.

Does Angiosarcoma of the Breast Need Nodal Staging?

Breast angiosarcoma is a rare malignancy classically associated with hematogenous metastases. We sought to determine the prevalence of pathologic nodal involvement in patients with nonmetastatic, resected breast angiosarcoma and its association with overall survival. The National Cancer Database was used to identify patients with nonmetastatic angiosarcoma of the breast who underwent surgical resection from 2004 to 2017. The prevalence of regional lymph node operation and nodal positivity was calculated. The Kaplan-Meier method was used to evaluate overall survival among node-positive and node-negative patients. Cox proportional hazard modeling was used to evaluate the adjusted association of nodal positivity with overall survival. We included 991 patients with angiosarcoma. The median age was 69 years (interquartile range 57 to 78), and the cohort was 99% female. A total of 298 patients (30%) had pathologic regional nodal evaluation. Of those, 15 (5.0%) had positive regional lymph nodes. Node-positive patients had significantly worse survival than patients with negative regional lymph nodes. After adjusting for patient, tumor, and treatment factors, a positive regional lymph node was associated with worse overall survival compared with patients with no nodal evaluation (hazard ratio 3.20; 95% CI 1.75 to 5.86; p < 0.001). Patients with nonmetastatic angiosarcoma of the breast have a 5% regional lymph node positivity rate, which is at a common threshold to consider evaluation, and identifies patients with poor survival. A prospective study to determine performance characteristics of sentinel lymph node biopsy is warranted.

Predictors of axillary node response in node-positive patients undergoing neoadjuvant chemotherapy for breast cancer.

Background:The ability to accurately predict which patients will achieve a pathologic complete response (pCR) after neoadjuvant chemotherapy could help identify those who could safely be spared the potential morbidity of axillary lymph node dissection. We performed a retrospective analysis of a cohort of clinically node-positive patients managed with neoadjuvant chemotherapy with the goal of identifying predictors of axillary pCR.Methods:Eligible patients were aged 18 years or older, had clinical T1–T4, N1–N3, M0 breast cancer and received neoadjuvant chemotherapy followed by surgical axillary lymph node staging between 2001 and 2017 at Misericordia Hospital, Edmonton, Alberta. Patient data, including tumour characteristics, details of neoadjuvant chemotherapy, imaging results before and after neoadjuvant chemotherapy, and final pathologic analysis, were collected from the appropriate provincial electronic data repositories. We summarized the data using descriptive statistics. We characterized associations between clinical/tumour characteristics and pCR using univariate and multivariate regression analysis.Results:Of the 323 patients included in the study, 130 (40.2%) achieved axillary pCR. Absence of residual disease in the breast was associated with axillary pCR (odds ratio 6.74, 95% confidence interval 2.89–15.67). HER2-positive, triple-negative and ER-positive/PR-negative/HER2-negative tumours were significantly associated with a pCR on univariate analysis; the association trended toward significance on multivariate analysis.Conclusion:Our findings support the routine use of neoadjuvant chemotherapy and sentinel lymph node biopsy in patients with an absence of residual disease in the breast, and potentially in those with HER2-positive or triple-negative subtypes, and highlight the ER-positive/PR-negative biomarker subtype as a potential predictor of nodal response.

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.

Outcomes in Clinically Node Positive Bladder Cancer Patients at a Tertiary Cancer Centre in the UK

Purpose: Poor prognosis TxN+M0 bladder cancer has limited evidence-based guidelines defining optimum management. We evaluated real-world outcomes and treatment approaches for patients at a tertiary oncology centre.

AXSANA: A European prospective multicenter cohort study to evaluate different surgical methods of axillary staging in clinically node-positive breast cancer patients treated with NACT

Background: The optimal surgical staging procedure of the axilla in breast cancer patients converting from a clinically positive (cN+) to a clinically negative node status (ycN0) through neoadjuvant chemotherapy remains controversial. Various techniques, such as Axillary Lymph Node Dissection (ALND), Targeted Axillary Dissection (TAD), Target Lymph Node Biopsy (TLNB) and Sentinel Lymph Node Biopsy (SLNB) are used but comparative data on oncological outcome and morbidity of these procedures are not available.

A0825 - Oncological outcomes, patterns of recurrence and impact of competing causes of mortality in clinically node-positive prostate cancer patients treated with radical prostatectomy

A0825 - Oncological outcomes, patterns of recurrence and impact of competing causes of mortality in clinically node-positive prostate cancer patients treated with radical prostatectomy

Evidence and implementation gaps in management of sentinel node–positive melanoma in the United States

BackgroundMelanoma clinical trials demonstrated that completion lymph node dissection is low value for most sentinel lymph node–positive patients. Contemporaneous trials of adjuvant systemic immunotherapy and BRAF/MEK targeted therapy showed improved recurrence-free survival in high-risk sentinel lymph node–positive patients. To better understand how oncologic evidence is incorporated into practice (implementation), we evaluated factors associated with discontinuation of completion lymph node dissection and adoption of systemic treatment at United States Commission on Cancer–accredited centers. MethodsIn a retrospective cohort study of adults with sentinel lymph node–positive melanoma treated from 2012 to 2017 using the National Cancer Database, we evaluated use of completion lymph node dissection and adjuvant systemic treatment using mixed-effects logistic regression, reporting results as odds ratios with 95% confidence intervals. ResultsAmong 10,240 sentinel lymph node–positive melanoma patients, performance of completion lymph node dissection declined from 60% to 27%. Adjuvant systemic treatment increased from 29% to 43% (37% in stage IIIA patients, 46% in IIIB–C). Completion lymph node dissection was less common with lower extremity tumors (odds ratio = 0.53, 95% confidence interval = 0.44–0.64) and more common with multiple positive sentinel lymph nodes (odds ratio = 2.36, 95% confidence interval = 2.08–2.67), treatment at a high- or moderate-volume center (odds ratiohigh = 1.49, 95% confidence interval = 1.05–2.12; odds ratiomoderate = 1.32, 95% confidence interval = 1.05–1.64), and receipt of systemic therapy (odds ratio = 1.44, 95% confidence interval = 1.27–1.63). The increased likelihood of completion lymph node dissection in patients receiving adjuvant systemic treatment persisted in the most recent study years and in patients with a single positive sentinel lymph node. ConclusionAt a population level, completion lymph node dissection declined and adjuvant systemic treatment increased, reflecting evidence-responsive care. Variation in persistent use of completion lymph node dissection and in provision of adjuvant treatment for lower risk patients highlights residual gaps in both evidence and implementation.

Assessment of compliance with hormonal therapy in early breast cancer patients with positive hormone receptor phenotype: A single institution study.

BackgroundAdherence to long-term adjuvant hormonal therapy in hormonal receptors (HR)-positive breast cancer is really challenging and can affect the survival outcome. The present study aims to assess rate of compliance with hormonal therapy and possible predictive factors in a single institute in Saudi Arabia.Patients &methodsWe recruited patients with HR-positive breast cancer who presented to oncology outpatient clinics. Patients were assessed for compliance using a study questionnaire. Compliance was defined as taking ≥80% of prescribed doses of oral hormonal therapy. Different epidemiological, clinical, pathological and treatment data were checked in patients’ medical records and correlated with compliance/interruption of hormonal therapy.ResultsAmong the 203 recruited patients, 95.1% were compliant with hormonal therapy, while it was interrupted in 16.7% of patients, and 58.1% reported missing intake of hormonal pills. Age >50 years, having permanent job and higher education level were significantly associated with non-compliance in univariate analysis. On multivariate analysis, job status was the only independent predictor of non-compliance. The following parameters were significantly related to hormonal therapy interruption: marital status (single: 28.8% vs married patients: 12.6%, p = 0.01) and residence location (Makkah: 11.7% vs. outside Makkah: 25.3%, p = 0.019), lymphovascular invasion (LVI) (No: 20.9%, Yes: 7.8%, p = 0.025) and N0 tumours (compared to node-positive patients, p = 0.008). On multivariate analysis, marital status, residence location and N-stage, maintained significance relation with hormonal therapy interruption.ConclusionCompliance with hormonal therapy was high in the study cohort. Marital status, residence location, job status and N-stage may be related to interruption/compliance with hormonal therapy.

The Utility of the Oncotype DX Test for Breast Cancer Patients in an Australian Multidisciplinary Setting.

Introduction The Oncotype DX test is a genomic assay that generates a Recurrence Score (RS) predicting the 10-year risk of recurrence and response to adjuvant chemotherapy in ER+/HER2− breast cancer patients. The aims were to determine breast cancer distant recurrence and correlate with adjuvant chemoendocrine prescribing patterns based on the Oncotype DX recurrence score. Methods We conducted a retrospective single-institution case series of 71 patients who had Oncotype DX assay testing after definitive surgery between 2012 and 2016. Both node-positive and node-negative patients were included. Patients were divided into Oncotype DX low risk (RS < 11) (n = 10, 14%), intermediate risk (RS 11–25) (n = 45, 63%), and high risk (RS > 25) (n = 16, 23%). Median follow-up was 6.1 years (range 4–8.9 years). Adjuvant treatment regimens and oncological outcomes were determined. Results. Mean age at diagnosis was 56 years (range, 33–77). Invasive ductal carcinoma (IDC) accounted for the majority (87%), with most tumors measuring between 10–20 mm (52%). 48% of the cohort were node positive. 15 of 16 high-risk patients (94%) received chemotherapy. 96% of intermediate-risk patients received endocrine therapy alone, one patient received chemoendocrine therapy (2%), and one declined systemic therapy (2%). In the low-risk group, 100% received endocrine therapy only. The high-risk group had the lowest mean ER% (P < 0.05), greatest mean mitotic rate (P < 0.05), and greatest proportion of Ki67% > 14. Five patients developed distant recurrence (7%): three from the intermediate-risk group (7%), one from the low-risk group (10%), and one from the high-risk group (6%). Conclusion This is the first Australian study reporting the experience with medium-term recurrence outcomes of using the Oncotype DX assay in breast cancer. Chemotherapy was rarely given for patients with low-to-intermediate RS and always offered in high RS. This pattern of prescribing was associated with low rates of distant recurrence. National funding models should be considered.

Postoperative hypofractionated-accelerated radiotherapy (HypoAR) for locally advanced rectal cancer.

despite the advances in preoperative hypofractionated-accelerated radiotherapy for patients with locally advanced rectal cancer, postoperative radiotherapy delivered with standard fractionation (46-50 Gy in 5weeks) remains a standard adjuvant schedule. The role of hypofractionated-accelerated radiotherapy in a postoperative setting remains largely unexplored. eighty-eight patients with rectal cancer infiltrating the rectal wall and/or having metastasis to the perirectal lymph nodes were treated with surgery followed by adjuvant chemotherapy and, subsequently, with hypofractionated-accelerated radiotherapy. Ten fractions of 3.4 Gy were delivered to the pelvis for 10 consecutive fractions, within 12days. The follow-up of patients alive at the time of analysis ranges from 12-120months (median 48). mild abdominal discomfort and diarrhoea were frequent, but medical medication was demanded in 14/88 (15.9%) of patients. The incidence of late toxicities was low; 4/88 (3.5%) patients complained for intermittent intestinal urgency. Locoregional recurrence occurred in 8/88 patients (9%). The 5-year locoregional relapse-free survival was achieved in 89.7% of patients, and this dropped to 84% in node-positive patients (P=0.45). The 5-year disease-specific overall survival was 72.4%. Nodal involvement showed a trend to negatively affect prognosis (5-year overall survival 68.2 vs. 79.6%; P=0.23). postoperative hypofractionated-accelerated radiotherapy has minimal early and late toxicity. The locoregional control and disease-specific survival rates are similar to the expected from conventional postoperative chemoradiotherapy. The 2.5-fold decrease of radiotherapy treatment time, reduction of waiting lists and the lower overall cost of radiotherapy are additional benefits associated with hypofractionated-accelerated radiotherapy.

Prognostic impact of miR-34b/c DNA methylation, gene expression, and promoter polymorphism in HPV-negative oral squamous cell carcinomas

Micro RNAs (miRNAs) have a key role in gene expression regulation in cancer. The aim of the current study is to evaluate the prognostic value of miR-34b/c promoter hypermethylation, gene expression, and polymorphism in HPV-negative oral squamous cell carcinomas (OSCC). MiR-34b/c promoter hypermethylation and pre-miR-34b/c polymorphism rs4938723 were evaluated in tumor tissues of 148 patients, and miR-34b expression in 123 HPV-negative OSCC. For risk assessment, the control group was comprised of 175 healthy individuals. MiR-34b/c promoter hypermethylation was determined by methylation-specific PCR. Gene expression, genotyping and HPV screening was assessed by Q-PCR. The data from our hospital cohort indicated that miR-34b/c DNA methylation was associated with nodal status (p = 0.048), and predicted the shorter overall survival of HPV-negative OSCC patients (p = 0.008). Down-regulated miR-34b/c expression was associated with smoking (p = 0.047), alcohol use (p = 0.009), stage (p = 0.025), recurrences (p = 0.000), and a poor survival (p = 0.00029). Median values of miR-34b expression were significantly lower in advanced stages III/IV as opposed to stage I/II, p = 0.006, and in nodal positive vs negative patients (p = 0.045). TCGA data also indicated that tumors with stage I–III expressed significantly higher levels of miR-34b, compared to tumors with stage IV (p = 0.035), Low miR-34b/c expression was associated with poor survival in smokers (p = 0.001) and patients with tongue carcinomas (p = 0.00003), and TCGA analysis confirmed these findings although miR-34b expression and miR-34b/c methylation were not associated with survival outcome in the whole TCGA cohort. A significant negative miR-34b/c expression–methylation correlation was observed in our hospital cohort (p = 0.017) and in TCGA cohort. Pre-miR-34b/c polymorphism was not associated with oral cancer risk. Our findings indicate that miR-34b/c hypermethylation and low miR-34b expression could promote the progression and predict the poor prognosis for HPV-negative OSCC, which suggests miR-34b/c as a promising biomarker and therapeutic target for OSCC in the future.