Node-positive Patients Research Articles

Nonmetastatic Axillary Lymph Nodes Have Distinct Morphology and Immunophenotype in Obese Patients with Breast Cancer at Risk for Metastasis

Obese breast cancer patients have worse outcomes than their normal weight counterparts, with a 50% to 80% increased rate of axillary nodal metastasis. Recent studies suggest a link between increased lymph node adipose tissue and breast cancer nodal metastasis. Further investigation into potential mechanisms underlying this link may reveal potential prognostic utility of fat-enlarged lymph nodes in breast cancer patients. This study uses a deep learning model to identify morphological differences in non-metastatic axillary nodes between obese, node-positive and node-negative breast cancer patients. The model was developed using nested cross-validation on 180 cases and achieved an AUC of 0.67 in differentiating patients using hematoxylin and eosin stained whole-slide images. The top predictive patches from the slides according to the model were reviewed by a pathologist and their morphological differences were quantified. This analysis showed an increased average adipocyte size (p-value=0.004), increased white space between lymphocytes (p-value<0.0001), and increased red blood cells (p-value<0.001) in non-metastatic lymph nodes of node-positive patients. Preliminary immunohistochemistry analysis on a subset of 30 patients showed a trend of decreased CD3 expression and increased leptin expression in fat-replaced axillary lymph nodes of obese, node-positive patients. These findings suggest a novel direction to further investigate the interaction between lymph node adiposity, lymphatic dysfunction, and breast cancer nodal metastases, highlighting a possible prognostic tool for obese breast cancer patients.

The use of axillary ultrasound (AUS) to assess the nodal status after neoadjuvant chemotherapy (NACT) in primary breast cancer patients

IntroductionAxillary Ultrasound (AUS) is standard for pre-therapeutic axillary staging in early breast cancer patients. 35–75 % of the breast cancer (BC) patients with positive axillary lymph nodes receiving neoadjuvant chemotherapy (NACT) convert to pathological node negative. For those patients, axillary surgery after NACT could be de-escalated, if an accurate prediction of the pathologic nodal status following NACT was possible. This study aims to answer the question, whether AUS can be used as a reliable diagnostic tool for restaging of axillary nodal status after NACT. Patients and methodsWe collected data of 96 patients with nodal positive primary breast cancer who received NACT between 2009 and 2015 at the Breast Cancer Center of the University Hospital Ulm. Patients were classified as node negative or positive by AUS after NACT (ycN + or ycN0) and the results were compared to the pathological result obtained after axillary lymph node dissection (ypN + vs ypN0) in all patients. Results58.3 % of the patients had pathological complete remission of axillary lymph nodes after NACT (ypN0). The sensitivity and specificity of AUS were 57.5 % and 78.6 %, respectively. The FNR was 42.5 %. The Positive and Negative Predictive Values (PPV and NPV) were 65.7 % and 72.1 %, respectively. The accuracy of AUS was 69.8 % and not associated with any of the investigated clinico-pathological parameters. ConclusionAUS alone is not accurate enough to replace surgical restaging of the axilla after NACT in initially node positive breast cancer patients.

Low axillary sampling to stage post neoadjuvant axilla in breast cancer patients - A practical approach in developing world

BackgroundPost-neoadjuvant sentinel lymph node biopsy or targeted axillary dissection in carcinoma breast patients need costly infrastructure, making it out of reach for resource constrained developing countries. This study assesses the diagnostic accuracy of low axillary node sampling to predict the nodal status of the post-chemotherapy node-negative axilla. Materials and methodsThis is a prospective study which included cytology proven node positive carcinoma breast patients who had node negative axilla after chemotherapy and underwent low axillary sampling with complete axillary lymph node dissection. Nodes below second intercostobrachial nerve were sent as low axillary sample. Results211 patients with carcinoma breast underwent FNAC of the axillary node prior to neoadjuvant systemic therapy (NAST). Low axillary sampling was performed on 77 patients who had clinically and radiologically node negative axilla after NAST. Out of 77, 24 (31%) had early breast cancer and 32 (41.5%) had T4 disease prior to NAST. In this cohort, 36 patients (47%) had a good biology tumour, 57 (74%) had Grade 3 tumour and 20 (26%) had lymphovascular invasion (LVI). Pathological complete response of breast and axilla was seen in 24 patients (31%). Low axillary sampling had a range of 1–12 nodes with median lymph nodal yield of 6. The false negative rate (FNR) of low axillary sampling was 8.3%. Good tumour biology, post NAST residual breast tumour and lymphovascular invasion were the independent predictors of positive low axillary nodes. ConclusionsLow axillary sampling is an economical and feasible option to de-escalate axillary surgery with acceptable false negative rate in carcinoma breast patients who had node negative axilla post neoadjuvant systemic therapy.

The Prognostic Role of Preoperative PSMA PET/CT in cN0M0 pN+ Prostate Cancer: A Multicenter Study

ContextDespite negative preoperative conventional imaging, up to 10% of patients with prostate cancer (PCa) harbor lymph-node involvement (LNI) at radical prostatectomy (RP). The advent of more accurate imaging modalities such as PET/CT improved the detection of LNI. However, their clinical impact and prognostic value are still unclear. We aimed to investigate the prognostic value of preoperative PET/CT in patients node positive (pN+) at RP. Evidence SynthesisWe retrospectively identified cN0M0 patients at conventional imaging (CT and/or MRI, and bone scan) who had pN+ PCa at RP at 17 referral centers. Patients with cN+ at PSMA/Choline PET/CT but cN0M0 at conventional imaging were also included. Systemic progression/recurrence was the primary outcome; Cox proportional hazards models were used for multivariate analysis. Evidence AcquisitionWe included 1163 pN+ men out of whom 95 and 100 had preoperative PSMA and/or Choline PET/CT, respectively. ISUP grade ≥4 was detected in 66.6%. Overall, 42% of patients had postoperative PSA persistence (≥0.1 ng/mL). Postoperative management included initial observation (34%), ADT (22.7%) and adjuvant RT+/-ADT (42.8%). Median follow-up was 42 months. Patients with cN+ on PSMA PET/CT had an increased risk of systemic progression (52.9% vs. 13.6% cN0 PSMA PET/CT vs. 21.5% cN0 at conventional imaging; P < .01). This held true at multivariable analysis: (HR 6.184, 95% CI: 3.386-11-295; P < .001) whilst no significant results were highlighted for Choline PET/CT. No significant associations for both PET types were found for local progression, BCR, and overall mortality (all P > .05). Observation as an initial management strategy instead of adjuvant treatments was related with an increased risk of metastases (HR 1.808; 95% CI: 1.069-3.058; P < .05). ConclusionsPSMA PET/CT cN+ patients with negative conventional imaging have an increased risk of systemic progression after RP compared to their counterparts with cN0M0 disease both at conventional and/or molecular imaging.

Sentinel-node biopsy in apparent early stage ovarian cancer: final results of a prospective multicentre study (SELLY)

AimTo evaluate the sensitivity and specificity of sentinel-lymph-node mapping compared with the gold standard of systematic lymphadenectomy in detecting lymph node metastasis in apparent early stage ovarian cancer. MethodsMulticenter, prospective, phase II trial, conducted in seven centers from March 2018 to July 2022. Patients with presumed stage I-II epithelial ovarian cancer planned for surgical staging were eligible. Patients received injection of indocyanine green in the infundibulo-pelvic and, when feasible, utero-ovarian ligaments and sentinel lymph node biopsy followed by pelvic and para-aortic lymphadenectomy was performed. Histopathological examination of all nodes was performed including ultra-staging protocol for the sentinel lymph node. Results174 patients were enrolled and 169 (97.1 %) received study interventions. 99 (58.6 %) patients had successful mapping of at least one sentinel lymph node and 15 (15.1 %) of them had positive nodes. Of these, 11 of 15 (73.3 %) had a correct identification of the disease in the sentinel lymph node; 7 of 11 (63.6 %) required ultra-staging protocol to detect nodal metastasis. Four (26.7 %) patients with node-positive disease had a negative sentinel-lymph-node (sensitivity 73.3 % and specificity 100.0 %). ConclusionsIn a multicenter setting, identifying sentinel-lymph nodes in apparent early stage epithelial ovarian cancer did not reach the expected sensitivity: 1 of 4 patients might have metastatic lymphatic disease unrecognized by sentinel-lymph-node biopsy. Nevertheless, 35.0 % of node positive patients was identified only thanks to ultra-staging protocol on sentinel-lymph-nodes.

Penile Cancers Attributed to Human Papillomavirus Are Associated with Improved Survival for Node-positive Patients. Findings from a Norwegian Cohort Study Spanning 50 Years

BackgroundHuman papillomavirus (HPV) infection is a risk factor for the development of penile squamous cell carcinoma (PSCC). It remains inconclusive whether HPV-related PSCC has a different prognosis from non–HPV-related PSCC. ObjectiveTo investigate the relationship between HPV status and survival as well as temporal changes in the proportion of HPV-related PSCC. Design, setting, and participantsA retrospective cohort of 277 patients treated in Norway between 1973 and 2022 was investigated for HPV DNA in tumor tissue. Clinicopathological variables and disease course were registered. Outcome measurements and statistical analysisKaplan-Meier curves and Cox regression were used to investigate the determinants of cancer-specific survival (CSS). The chi-square test for trend in proportions enabled investigation of temporal changes in the HPV-related proportion of PSCC patients treated in Western Norway (n = 211). Results and limitationsHPV DNA was detected in tumor tissue from 131 (47%) patients. Stratified by HPV status, 5-yr CSS did not differ between groups (p = 0.37). When investigating only node-positive patients, however, presence of HPV DNA was an independent predictor of better survival in multivariable Cox regression after adjustment for age, nodal stage, and adjuvant therapy (hazard ratio 0.54, 95% confidence interval: [0.30–0.99], p = 0.04). In cases from Western Norway, an increasing proportion of HPV-related cases over time was found (p = 0.01). The main limitation is the retrospective study design. ConclusionsHPV DNA in tumor tissue was associated with significantly better CSS for node-positive patients. The proportion of HPV DNA–positive PSCC has increased significantly in Western Norway over the past 50 yr. Patient summaryWe investigated the impact of human papillomavirus (HPV) on the survival of penile cancer patients treated over a 50-yr period in Norway. We found that for patients with lymph node metastasis, survival was better for HPV-related cases. We also found that the proportion of cases due to HPV has increased in Western Norway.

Conservative Axillary Surgery May Prevent Arm Lymphedema without Increasing Axillary Recurrence in the Surgical Management of Breast Cancer.

Axillary lymph node dissection (ALND) has been associated with postoperative morbidities, including arm lymphedema, shoulder dysfunction, and paresthesia. Sentinel lymph node (SLN) biopsy emerged as a method to assess axillary nodal status and possibly obviate the need for ALND in patients with clinically node-negative (cN0) breast cancer. The majority of breast cancer patients are eligible for SLN biopsy only, so ALND can be avoided. However, there are subsets of patients in whom ALND cannot be eliminated. ALND is still needed in patients with three or more positive SLNs or those with gross extranodal or matted nodal disease. Moreover, ALND has conventionally been performed to establish local control in clinically node-positive (cN+) patients with a heavy axillary tumor burden. The sole method to avoid ALND is through neoadjuvant chemotherapy (NAC). Recently, various forms of conservative axillary surgery have been developed in order to minimize arm lymphedema without increasing axillary recurrence. In the era of effective multimodality therapy, conventional ALND may not be necessary in either cN0 or cN+ patients. Further studies with a longer follow-up period are needed to determine the safety of conservative axillary surgery.

Axillary Reverse Mapping in Clinically Node-Positive Breast Cancer Patients

Background: Axillary reverse mapping (ARM) nodes are involved in a significant proportion of clinically node-positive (cN+) breast cancer patients. However, neoadjuvant chemotherapy (NAC) is effective at decreasing the incidence of nodal metastases in cN+ patients. Patients and methods: One hundred forty-five cN+ patients with confirmed nodal involvement on ultrasound-guided fine needle aspiration cytology were enrolled in this study: one group underwent axillary lymph node dissection (ALND) without NAC (upfront surgery group), and the other group underwent ALND following NAC (NAC group). The patients underwent 18F-FDG-positron emission tomography/computed tomography (18F-FDG-PET/CT) before surgery, as well as an ARM procedure during ALND. Results: the rates of involvement of ARM nodes in the NAC group were significantly lower than those of the upfront surgery group (36.6% vs. 62.2%, p &lt; 0.01). Notably, involvement was significantly decreased after NAC in non-luminal-type tumors as compared to the luminal-type (18.4% vs. 48.5%: p &lt; 0.01). Moreover, there was a significant difference in ARM node involvement after NAC between patients with or without axillary uptake of 18F-FDG (61.5% vs. 32.5%: p &lt; 0.01). Conclusions: NAC significantly decreased the risk of ARM node metastases in cN+ patients, but 18F-FDG-PET/CT was not suitable to detect residual metastatic disease of the axilla after NAC.

Time to extend the indication for sentinel node biopsy in vulvar cancer? Results from a prospective nationwide Swedish study

ObjectiveTo assess detection rates and negative predictive values of sentinel node biopsy in vulvar squamous cell carcinoma with tumors ≥4 cm, multifocal tumors, and in locally recurrent disease.MethodsBetween December 2019...

Significance of tumor size and number of positive nodes in patients with FIGO 2018 stage IIIC1 cervical cancer.

This study aimed to investigate the prognostic significance of tumor size and number of positive pelvic lymph nodes (PLN) in International Federation of Gynecology and Obstetrics (FIGO) 2018 stage IIIC1 cervical cancer patients. Clinical data from 626 women with cervical cancer treated at Osaka International Cancer Center in 2010-2020 were retrospectively reviewed. Using the cutoff value obtained on the receiver operating characteristic analysis, the prognostic significance of tumor size and number of positive PLN in stage IIIC1 patients was first evaluated via uni- and multivariate analyses. Then, the impact of incorporating tumor size and number of positive PLN into the FIGO staging system was investigated using the Kaplan-Meier method. Among 196 women with Stage IIIC1 disease, larger tumors (>4cm) and multiple PLN metastases (≥4) were independent predictors of progression-free survival (PFS) in patients with stage IIIC1 cervical cancer. The PFS of patients with stage IIIC1 disease was inversely associated with the number of risk factors. Although patients with stage IIIC1 disease had significantly increased survival rates compared to those with stage IIIA or IIIB disease in the original FIGO 2018 staging system, this reversal phenomenon was resolved by incorporating larger tumors (>4cm) and multiple PLN metastases (≥4) into the revised staging system. Incorporating tumor size and number of metastatic lymph nodes into the FIGO staging system allows additional risk stratification for women with stage IIIC1 cervical cancer and improves survival prediction performance.

Lymph node staging in grade 1–2 endometrioid ovarian carcinoma apparently confined to the ovary: Is it worth?

ObjectiveThe aim of this study was to assess the disease-free survival (DFS) and overall survival (OS) of patients with grade 1–2 endometrioid ovarian carcinoma apparently confined to the ovary, according to surgical staging. MethodsMulticenter, retrospective, observational cohort study. Patients with endometrioid ovarian carcinoma, surgical procedure performed between May 1985 and December 2019, stage pT1 N0/N1/Nx, grade 1–2 were included. Patients were stratified according to lymphadenectomy (defined as removal of any lymph node versus no lymph node assessment), and subgroup analyses according to tumor grade were performed. Kaplan-Meier curves and cox regression analyses were used to perform survival analyses. Results298 patients were included. 199 (66.8 %) patients underwent lymph node assessment. Of these, 166 (83.4 %) had unilateral/bilateral pelvic and para-aortic/caval lymphadenectomy. Eleven (5.5 %) patients of those who underwent lymph node assessment showed pathologic metastatic lymph nodes (FIGO stage IIIA1). Twenty-seven patients (9.1 %) had synchronous endometrioid endometrial cancer. After a median follow up of 45 months (95 %CI:37.5–52.5), 5-year DFS and OS of the entire cohort were 89.8 % and 96.2 %, respectively. Age ≤ 51 years (HR=0.24, 95 %CI:0.06–0.91; p = 0.036) and performance of lymphadenectomy (HR=0.25, 95 %CI: 0.07–0.82; p = 0.022) represented independent protective factors toward risk of death. Patients undergoing lymphadenectomy had better 5-year DFS and OS compared to those not receiving lymphadenectomy, 92.0 % versus 85.6 % (p = 0.016) and 97.7 % versus 92.8 % (p = 0.013), respectively. This result was confirmed after exclusion of node-positive patients. When stratifying according to tumor grade (node-positive excluded), patients with grade 2 who underwent lymphadenectomy had better 5-year DFS and OS than those without lymphadenectomy (93.0 % versus 83.1 %, p = 0.040 % and 96.5 % versus 90.6 %, p = 0.037, respectively). ConclusionStaging lymphadenectomy in grade 2 endometrioid ovarian carcinoma patients was associated with improved DFS and OS. Grade 1 and grade 2 might be considered as two different entities, which could benefit from different approach in terms of surgical staging. Prospective studies, including molecular profiles are needed to confirm the survival drivers in this rare setting.

Our house believes that: The clipped lymph node is the true sentinel node after neoadjuvant chemotherapy in N+ patients

Axillary staging is an important prognostic factor in breast cancer, being sentinel lymph node biopsy (SLNB) the gold standard staging method in early stages. However, in clinically node positive (cN+) patients who converted to clinically node-negative (cN0) after primary systemic therapy (PST) the axillary staging method during surgery remains controversial. There are at least three validated methods: SLNB, targeted axillary dissection (TAD) and marking axillary nodes with radioactive iodine seeds (MARI) procedure. Our house believe that the biopsied and clipped lymph node could predict response to systemic treatment.

Is Systemic Chemotherapy Useful in Patients Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for Colorectal Peritoneal Metastases? A Propensity-Score Analysis.

Multimodal treatment of colorectal (CRC) peritoneal metastases (PM) includes systemic chemotherapy (SC) and surgical cytoreduction (CRS), eventually with hyperthermic intraperitoneal chemotherapy (HIPEC), in select patients. Considering lack of clear guidelines, this study was designed to analyze the role of chemotherapy and its timing in patients treated with CRS-HIPEC. Data from 13 Italian centers with PM expertise were collected by a collaborative group of the Italian Society of Surgical Oncology (SICO). Clinicopathological variables, SC use, and timing of administration were correlated with overall survival (OS), disease-free survival (DFS), and local (peritoneal) DFS (LDFS) after propensity-score (PS) weighting to reduce confounding factors. A total of 367 patients treated with CRS-HIPEC were included in the propensity-score weighting. Of the total patients, 19.9% did not receive chemotherapy within 6 months of surgery, 32.4% received chemotherapy before surgery (pregroup), 28.9% after (post), and 18.8% received both pre- and post-CRS-HIPEC treatment (peri). SC was preferentially administered to younger (p = 0.02) and node-positive (p = 0.010) patients. Preoperative SC is associated with increased rate of major complications (26.9 vs. 11.3%, p = 0.0009). After PS weighting, there were no differences in OS, DFS, or LDFS (p = 0.56, 0.50, and 0.17) between chemotherapy-treated and untreated patients. Considering SC timing, the post CRS-HIPEC group had a longer DFS and LDFS than the pre-group (median DFS 15.4 vs. 9.8 m, p = 0.003; median LDFS 26.3 vs. 15.8 m, p = 0.026). In patients with CRC-PM treated with CRS-HIPEC, systemic chemotherapy was not associated with overall survival benefit. The adjuvant schedule was related to prolonged disease-free intervals. Additional, randomized studies are required to clarify the role and timing of systemic chemotherapy in this patient subset.

Evaluation of combined pathological responses in primary tumor and lymph nodes following neoadjuvant chemoimmunotherapy in non-small cell lung cancer

BackgroundInconsistent pathological responses of tumor and lymph nodes (LNs) were frequently observed in non-small cell lung cancer (NSCLC) receiving neoadjuvant chemoimmunotherapy. However, there is a lack of studies to report the prognostic significance and the relevant clinicopathological factors of tumor-nodal inconsistent responses after neoadjuvant immunotherapy or chemoimmunotherapy. Therefore, this study aimed to depict the inconsistent pathological combined tumor-nodal responses in NSCLC patients after neoadjuvant chemoimmunotherapy as well as the underlying clinical significance. MethodsA total of 81 node-positive NSCLC patients who underwent neoadjuvant chemoimmunotherapy were eligible for inclusion. Demographic, radiologic, and pathological features of patients were recorded. Patients with pathological complete response of both tumor (ypT(pCR)) and LNs (ypN0) were classified into the combined good responder group and the relevant clinicopathological features were evaluated. The event-free survival (EFS) outcome was analyzed using Kaplan-Meier analysis. ResultsThe ypN0 and ypT(pCR) rates were 74.1 % and 42.0 %, respectively. A significant correlation was observed between ypT(pCR) and ypN0 (P = 0.003), but inconsistent responses remained. The combined responses of the primary tumor and LNs demonstrated a significant association with the prognosis outcome (P = 0.005). Notably,patients who received at least twice of their infusions of immune checkpoint inhibitors after 15:30 had a worse prognosis (P = 0.015). ConclusionA significant but not absolute correlation was observed between good tumor response and good nodal response in NSCLC patients after neoadjuvant chemoimmunotherapy, but inconsistent responses were also found. The combination of tumor and nodal responses is significantly associated with prognosis and combined good responder can be used as a reliable prognosis predictor.

This house believes that: MARI/TAD is better than sentinel node biopsy after PST for cN+ patients.

The increasing use and effectiveness of primary systemic treatment (PST) enables tailored locoregional treatment. About one third of clinically node positive (cN+) breast cancer patients achieve pathologic complete response (pCR) of the axilla, with higher rates observed in Human Epidermal growth factor Receptor (HER)2-positive or triple negative (TN) breast cancer subtypes. Tailoring axillary treatment for patients with axillary pCR is necessary, as they are unlikely to benefit from axillary lymph node dissection (ALND), but may suffer complications and long-term morbidity such as lymphedema and impaired shoulder motion. By combining pre-PST and post-PST axillary staging techniques, ALND can be omitted in most cN+patients with pCR. Different post-PST staging techniques (MARI/TAD/SN) show low or ultra-low false negative rates for detection of residual disease. More importantly, trials using the MARI (Marking Axillary lymph nodes with Radioactive Iodine seeds) procedure or sentinel lymph node biopsy (SLNB) as axillary staging technique post-PST have already shown the safety of tailoring axillary treatment in patients with an excellent response. Tailored axillary treatment using the MARI procedure in stage I-III breast cancer resulted in 80% reduction of ALND and excellent five-year axillary recurrence free interval (aRFI) of 97%. Similar oncologic outcomes were seen for post-SLNB in stage I-II patients. The MARI technique requires only one invasive procedure pre-NST and a median of one node is removed post-PST, whereas for the SLNB and TAD techniques two to four nodes are removed. A disadvantage of the MARI technique is its use of radioactive iodine, which is subject to extensive regulations.

Long Term Patient Reported Quality of Life Outcomes and Patient Satisfaction of 1-Week Hypofractionated Whole Breast Radiation Therapy Using IMRT for Early-Stage Breast Cancer

Novel whole breast radiation therapy (WBRT) regimens have been recently reported with the aim of improving patient convenience while preserving local control and breast cosmesis. The UK FAST Forward trial showed that 26 Gy in 5 fx using 3D conformal WBRT was equivalent to the standard 3-week regimen. However, the use of inverse planned intensity modulated radiation therapy (IMRT) for this novel ultra-hypofractionated regimen has not been previously studied. We aim to study the patient reported quality of life (QOL) outcomes and patient satisfaction of WBRT using IMRT delivering 26 Gy in 5 fractions. Patients receiving WBRT with 26 Gy in 5 fractions using IMRT at our institution from 2020 to 2022 were included. Patients were treated with 26 Gy in 5 daily fx with or without a single fx boost of 4-5.2 Gy. IMRT plans were generated using inverse planning with 2 to 3 volumetric modulated arcs (VMAT). To assess patient-reported QOL outcomes, a questionnaire was prospectively administered at 1 month post treatment and yearly thereafter including the EORTC QLQ-BR23 breast cancer module and other patient satisfaction questions. Patient assessment involved a four-point scale (not at all, a little, quite a bit, and very much; very satisfied, moderately satisfied, moderately dissatisfied, and very dissatisfied). Here, we report the 1-year patient reported acute toxicity QOL outcomes and patient satisfaction for those undergoing IMRT based WBRT. Cross-sectional analyses were used to determine the prevalence of "quite a bit" or "very much" effects versus "not at all" or "a little" effects. A total of 96 patients were included. The median age at diagnosis was 65 years. The most common histology was invasive ductal carcinoma (53.1%). ER-positivity was found in 75.5% patients. Oncoplastic reconstruction was used in 51.0% patients. The median tumor size was 1.5 cm. There were 4/98 (4.3%) node positive patients and 22.5% received adjuvant chemotherapy. Endocrine therapy was used in 74.5% patients. A boost fraction was delivered in 95.9% patients. At the 1-year assessment, only 1/35 (2.9%), 2/35 (5.7%), and 4/35 (11.4%) patients reported "quite a bit" or "very much" breast pain, skin problems, and changes in breast appearance respectively. Additionally, 32/35 (91.4%) patients were either "very satisfied" or "moderately satisfied" with their treatment, while 32/35 (91.4%) patients reported "excellent" (n = 12) or "good" (n = 20) physical appearance of the breast. WBRT using inverse planned IMRT with 26 Gy in 5 fx shows excellent patient reported QOL and patient satisfaction at 1-year post RT. Longer follow up is needed to assess the long-term toxicity, normal tissue effects, and cosmetic outcomes of IMRT based delivery of this ultra-hypofractionated regimen.

Postmastectomy Radiation in HER-2 Positive Breast Cancer after Neoadjuvant Therapy: Secondary Analysis of Two Randomized Trials

The role of postmastectomy radiation therapy (PMRT) following primary systemic therapy (PST) in HER-2 positive breast cancer (Her2+BC) remains poorly understood. The current study evaluates PMRT based on the pathological response to PST in Her2+BC. TRYPHAENA and NeoSphere are randomized phase II trials that investigated PST for Her2+BC. Our study is a pooled analysis of both trials, including 312 node-positive patients treated with HER-2 targeted PST followed by mastectomy with or without PMRT. The primary endpoint is loco-regional recurrence-free survival (LRRFS). Our analysis included 172 (55%) patients who achieved nodal pCR and 140 (45%) patients who did not. Patients with nodal pCR had a 5-year LRRFS of 97% with PMRT delivered in 98 patients (57%). Patients without nodal pCR had a 5-year LRRFS of 87% with PMRT delivered in 93 patients (66%). Patients with ypN1 (n = 62) disease who received PMRT (n = 40) had a 5-year LRRFS of 85% as compared to 89% in those who did not (n = 22); (p = 0.60). A significant LRRFS difference was noted in patients with ypN2-3 (n = 78) disease who received PMRT (n = 53) compared to those who did not (n = 25) (5-year LRRFS 92% vs. 75%; p = 0.019). On multivariate analysis, clinical nodal disease at diagnosis and nodal pCR were significantly associated with loco-regional recurrence (LRR). Her2+BC patients who achieve nodal pCR after PST have excellent loco-regional control which supports de-escalation of PMRT.

Axillary ultrasound for predicting response to neoadjuvant treatment in breast cancer patients—a single institution experience

BackgroundIn node-positive breast cancer patients at diagnosis (cN +) that render node-negative after neoadjuvant systemic treatment (NAST), axillary lymph node dissection (ALND) can be avoided in selected cases. Axillary ultrasound (AUS) is most often used for re-staging after NAST. We aimed to determine sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of AUS after NAST for predicting nodal response at the Institute of Oncology, Ljubljana.MethodsBiopsy-confirmed cN + patients consecutively diagnosed at our institution between 2008 and 2021, who received NAST, followed by surgery were identified retrospectively. Only patients that underwent AUS after NAST were included. AUS results were compared to definite nodal histopathology results. We calculated sensitivity, specificity, PPV and NPV of AUS. We also calculated the proportion of patients with false-positive AUS that results in surgical overtreatment (unnecessary ALND).ResultsWe identified 437 cN + patients. In 244 (55.8%) AUS after NAST was performed. Among those, 42/244 (17.2%) were triple negative (TN), 78/244 (32.0%) Her-2 positive (Her-2 +), and 124/244 (50,8%) luminal Her-2 negative cancers. AUS was negative in 179/244 (73.4%), suspicious/positive in 65/244 (26.6%) (11/42 (26.2%) TN, 19/78 (24.4%) Her-2 + , and 35/124 (28.2%) luminal Her-2 negative cancers). On definite histopathology, nodal complete response (pCR) was observed in 89/244 (36.5%) (19/42 (45.2%) TN, 55/78 (70.5%) Her-2 + , and 15/124 (12.1%) luminal Her-2 negative cancers). Among patients with suspicious/positive AUS, pCR was observed in 20/65 (30.8%) (6/11 (54.5%) TN, 13/19 (68.4%) Her-2 + and 1/35 (2.9%) luminal Her-2 negative cancers). Sensitivity was 29.0%, specificity 77,5%, PPV 69.2%, NPV 38.5%. Specificity and PPV in TN was 68.4% and 45.4%, in Her-2 + 76.4% and 31.6%, in luminal Her-2 negative 93,3% and 97,1%, respectively.ConclusionIn approximately half of the patients, AUS falsely predicts nodal response after NAST and may lead to overtreatment in 30% of the cases (ALND). However, AUS has to be interpreted in context with tumor subtype. In luminal Her-2 negative cancers, it has a high PPV and is therefore useful.

Abstract PO-021: TCGA differentially expressed genes between Caucasians and African Americans at variable analytic stringencies

Abstract Introduction: In interrogating large dimensional datasets, many methods have evolved to correctly identify differentially expressed genes at acceptable false discovery rates. We examined the NCI TCGA head and neck gene set with open source programs (at varying stringencie)s between Caucasian and African-Americans (AA) specimens and catalogued differentially expressed genes. Procedures: cBioPortal and UALCAN were utilized to investigate the Tumor Cancer Genome Atlas (TCGA). We compared AA and Caucasian samples for this analysis. Tumor samples for both groups were controlled for tumor stage (T3 and T4), HPV status (-), and age (40-75). Three different methods were utilized to identify potential genes at acceptable high stringency (defined as probability &amp;lt;2 false positives out of 20,000 genes being tested). First, those genes differentially expressed in AA vs Cau populations, as well as, those significantly differentially expressed in lymph node-positive (N+) vs negative (N0) patients were investigated (p&amp;lt;0.01 in both groups). Secondly, Benjamin-Hochberg (BH) analysis analyzed differentially expressed genes between just AA vs Cau groups (q&amp;lt;0.05). Finally, genes between these two groups possessing a p-value &amp;lt;0.0001, but not included in the BH analysis, were included in a third analysis. Results: Benjamin-Hochberg analysis identified four differentially expressed genes (q&amp;lt;0.05). There were 15 additional genes in this groups with p-values &amp;lt;0.0001. Analysis of genes differentially expressed in both AA N+ vs N0, as well as, those differentially expressed in AA vs Cau (p&amp;lt;0.01) identified one additional gene (PPIL2). Expression of this gene was found to be increased in a step-wise fashion with increased tumor grade (p&amp;lt;0.05). Three of the four genes identified by BH analysis were differentially expressed in HNSCC tumors vs control (LIN52, CTNNA2, PRMT6). Increased expression of LIN52 and PRMT6 were grade dependent (p&amp;lt;0.05). In the third analysis (AA vs Cau differentially expressed genes with p&amp;lt;0.0001), seven of 15 genes were overexpressed in tumor vs normal tissue; five of these were associated with increased tumor grade (p&amp;lt;0.05). All genes associated with increased tumor grade were demonstrated increased expression in AA groups vs Cau. Conclusions: We conclude open source TCGA programs could be readily employed to identify differentially expressed genes between both groups at varying stringencies. The high-stringency Benjamin-Hochberg analytical tool identified 4 genes differentially expressed between AA vs Cau T3/T4 HPV- tumors. Genes differentially expressed in both AA N+ vs N0, as well as, AA vs Cau revealed one potential gene of interest. When applying a p-value of &amp;lt; 0.0001, 15 additional genes were identified. The low overall number of AA specimens in this dataset was limiting and future biobanks should favor enriched collection of all stages of head and neck cancer in under represented groups. Citation Format: Seth Buryska, Jacob Tupa, Frank Ondrey. TCGA differentially expressed genes between Caucasians and African Americans at variable analytic stringencies [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Innovating through Basic, Clinical, and Translational Research; 2023 Jul 7-8; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2023;29(18_Suppl):Abstract nr PO-021.

Tumor Characteristics Associated with Axillary Nodal Positivity in Triple Negative Breast Cancer.

Larger-size primary tumors are correlated with axillary metastases and worse outcomes. We evaluated the relationships among tumor size, location, and distance to nipple relative to axillary node metastases in triple-negative breast cancer (TNBC) patients, as well as the predictive capacity of imaging. We conducted a single-institution, retrospective chart review of stage I-III TNBC patients diagnosed from 1998 to 2019 who underwent upfront surgery. Seventy-three patients had a mean tumor size of 20 mm (range 1-53 mm). All patients were clinically node negative. Thirty-two patients were sentinel lymph node positive, of whom 25 underwent axillary lymph node dissection. Larger tumor size was associated with positive nodes (p < 0.001): the mean tumor size was 14.30 mm in node negative patients and 27.31 mm in node positive patients. Tumor to nipple distance was shorter in node positive patients (51.0 mm) vs. node negative patients (73.3 mm) (p = 0.005). The presence of LVI was associated with nodal positivity (p < 0.001). Tumor quadrant was not associated with nodal metastasis. Ultrasound yielded the largest number of suspicious findings (21/49), with sensitivity of 0.25 and specificity of 0.40. On univariate analysis, age younger than 60 at diagnosis was also associated with nodal positivity (p < 0.002). Comparative analyses with other subtypes may identify biologic determinants.