Node Response Rate Research Articles

Albumin-To-Alkaline Phosphatase Ratio as a New Early Predictive Marker of Axillary Response in Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy: A Pilot Study

Background and Objectives: The Albumin-to-Alkaline Phosphatase ratio (AAPR) is an easily applicable and cost-effective marker investigated as an outcome predictor in solid cancers. Preliminary evidence in breast cancer suggests that a low AAPR correlates with a poor response to neoadjuvant chemotherapy (NAC) in primary tumors. However, data regarding the axillary response are lacking. This study aims to evaluate whether the AAPR can predict the axillary response in initially nodal-positive (cN+) breast cancer patients undergoing NAC. Materials and Methods: Clinical and biochemical variables of cN+ breast cancer patients undergoing NAC were collected. Pre-NAC albumin and alkaline phosphatase serum values were utilized in the AAPR calculation. Fisher’s exact test was performed to identify differences between the two groups of patients (high and low AAPR according to the cut-off reported in the literature). The primary outcome was the nodal pathologic complete response (pCR) rate in the two groups of patients. Results: Nodal pCR was achieved in 20/45 (44.4%) patients. A total of 36/45 (80%) patients had an AAPR > 0.583. Among patient and tumor characteristics, the only statistically significant difference between the two groups was the axillary pCR between the low and high AAPR groups (p-value = 0.03, OR = 0.129, 95% CI = 0.00–0.835). Conclusions: This pilot study suggests that the pre-treatment AAPR might be an early predictor of axillary response in cN+ breast cancer patients undergoing NAC. This result justifies further investigation in larger prospective trials to validate this finding.

The Role of Neoadjuvant Immunotherapy in the Management of Merkel Cell Carcinoma with Clinically Detected Regional Lymph Node Metastasis

BackgroundImmunotherapy is emerging as a promising option for certain locally advanced and metastatic cutaneous malignancies. However, the role of neoadjuvant immunotherapy (NIO) in Merkel cell carcinoma (MCC) with clinically detected regional lymph node metastasis (CDRLNM) has not been fully elucidated.MethodsFor this study, MCC patients with CDRLNM who underwent surgical excision were selected from the National Cancer Database (NCDB). Those who received NIO were propensity-matched with those who did not, and Kaplan-Meier analysis was used to compare overall survival (OS).ResultsOf the 1809 selected patients, 356 (19.7%) received NIO followed by wide excision (n = 352, 98.9%) or amputation (n = 4, 1.1%). The rate of complete pathologic response for the primary tumor (ypT0) was 45.2%. Only 223 patents (63.4%) also underwent lymph node dissection (LND). The complete pathologic nodal response (ypN0) rate for these patients was 17.9%. A pathologic complete response of both the primary tumor and the nodal basin (ypT0 ypN0) was seen in 16 of the 223 patients who underwent both primary tumor surgery and LND. Subsequently, 151 pairs were matched between the NIO and no-NIO groups (including only patients with LND). Kaplan-Meier analysis demonstrated a significant OS improvement with NIO (median not reached vs. 35.0 ± 8.0 months; p = 0.025). The 5-year OS was 57% in the NIO group versus 44% in no-NIO group (p = 0.021).ConclusionThe study suggests that NIO in MCC with CDRLNM provides improved OS in addition to promising rates of primary complete response, which could change the profile of surgical resection. This supports ongoing clinical trials exploring the use of NIO in MCC.

Lymph Node Metastasis in Extraperitoneal Rectal Cancer After Neoadjuvant Therapy: An Unsolved Problem?

Thanks to the promising benefits obtained in terms of quality of life, there has been growing interest in organ-sparing approaches after neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced rectal cancer, mainly represented by transanal local excision and watch-and-wait. The main mandatory criterion is complete lymph nodal response (pN0). However, considering the reduced specificity of current radiological means in identifying one-to-one correspondence between clinical and pathological staging, the problem of underestimating lymph nodal involvement remains unsolved. The aim of this study was to identify the true percentage of patients eligible for conservative surgery and possible predictive factors. Data for 59 patients with rectal cancer treated with nCRT followed by total mesorectal excision were analyzed. Patients with metastatic tumors and tumors treated with up-front surgery were excluded. Our primary endpoint was the pathological lymph nodal response rate after neoadjuvant chemoradiotherapy. The secondary endpoint was to identify predictive factors for lymph nodal response. The percentage of patients with pN0 was 62.71%, while in 37.28%, an organ-sparing approach would have not been oncologically correct. Parameters associated with pN0 were lower tumor size (T0-T2) (p=0.013) and lower grading (<G3) (p=0.06). Parameters associated with poorer disease-free survival were pN+ (p=0.019), higher lymph node ratio (p=0.001), and higher stage (p=0.038). Organ-sparing approaches may be a promising option in patients with extraperitoneal rectal cancerthat respond to nCRT. Nevertheless, it is essential to consider the limit of lymph node metastases to ensure oncological safety and, especially in cases with advanced tumors, total mesorectal excision should be the approach of choice.

Axillary pathologic response after neoadjuvant chemotherapy and surgery according to breast cancers subtypes and survival impact

To retrospectively assess the rate of pathologic complete response in the axilla according to breast cancer biologic subtypes, and to study the impact of nodal response on survival. Inclusion criteria were all T-stage breast cancers with initial lymph node involvement, non-metastatic, treated with neoadjuvant chemotherapy followed by surgery with axillary lymph node dissection, managed at the George-François Leclerc Cancer Center in Dijon, France, between 2000 and 2018. Among 437 patients included, the rate of complete nodal response rate varied according to tumor subtypes: 69.4% in Hormone Receptors (HR)-/HER2-positive, 47.4% in HR-/HER2-negative, 46.7% in HR+/HER2-positive, 8.5% in HR+/HER2-negative. By multivariate analysis, the factors significantly associated with complete nodal response were HER2-positive profile (OR 4.48 [2.14-9.65], P<0.001 if HR+; OR 8.02 [3.54-18.74], P<0.001 if HR-), triple negative tumors (OR 3.01 [1.40-6.58], P=0.005), SBRIII grade (OR 6.85 [2.28-29.58], P=0.002) and breast complete response (OR 18.69 [9.67-38.53], P<0.001). Five-year recurrence rates were 15.7% in ypN0, 23% in ypN1, 41.2% in ypN2, 50% in ypN3 patients (P<0.001). Five-year overall survival rates were 92.2% in ypN0, 85.7% in ypN1, 72.2% in ypN2, 65.4% in ypN3 patients (P<0.001). The impact of nodal response on survival was significant. Pathologic complete response in the axilla appears to be a good surrogate marker of long-term outcome in patients treated for these cancers.

MP56-06 PATHOLOGIC DOWNSTAGING RATE AND PREDICTIVE BIOMARKER EXPLORATION IN PATIENTS WITH BIOPSY-PROVEN CLINICALLY NODE POSITIVE BLADDER CANCER UNDERGOING CHEMOTHERAPY FOLLOWED BY RADICAL CYSTECTOMY

You have accessJournal of UrologyCME1 Apr 2023MP56-06 PATHOLOGIC DOWNSTAGING RATE AND PREDICTIVE BIOMARKER EXPLORATION IN PATIENTS WITH BIOPSY-PROVEN CLINICALLY NODE POSITIVE BLADDER CANCER UNDERGOING CHEMOTHERAPY FOLLOWED BY RADICAL CYSTECTOMY Amy Lim, Akshay Sood, Vikram Narayan, Mohammed Seif, Justin Matulay, Kelly Bree, Matt Campbell, Ashish Kamat, Colin Dinney, and Neema Navai Amy LimAmy Lim More articles by this author , Akshay SoodAkshay Sood More articles by this author , Vikram NarayanVikram Narayan More articles by this author , Mohammed SeifMohammed Seif More articles by this author , Justin MatulayJustin Matulay More articles by this author , Kelly BreeKelly Bree More articles by this author , Matt CampbellMatt Campbell More articles by this author , Ashish KamatAshish Kamat More articles by this author , Colin DinneyColin Dinney More articles by this author , and Neema NavaiNeema Navai More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003309.06AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Studies assessing the efficacy of preoperative chemotherapy in bladder cancer rarely include clinically node positive (cN+) patients. Further, the cN+ patients that are included are frequently categorized as cN+ based on imaging only. Therefore, true nodal response rates and oncological outcomes in this select patient group are generally unknown. Additionally, studies examining responder characteristics are lacking. METHODS: Data were collected retrospectively on patients with cTanyN1-3M0 bladder cancer who underwent radical cystectomy at the University of Texas MD Anderson Cancer Center (2006-2017). Complete nodal response (pN0) and bladder tumor response (pT0), recurrence free survival (RFS) and overall survival (OS) for patients with a positive lymph-node (LN) biopsy were recorded. Tissue mRNA microarray expression profiling was performed on LN and primary tumor tissue (pre-therapy) and compared among responders (pN0) and non-responders. RESULTS: Among the 120 patients identified with cTanyN1-3M0 disease, 26 (21.7%) patients had a positive LN biopsy. Induction chemotherapy was administered in all patients. Nine (34.6%) were pN0 and 9 (34.6%) were pT0 after primary chemotherapy. Seven were pT0N0. Lower stage disease on final pathology was associated with improved RFS and OS (p<0.001). Fourteen differentially expressed genes in the LNs and 68 differentially expressed genes in the bladder were predictive of pN0 response to primary chemotherapy in the LNs (FDR<0.1; Figure). CONCLUSIONS: Among cN+ patients, the true response rate to primary chemotherapy appears to be∼35%. Pathologic bladder response correlates well with nodal response. Finally, our study suggests that a panel of genes may be useful in distinguishing cN+ chemo-responders vs not, and thus could help reduce over- and undertreatment. These exploratory findings need prospective validation. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e775 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Amy Lim More articles by this author Akshay Sood More articles by this author Vikram Narayan More articles by this author Mohammed Seif More articles by this author Justin Matulay More articles by this author Kelly Bree More articles by this author Matt Campbell More articles by this author Ashish Kamat More articles by this author Colin Dinney More articles by this author Neema Navai More articles by this author Expand All Advertisement PDF downloadLoading ...

Cooperative self-scheduling routing protocol based IOT communication for improving life time duty cycled energy efficient protocol in SDN controlled embedded network

Internet of Things (IoT) is a developing interconnecting medium in a wireless network through internet of communication in network devices like sensors, smart devices and controllers. This interconnect the devices via the internet to make communication. Due to large sectors IoT devices and Software-Defined Networking (SDN) controllers contains energy constraints in improper routing strategies. Specifically in health care industries, the patient monitoring data's consumes higher energy to reduce the lifetime of network communication leads data losses during the IoT devices collecting the information become loss.The embedded communication are relatively controls through the Software defined network to maintain the energy consumption to improve the lifetime of energy efficient network. But leastpropagation energy losses arise communication losses because of traffic, packet losses, latency beyond with throughput limits. The main problem is Passive Infrared Sensor (PHR) sensor nodes and Relay nodes attain more energy because of non-uniform node displacement in routing in uneven energy drainage. So resolving these problems, in this system propose a cooperative self-scheduling routing protocol based IoT communication for improving energy efficient SDN controlled embedded network.Initially this construct the Neighbor Distance Discovery Protocol (NDDP) to identify the minimum depletion path by identifying Sensor closest route to the relay node. Then construct the Multipath Cooperative Self-Scheduling Protocol (MCSSP) to formalize the non-traffic route. By estimating the energy consumption on each sensor node on routing medium, this considers the prior routing communication rate by calculating average transmission delay, sensor absorption rate, power consumption, node response rate, and packet loss rate. UsingLife Time Duty Cycled Energy Efficient Protocol (LTDCEEP) to calculate the delimit of the feature limits along the network threshold latency energy limits. Based on the transition limit the weights of the nodes are estimated by energy consumption from each duty cycle by consuming more transmission energy, the route be scheduled to optimize the communication delay to reduce the power consumption in the sense of responsive nodes. This improves the power consumption rate, latency, power quality in transmission, throughput ratio in SDN network communication.

Neoadjuvant Chemotherapy and Nodal Response Rates in Luminal Breast Cancer: Effects of Age and Tumor Ki67.

Neoadjuvant chemotherapy (NAC) is standard for most triple-negative and human epidermal growth factor receptor 2 (HER2)+ breast cancers, and frequently downstages node-positive (cN+) disease, permitting omission of axillary dissection. In estrogen receptor (ER)+/HER2- disease, response rates are lower. Whether Ki67 is associated with axillary downstaging in ER+/HER2- diseaseis unknown. With institutional review board approval, we queried our institutional database to identify all patients with primary ER+/HER2- biopsy-proven cN+ breast cancer treated with NAC followed by surgery from January 2012 to December 2021. Nodal pathologic complete response (pCR) rates were evaluated by pretreatment Ki67 and patient age. 315 patients (median age 50years) were included. Nodal pCR rate was 24.8% (78/315) and was higher in patients aged < 50years than ≥ 50years (31.8% versus 17.7%, p = 0.004). Ki67 was available on 236 patients (74.9%). Median Ki67 was 29.0% (range 1-98%) and did not differ by age category (p = 0.23). Patients with nodal pCR had higher Ki67 (median 40.3% versus 25.0%, p < 0.001). Nodal pCR rates were 28.4% (Ki67 ≥ 20%) versus 8.1% (Ki67 < 20%) (p < 0.001). On multivariable analysis, Ki67 and age category were predictive of nodal pCR. Combining these two parameters together, nodal pCR rates in age < 50years were 35.8% when Ki67 ≥ 20% versus 14.3% with Ki67 < 20% (p = 0.02). In contrast, for age ≥ 50years, nodal pCR was 21.0% for Ki67 ≥ 20% versus 2.6% with Ki67 < 20% (p = 0.008). In ER+/HER2- breast cancer, nodal downstaging with NAC is associated with age (< 50years) and Ki67 (≥ 20%). Age and Ki67 should be considered for NAC decision-making and can identify patients with high rates of nodal downstaging (36%) who would benefit from NAC to enable axillary preservation.

P-OGC29 Pathological response profiles of FLOT and ECX neoadjuvant chemotherapy in oesophageal adenocarcinoma

Abstract Background 70% of patients undergoing neo-adjuvant ECX chemotherapy for adenocarcinoma of the oesophagus, show little to know response in their primary tumour (Mandard 4,5). However, among these patients, those who have a complete nodal response (cN+ to ypN0) have equivalent survival to those with Mandard 1,2,3 tumours. FLOT chemotherapy has shown a survival advantage to ECX, however, rates of primary tumour response and nodal response are yet to be the focus of published study. Methods Retrospective cohort study comparing patients undergoing ECX and FLOT neoadjuvant chemotherapy between 2014 and 2021. Pathological outcomes were examined including, Mandard tumour regression grade (1-5), complete nodal response (cN+ to ypN0), clinically node negative nodal progression (cN0 to ypN+). Results 226 patients had data available for analysis (193 ECX and 33 FLOT). 27% (52/193) of patients receiving ECX showed a response in the primary tumour (Mandard 1,2,3) compared to 63% (21/33) with patients undergoing FLOT (p &amp;lt; 0.001). Complete nodal response rates were 25% in ECX patients and 21% FLOT patients (p = 0.556). Clinically node negative nodal upstaging (cN0 to pN+) was higher among FLOT patients 30% (13/33) than ECX patients 12% (24/193) (p &amp;lt; 0.001). Conclusions FLOT chemotherapy confers improved primary tumour response. However, these findings were not echoed in locoregional nodal responses. Survival advantages with FLOT may result from improved responses in primary tumour and not improved systemic coverage. More data will be needed to explore this and over-come the confounding effect of staging inaccuracies. However, understanding systemic and loco-regional responses of different chemotherapy regimens will be needed to tailor future neoadjuvant treatment regimens.

Surgical Management of Axilla Following Neoadjuvant Endocrine Therapy.

BackgroundRandomized clinical trials support deescalation of axillary surgery in breast cancer patients with low-volume axillary disease treated with a surgery-first approach. However, few data exist to guide axillary surgery following neoadjuvant endocrine therapy (NET). Therefore, we evaluated the extent and outcomes of axillary surgery in a contemporary cohort of NET patients, a treatment approach that has become particularly relevant during the coronavirus disease-19 (COVID-19) pandemic.Patients and MethodsWe identified invasive breast cancer patients treated with NET between October 2008 and November 2019. Patients presenting with stage IV disease or recurrent disease were excluded. Statistical analyses were performed using chi-square, Fisher’s exact, and Wilcoxon rank-sum tests.Results194 invasive breast cancers in 186 patients (median age 66 years) were evaluated; 81 patients had breast-conserving surgery (BCS), while 113 underwent mastectomy. Eighty-four patients (43.3%) were biopsy-proven cN+ with 4/84 (4.8%) ypN0 following NET. Among cN+ patients, 14 (16.7%) had sentinel lymph node biopsy (SLNB) only, 27 (32.1%) had SLNB + axillary lymph node dissection (ALND), and 43 (51.2%) had ALND. Among 110 cN0 patients, 99 had axillary surgery with 28/99 (28.3%) ypN+: SLNB in 83 (75.5%), SLNB+ALND in 14 (12.7%), and ALND in 2 (1.8%). Among all ypN+ patients, 23/108 (21.3%) had SLNB alone: 18/43 (41.9%) of BCS and 5/65 (7.7%) mastectomy patients (p < 0.001). After median follow-up of 35 months, no regional recurrences were observed.ConclusionsAmong biopsy-proven cN+ NET patients, we observed deescalation of axillary surgery in selected patients, despite a low nodal pathologic complete response (pCR) rate, without nodal recurrences. These data suggest that patients with low-volume axillary disease treated with NET may be managed similarly to patients treated with a surgery-first approach.Supplementary InformationThe online version contains supplementary material available at 10.1245/s10434-021-10385-4.

Exposure-Response of Idelalisib Administered in Combination with Bendamustine and Rituximab for the Treatment of Relapsed Chronic Lymphocytic Leukemi

Background: Idelalisib (IDELA) is a potent and selective PI3Kδ inhibitor approved for the treatment of relapsed chronic lymphocytic leukemia (CLL) (in combination with rituximab) and relapsed indolent non-Hodgkin lymphoma (iNHL) subtypes, follicular lymphoma, and small-cell lymphocytic lymphoma. The relationship between plasma exposures of IDELA and clinical efficacy and safety were evaluated in relapsed/refractory CLL subjects following administration of IDELA 150 mg twice daily (BID) in combination with bendamustine (B) and rituximab (R; Study GS-US-312-0115).Methods: IDELA peak and trough plasma samples were collected every 4 weeks (up to 24 weeks) starting at baseline. Data for safety and efficacy endpoints were collected every 2 and 12 weeks, respectively. IDELA plasma exposures (Cmax, AUCtau, and Ctau) were generated using a previously developed population pharmacokinetic (PK) model (Jin F, et al. CCP . 77: 89-98, 2016). Efficacy and safety data from the phase 3, randomized, double-blind, placebo-controlled study (GS-US-312-0115) were included in the PK/pharmacodynamics (PD) analyses. Efficacy endpoints, including best overall response rate (BOR), duration of response (DOR), progression-free survival (PFS), sum of products of the greatest perpendicular diameters (SPD) of index lesions, and lymph node response rate (LNR), were evaluated against IDELA exposures (AUCtau and Ctau). Safety endpoints, including Grade 3 or 4 adverse events of neutropenia, skin rash, infection, pneumonia, pneumonitis, diarrhea, colitis, and aspartate aminotransferase (AST) or alanine aminotransferase (ALT) elevation, were evaluated versus IDELA exposures (AUCtau and Cmax). The relationship between average daily dose of IDELA versus exposures (AUCtau and Cmax) was also evaluated. Statistical analysis (such as Kaplan-Meier survival analysis, Cox proportional hazard model, or logistic regression) was conducted for selected efficacy and safety endpoints.Results: Median IDELA exposures were similar in subjects who achieved an objective response (complete response or partial response) and subjects who did not respond (stable disease or progressive disease) and across the 4 response categories (p=0.68; Table 1). As IDELA exposure increased over quartiles, there was no clear trend of prolonged DOR (p=0.50), PFS (p=0.69), or change in SPD. No relationship between LNR (responder versus non-responder) and IDELA exposure was observed. No association was observed between IDELA exposure vs incidence of neutropenia (p=0.35), diarrhea (p=0.78), pneumonia (p³0.12), colitis (p=0.62), AST or ALT elevation (p=0.45), skin rash, and pneumonitis. An increase in the incidence of Grade 3 or 4 infections with higher IDELA exposures was observed (p=0.021). Overall, IDELA in combination with BR was well tolerated, as indicated by the comparable average daily doses (~300 mg) administered across quartiles of IDELA exposure.Conclusions: No exposure-response relationships were observed for efficacy or safety (except infections) endpoints at IDELA 150 mg BID. These results are consistent with the previously observed IDELA exposure-response relationship in subjects with CLL (in combination with rituximab or ofatumumab) and iNHL. Overall, this analysis supports IDELA 150 mg BID in combination with BR for the treatment of relapsed CLL in patients who are fit for immunochemotherapy. [Display omitted] DisclosuresDaryani:Gilead Sciences, Inc.: Employment, Equity Ownership. Sharma:Gilead Sciences, Inc.: Employment, Equity Ownership. Xing:Gilead: Employment, Equity Ownership. Silverman:Gilead Sciences, Inc.: Employment, Equity Ownership. Adewoye:Gilead Sciences, Inc.: Employment, Equity Ownership. Mathias:Gilead Sciences, Inc.: Employment, Equity Ownership.

Neoadjuvant Capecitabine and Oxaliplatin Before Concurrent Capecitabine and Radiation in Locally Advanced Rectal Cancers: Experience of a Cancer Hospital in Pakistan.

PURPOSETo report the toxicity and pathologic response rates after adding neoadjuvant capecitabine and oxaliplatin (CAPOX) followed by concurrent radiation and capecitabine (CAPRT) and surgery in patients with locally advanced rectal cancer.MATERIALS AND METHODSWe retrospectively analyzed medical records of 301 patients between January 2007 and December 2014. Patients were treated with four cycles of neoadjuvant chemotherapy comprising CAPOX, followed by radiotherapy at doses of 45-54 Gy in 25-30 fractions with concurrent capecitabine. A response assessment scan was performed at 4-6 weeks postradiation followed by surgical evaluation at 6-8 weeks. Pathologic tumor and nodal response rates as well as circumferential resection margin were assessed on surgical specimens.RESULTSThe median age of the patients was 43 years (range, 16-78). Overall, 227 (75.4%) patients were able to complete four cycles of CAPOX. Neoadjuvant chemotherapy was well-tolerated with no serious adverse effects. The most common toxicity was diarrhea (grade 2, n = 108; 35.8%; grade 3, n = 57; 18.9%; grade 4, n = 25; 8.3%) followed by neuropathy (grade 2, n = 132; 43.8%; grade 3, n = 54; 17.9%) and oral mucositis (grade 2, n = 108; 35.8%; grade 3, n = 47; 15.6%; grade 4, n = 9; 2.99%). A total of 229 (76.1%) patients underwent surgery. Pathologic complete response was seen in 52 (22.7%; 95% CI, 13 to 28), whereas 200 (87.3%; 95% CI, 82 to 99) patients had a negative circumferential resection margin on pathology.CONCLUSIONNeoadjuvant chemotherapy with CAPOX before CAPRT and planned total mesorectal excision surgery result in good tumor regression and substantial pathologic complete response rates with acceptable toxicity. With growing interest in organ preservation in rectal cancer, the strategy of completing all chemotherapy and chemoradiotherapy before planned surgery offers a favorable paradigm. However, further randomized clinical trials are needed to support this evidence.

Targeted axillary biopsy and sentinel lymph node biopsy for axillary restaging after neoadjuvant chemotherapy.

PurposeAccurate restaging of the axilla after neoadjuvant chemotherapy (NAC) is an important issue to ensure deescalating axillary surgery in patients with initial metastatic nodes. We aimed to present our results of targeted axillary biopsy (TAB) combined with sentinel lymph node biopsy (SLNB) for axillary restaging after NAC.MethodsIn 64 breast cancer patients who underwent NAC, biopsy-proven positive nodes were marked with clips before NAC, and ultrasound-guided wire localization of clip-marked nodes was performed after NAC. Patients underwent TAB and SLNB for post-NAC axilla restaging.ResultsIdentification rates of post-NAC TAB and SLNB were 98.4% and 87.5%, respectively (P = 0.033). Histopathology revealed a nodal pathologic complete response (pCR) rate of 47% in which axillary lymph node dissection (ALND) was avoided. TAB alone and SLNB alone detected residual disease in 29 (85.3%) and 20 (58.8%) patients (P = 0.029), respectively. Whereas rates of up to 97% had been achieved with a combination of TAB and SLNB. The pCR rates after NAC were 64.3% for human epidermal growth factor receptor 2 positive and triple-negative tumors and 13.6% in luminal tumors (P = 0.0002).ConclusionPathologic analysis following TAB combined with SLNB revealed the pCR rates to NAC in a considerable number of patients that provided de-escalation of axillary surgery. A combination of SLNB and TAB was found to be an accurate procedure in establishing residual nodal disease. This combined procedure in patients with initially positive nodes was a reliable method for post-NAC axillary restaging.

Residual tumor characteristics of esophageal squamous cell carcinoma after neoadjuvant chemoradiotherapy

ObjectiveThe study was to investigate the characteristics of residual tumors of esophageal squamous cell carcinoma after neoadjuvant chemoradiotherapy. MethodsThe resection specimens of 187 patients undergoing surgery after neoadjuvant chemoradiotherapy in Zhongshan Hospital of Fudan University were reevaluated. Tumor regression grade determined by residual tumor ratios was scored for each specific layer of the esophageal wall and all removed lymph nodes for 4 grades as tumor regression grade 1, 0% residual tumors, tumor regression grade 2, less than 10%; tumor regression grade 3, 10% to 50%; tumor regression grade 4, greater than 50%. The pretreatment pathologic tumor stage and pretreatment pathologic lymph node stage before neoadjuvant chemoradiotherapy were recorded reflecting the original depth of primary tumor and number of originally involved lymph nodes, respectively. According to regression directionality, regression pattern was classified into 4 categories as type I: regression toward the lumen, type II: regression toward the invasive front, type III: concentric regression, and type IV: scattered regression. Statistical analyses were performed using Mann–Whitney, chi-square, Cochran Q tests, and Kendall τ-b coefficient, appropriately. ResultsA total of 138 patients have residual tumors, and 97 patients (70.3%), 100 patients (72.5%), 89 patients (64.5%), 63 patients (45.7%), and 68 patients (49.3%) have malignant cells in mucosa, submucosa, muscularis propria, adventitia/surrounding stroma, and lymph nodes, respectively. A total of 115 patients (83.3%) had residual tumors in the mucosa or submucosa, but 63 (54.8%) were graded as tumor regression grade 2 with small amounts of tumors in these 2 layers, 9 patients (6.5%) had residual tumors only in the deep 2 layers, and 14 patients (10.1%) had residual tumors only in lymph nodes. Overall, 86 patients (62.7%) with residual tumors are difficult to identify via present techniques. In patients with tumors that involved all esophageal layers before neoadjuvant chemoradiotherapy, only muscularis propria contained residual tumors significantly more frequently than the adventitia/surrounding stroma (P < .001). The random type IV and nonrandom regression patterns of type I to III were comparable with 48.9% and 51.1%, respectively. In patients with positive lymph node before neoadjuvant chemoradiotherapy, only a small portion of patients (29.2%, 28/96) achieved ypN0 status (nodes pathological complete response), even worse than the primary lesions (33.6%, 63/187) in esophageal squamous cell carcinoma. ConclusionsThe small amount of viable tumor cells in the superficial layers, low pathological complete response rate of lymph nodes, and diverse regression patterns lead to difficulty of detecting residual tumors in esophageal squamous cell carcinoma.

Combined Nimotuzumab with Chemoradiotherapy for Locally Advanced Head and Neck Squamous Cell Carcinoma.

BackgroundMost head and neck cancers (HNCs), specifically squamous cell carcinoma, express epidermal growth factor and are associated with an inadequate response to radiotherapy and chemotherapy. Anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (mAb) increase response rates and survival when combined with radiotherapy or chemoradiotherapy (CRT). This study evaluates the outcome and toxicity of the nimotuzumab-CRT combination for stage III, IVa, and IVb squamous cell carcinoma of the head and neck.MethodsEighty-seven patients with squamous cell carcinoma of the head and neck, stage III, IVa, or IVb were enrolled in a prospective comparative study. The nimotuzumab plus CRT group consisted of patients who received nimotuzumab 200 mg every week for six consecutive weeks chemoradiation therapy; cisplatin 30 mg/m2 every week for six weeks; radiotherapy of 2-Gy/fraction, five fractions/week for a total dose of 70 Gy; and neck lymph node invasion prophylaxis at 50 Gy. The CRT alone arm was treated with CRT (without nimotuzumab).ResultsTumor response rate of 90.6% was achieved in nimotuzumab plus CRT group (complete response: 58.1%), and 70.4% in CRT alone arm (complete response: 38.6%; p=0.029). The lymph node response rate was 83.4% in nimotuzumab plus CRT group (complete response: 46.7%), and 73.0% in CRT group (complete response: 23.0%). The general response rate in nimotuzumab plus CRT group was 86.0% (complete response: 48.8%), and 68.0% in CRT alone arm (complete response: 36.0%). Twelve-month overall survival (OS) was 75.1% for the nimotuzumab plus CRT group and 54.4% for the CRT group. The 24-month survival was 48.0% (nimotuzumab plus CRT group) and 29.0% (CRT alone arm). The median OS was 20 months and 13 months for nimotuzumab plus CRT group and CRT alone arm, respectively. Progression-free survival (PFS) in the nimotuzumab plus CRT group at 12 months and 24 months was 64.2% and 37.4%, respectively. PFS in the CRT group at 12 months and 24 months was 39.5% and 21.3%, respectively. Infusion reaction presented mildly in two of 43 patients in the nimotuzumab plus CRT group, and no shock occurred. Other toxicity occurrences were similar between the two groups, mainly in grade I, II. Skin rash (grade I only) occurred at a rate of 4.7% in the nimotuzumab plus CRT group.ConclusionNimotuzumab in combination with CRT was well tolerated as a treatment program for locally advanced head and neck squamous cell carcinoma.

Abstract P2-16-06: In-breast pathologic complete response (pCR) following neoadjuvant chemotherapy predicts nodal pCR in early stage breast cancer

Abstract Background: With advances in neoadjuvant chemotherapy (NAC), an increasing number of breast cancer patients achieve a pathologic complete response (pCR). Efforts are underway to non-invasively identify pCR in the breast, such that characterization of the concomitant nodal response will be invaluable for locoregional treatment planning. Here, we sought to evaluate the correlation between in-breast response and residual nodal disease among early stage breast cancer patients. Materials/Methods: We identified 728 patients who received NAC at our institution from 2006 to 2016. Breast and nodal response rates were evaluated and further stratified by clinicopathologic features, and biologic subtype approximation (hormone receptor positive [HR+], HER2 negative [HER2-] and low or intermediate grade = luminal A; HR+/HER2- and high grade = luminal B; HER2/neu-amplified = HER2+; ER-/HER2- = triple negative). Descriptive statistics and univariate analyses were employed to evaluate the correlation between breast and nodal response. Results: Of 728 patients, 269 (37%) were clinically node negative (cN0) and 459 (63%) were clinically node positive (cN+). Median age was 51 and median tumor size was 4.0cm (IQR 2.7 - 5.5cm). The cohort comprised 13% luminal A patients, 20% luminal B, 38% HER2, and 29% triple negative. Following NAC, the overall pCR rate (breast and nodes) was 29.8%. Among all cN0 patients who had a breast pCR (ypT0; n = 96), none exhibited residual nodal disease (100% ypN0). Among cN+ patients who had a breast pCR (n = 128), only 5.4% (n = 7) had residual nodal disease (ypN+). Rates of residual nodal disease among cN+ patients who achieved breast pCR varied by biologic subtype: luminal A patients with pCR in the breast had a 50.0% probability of residual nodal disease (n = 1/2 were ypT0N+), luminal B 6.7% (1/15), HER2+ 2.5% (2/80) and triple-negative 9.6% (3/31) (p=0.03). Conversely, among cN+ patients who exhibited nodal pCR following NAC, the rate of residual in-breast disease varied by receptor subtype: 80.0% of clinically node-positive luminal A patients who became ypN0 had residual in-breast disease (ypT+N0; n = 4/5), 60.0% of luminal B (21/35), 38.1% HER2+ (48/126), and 50.9% triple negative (29/57) (p=0.03). Conclusions: Among early stage breast cancer patients receiving NAC, in-breast pCR is predictive of nodal pCR. Among 96 cN0 patients who had in-breast pCR, we found none with residual nodal disease, representing a population that may be suitable for further limiting nodal therapy. The ability to pre-operatively identify in-breast pCR in this population would be particularly valuable if nodal pCR can consequently be inferred, potentially paving the way for studies of therapeutic de-escalation. Citation Format: Achraf Shamseddine, Jessica Flynn, Zhigang Zhang, Monica Morrow, Boris Mueller, Erin Gillespie, Atif Khan, Beryl McCormick, Oren Cahlon, Simon Powell, Andrea Barrio, Lior Z Braunstein. In-breast pathologic complete response (pCR) following neoadjuvant chemotherapy predicts nodal pCR in early stage breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-16-06.

Administration of nimotuzumab combined with cisplatin plus 5-fluorouracil as induction therapy improves treatment response and tolerance in patients with locally advanced nasopharyngeal carcinoma receiving concurrent radiochemotherapy: a multicenter randomized controlled study

BackgroundNimotuzumab (NTZ) is an anti-EGFR monoclonal antibody. However,the effect of targeted drugs combined with induction therapy in locally advanced nasopharyngeal carcinoma remains unclear. The aim of this study is to investigate the safety and efficacy of NTZ combined with cisplatin plus 5-fluorouracil (PF) as induction regimen in locally advanced nasopharyngeal carcinoma (NPC) patients receiving concurrent radiochemotherapy.MethodsThis was a multicenter randomized controlled study performed in eight Guangxi hospitals in 2015–2017. Eligible patients with NPC were randomized into nimotuzumab/PF (NPF group) and docetaxel/PF (DPF group) regimens, respectively, as induction therapy. After 2 cycles of induction therapy, all patients received cisplatin and concurrent intensity modulated radiation therapy (IMRT). Then, the two groups were compared for safety and efficacy.ResultsA total of 118 patients with stage III-IVa NPC were assessed, with 58 and 60 in the NPF and DPF groups, respectively. Compared with DPF treatment, NPF induction therapy showed a more pronounced effect on cervical lymph nodes (P = 0.036), with higher response rate (RR) (81% vs 60%). Compared with the DPF group, the NPF group showed significantly reduced leukopenia, neutropenia and gastrointestinal reactions (all P < 0.05); rash only appeared in the NPF group, but all cases were grade 1. During concurrent treatment with radiotherapy and chemotherapy, the NPF group showed better tolerance to radiotherapy and chemotherapy; neutropenia, anemia, gastrointestinal reactions, oral mucositis and radiation dermatitis in the NPF group were significantly reduced (P < 0.05). The expression rate of EGFR was 94.9% (112/118). Compared with the DPF group, patients with EGFR expression in the NPF group showed better response (77.8% vs 63.0%, P = 0.033).ConclusionFor locally advanced NPC patients receiving follow-up cisplatin and IMRT, nimotuzumab/PF for induction therapy has better lymph node response rate and milder adverse reactions than the DPF regimen. In addition, the patients have better tolerance in subsequent concurrent radiotherapy and chemotherapy; however, long-term efficacy needs further follow-up evaluation.Trial registrationThe registration number of the clinical trial is ChiCTR-OIC-16008201 and retrospectively registered on March 31, 2016.

A Phase 2, Randomized, Open-Label, 2-Arm Study Comparing 2 Intermittent Dosing Schedules of Duvelisib in Patients with Indolent Non-Hodgkin Lymphoma (iNHL) (TEMPO)

Background Duvelisib, an oral dual PI3K-δ and PI3K-γ inhibitor, is approved by the US Food and Drug Administration for the treatment of adult patients with relapsed or refractory (R/R) follicular lymphoma (FL) after ≥ 2 prior systemic therapies. In multiple phase 1-3 studies that included patients with iNHL, duvelisib was shown to be efficacious, with a favorable risk-benefit profile. This study will evaluate whether duvelisib efficacy at the approved 25 mg twice daily (BID) dose can be achieved and maintained with an acceptable or improved safety profile by the inclusion of prespecified 2-week drug holidays in patients with R/R iNHL. Study Design and Methods TEMPO is a randomized, open-label, multicenter, international, phase 2 study of duvelisib in adult patients with R/R iNHL in whom ≥ 1 line of prior therapy has failed. The primary objective is to evaluate the efficacy of duvelisib administered with prescribed drug holidays, with the primary endpoint of overall response rate (ORR) by the 2007 revised International Working Group criteria. Key secondary endpoints include ORR by the 2014 Lugano criteria, progression-free survival, overall survival, time to treatment failure, duration of response, lymph node response rate, time to the first response, adverse event profile, and determination of pharmacokinetics parameters. Exploratory objectives include assessment of quality of life and biomarkers of treatment response and toxicity. Key inclusion criteria include histologically confirmed FL grades 1 to 3a, marginal zone lymphoma (splenic, nodal, or extranodal) or small lymphocytic lymphoma, radiological evidence of disease progression and ≥ 1 bidimensionally measurable lesion ≥ 1.5 cm, adequate organ function, and Eastern Cooperative Oncology Group performance status ≤ 2. Key exclusion criteria include prior allogeneic hematopoietic stem cell transplant; previous treatment with a PI3K inhibitor; history of drug-induced colitis or drug-induced pneumonitis; ongoing treatment for systemic infection; central nervous system NHL; prolonged QT interval; history of tuberculosis treatment within the 2 past years; history of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or mechanical control within the past 6 months; history of or concurrent interstitial lung disease of any severity and/or severely impaired lung function; ongoing treatment with chronic immunosuppressants; and any unstable or severe uncontrolled medical condition. A total of 102 patients are planned to be enrolled. Patients will be randomized 1:1 to 2 arms and stratified by number of prior therapies (1 or &gt; 1), bulky disease status (longest diameter of baseline lesion &lt; 5 cm or ≥ 5 cm), and time since last recurrence (≥ 24 months or &lt; 24 months). In arm 1, patients will receive duvelisib 25 mg BID for one 10-week (W) cycle followed by 25 mg BID on W3 and W4 of each subsequent 4-week cycle. In arm 2, patients will receive duvelisib 25 mg BID on W1, W2, W5, W6, W9, and W10 of one 10-week cycle and then on W3 and W4 of each subsequent 4-week cycle. Patients will be treated until disease progression, unacceptable toxicity, or withdrawal. This study will test the null hypothesis that the ORR in each arm is ≤ 30% against the alternative that the ORR is ≥ 55%. The study has a 2-stage design. In stage 1, 15 patients will be enrolled in each arm, with response assessment after ≥ 3 cycles. If there are fewer than 6 partial or complete responses, consideration may be given to terminating the arm. Otherwise, in stage 2, 36 additional patients will be enrolled, for a total of 51 per arm. Enrollment is planned to be initiated in August 2019. Approximately 50 sites will be open for enrollment across the United States, Europe, and Asia. Disclosures Karmali: Takeda, BMS: Other: Research Funding to Institution; Gilead/Kite; Juno/Celgene: Consultancy, Speakers Bureau; Astrazeneca: Speakers Bureau. Youssoufian:Verastem Oncology: Consultancy, Equity Ownership. Sprott:SMOC Therapeutics: Employment, Equity Ownership; Verastem Oncology: Employment, Equity Ownership. Weaver:FemtoDx: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Patents &amp; Royalties: Inventor; Verastem Oncology: Employment, Equity Ownership, Patents &amp; Royalties: Inventor; Hillstream Biopharma: Consultancy, Equity Ownership. Narasimhan:Verastem: Employment, Equity Ownership. Lustgarten:Verastem: Employment. Patrick:Verastem Oncology: Employment. Zalutskaya:Verastem Inc: Employment, Equity Ownership. Gordon:Gilead: Other: Advisory Board; Juno/Celgene: Other: Advisory Board, Research Funding; Zylem LLC: Other: co-founder; research in nanoparticles in cancer; Bayer: Other: Advisory Board. OffLabel Disclosure: Duvelisib (DUV), a dual PI3K-delta,gamma inhibitor, is US FDA approved at 25 mg twice daily (BID) for the treatment of R/R chronic lymphocytic leukemia or small lymphocytic lymphoma after at least 2 lines of prior therapy and R/R follicular lymphoma after at least two prior systemic therapies.

Patterns in the Use of Axillary Operations for Patients with Node-Positive Breast Cancer After Neoadjuvant Chemotherapy: A National Cancer Database (NCDB) Analysis.

The American College of Surgeons Oncology Group (ACOSOG) Z1071 and Sentinel Neoadjuvant (SENTINA) trials of sentinel node biopsy for node-positive breast cancer treated with neoadjuvant chemotherapy (NAC) demonstrated false-negative rates that varied on the basis of surgical technique. This study evaluated trends in axillary operations before and after publication of these trials. This study analyzed patients from National Cancer Database (NCDB) with clinical T0 through T4, N1 and N2, M0 breast cancer who received NAC from 1 January 2012 to 31 December 2015 and sentinel lymph node biopsy (SNB) or axillary lymph node dissection (ALND). The patients were divided into the following groups: SNB, ALND, and (SNB + ALND). Of the 32,036 evaluable patients identified in this study. 5565 had SNB, 19,930 had ALND, and 6541 had SNB + ALND. Compared with the ALND group, the SNB group was younger, had more invasive ductal cancers, and had lower clinical T- and N-stage disease (p < 0.001). The patients in the SNB group had a higher rate of estrogen receptor-positive and triple-negative breast cancers, but a lower rate of human epidermal growth factor receptor 2 (HER2)-positive cancer (p < 0.001). The nodal pathologic complete response (PCR) rate, defined as no residual invasive cancer, was 66.5% in the SNB group and 33.1% in the ALND group. Since 2013, the rate of ALND has decreased from 88.7 to 77.1% in both community and academic institutions (p < 0.001). Since publication of the ACOSOG Z1071 and SENTINA trials, the national rates of ALND in node positive breast cancer treated with NAC have decreased despite reported false-negative SNB rates and lack of prospective outcome data regarding the oncologic safety of ALND omission.

Comparative analysis of biopsy proven lymph node positive bladder cancer patients to those with biopsy proven lymph node negative disease prior treatment.

475 Background: Many studies assessing the efficacy of chemotherapy before surgery include few clinically node positive patients or completely exclude them which make response rates in this particular subset of patients difficult to determine. Additionally, these patients are clinically node positive, making true nodal response rates unable to be determined. We report a descriptive analysis of patients with clinically node positive disease who underwent lymph node biopsy prior to any treatment and their outcomes. Methods: Data was obtained retrospectively from patients with cTanyN1-3M0 bladder cancer from 2006-2017 who underwent radical cystectomy at MD Anderson. SPSS was used for statistical analysis. Results: Among the 120 patients with cTanyN1-3M0 (median follow up 27.4 months), 40 patients underwent lymph node biopsy (LNBx). 26 (65%) patients had a positive LNBx, 14 (35%) were negative. 100% of the patients with a positive LNBx underwent primary chemotherapy. On final cystectomy, 9 (34.6%) of those patients had complete nodal response (pN0) and 9 (34.6%) had complete bladder response (pT0). 7 were pT0N0. Of the patients with a negative LNBx, 11 (78.6%) underwent neoadjuvant chemotherapy and of those patients, 7 (63.6%) were pN0 and 4 (36.4%) were pT0. Of patients that did not undergo LNBx that received primary chemotherapy (78 patients), 41 (52.6%) were pN0 and 22 (28.2%) were T0. There was no significant difference in overall or recurrence free survival between patients with a positive or negative biopsy or who did not undergo biopsy (p = .474). There was a significant improvement in overall and recurrence free survival in patients with negative nodal disease on final pathology compared to those with positive nodal disease (p &lt; 0.001). Conclusions: Patients that had a negative LNBx were less likely to undergo primary chemotherapy. Pathologic bladder response rates correlate with nodal response rates. In cN+ patients, overall survival and recurrence free rates are not significantly different in patients without a lymph node biopsy, a positive biopsy or a negative biopsy. Finally, advanced final pathologic stage predicts worse outcomes.

Prognostic Value of Nodal Response After Preoperative Treatment of Gastric Adenocarcinoma.

Background: Pathologically positive lymph nodes (ypN+) after preoperative chemotherapy are associated with poor survival in patients with gastric cancer. Little is known about the association between response to preoperative therapy and the benefit of postoperative therapy. Methods: This retrospective cohort study of the National Cancer Database included patients with clinically node-positive (cN+) gastric cancer treated with preoperative therapy followed by surgery (2006-2014). Preoperative treatment modality was categorized as the inclusion of radiation therapy (RT) or chemotherapy alone. Pretreatment clinical and pathologic stages were used to determine pathologic treatment response rates. The association between overall risk of death and preoperative treatment, disease response, and adjuvant therapy use was evaluated using multivariable Cox regression. Results: Preoperative RT was used in 53.6% of 1,976 patients with cN+ gastric cancer, (74.3% cardia and 10.1% noncardia). The nodal response rate was 38.9% and was higher with RT than with chemotherapy alone (cardia, 46.0% vs 29.1%; P<.001; noncardia, 43.8% vs 31.9%; P=.06). Preoperative RT was associated with an approximate 2-fold increase in the odds of pathologic response compared with chemotherapy. Overall, use of adjuvant therapy was not associated with a decreased risk of death. A primary tumor response with residual nodal disease was not associated with survival (hazard ratio [HR], 1.03; 95% CI, 0.66-1.60). However, a nodal response with residual primary disease was significantly associated with survival (HR, 0.54; 95% CI, 0.44-0.65). Conclusions: More than one-third of node-positive gastric cancers showed pathologic nodal response with preoperative treatment. RT is associated with a higher response than chemotherapy. Patients with ypN+ disease have worse survival, regardless of whether they receive postoperative therapy. Future gastric cancer trials should evaluate the role of preoperative RT and individualize postoperative therapy use.